1,177,523 Matching Annotations
  1. Oct 2024
    1. two points with regard to the logical dimen-sion of incorporeal sense to be related to the physical notion of theincorporeal event-effe

      incorporeal event-effect = sayable, the thing that can be said logical dimension = Sinn = sense-events, the extra meaning of any statement is an event constituted in relation to the sayable. Sinn is an event that captures the sayable, itself an event.

    2. Sense is something ‘extra’ – an altogetherdifferent type of entity – added on to or extracted from the actualutterance. It thus follows that in order to explicitly state the sense ofwhat I say, the sense of my utterance must be taken as the object ofa second utterance. But this second utterance also expresses a sensewhich is, in turn, not identical with that utterance

      tracking Derrida here

    3. incorporeal sense

      remember that paper I wrote I think for Ashley Thompson where I talked about the penumbral quality of things... But also th paper i wrote for Stephania in which the thing that exists is the thing (person) that continually is recreated - three papers now from early grad school I need to try to find!

    4. Zeichen-Sinn-Bedeutung

      Sinn could be sense or deeper meaning, meaning of life but also reason (eg senseless) or orientation, direction Bedeutung - dictionary definition, narrow meaning. these bear relevantly on my trying to figure out the meaning of meaning, mean, orientation, direction, intention - the etymology. Glass half full/empty - same bedeutung, very different Sinn. Zeichen = sign

      Oxford reference" Sign" - "Gottlob Frege invented a method of investigating the relationships in such a triangle through mathematical modeling. His terms for the three parts of the sign are Zeichen, Sinn, and Bedeutung. His study proceeded through a meticulous and mathematically strict analysis of synonymy and in a novel manner linked the logic of representation to truth relations."

    5. two are bodies – the utterance and the name-bearer; but one isincorporeal – the state of affairs signified and sayable, which is true orfalse.

      the event is a sayable in the sense that it is a [thing] that can be said. sayable /= the words but das ding.

    6. The predicate shouldperhaps be thought of less as an extra entity that appears on the scenethan as an aspect of the cut flesh which we abstract in order to present aproper causal analysis

      interesting, not totally sure I follow the ramifications

    7. For the Stoics, whena physical body acts upon another such body, it produces an effector event which is not itself a body but an incorporeal predicate orsayable, corresponding to the verb of the proposition

      helpful

    8. Place is defined, by contrast, asthis which an existent effectively does occupy, or which can be par-tially occupied and partially unoccupied with respect to a particularbody, though without being itself a body

      If void is the possibility of inhabiting is place something like inhabitation? See also place and Aion seem to anticipate Kantian categories, perhaps incorporeals could be see as alternatives.

    9. It is presentin all things which exist and happen, and in this way uses the propernature of all existing things for the government of all

      discussions around pastoral power...

    10. he verb ‘to grow’

      the point here is that it's verb centric. the verb process introduces time, it introduces multiplicity of being and it even makes it possible to say "alice" because the thing designated is apparent or immanent in its continuity across change.

    11. 10

      see note ...the names of pauses and rest... interesting passage personal uncertainty is an objective structure of the event itself quote from LS 3. Events convey and essential irreality.

    Annotators

    1. With confidence in our armed forces—with the unbounding determination of our people—we will gain the inevitable triumph, so help us God.

      Here Roosevelt invokes divine intervention, asserting that they are backed by a higher power.

    2. No matter how long it may take us to overcome this premeditated invasion, the American people in their righteous might will win through to absolute victory.

      This statement highlights the determination and resolve , projecting Americas confidence.

    3. Last night Japanese forces attacked Hong Kong. Last night Japanese forces attacked Guam. Last night Japanese forces attacked the Philippine Islands. Last night the Japanese attacked Wake Island. And this morning the Japanese attacked Midway Island.

      he creates a rapid sequence to convey the scale of the attacks.

    4. Yesterday, December 7, 1941—a date which will live in infamy

      Roosevelt’s language is direct and emphatic, making it clear that this is a historic moment requiring immediate attention.

    1. We are now in this war. We are all in it—all the way. Every single man, woman and child is a partner in the most tremendous undertaking of our American history.

      Roosevelt expresses here the total commitment needed from every citizen.

    1. Modifi-cations in the constitution of the Church resulted from theattempt to separate regenerate from unregenerate Christians,those who were from those who were not prepared for thesacrament, to keep the government of the Church or someother privilege in the hands of the former, and only to ordainministers of whom there was no question

      while you no longer needed to earn your salvation from God- you had to prove to the church that you deserved it and belonged to an IN crowd

    2. his conscious-ness of divine grace of the elect and holy was accompanied by anattitude toward the sin of one’s neighbour, not of sympatheticunderstanding based on consciousness of one’s own weakness,but of hatred and contempt for him as an enemy of God bearingthe signs of eternal damnation

      more us and then in pre-destination- drove towards hatred for the enemy

    3. he idea of the necessity of proving one’sfaith in worldly activity

      proving one's faith- not necessarily earning it- an endless pursuit not derived out of attaining something but closer to deserving what you've given

    4. the world the spiritual aristocracy of the predestined saints ofGod within the world

      the final boss form of spiritual life isn't ascetism- living like a monk but more resembled the life of the saints WITHIN the world

    5. In practice this means that God helps those who help them-selves.63 Thus the Calvinist, as it is sometimes put, himselfcreates64 his own salvation, or, as would be more correct, theconviction of it. But this creation cannot, as in Catholicism, con-sist in a gradual accumulation of individual good works to one’scredit, but rather in a systematic self-control which at everymoment stands before the inexorable alternative, chosen orthe religious foundations of worldly asceticism 69

      Calvinists earn salvation in a sense but looks very different than Catholic means- not ceremonies and certain good works but by continual tedious self control

    6. They are the tech-nical means, not of purchasing salvation, but of getting rid of thefear of damnation. In this sense they are occasionally referred toas directly necessary for salvation61 or the possessio salutis is madeconditional on them

      in a weird extended chain of reasoning- everyday action necessary for means of salvation

      action gets rid of fear of damnation- makes it necessary for salvation

    7. Deep-lying differences of the mostimportant conditions of salvation 50 which apply to the classifica-tion of all practical religious activity appear here. The religiousbeliever can make himself sure of his state of grace either in thathe feels himself to be the vessel of the Holy Spirit or the tool ofthe divine will.

      nothing affectively can occur on a mental or theoretical level on participants behalf in their quest for salvation- God's decisions have been made- can't think your way into being "the chosen"

      Instead- can express fulfillment of role as the chosen through action

    8. so to speak, be considered the mostsuitable means of counteracting feelings of religious anxiety,finds its explanation in the fundamental peculiarities of religiousfeeling in the Reformed Church, which come most clearly tolight in its differences from Lutheranism in the doctrine of justi-fication by faith.

      worldly activity is a means of dealing with religious anxiety

    9. On the other hand, in order toattain that self-confidence intense worldly activity is recom-mended as the most suitable means.47

      other hand- engage intensely with worldly activity to be more confident in pre-dest. status

    10. The exhortation of the apostle to make fast one’s own callis here interpreted as a duty to attain certainty of one’s ownelection and justification in the daily struggle of life.

      be sure about your status in the after life

    11. So far as predestination was not reinterpreted, toneddown, or fundamentally abandoned, 44 two principal, mutuallyconnected, types of pastoral advice appea

      two ways to comfort the congregation dealing with the stress of predestination

    12. How was this doctrine borne36in an age to which the after-life was not only more important,but in many ways also more certain, than all the interests of lifein this world?

      how did everyone not fall into existential questioning spirals about whether or not they were apart of the chosen

    13. Brotherly love, since it may only be prac-tised for the glory of God33 and not in the service of the flesh, 34is expressed in the first place in the fulfilment of the daily tasksgiven by the lex naturæ and in the process this fulfilment assumes apeculiarly objective and impersonal character, that of service inthe interest of the rational organization of our social environ-ment.

      This is def "the answer" but idk what they're saying tbh

    14. . In spite of the necessity of mem-bership in the true Church 27 for salvation, the Calvinist’s inter-course with his God was carried on in deep spiritual isolation

      Calvinists were deeply spiritually isolated

    15. There was not only no magical means of attaining the grace ofGod for those to whom God had decided to deny it, but nomeans whatever.

      beyond just taking mysticism out- remove all availability to earn redemption through action

    16. The genuine Puritan even rejected all signs of religious cere-mony at the grave and buried his nearest and dearest withoutsong or ritual in order that no superstition, no trust in the effectsof magical and sacramental forces on salvation, should creep in

      oh that's why...

    17. his, the complete elimination of salvation through the Churchand the sacraments (which was in Lutheranism by nomeans developed to its final conclusions), was what formed theabsolutely decisive difference from Catholicism.

      opposite of Catholicism- church can't do shiiii

    18. On the other hand, however, we have no intention whateverof maintaining such a foolish and doctrinaire thesis32 as that thespirit of capitalism (in the provisional sense of the termexplained above

      bars tbh

    19. Calvin

      Calvin is the culprit

    20. ne may attain salvation in any walk oflife; on the short pilgrimage of life there is no use in layingweight on the form of occupation.

      older biblical interpretations did not tie occupation to a means of gaining salvation

    21. But at least onething was unquestionably new: the valuation of the fulfilment ofduty in worldly affairs as the highest form which the moralactivity of the individual could assume

      rise of the term calling - fulfilment of duty in worldly affairs as the highest form of moral action

    22. Rationalism is an historical concept which coversa whole world of different things. It will be our task to find outwhose intellectual child the particular concrete form of rationalthought was, from which the idea of a calling and the devotionto labour in the calling has grown, which is, as we have seen,so irrational from the standpoint of purely eudæmonisticself-interest, but which has been and still is one of the mostcharacteristic elements of our capitalistic culture

      capitalism too specific to place under umbrella category of rationalism- must figure out what led to this type of rationalism specifically

    23. o speak here of a reflection ofmaterial conditions in the ideal superstructure would be patentnonsense

      not just material conditions or consumption bc same values of capitalism excited in the back woods

    24. Their life-work was, so long as they clung to thetradition of the Church, at best something morally indifferent. Itwas tolerated, but was still, even if only on account of the con-tinual danger of collision with the Church’s doctrine on usury,somewhat dangerous to salvation

      older capitalism would not have considered it "moral"- its ethicality ran the risk of clashing with the church

    25. In such circumstances men’s commercial andsocial interests do tend to determine their opinions and atti-tudes. Whoever does not adapt his manner of life to the condi-tions of capitalistic success must go under, or at least cannot rise.But these are phenomena of a time in which modern capitalismhas become dominant and has become emancipated from its oldsupport

      adaptation to capitalist mindset in order to survive is a modern phenom- there was once a time when a capitalist mindset wasn't necessary to survive

    1. What does it mean exactly to recognise properties and relations as objective entities?

      This is very close to what Bowden is saying about the Stoics in Logic and Sense

    1. When transgender citizens and workers askedthe state to recognize their gender and to treat andpay them accordingly, their pushback made visiblethe way that new technologies, far from being neu-tral, were in fact a battleground in the process ofdefining and stabilizing “traditional” or normativeconcepts of gender

      Here Hicks describes this computation: Input: Transgender citizens and workers asking to be treated Ouput: British government said no and made a pushback to the idea

    2. Hergovernment employers wrote that it was in her“own interest” (in their opinion) to “continuewearing men’s clothes for the time being” inorder to avoid a significant reduction in pay.

      Here Hicks describes this social norm "Wearing men's clothes for the time being in order to avoid a significant reduction in pay". Because Ferguson is now a transitioned into a male they expect him to wear male clothes and not female clothes.

    1. Using analogies can take your idea-generation sessions to a whole new level of creativit

      Yes, I love using analogies because it encourages me to think outside the box and draw inspiration from other successful models! For example, when I was researching how to encourage more diverse students to enroll in AP classes, I thought about how looking at options on Amazon and reviews help people make informed buying decisions. Taking inspiration from this, I came up with a database which shared syllabi of AP classes, prerequisites, and student reviews, to help students choose the best AP classes for themselves.

    2. onstraints

      I hear what they are saying about constraints stifling our creativity. However, personally, when someone gives me so much freedom, I go blank. Therefore, maybe it would be helpful to remove one constraint at a time. For example, in the first ideation round, we may decide not to constrain ourselves financially; in the next, we may ease the constraints of the political environment around us. I feel like this more focused approach would help me generate a greater number of ideas.

    3. bad ideas only.

      What an innovative idea! :) This might be the convergent-thinker in me, but I feel like I would need to have a few guidelines of what "worst" means in order to be productive. Also, maybe we should rename it "improbable/outlandish ideas" instead of "worst." The term "worst" suggests that it exacerbates the issue. However, design thinkers, I think we have the duty to propose solutions that at least doesn't make systemic equity worse.

    4. an hour-long

      Wow, an hour long?? I think I would have to be in a group to sustain the ideation process.

    5. criticism is eliminate

      Interestingly, I find that I criticize my own ideas more than others' ideas. When talking to others, I think my pursue to create a positive, encouraging environment results in my building on ideas and asking follow-up questions. On the other hand, when I brainstorm alone, my mind automatically filters ideas and determine which ones make it to the paper. I am excited to continue reading and hopefully find solutions to alleviate this issue.

    1. I should have been a pair of ragged claws Scuttling across the floors of silent seas.

      Conveys the hardships and uncaring natures of life and how painful it is to have the sentience to realize this. The speaker decides it would be better to be a creature that is blissful to the nature of life

    1. The heaving speech of air, a summer sound    Repeated in a summer without end And sound alone.

      Conveys the possible meaningless of life that is a strong theme in modernism.

    1. What brought the kindred spider to that height,Then steered the white moth thither in the night?

      Conveys how life can be confusing and cruel by showing how there was no real reason or force other than chance that the moth came.

    2. Assorted characters of death and blightMixed ready to begin the morning right,

      Conveys how there will always be tragedy in life by symbolizing the spider as death and the light as life

    1. And life is too much like a pathless wood Where your face burns and tickles with the cobwebs Broken across it, and one eye is weeping

      Could be trying to convey the hardship and meaningless of life by comparing it to being lost in the woods. Being lost is often thought of as being concerning and the forest being uncaring that you are lost, representing life.

    1. NATURAL RESOURCESINTRODUCTIONThis section describes both the land and water resources of Shenandoah County. Itpresents information on the County's topography, geology, soils, and water resources. Theseresources provide many opportunities, but also pose some severe environmental problems.Development should be guided away from areas with serious limitations, such as steep slopes,shallow depth to bedrock, flood plains, prime agricultural lands, wetlands, and sinkholes. Mapsshowing general geology, general soils, the hydrogeologic survey of Shenandoah County, andgeneralized development limitations are included.Natural resources were briefly addressed in individual paragraphs about topography,climatology, minerals, soils, hydrology, and forests in the 1973 Plan, along with a general soilsmap. Soils data has since been updated with the Shenandoah County Soils Survey.
    1. For audiences versed in these local meanings, then, a dancer who is performing on pointe and sticking out her chest does not move like the type of person who should be a revolutionary hero in a Chinese socialist story.

      YES

    2. hus, in 1956, when others were criticizing the BDS graduation performance for what they saw as excessive ballet influences, You published an article in the People’s Daily in which he reviewed the show positively and called for even more ballet in the future

      the duality, the author argues ballet gained support because it finally had its own identity and way to differentiate itself

    1. When in the Course of human events, it becomes necessary for one people to dissolve the political bands which have connected them with another, and to assume among the powers of the earth, the separate and equal station to which the Laws of Nature and of Nature’s God entitle them, a decent respect to the opinions of mankind requires that they should declare the causes which impel them to the separation. We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness.–That to secure these rights, Governments are instituted among Men, deriving their just powers from the consent of the governed, –That whenever any Form of Government becomes destructive of these ends, it is the Right of the People to alter or to abolish it, and to institute new Government, laying its foundation on such principles and organizing its powers in such form, as to them shall seem most likely to effect their Safety and Happiness. Prudence, indeed, will dictate that Governments long established should not be changed for light and transient causes; and accordingly all experience hath shewn, that mankind are more disposed to suffer, while evils are sufferable, than to right themselves by abolishing the forms to which they are accustomed. But when a long train of abuses and usurpations, pursuing invariably the same Object evinces a design to reduce them under absolute Despotism, it is their right, it is their duty, to throw off such Government, and to provide new Guards for their future security.–Such has been the patient sufferance of these Colonies; and such is now the necessity which constrains them to alter their former Systems of Government. The history of the present King of Great Britain is a history of repeated injuries and usurpations, all having in direct object the establishment of an absolute Tyranny over these States. To prove this, let Facts be submitted to a candid world.

      This ideal of equality in 1776 excluded women, Indigenous people, and enslaved Africans.

    1. Limestone & Karst Terrain The Valley’s abundant limestone is evidence that the area was once under ocean water, long before the tectonic plates collided. Limestone forms in warm, shallow seas when generations of tiny sea creatures die and accumulate on the ocean floor, later to compress into solid rock. Karst Because of its limestone base, the Shenandoah Valley is karst, a terrain type with distinctive landforms and water resources. Slightly acidic water wore through the bedrock over many millions of years, leaving caves, caverns, and sinkholes. Streams and springs disappear and reappear over time. Aquifers Water that filters through the rocks collects in underground reservoirs, or aquifers. Aquifers are underground rock layers filled with groundwater in the spaces between fractured limestone, silt, gravel, and sand. Aquifers closer to the surface, used for irrigation and drinking water, are re-charged by rainwater. They are very useful but also extremely vulnerable to contamination. Caves & Caverns The water that dissolves limestone and other soluble rocks in the Shenandoah Valley leaves behind caves and caverns. In some caves and caverns, the deposits of dissolved minerals left by dripping water make the features of stalactites, stalagmites, and columns. Luray Caverns, a National Natural Landmark in the Valley, is ornately decorated with cascades, columns, stalactites, stalagmites and pools. Other Rocks & Minerals Many rocks and minerals occupy the Shenandoah Valley besides limestone. Other sedimentary rocks in the region are sandstone, shale, and coal. There are igneous rocks like granite, gabbro, and basalt, and metamorphic rocks like slate, gneiss, and quartzite. Manganese, iron ores, zinc, lead, sulfur, gypsum, and pyrite are relatively common Shenandoah Valley minerals. The Valley yields small amounts of oil and natural gas. Also present is red clay, an oceanic sediment with iron oxide, along with fossils of sea creatures like brachiopods and trilobites.
    2. Mountain & Valley Building About half a billion years ago, the rocks that now make up the Shenandoah Valley solidified from ancient tidal flat sediments into vast, horizontal layers of limestone, shale, sandstone, and dolomite.
    3. Geology of the Shenandoah Valley Cedar Creek & Belle Grove National Historical Park blockquote {border-left: 5px solid #fff;} Wall made from limestone removed from the roadbed during construction of Valley Turnpike NPS Photo by Ann & Rob Simpson Underground and surface forces, acting over many millions of years, created the Shenandoah Valley and its surrounding hills and ridges. These long, slow processes continue today as the Valley region gradually weathers, erodes, levels, and deposits soil.
    1. To get a list of all the public domain scans, as of this writing:

      ```` javascript ([ ...document.querySelectorAll("table.auto-style21 a") ]). filter((x) => ( x.textContent.includes("19") && !x.textContent.includes("1929") && !x.textContent.includes("193") && !x.textContent.includes("194"))). map((x) => { let when = x.textContent; if (!when.includes(",")) when = when.split().reverse().join(" ") + " 01";

      try {
        var result = (new Date(when)).toISOString().substr(0, ("1928-10-29T...").indexOf("T"));
      } catch (ex) {
        console.log(x.textContent, when, ex);
      }
      
      if (when != x.textContent) {
        result = result.substr(0, ("1987-12-09").length - ("-09").length);
      }
      return result;
      

      }) ````

    1. Residents Library $(function () { var widgetContext = "widget_3_0_1631"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2flibrary", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Library"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2flibrary" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); Clarke County Library — part of the Handley Regional Library system — is a great resource for books, audio books, CDs, and DVDs for kids, teens, and adults. The library also has meeting rooms and public WiFi, and it hosts special programs for children and adults. Library cards are free for residents of Clarke and Frederick counties and City of Winchester. Clarke County Library is located in the Berryville-Clarke County Government Center (first floor) at 101 Chalmers Ct. in Berryville, Va. Hours 10 a.m. to 8 p.m. Monday through Thursday 10 a.m. to 5 p.m. Friday and Saturday Office (540) 955-5144 ccl@handleyregional.org (540) 955-5178 (fax) Clarke County Branch Manager Alison Waddell (540) 955-5190 awaddell@handleyregional.org
    1. Services Local, State, and U.S. government links $(function () { var widgetContext = "widget_3_1231_1375"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fservices%2flocal-state-and-u-s-government", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Local%2c+State%2c+and+U.S.+government+links"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fservices%2flocal-state-and-u-s-government" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); The external websites listed below are for your convenience. The appearance of a link on this or any other Clarke County government site does not constitute an endorsement, recommendation, or certification, nor should the presence of a link suggest the site has any relationship with Clarke County government.  Local Town of Berryville  Town of Boyce Clarke Conservation Easement Authority Clarke County Public Schools John H. Enders Fire Company & Rescue Squad Blue Ridge Volunteer Fire & Rescue Co.  Boyce Volunteer Fire Company Top of Virginia Regional Chamber includes Clarke County and Town of Berryville  Handley Regional Library includes Clarke County Library State Virginia Association of Counties Commonwealth of Virginia official website Virginia Department of Forestry Virginia Department of Motor Vehicles Virginia Department of Transportation VDOT builds, maintains, and operates roads, bridges, and tunnels in the Commonwealth. Virginia Department of Emergency Management VineLink Virginia Victim Information & Notification Everyday (VINE) provides victims of crime timely information about criminal cases and the status of offenders. Water Information from the EPA - Shenandoah Watershed Profile  includes water sources, pollutants, stream flows, and more U.S. Census Bureau - American Fact Finder  ICC - International Code Council a non-profit association dedicated to building safety Social Security Administration Ready  Federal Emergency Management Agency (FEMA)
    1. Government » Fire, EMS & Emergency Management Outdoor Burning Restrictions $(function () { var widgetContext = "widget_3_1163_1263"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fgovernment%2ffire-ems-emergency-management%2foutdoor-burning", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Outdoor+Burning+Restrictions"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fgovernment%2ffire-ems-emergency-management%2foutdoor-burning" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); Before starting an outdoor fire of any kind, residents should call the Clarke County Emergency Communications Center at (540) 955-1234. By doing so, ECC operators will know how to respond should a passerby call 911 to report a fire, and ECC will know where outdoor burning is taking place should the fire get out of control. What are the rules for open burning in Virginia? The State Air Pollution Control Board’s Regulation for Open Burning specifies what materials may or may not be burned, and has seasonal restrictions on open burning for certain localities. The Virginia Department of Forestry provides information regarding outdoor fire laws and burn ban restrictions. What am I not allowed to burn? No one in Virginia may burn tires or other hazardous materials at any time. Regulation 9VAC-130-30 has a complete list of opening burning prohibitions. If you live in an area that restricts open burning, you must observe your local ordinance. If you live in an area with a smog problem, there are specific prohibitions on certain activities during the prime smog months of May through September. What can I burn? If you live in an area that does not have a local burning ordinance and you do not have curbside pickup, you can burn leaves and some household trash. Regulation 9VAC5-130-40 has a complete list of what and when households and certain businesses may burn. Helpful Tips: • Keep a garden hose handy in case of sudden, uncontrolled fire spread. • Burn dry leaves. Wet leaves produce unnecessary smoke. • Burn small piles no more than 3-feet wide and 2-feet tall. Large piles do not always burn completely. • Never use gas, lighter fluid, or any other fuel to kindle or rekindle a fire. If leaves need fuel to burn, they are too wet, creating potential for injury. • Keep small children away from fires and out of the smoke.
    1. Residents Outdoor Burning $(function () { var widgetContext = "widget_3_0_1463"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2foutdoor-burning", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Outdoor+Burning"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2foutdoor-burning" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); Before starting an outdoor fire of any kind, residents must call the Emergency Communications Center at (540) 955-1234. By doing this, ECC operators will know how to respond should a passerby call 911 to report a fire, and they will know where outdoor burning is taking place should a fire get out of control. Virginia law restricts outdoor burning from Feb. 15 through April 30 every year, when high winds are most prevalent during daytime hours. Outdoor burning is only permitted between 4 p.m. and midnight during this 11-week period.   Burning garbage, refuse, trash, rubbish, and other forms of liquid or solid waste is prohibited at all times in Clarke County. Burning wood, brush, grass, trimmings, and/or leaves is permitted in all areas of Clarke County, provided: • Fire must be a minimum of 50 feet from any structure and 300 feet from any occupied dwelling. • Anyone who intends to burn brush must have written permission from those who occupy dwellings 300 feet away. • Anyone who intends to burn brush must constantly attend the fire at all times. • Burning must be done in such a way as to minimize any nuisance to neighbors. • Open burning for land and site clearing operations for commercial, industrial, or residential development is permitted only after obtaining a permit from Clarke County Fire & EMS and Emergency Management. Call (540) 955-5113. Open burning for these purposes is permitted provided conditions required by Clarke County Fire, EMS & Emergency Management and Clarke County Building Department are met. Recreational bonfires and campfires are permitted if the fuel consists only of seasonal dry hardwood, ignited with a small quantity of paper. Fires can be no more than 5-by-5 feet in circumference and may not burn more than 3 hours at any one time. At no time shall bonfires or campfires be used for waste disposal purposes. Helpful Tips: • Keep a garden hose handy in case of sudden, uncontrolled fire spread. • Burn dry leaves. Wet leaves produce unnecessary smoke. • Burn small piles no more than 3-feet wide and 2-feet tall. Large piles do not always burn completely. • Never use gas, lighter fluid, or any other fuel to kindle or rekindle a fire. If leaves need fuel to burn, they are too wet, creating potential for injury. • Keep small children away from fires and out of the smoke.   Read more about Outdoor Burning Restrictions.
    1. Residents Public Safety $(function () { var widgetContext = "widget_3_0_1353"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2fpublic-safety", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Public+Safety"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2fpublic-safety" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); Sign up for emergency notifications using the “CodeRED” and “Text-to-911”  links at left. If using a smartphone, jump to subpage.  Clarke County’s main public safety departments are:  • Clarke County Sheriff’s Office, 100 N. Church St., Berryville, (540) 955-5152 • Fire, EMS & Emergency Management, 101 Chalmers Ct., Berryville, (540) 955-5113 • Clarke County Communications Center, 100 N. Church St., Berryville, emergency 911 and non-emergency (540) 955 1234
    2. The Sheriff's Office also has a drug collection unit in the lobby of its office at 100 N. Church St. in Berryville. Access to the collection unit is available 24 hours a day. The drug collection unit helps residents safely dispose of expired or unwanted medications, including controlled substances, that may otherwise be diverted, abused, or contaminate rivers, streams, and the public water supply.
    1. eptic Tank Cleaning Repair and Installation You might feel overwhelmed or clueless about where your septic is going?  Do not worry, Johnny Blue is here to help educate you and other homeowners about how their septic works and why it is very important to have it maintained.  With experience and knowledge, the licensed experts at Johnny Blue Inc. understand that when a septic back up happens, it needs attention right away.  If you have an emergency, we have experienced staff standing by who are ready to help.  When it comes to regular maintenance, we recommend pumping the solid tank every 3-5 years.  When solids are not pumped regularly, the solid waste material can enter your drainfield and cause clog.  Septic repair can be very simple like cleaning a filter or it can also be costly like replacement of a drainfield.  If you have questions, call us.  We are here to help you!  Our team of licensed professional does not cut corners.  Quality work is the only work we do.
    1. Our Septic Installation Process Our approach to septic tank installation service is comprehensive and meticulous. Here’s a quick look at how we handle each project: 1. Site Evaluation We first visit your property to assess the best location for your new septic system. This involves evaluating the land layout, proximity to water bodies, and other crucial factors. 2. Soil Testing We perform soil testing to determine the soil’s capacity to absorb and treat wastewater. This step is critical in ensuring the longevity and effectiveness of your septic system. 3. Permit Acquisition We handle all the paperwork for you, acquiring the necessary permits for septic tank installation according to local regulations. 4. Excavation and Tank Placement Our team carefully excavates the site and strategically places the tank to ensure optimal functionality. 5. Leach Field Installation We then install the leach or drain field to distribute the treated wastewater into the ground. 6. Final Inspection After the installation, we conduct a thorough final inspection to ensure everything functions as it should.
    1. For more information about septic pump-outs, contact the Natural Resource Department located in the Berryville-Clarke County Government Center (second floor) located at 101 Chalmers Ct., in Berryville, Va. Hours 8:30 a.m. to 4:30 p.m. Monday through Friday Lorien Lemmon Conservation Planner & GIS Coordinator (540) 955-5134 llemmon@clarkecounty.gov
    2. 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encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Septic+Pump+Out"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2fseptic-pump-out" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); Onsite septic systems are among the top contamination sources for local and regional water, including the Chesapeake Bay. An average of 40 percent of wells tested across Clarke County in the 1990s had coliform levels that exceeded water quality standards. Recent studies of Clarke County wells indicate 57 percent of samples have coliform levels exceeding water quality standards, indicating a worsening problem for the groundwater, which is the source of well water.
    1. Services Trash & Recycling $(function () { var widgetContext = "widget_3_1222_1355"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fservices%2ftrash-recycling", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Trash+%26+Recycling"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fservices%2ftrash-recycling" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); Clarke County Convenience Center, located at 90 Quarry Rd. (Rt. 612) in the northeastern part of the county, is county operated for Clarke residents only. This facility is not for commercial use. The center accepts bagged household trash (10 bags maximum) and un-bagged recyclables. (See details below.) An attendant is always on site to assist residents, maintain the site, and ensure residents comply with posted policies. Find more details about local trash collection as well as where to dispose of hazardous materials, appliances, yard waste (including Christmas trees), etc. using the links at left. If using a smartphone, jump to subpage. The Quarry Road facility is open: • 3 to 7 p.m. Friday • 7 a.m. to 6 p.m. Saturday • 10 a.m. to 3 p.m. Sunday • 9 a.m. to 3 p.m. Monday Hours may change because of weather or other conditions. If use greatly increases, Clarke County may revise the schedule and open on other weekdays. Convenience Center is closed: • New Year’s Day • Easter Sunday • Memorial Day • Independence Day • Labor Day • Thanksgiving Day • Christmas Day Clarke County residents may use any of these six trash facilities: • 90 Quarry Rd., Berryville (operated by Clarke County) • 280 Landfill Rd., Winchester (operated by Frederick County) • 4201 Stonewall Jackson Hwy., White Post (operated by Frederick County) • 235 Hot Run Dr., Stephenson (operated by Frederick County) • 801 Greenwood Rd., Winchester (operated by Frederick County) • 47 Blue Mountain Rd., Front Royal (operated by Warren County) Clarke County Convenience Center has separate recycling containers for paper, cardboard, aluminum and steel cans, clean glass bottles and jars (with corks, caps, and lids removed), and plastic (#1 and #2). The facility does not accept plastics #3 through #7. The Convenience Center accepts clean glass bottles and jars for recycling. Residents must remove all corks, caps, and lids before placing glass in the container. Do NOT put mirrors, windows, heat-tempered glass such as Pyrex and mixing bowls, ceramic mugs and plates, wine glasses, or any trash (including plastic bags) in the recycling container. For glass recycling to continue in Clarke County, glass bottles and jars must be clean. Do not put plastic bags of any kind in any of the recycling containers. The Quarry Road facility does not accept yard waste, appliances, furniture, or hazardous materials of any kind. See “Yard Waste, Appliances & Hazardous Materials” link at left. If using a smartphone, jump to subpage.   Dumping trash of any kind on the ground or around the Clarke County Convenience Center property is prohibited and violators will be prosecuted. Illegal dumping constitutes a Class 1 misdemeanor punishable by a fine up to $2,500 and/or up to one year in imprisonment. The Clarke County Convenience Center site is under video surveillance 24/7. Town of Berryville provides trash pickup and recycling for residents and businesses within its town limits. Town of Boyce provides trash pickup for its residents.
    1. Mission The purpose of Blandy Experimental Farm is to increase understanding of the natural environment through research and education. In that natural systems support and increasingly are affected by humans, ecological and environmental literacy are fundamental requirements for citizens, policy-makers, and society as a whole. Blandy Experimental Farm exists to promote this understanding through education and research on plants, plant biology, ecology, evolution, the environmental sciences, and the manner in which all of these are used and affected by humans.  The three principal programs designed to achieve this mission include: University research and education Outreach and environmental education The State Arboretum of Virginia
    1. BRCTH provides life-enhancing, equine-assisted activities for individuals with disabling conditions, including those who are “at risk”, in the northern Shenandoah Valley of Virginia and contingent counties in WV.   We serve adults and children from age four.  In order to provide these services to the community, we rely upon a dedicated team of volunteers.  See our Volunteer page for more information. BRCTH is located at Almeda Farm, 749 Salem Church Rd, Boyce, VA 22620 in Clarke County.  The facility features large indoor and outdoor arenas, rolling pastureland, riding trails and a functional, well-appointed barn. Our herd consists of our pony, Honey, and two horses, Dillon and Dublin. We are currently looking for another horse to add to the herd. Contact us for more details and let us know if have any leads.
    1. Serenity Farm Virginia A Sanctuary Where People Heal Animals and Animals Heal People
    1. Government Social Services $(function () { var widgetContext = "widget_3_0_1155"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fgovernment%2fsocial-services", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Social+Services"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fgovernment%2fsocial-services" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); Clarke County Department of Social Services (CCDSS) is the locally administered office of the Virginia Department of Social Services. CCDSS administers Child Protective Services, In-Home and Prevention Services, Foster Care, Fostering Futures, and Adoption for families and children. CCDSS also provides Adult Protect Services and Adult Services for the elderly and disabled. In addition to services programs, Clarke County Department of Social Services administers benefit programs such as the Supplemental Nutrition Assistance Program (SNAP, formerly known as food stamps), Medicaid, Temporary Assistance for Needy Families (TANF), Child Care Subsidy, Employment Assistance, and Energy Assistance programs. Find more benefits and services information use the links at left. If using a smartphone, jump to subpage. Clarke County Department of Social Services is located at 311 E. Main St. in Berryville, Va.  Hours: 8:30 a.m. to 4:30 p.m. Monday through Friday Fax: (540) 955-3958 Jen Parker Director of Social Services (540) 955-3700 (800) 552-7096 (DSS hotline) jennifer.l.parker@dss.virginia.gov Sarita Emmons Family, Child, and Adult Services Supervisor (540) 955-5167 sarita.emmons1@dss.virginia.gov Christy Ryan Human Services Assistant III (540) 955-3700 christina.ryan@dss.virginia.gov Johanna Arauz Ponce de Leon Administrative Services Manager (540) 955-3701 Johanna.Arauz-PoncedeLeon@dss.virginia.gov Clarke County Social Services FY 2023 Annual Report Clarke County Social Services 2023-25 Strategic Plan Clarke County Social Services FY 2021 Annual Report Clarke County Board of Social Services Children’s Services Act (CSA) 2024 Senior Angel Program  2024 Children Angel Program
    1. 2024 General Reassessment process As required by law, Clarke County has been working on a general reassessment of real estate in the county this past year. To complete this work, the county hired Wampler-Eanes to visit each property and provide an updated value of the property and improvements. Wampler-Eanes also completed a sales ratio report based on recent real estate transactions in the county. While the final numbers are still being computed, we do expect a significant increase in values as the last reassessment was completed in 2019. A recent Washington Post article noted that nationwide, home prices have surged 54% since 2019. The new values become effective January 1, 2025.
    1. Residents Clarke County Citizens Academy $(function () { var widgetContext = "widget_3_0_1662"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2fclarke-county-citizens-academy", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Clarke+County+Citizens+Academy"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2fclarke-county-citizens-academy" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); Clarke County Supervisors and government employees value civic engagement and want to create opportunities for individuals to learn more about how their government offices, boards, commissions, and departments function. Clarke residents and business owners ages 18 and up may enroll in the Clarke County Citizens Academy, a program designed to engage as well as elicit feedback.
    1. COSTS: All Points Broadband will notify property owners approximately 60 to 90 days before service becomes available to their addresses. For the first 12 months after service is available at any location, All Points Broadband’s standard installation fee of $199 will include any length of service drop required to make service available to a location. The lowest speed plan of 50/50 mbps is estimated to cost $59.99 per month with plans as large as 1/1 gbps also available.
    2. Residents Broadband Internet Access $(function () { var widgetContext = "widget_3_0_1459"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2fbroadband-internet-access", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Broadband+Internet+Access"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fresidents%2fbroadband-internet-access" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); All Points Broadband (APB) and the Northern Shenandoah Valley Regional Commission (NSVRC) provide regular updates to Clarke County during their multi-year infrastructure construction of the universal broadband project in seven counties, including Clarke. In Clarke, APB will install 270 miles of fiber infrastructure in order to reach more than 3,200 currently unserved locations; substantial completion of last-mile network is expected in 2025. On May 2, 2024, APB presented this “All Points Broadband NSVRC Project Update” to representatives from the seven-county project area. To check eventual availability in your area, go to www.apbfiber.com and click “Get Started.”
    1. Government Treasurer $(function () { var widgetContext = "widget_3_1271_1157"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fgovernment%2ftreasurer-s-office", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Treasurer"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fgovernment%2ftreasurer-s-office" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); The Treasurer’s Office collects real estate and personal property taxes, and sells dog licenses. Treasurer is an elected position. Make Clarke County tax payments online – with or without an account – at tax.clarkecounty.gov. View tax payment history, report a change of address, report new, sold, moved, and disposed of vehicles, report vehicle high mileage, and register dogs to comply with local dog licensing regulations. Online e-checks incur no processing fees, and credit card payment fees are the same online as they are for payments made at the Treasurer’s Office. The Treasurer’s Office is located in the Berryville-Clarke County Government Center (first floor) at 101 Chalmers Ct. in Berryville, Va. Hours 8:30 a.m. to 4:30 p.m. Monday through Friday Account payments accepted until 4:15 p.m.   Sharon Keeler Treasurer (540) 955-5160 treasurer@clarkecounty.gov Ron Crouse Chief Deputy (540) 955-5160 rcrouse@clarkecounty.gov Glenda Hernandez Deputy I (540) 955-5160 ghernandez@clarkecounty.gov Julie Sweetser Deputy I (540) 955-5160 jsweetser@clarkecounty.gov Tracy Wilkerson Deputy II (540) 955-5160 twilkerson@clarkecounty.gov   Additional Information Direct questions regarding the valuation of Real or Personal property (including vehicles) to the Commissioner of Revenue. Direct questions regarding water and sewer bills to the Clarke County Sanitary Authority. View Commissioner of Revenue Forms. Important Dates Jan. 31: Dog tags due for renewal each year; tags and licenses go on sale each Nov. 1 June 5: County Real Estate and Personal Property Tax due (first half) Dec. 5: County Real Estate & Personal Property Tax due (second half)   NOTICE: The Clarke County Cigarette Tax increased on Jan. 1, 2023. Stamps are 40 cents each. Businesses that sell cigarettes should know: • Stamps can be purchased at the Clarke County Treasurer’s Office located on the first floor of the government center at 101 Chalmers Ct. in Berryville. Normal business hours are 8:30 a.m. to 5 p.m. Monday through Friday. A completed Stamp Order Form and full payment is required at the time of purchase. • Stamps can also be purchased by mail. Send a completed and signed Stamp Order Form along with full payment to: Clarke County Treasurer’s Office, P.O. Box 537, Berryville VA 22611 • The completed Stamp Order Form must include your shipping information, including location and shipping account number. The Treasurer’s Office will do its best to mail stamps as quickly as possible, but the office is busier at certain times of the year than others. 2023 Stamp Order Form Non-Judicial Real Estate Sale
    1. Water & Sewer $(function () { var widgetContext = "widget_3_0_1161"; //start VISPP-4466 var useDesignThemFontSizeCss = window.visionOptions.useDesignThemFontSizeCss; var folderPath = useDesignThemFontSizeCss == true ? window.visionOptions.currentDesignFolderPath : window.visionOptions.mainFolderPath; if (!folderPath) folderPath = window.visionOptions.mainFolderPath; var resizeTimer; var resizeFaqTabs = function () { $(".faq_widget").each(function () { var tabheight = $(this).find(".faq_tab_nav").height(); $(this).find(".faqtab_section").attr("style", "min-height: " + (tabheight - 42) + "px"); }); }; var SetFontSize = function (fontsize) { $("#active_font").attr("href", folderPath + fontsize).attr("data-css", fontsize); var url = window.location.origin + visionOptions.virtualApplicationPath + "Shared/ChangeFontSizeCookie"; var cookieValue = fontsize ? fontsize : "small.css"; var cookieInt; switch(cookieValue){ case("xx-small.css"): cookieInt=1; break; case ("x-small.css"): cookieInt = 2; break; case ("small.css"): default: cookieInt = 3; break; case("medium.css"): cookieInt=4; break; case ("large.css"): cookieInt = 5; break; } $.frontendAjax({ url: url, type: 'POST', contentType: 'application/json', data: JSON.stringify({ cookieValue: cookieInt}), success: function (data, textStatus, jqXHR) { if (data && data.success) { $("#active_font").attr("href", window.visionOptions.mainFolderPath + cookieValue).attr("data-css", cookieValue); } } }); if ($(".faq_tab_nav").length > 0) { clearTimeout(resizeTimer); resizeTimer = setTimeout(function () { resizeFaqTabs(); }, 200); } }; $(".font_larger").on("click", function () { switch ($("#active_font").attr("data-css")) { case "medium.css": SetFontSize("large.css"); break; case "small.css": SetFontSize("medium.css"); break; case "x-small.css": SetFontSize("small.css"); break; case "xx-small.css": SetFontSize("x-small.css"); break; } return false; }); $(".font_smaller").on("click", function () { switch ($("#active_font").attr("data-css")) { case "large.css": SetFontSize("medium.css"); break; case "medium.css": SetFontSize("small.css"); break; case "small.css": SetFontSize("x-small.css"); break; case "x-small.css": SetFontSize("xx-small.css"); break; } return false; }); $(".text_size").on("click", function () { SetFontSize("x-small.css"); return false; }); //end VISPP-4466 $("#" + widgetContext + " #share").click(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); else $("#" + widgetContext + " div#share").find("ul").hide(); }); $("div").click(function () { if ($("#" + widgetContext + " div#share").hasClass("click-active")) { $("#" + widgetContext + " div#share").find("ul").hide(); } }); $(document).click(function (e) { if (!$(e.target).closest("#share").length > 0) { $("#" + widgetContext + " div#share").removeClass("click-active"); $("#" + widgetContext + " div#share").find("ul").hide(); } }); var shareContainerTimeout = null; $("#" + widgetContext + " #share").bind('mouseover', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").show(); }, 100); }); $("#" + widgetContext + " #share").bind('mouseleave', function () { //If not relate to click event if (shareContainerTimeout) { clearTimeout(shareContainerTimeout); shareContainerTimeout = null; } shareContainerTimeout = setTimeout(function () { if (!$("#" + widgetContext + " div#share").hasClass("click-active")) $("#" + widgetContext + " div#share").find("ul").hide(); }, 200); }); $("header#" + widgetContext + " a.feedback_link").click(function () { var windowHeight = 485; if (window.innerWidth <= 648) { windowHeight = 545; } var opts = { title: "Feedback", url: "/Template/GetFeedbackPartial?feedbackUrl=https%3a%2f%2fwww.clarkecounty.gov%2fgovernment%2fwater-sewer", useFrame: true, height: windowHeight, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.feedback_link").focus(); }, skin: 'viClientDialog feedback_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); //Safari iOS: No click event $("header#" + widgetContext + " a.send_share_email").bind("click touchstart", function () { var shareEmailTitle = document.itemTitle ? encodeURIComponent(document.itemTitle.trim()).replace(/[!'()*]/g, escape) : "Water+%26+Sewer"; var opts = { title: "Click to submit an email online", url: "/Template/GetShareEmailPartial?shareUrl=https%3a%2f%2fwww.clarkecounty.gov%2fgovernment%2fwater-sewer" + "&shareTitle=" + shareEmailTitle, useFrame: true, height: 485, onClosed: function (result) { if (result != undefined && result.IsOk == true) { $.refreshTempMessage(result.Message); } $("header#" + widgetContext + " a.send_share_email").focus(); }, skin: 'viClientDialog send_share_email_lightbox', fixed: false }; $.viClientDialog(opts).open(); }); }); Clarke County Sanitary Authority operates the public water and sewer systems that serve the Town of Boyce, the villages of Millwood and White Post (water only), and commercial uses at the intersection of U.S. 50 and U.S. 340. The Clarke County Sanitary Authority is a governmental corporation created by the Board of Supervisors in 1988.  Prospect Hill Spring provides water for approximately 400 households and businesses in Boyce, Millwood, and White Post as well as the Waterloo Commercial District. Sewage is processed at the Boyce Sewage Treatment Facility. Inboden Environmental Services Inc. manages the water and sewer systems. Find water quality reports and CCSA forms using the links at left. If using a smartphone, use jump to subpage at top. The Clarke County Sanitary Authority office is located at 129 Ramsburg Lane in Berryville, Va. Hours 8 a.m. to 4 p.m. Monday through Friday Sarah Shiley Sanitary Authority Senior Billing Manager-Clerk (540) 955-5185 ccsa@clarkecounty.gov Inboden Environmental Services (800) 648-1010 (office) (540) 325-0748 (emergency) minboden@4ies.com Boyce Wastewater Treatment Plant (540) 837-2092
    1. There arethree major ways in which semiosis relates to other elements of social practices and of social events:as a facet of action; in the construal (representation) of aspects of the world; and in the constitutionof identities. And there are three semiotic (or discourse-analytical) categories corresponding tothese: genre, discourse and style.

      Semiotikken forholder sig til andre elementer af sociale praksisser som et aspekt af handling, repræsentation af verden og konstruktionen af identiteter. Disse svarer til genre, diskurs og stil, som henholdsvis forholder sig til: måder at handle, det sprog man bruger og måden praksis formidles; sprogbruget, der repræsenterer verden indenfor samme felt på forskellige måder og; stile, som aktører indordner sig under.

    2. The social process can be seen as the interplay between three levels of social reality: socialstructures, practices and events

      I tilfældet af cookies kunne den sociale struktur være EU, praksissen kunne være sikringen af online-privatliv og sikkerhed gennem valget, og begivenheden kunne være brugeren, som bliver bedt om at tage stilling til cookies.

  2. pressbooks.library.torontomu.ca pressbooks.library.torontomu.ca
    1. 12:20

      The timestamps in O'Hara's poem serve as a journal of his day, structuring the poem and adding a personal touch. The multiple timestamps in the first stanza further highlight the journal-like quality of the poem, and the importance of time recording and demonstration for O'Hara.

  3. pressbooks.library.torontomu.ca pressbooks.library.torontomu.ca
    1. certain

      Using certain and certainly further emphasizes the sentences within Matisse and the words following certain/ certainly. Also, having the following words pop out to the reader to see why certain/ certainly were used.

      https://www.etymonline.com/word/certainly#:~:text=%22without%20doubt%20or%20question%2C%20assuredly,%2B%20%2Dly%20(2).

    1. Second, ANT focuses attention on the black boxes em-ployed by actants, those who act or cause others to act. Black boxes, once enlisted,become actants themselves, inscribing and shaping the behavior of those employingthem

      Cookie-accept banneret kan måske ses som en af disse black-boxes, som "pr. selvfølgelige forståelser" har til mål at højne graden af privatliv og sikkerhed på nettet.

    2. We were struck by the common discourse in these literatures – privacy isimportant, the computer is an important cause of privacy issues, and governmentlegislation and business practices are progressively addressing the issues throughinternational standards, such as FIP. The literature was unable to explain how, ifprivacy was so important, this local issue and legislation supposedly protecting pri-vacy could be so easily dismissed.

      Interessant at debatten staid hviler på nogle af de samme forudsætninger, og hvordan Cookie-politikken er udtryk for en udvidelse af samme. Hvad gør valget ved debatten; indlejrer det de samme forudsætninger som dem FIP bygger på, eller ændrer det diskursen?

    1. You can link to a block by adding #^ at the end of your link destination followed by a unique block identifier. For example, [[2023-01-01#^37066d]].

      Genera automáticamente el identificador y lo agrega al contenido de referencia, lo cual deja la marca en caso de no usar una otra herramienta que no sea Obsidian.

      Por una parte me parece una funcionalidad muy interesante, pero por otra, es contraria, en cierta manera, al sentido y filosofía de Markdown.

    1. Existing facilities that can filter carbon dioxide out of the air only have the capacity to capture 0.01 million metric tons of CO2 globally today, costing companies like Microsoft as much as $600 per ton of CO2. That’s very little capacity with a very high price tag.

      Calma, Justine. “Trying to Reverse Climate Change Won’t Save Us, Scientists Warn.” Msn.Com, 1729, https://www.msn.com/en-us/news/technology/trying-to-reverse-climate-change-won-t-save-us-scientists-warn/ar-AA1sN6OC?ocid=msedgntp&cvid=20987699b6484dd5c9aad7c390f9e4cd&ei=4.

    1. If loneliness is an archetypal sense built into us all from the very beginning, then, to be alive is also to be lonely. Loneliness, therefore, will come and go as it chooses in the course of a lifetime, quite apart from our efforts to deny or avoid this reality.

      如果孤独是一种从一开始就根植于我们所有人的原型感觉,那么活着也就意味着孤独。因此,孤独会在一生中不由我们控制地来来去去,不管我们如何努力否认或避免这一现实。

    1. Kerr (1975)

      paper illustrates some of the problems you might run into when you try to use incentive schemes in real life

    1. as they layher on turtle’s back, the woman releases a seed she had carried from theSky World, and the earth is born.

      I really enjoy how however detailed the story becomes, it always refocuses back to the earth, which emphasizes the significance of land and rootedness in Native American culture.

    2. where they have lived like verybad philosophers, preferring, on the basis of a foolishreasoning, the savage to the French life

      It is interesting how the Native American lifestyle is compared to the French, but only such that the French remain superior. The fact that Native Americans' lives did not align with French values deemed the Native Americans as "foolish" and "bad philosophers". This emphasizes the ignorance and strong mindset that the westernized way of living is always 'correct' and better.

    3. common pot

      Europeans’ exploitative tendencies—driven by wealth accumulation and dominance—were seen as harmful to the “common pot,” representing a misalignment with the interdependent nature of Native communities.

    4. Sky Woman, only a mass of water exists beneath the sky, and the wateranimals are its only inhabitants.

      This story not only illustrates the primacy of water but also the resourcefulness and interdependence of various beings. The story reflects values of shared responsibility, adaptability, and communal intelligence, providing a philosophical basis for the interconnectedness in Native thought.

    5. According to Abenaki author Peter Paul Wzokhilain, alnôba-wôgan means both “human nature” and “birth.” It is translated literallyas the activity of “being (or becoming) human.”

      This view contrasts with European perspectives by emphasizing the transformative and relational aspects of humanity rather than mortality.

    1. Shape the NextGeneration of AI withyour ExpertiseVIEW OPPORTUNITIESGet paid training cutting-edge AI on your own schedule

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    1. The Blitz, as the British called the nightly bombing raids on London, killed at least 40,000 civilians.

      Every time I read about the civilians dying, I just feel so angry. Do the invaders or attackers not know that it is so unfair as most civilians were not even involved? Why should they have to die for your desire for something. You’re already killing the soldiers why the civilians too? It makes me so upset.

    2. But no one in the U.S government was going to propose declaring war on Japan to save the Chinese.

      I really hope another state came to help and save the Chinese. I can not imagine being afraid to be the next to die, and praying to be saved without knowing that no other state is willing to come save me and my family. It’s honestly really sad.

    3. Japanese troops raped up to 100,000 women and girls and then shot or bayonetted most of them in what is now recognized as one of the worst atrocities of WWII.

      I feel disgusted and sad. I feel bad for all the women and girls. I feel that the only reason why they probably killed the women and girls after, is because they are evil (obviously) and did not want them to get pregnant with their child. That is absolutely cruel. I also hope that when they mention girls, they don’t mean children through 12-15.

    1. Kant shifted the referent of the term from the terrifying object to the perceiving subject's experience of that object. In this way, the sublime became a potentially empowering model in which the subject, at first overwhelmed by terror or incomprehension, as in Burke's account, then had recourse to the faculty of Reason, and became assured of its own independent powers of consciousness.

      Kant

    1. Introducing The Internet's Files API

    2. accessing private files
      • generating a time-limited access URL or
      • creating a public group for your files.
    3. creating a private file storage solution with full CDN support and built-in access controls

      built in access control

    4. appreciate the immutability and content addressability of IPFS

      immutability and content addressability

    5. Surviving and scaling through the NFT boom was our trial by fire

      NFT boom tril by fire

    6. Building the largest and most scalable IPFS pinning service

      scalable pining service

    7. Introducing The Internet's Files API

      Description

    1. Playground is here: Build, test, and iterate on RAG apps with intuitive, low-code tools.Read the blog
    2. Elasticsearch is Open Source.  Again!(It's also the world's most popular vector database.)

      vector database

      to - open source again

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    1. As the title promises, the structure of ‘Walking’ is meandering, almost desultory. …. The strategy of the essay is to unsettle expectations by providing, instead of a walk between specified locations, a directionless meditation on the activity in its abstract form. As a result, the essay is not an excursion that its readers can enjoy from the safe remove of time and space, but an aimless collection of philosophical remarks, a labyrinth in which Thoreau's readers lose themselves and, in losing themselves, are implicated in the ‘truth’ of the essay

      The act of writing as a transgression

    1. motions and distractions can also interfere with our clarity. Being aware of the varying levels of abstraction within language can help us create clearer and more “whole” messages.

      Since I travel alot for work, I am always meeting new people. Speaking up clearly and loudly is something I've noticed I do not do very well. It seems the nerves get the best of me and I am unable to speak how I normally would. I will be focusing on this more as I grow in my communication journey

    1. exam, that retains the same meaning. And last, we can form new words by blending old ones together. Words like breakfast and lunch blend letters and meaning to form a new word—brunch.

      The language the kids are using now a days is just insane. "Skibity rizz' means you have charisma or charm. These are not just words used around friends, kids are saying these words in social context where there should be some level of respect. Language seems to be changing for the worst. Maybe I am just getting old but there seems to be a dumbing down of language with the younger generation.

    2. “queer” movement of the 1980s and ’90s that reclaimed queer as a positive identity marker for some gay, lesbian, bisexual, and transgender people. Even though some people embrace reclaimed words, they still carry their negative connotations and are not openly accepted by everyone.

      Situations like this have always peaked some curiosity inside me. I've thought about this quite a bit, the LGBT community reclaimed this word and put a positive spin on, however referring to someone as queer if your not in that community is seen as derogitory. Even when just describing it. Why does language seem to get captured in different groups and only able to be used by those groups? Does society just generally agree that this is the case and we all accept it?

    3. Some people are generally not good at or comfortable with receiving and processing other people’s feelings. Even those with good empathetic listening skills can be positively or negatively affected by others’ emotions. Expressions of anger can be especially difficult to manage because they represent a threat to the face and self-esteem of others

      I remember being in a relationship where I was unable to express my emotions. If something bothered me it was an attack on the other person. I also see this alot in the workplace, they preach safety culture but as soon as you speak up about the unsafe practices you are attacking the company and the management. It is not healthy to live like that but unfortunatley thats the reality. Hopefully this course will teach me how to properly recieve the response and rebuttle it.

    1. As we just learned, the relationship between the symbols that make up our language and their referents is arbitrary, which means they have no meaning until we assign it to them.

      This is a tricky one because words in different regions of our own country have different meaning. For example when I moved to Tennessee for a couple years they use tabogins. I had to no idea what they were referring to, but turns out thats just a beanie. Moving to the south I had to basically learn a whole new vocabulary, Kinfolk which is family member or close friend. Holler, didint mean to yell but it means a valley or long road in the base of the hills where people live.

    2. a farmer might have kept a pebble in a box to represent each chicken he owned. As further advancements made keeping track of objects-representing-objects more difficult, more abstract symbols and later written words were able to stand in for an idea or object. Despite the fact that these transitions occurred many thousands of years ago, we can trace some words that we still use today back to their much more direct and much less abstract origins.

      I feel like language has become so complex that it is again becoming a thing for the pepople of power and status. Think about taxes, or Wall Street, the language they use is so complex but it boils down to such simple meanings. I think they do this to keep normal people from being able to play the game by making it so complicated that the average person just gives up. Language is being used as a form of war on the average people.

    1. The two nations agreed to a cease-fire on August 12 and formally signed the Treaty of Paris in December.

      received Guam, Puerto Rico, Philippines.

    1. Importantly, reversible protein phosphorylation provides a major regulatory mechanism in conformational dynamics and compaction of IDPs

      Have you explored whether this phosphorylation-dependent structural rearrangement may play a role in the function of other NHR AF1 or F domains?

    2. The ability of AF1c phosphovariants to adopt multiple structural changes likely creates distinct binding surfaces within the NTD, enabling GR to selectively interact with different regulatory complexes along its signal transduction pathway.

      This is a very insightful study! I'm curious if you can model how this newly formed helical structure binds to AF1 interacting domains present on such proteins as TBP?

    1. borylation processes in good yield

      Alkyl arenes underwent borylation forming a single product or a mixture of products depending on the substitution pattern, ortho, meta or para.

    2. Neither substrate underwent

      No borylation takes place at the hindered geminal dimethyl groups.

    3. more hindered tert-butyl group

      Monoborylation took place at the n-butyl group and not at the more hindered t-butyl group.

    4. These reactions occurred without direction by the existing functional groups.

      Several functional groups that containied methyl groups underwent borylation at the primary C-H bonds. Once again, the specificity of the C-H bonds was proven.

    5. Likewise, the reaction of pentylcyclohexane,

      When the borylation reaction was conducted with pentylcyclohexane with only one set of primary C-H bonds, only these bonds reacted. This shows the high specificity of the catalyst [Ir(OMe)(COD)]2 and 2-mphen for the primary C-H bonds.

    6. Thus, the reactions in the remainder of the study were conducted in cyclooctane as solvent.

      When reactions were performed in solvents such as cyclohexane and cyclooctane, it was found that borylation occurred on the substrate rather than on cyclohexane or cyclooctane. Between cyclohexane and cyclooctane, cyclooctane was more inert towards borylation. Therefore, all reactions were conducted in cyclooctane as the solvent.

    7. The use of 2-methylphenanthroline (2-mphen) as ligand

      When the ligand is 2-methylphenanthroline, the catalyst is way more reactive than when coordinated by other ligands and shows selectivity for primary C-H bonds.

    8. Here, we report iridium-catalyzed borylations of primary C–H bonds

      Borylations carried out in the presence of iridium catalysts are selective for primary C-H bonds in a wide range of substrates.

    1. Among the 12 most highly ranked features across protein families are hydrogen bonds (MI=0.775), total surface tension (MI=0.763), london dispersion forces (MI=0.758), repulsive interactions (MI=0.722), internal tension (MI=0.708), ASA (MI=0.694), hydrophobic contacts (MI=0.561), TG frequency (MI=0.562), internal hydrophobicity (MI=0.561), VN frequency (MI=0.556), total hydrophobicity (MI=0.539), and GG frequency (MI=0.509).

      This is really interesting! I think it could also be interesting to see if any of the features (these or others) correlate or if any features could be predictive of others?

    2. Here we present InteracTor, a new toolkit for the extraction of three types of protein feature encodings: interaction features, physicochemical features, and compositional features.

      This is super cool! I can't wait to try it out!

    3. Extract atom, residue, and sequence information from PDB file (Figure 1A): This step involves parsing the Protein Data Bank (PDB) file to obtain the atomic types, 3D coordinates, and the amino acid sequence of the protein

      I'm curious if you can use this with structures predicted by AlphaFold or ESMFold. Related to that, I'm curious if you need to do any sort of pre-processing of the structures (mostly for AlphaFold and ESMFold structures because they're known to not always have optimal side chain placement).

    1. eLife Assessment

      This valuable study shows that eliminating a large portion of the principal neurons in the mammalian olfactory bulb does not affect the initial establishment of the circuit but has an impact on its maintenance. The strength of the paper is that the anatomical changes induced by genetic ablation of neurons are clear-cut. There is solid support for the findings, with a description of the structural and behavioral effects of ablating the majority of M/T neurons.

    2. Reviewer #1 (Public Review):

      This paper aims to address the establishment and maintenance of neural circuitry in the case of a massive loss of neurons. The authors used genetic manipulations to ablate the principal projection neurons, the mitral/tufted cells, in the mouse olfactory bulb. Using diphtheria toxin (Tbx21-Cre:: loxP-DTA line) the authors ablated progressively large numbers of M/T cells postnatally. By injecting diphtheria toxin (DT) into the Tbx21-Cre:: loxP-iDTR line, the authors were able to control the timing of the ablation in the adult stage. Both methods led to the successful elimination of a majority of M/TCs by 4 months of age. The authors made a few interesting observations. First, they found that the initial pruning of the remaining M/T cell primary dendrite was unaffected. However, in adulthood, a significant portion of these cells extended primary dendrites to innervate multiple glomeruli. Moreover, the incoming olfactory sensory neuron (OSN) axons, as examined for those expressing the M72 receptor, showed a divergent innervation pattern as well. The authors conclude that M/T cell density is required to maintain the dendritic structures and the olfactory map. To address the functional consequences of eliminating a large portion of principal neurons, the authors conducted a series of behavioral assays. They found that learned odor discrimination was largely intact. On the other hand, mating and aggression were reduced. The authors concluded that learned behaviors are more resilient than innate ones.

      The study is technically sound, and the results are clear-cut. The most striking result is the contrast between the normal dendritic pruning during early development and the expanded dendritic innervation in adulthood. It is a novel discovery that can lead to further investigation of how the single-glomerulus dendritic innervation is maintained. The authors conducted a few experiments to address potential mechanisms, but it is inconclusive, as detailed below. It is also interesting to see that the massive neuronal loss did not severely impact learned odor discrimination. This result, together with previous studies showing nearly normal odor discrimination in the absence of large portions of the olfactory bulb or scrambled innervation patterns, attests to the redundancy and robustness of the sensory system.

    3. Reviewer #2 (Public review):

      The authors make the interesting observation that the developmental refinement of apical M/T cell dendrites into individual glomeruli proceeds normally even when the majority of neighboring M/T cells are ablated. At later stages, the remaining neurons develop additional dendrites that invade multiple glomeruli ectopically and, similarly, OSN inputs to glomeruli lose projection specificity as well. The authors conclude that the normal density of M/T neurons is not required for developmental refinement, but rather for maintaining specific connectivity in adults.

      Comments on revised submission:

      The authors have adjusted the interpretation of their findings and as a consequence, the conclusions are now better supported by the data. However, the evidence for the absence of a role of firing in regulating ectopic dendrites is still insufficient.

    4. Author response:

      The following is the authors’ response to the original reviews.

      Reviewer #1 (Public Review):

      This paper aims to address the establishment and maintenance of neural circuitry in the case of a massive loss of neurons. The authors used genetic manipulations to ablate the principal projection neurons, the mitral/tufted cells, in the mouse olfactory bulb. Using diphtheria toxin (Tbx21-Cre:: loxP-DTA line) the authors ablated progressively large numbers of M/T cells postnatally. By injecting diphtheria toxin (DT) into the Tbx21-Cre:: loxP-iDTR line, the authors were able to control the timing of the ablation in the adult stage. Both methods led to the successful elimination of a majority of M/TCs by 4 months of age. The authors made a few interesting observations. First, they found that the initial pruning of the remaining M/T cell primary dendrite was unaffected. However, in adulthood, a significant portion of these cells extended primary dendrites to innervate multiple glomeruli. Moreover, the incoming olfactory sensory neuron (OSN) axons, as examined for those expressing the M72 receptor, showed a divergent innervation pattern as well. The authors conclude that M/T cell density is required to maintain the dendritic structures and the olfactory map. To address the functional consequences of eliminating a large portion of principal neurons, the authors conducted a series of behavioral assays. They found that learned odor discrimination was largely intact. On the other hand, mating and aggression were reduced. The authors concluded that learned behaviors are more resilient than innate ones.

      The study is technically sound, and the results are clear-cut. The most striking result is the contrast between the normal dendritic pruning during early development and the expanded dendritic innervation in adulthood. It is a novel discovery that can lead to further investigation of how the single-glomerulus dendritic innervation is maintained. The authors conducted a

      few experiments to address potential mechanisms, but it is inconclusive, as detailed below. It is also interesting to see that the massive neuronal loss did not severely impact learned odor discrimination. This result, together with previous studies showing nearly normal odor discrimination in the absence of large portions of the olfactory bulb or scrambled innervation patterns, attests to the redundancy and robustness of the sensory system. The discussion should take into account these other studies in a historical context.

      Main comments:

      (1) In previous studies, it has been concluded that dendritic pruning unfolds independently, regardless of the innervation pattern or activity of the OSNs. The new observation bolsters this conclusion by showing that a loss of neighboring M/T cells does not affect the developmental process. A more nuanced discussion comparing the results of these studies would strengthen the paper.

      We thank the reviewer for the suggestion. We now include an extended discussion citing relevant previous works in the manuscript (Lines 351-374).

      (2) The authors propose that a certain density of M/T is required to prevent the divergent innervation of primary dendrites, but the evidence is not sufficient to support this proposal. The experiment with low-dose DT injection to ablate a smaller portion of M/T cells did not change the percentage of cells innervating two or more glomeruli. The authors suggest that a threshold must be met, but this threshold is not determined.  

      In our experiments using high-dose DT, we hypothesized that there may be many empty glomeruli (glomeruli not innervated by M/T cells), and as a result, that some of the remaining M/T cells could branch their apical dendrite tuft into multiple empty glomeruli. To test this hypothesis, we carried out another experiment using a lower dose of DT. In this experiment, the fraction of remaining M/T cells was 25% (~10,000 M/T cells), which was higher than with the high DT dose (5%, or around 2,000 M/T cells) , but still significantly lower than wild type mice (~40,000 cells M/T cells). With around 2,000 glomeruli and 10,000 M/T per bulb, it could be expected that each glomerulus would be innervated by ~5 M/T cells (on average). However, we found that the percentage of M/T cells projecting to multiple glomeruli (around 40%) was similar when either 10,000 or 2,000 of M/T remained in the bulb. In addition, it is important to emphasize that even in wt animals with a full set of M/T cells, a small percentage of M/T cells still innervate more than one glomerulus (Lin et al., 2000). Together, these observations suggest that the innervation of multiple glomeruli by M/T cells is not simply due to the presence of empty glomeruli, and that our hypothesis was not correct.

      We have added a comment explaining this issue in the Results section (Lines 200-203).

      (3) The authors suggest that neural activity is not required for this plasticity. The evidence was derived primarily from naris occlusion and neuronal silencing using Kir2.1. While the results are consistent with the notion, it is a rather narrow interpretation of how neural activity affects circuit configuration. Perturbation of neural activity also entails an increase in firing. Inducing the activity of the neurons may alter this plasticity. Silencing per se may induce a homeostatic response that expands the neurite innervation pattern to increase synaptic input to compensate for the loss of activity. Thus, further silencing the cells may not reduce multiglomerular innervation, but an increased activity may.

      The experiments with Kir2.1 demonstrate that the structural plasticity observed after reducing the total number of M/T cells in an animal is not regulated by the firing action potentials in the remaining cells. Instead, this experiment indicates that the observed structural plasticity may be regulated by other types of mechanisms (including increased synaptic excitation as suggested by the reviewer) that do not require the firing of action potentials in M/T cells. 

      We now have included a comment regarding this point (Lines 243-247).  

      (4) There is a discrepancy between this study and the one by Fujimoto et al. (Developmental Cell; 2023), which shows that not only glutamatergic inputs to the primary dendrite can facilitate pruning of remaining dendrites but also Kir2.1 overexpression can significantly perturb dendritic pruning. This discrepancy is not discussed by the authors.

      We agree that it would be useful to contrast these two works.

      In our experiments, performed in adult animals, we blocked sensory input by performing naris occlusion before we induced ablation of M/T cells. In a separate experiment, also in adult animals, we expressed the Kir2.1 channel, to reduce the ability of neurons to fire action potentials. With both types of manipulations, we observed that the ablation of a large fraction of M/T cells still caused the remaining M/T cells to maintain a single apical dendrite that sprouts several new tufts towards multiple glomeruli. A recent paper (Fujimoto et al., 2023)) in which Kir2.1 was expressed in a large percentage of M/T starting during embryonic development showed that these “silent” M/T cells failed to prune their arbors to a single dendrite. In aggregate, these observations indicate that action potentials are necessary for the normal pruning that occurs during perinatal development (Fujimoto et al., 2023), but are not required for the expansion of dendritic trees caused by ablating a large fraction of M/T cells in adult animals (our current manuscript).

      We have now explained the differences between both studies in the manuscript (Lines 427-439).

      (5) An alternative interpretation of the discrepancy between the apparent normal pruning by p10 and expanded dendritic innervation in adulthood is that there are more cells before P10, when ~25% of M/T cells are present, but at a later date only 1-3% are present. 

      The relationship between the number of M/T cells and single glomerulus innervation has not been explored during postnatal development. It would be important to test this hypothesis.

      We agree with this comment, and in lines 375-381 we discuss the discrepancy between normal refinement during development, and dendritic sprouting in adults.

      Cre is expressed in M/T cells and it induces DTA expression starting around P0. The elimination of M/T cells starts at this time, and continues until by P10, when more than 75% of M/T have been eliminated. At P21 more than 90% of M/T have been eliminated, and their number remains stable thereafter.

      Pruning of the dendrites of M/T cells starts at P0 and it is mostly complete by P10. Therefore, it is possible that between P0 and P7, when dendrites are being pruned, the number of M/T cells remaining in the bulb is still over a threshold that does not interfere with the process of normal dendrite pruning. We agree that it would be very informative to perform additional experiments in the future where a large set of M/T cells could be ablated before pruning occurs (ideally before P0). 

      (6) The authors attribute the change in the olfactory map to the loss of M/T cells. Another obvious possibility is that the diffused projection is a response to the change in the olfactory bulb size. With less space to occupy, the axons may be forced to innervate neighboring glomeruli. It is not known how the total number of glomeruli is affected. This question could be addressed by tracking developmental changes in bulb volume and glomerular numbers.

      Certainly, this is a possibility, and we have now included a comment on this regard in the manuscript (Lines 473-480). 

      We believe that there are three likely scenarios that could account for these observations:

      (a) After ablating M/T cells, the tufts of the remaining M/T cells sprout into multiple glomeruli, and this causes the axons of OSNs to project into multiple glomeruli.

      (b) Ablating M/T cells may cause changes in other OB cells that make synapses in the glomeruli (ETCs, PGCs, sAC, etc…), and the misrouting of OSN axons that we observed in our experiments may be a secondary effect caused by the elimination of M/T cells.

      (c) After ablating the majority of M/T cells, the olfactory bulb gets reduced in size, and the axons of OSNs find it difficult to precisely converge on a target that now has become smaller. As a result, the axons of OSNs fail to converge on single glomeruli.

      (7) The retained ability to discriminate odors upon reinforced training is not surprising in light of a number of earlier studies. For example, Slotnick and colleagues have shown that rats losing ~90% of the OB can retain odor discrimination. Weiss et al have shown that humans without an olfactory bulb can perform normal olfactory tasks. Gronowitz et al have used theoretical prediction and experimental results to demonstrate that perturbing the olfactory map does not have a major impact on olfactory discrimination. Fleischmann et al have shown that mice with a monoclonal nose can discriminate odors. The authors should discuss their results in these contexts.

      We apologize for this important oversight - we now include a more elaborate discussion including the relevant references as suggested in the manuscript (Line 483-496).

      (8) It should be noted that odor discrimination resulting from reinforcement training does not mean normal olfactory function. It is a highly artificial situation as the animals are overtrained. It should not be used as a measure of the robustness of the olfactory sense. Natural odor discrimination (without training), detection threshold, and innate appetitive/aversive response to certain odors may be affected. These experiments were not conducted.

      We agree that the standard tests commonly used to measure olfactory function require substantial training, and thus, are quite artificial. However, these tests are used because they allow a more precise quantification of olfactory function than those relying on natural behaviors.  

      We have now included a few sentences to address this point in the results (Lines 321322) and discussion sections (Lines 541-543).

      (9) The social behaviors were conducted using relatively coarse measures (vaginal plug and display of aggression). Moreover, these behaviors are most likely affected by the disruption of the AOB mitral cells and have little to do with the dendritic pruning process described in the paper. It is misleading to lump social behaviors with innate responses to odors.

      This point follows the same logic as the previous one. The olfactory tests that rely on natural behaviors are quite coarse and difficult to quantify. In contrast, the olfactory tests using apparatuses such as olfactometers can be quantified with precision, but they are artificial. We agree that some of the naturalistic behaviors that we studied such as mating or aggression may depend to a large extent on the AOB (although it is possible that the MOB may also be involved in these tasks to a degree). In our initial version of the manuscript, we commented on the anticipated relative involvement of the MOB and AOB in the studied tasks, but we have now added some additional sentences to make this point clearer. In addition, we now add a comment indicating that it is possible that the abnormal behaviors could simply be due to a reduction in the number of AOB M/T cells (~98.5% and ~ 85% elimination of M/T cells in the AOB in Tbx::DTA and Tbx::iDTR mice, respectively), regardless of the abnormal dendritic pruning of main OB M/T cells (Lines 530-534).

      See Figure 5E - M/T cells in AOB (Lines 1238-1239). 

      Reviewer #2 (Public Review):

      The authors make the interesting observation that the developmental refinement of apical M/T cell dendrites into individual glomeruli proceeds normally even when the majority of neighboring M/T cells are ablated. At later stages, the remaining neurons develop additional dendrites that invade multiple glomeruli ectopically, and similarly, OSN inputs to glomeruli lose projection specificity as well. The authors conclude that the normal density of M/T neurons is not required for developmental refinement, but rather for maintaining specific connectivity in adults.

      The observations are indeed quite striking; however, the authors' conclusions are not entirely supported by the data.

      (1) It is unclear whether the expression of diphtheria toxin that eventually leads to the ablation of the large majority of M/T neurons compromises the cell biology of the remaining ones.

      DT is an extremely potent toxin that kills cells by inhibiting proteins translation, and it has been demonstrated that the presence of a single DT molecule in a cell is sufficient to kill it, because of its highly efficient catalytic activity. Accordingly, previous experiments have shown that DT kills cells within a few hours after its appearance in the cytoplasm (Yamaizumi et al., 1978). In other words, all the published evidence suggests that if a cell is exposed to the action of DT, that cell will die shortly. There is no evidence that cells exposed to DT can survive and experience long-term effects. Finally, previous works have not observed any long-term changes in neurons directly caused by the actions of DT (Johnson et al., 2017).

      (2) The authors interpret the growth of ectopic dendrites later in life as a lack of maintenance of dendrite structure; however, maybe the observed changes reflect actually adaptations that optimize wiring for extremely low numbers of M/T neurons. The finding that olfactory behavior was less affected than predicted supports this interpretation.

      We do not know the cellular or molecular mechanisms that explain why reducing the density of M/T cells is followed by the growth of ectopic dendrites from the remaining M/T cells. We agree that the functional outcome of growing ectopic dendrites may result in an optimization of wiring in the bulb and could explain why olfactory function is relatively preserved. We now include a comment regarding this possibility (Lines 513-525).   

      (3) The number of remaining M/T neurons is much higher at P10 than later. Can the relatively large number of remaining neurons (or their better health status) be the reason that dendrites refine normally at the early developmental stages rather than a (currently unknown) developmental capacity that preserves refinement?

      We thank the reviewer for the suggestion, which was also raised by reviewer 1. 

      We agree with this comment, and in lines 375-381 we discuss the discrepancy between normal refinement during development, and dendritic sprouting in adults.

      Cre is expressed in M/T cells and it induces DTA expression starting around P0. The elimination of M/T cells starts at this time, and continues until by P10, when more than 75% of M/T have been eliminated. At P21 more than 90% of M/T have been eliminated, and their number remains stable thereafter.

      Pruning of the dendrites of M/T cells starts at P0 and it is mostly complete by P10. Therefore, it is possible that between P0 and P7, when dendrites are being pruned, the number of M/T cells remaining in the bulb is still over a threshold that does not interfere with the process of normal dendrite pruning. We agree that it would be very informative to perform additional experiments in the future where a large set of M/T cells could be ablated before pruning occurs (ideally before P0). 

      (4) While the effect of reduced M/T neuron density on both M/T dendrites and OSN axons is described well, the relationship between both needs to be characterized better: Is one effect preceding the other or do they occur simultaneously? Can one be the consequence of the other?

      Previous works have demonstrated that disrupting the topographic projection of the OSN axons has no effect on the structure of the apical dendrite of M/T cells (Ma et al., 2014; Nishizumi et al., 2019). Our experiments ablating a large fraction of M/T cells suggest that they are necessary for the correct targeting of OSN axons into the bulb. However, our experiments do not allow us to tell apart these 2 scenarios: 

      (a) the ablation of a large fraction of M/T cells directly causes the sprouting of the apical dendrite of M/T cells, and that this sprouting in turn causes the abnormal projection of OSN axons onto the bulb. 

      (b) the ablation of a large fraction of M/T cells first causes the axons of OSN to project abnormally onto multiple glomeruli in the bulb, and this in turn causes the dendrite of remaining M/T cells to sprout onto multiple glomeruli. 

      We now include a comment on the manuscript explaining this point. (Lines 473-492)

      (5) Page 7: the observation that not all neurons develop additional dendrites is not a sign of differences between cell types, it may be purely stochastic.

      This is correct, and we mention these 2 scenarios in the discussion (Line 407-408). 

      (6) Page 8: the fact that activity blockade did not affect the formation of ectopic dendrites does not suggest that the process is not activity-dependent: both manipulations have the same effect and may just mask each other.

      The experiments with Kir2.1 demonstrate that the structural plasticity observed after reducing the total number of M/T cells in an animal is not regulated by the firing action potentials in the remaining cells. Instead, this experiment indicates that the observed structural plasticity may be regulated by other types of mechanisms (including increased synaptic excitation as suggested by the reviewer) that do not require the firing of action potentials in M/T cells. 

      We now have included a comment regarding this point (Lines 243-247).  

      (7) It remains unclear how the observed structural changes can explain the behavioral effects.

      We agree that the relationship between structural changes and behavior was not appropriately explained in our manuscript. Our manipulations cause two major changes in the olfactory system, one primary, and several secondary. The primary change is a large reduction in the number of M/T cells both in the MOB and AOB. This reduction in M/T cell number triggers significant secondary changes in the connectivity of the bulb, including an abnormal projection of OSNs onto the OB, and the growth of ectopic dendrites from the remaining M/T cells into multiple glomeruli.

      The behavioral abnormalities displayed by these mice is ultimately caused by the reduction in the number of M/T cells, but it is likely that the secondary structural changes could regulate some of the behavioral phenomena that we observed. For example, in principle, it is possible that the ectopic dendrites innervating several glomeruli could help the bulb to perceive smells with a much reduced number of M/T cells. On the other hand, this promiscuous growth of dendrites into multiple glomeruli could make it more difficult for the animals to discriminate between smells. The same argument could be made about the fact that OSN axons project onto multiple glomeruli: we simply do not know if this change helps or makes it more difficult for the animal to detect smells.  

      We now include a comment regarding this issue (Lines 513-525).   

      Reviewer #1 (Recommendations For The Authors):

      Additional experiments and a more thorough discussion of the results, as suggested in the public review, would significantly strengthen the paper. Below are some specific parts that need to be addressed.

      There is a lack of information on how M/T cell numbers are quantified. Without the information, it is difficult to evaluate the claim. Using the tdTomato signal may miss cells that are not labeled due to the transgenic effect. 

      Although we cannot conclude that we are identifying the complete set of M/T cells (because the transgenic lines may fail to label some M/T cells), the number of M/T cells that we observed is similar to that previously reported (Richard et al., 2010). This concern has been included in the Results section (Lines 121-124).

      A more detailed description about M/T cells quantification has been added into the method section (Lines 627-632).

      There is a lack of information on the timeline of treatment and how measurement of the olfactory bulb volume is conducted.

      We now include a more detailed description of how the volume of the OB was measured in the methods (Lines 621-623).

      The volume measurement is inconsistent with the pictures shown. In Figure 1, supplemental data 2 panels B and C, it appears that the bulbs in DTA and DTR mice are about half in length in each dimension. This would translate into ~1/8 of the volume of the control mice.

      We measured the volume of the bulbs based on the Neurolucida reconstructions, and we observed that in both DTA and iDTR mice the volumes of their bulbs are roughly 50% compared to a wild type mouse. In Figure 1 - figure supplement 2 the sections that were shown for wild type, DTA and iDTR mice were not taken at the same position in the bulb, and this gave the impression that the bulbs from DTA and iDTR were much smaller than they really are. We now show sections for these three animals at equivalent positions in the bulb. 

      Figure 1 E and F have no legend.

      We apologize for this mistake - we have now added the legend for Figures 1E and F (Lines 1009-1013).

      Figure 3, supplemental data 2, it is not clear what the readers should be looking at. The data is confusing even for experts in the field. The authors should describe the figures more clearly, pointing out what they are supposed to show.

      We apologize for this, and we have now added a more detailed description of Figure3 – figure supplement 2 (Lines 1153-1167).

      In several figures, it is not clearly written what the comparisons were for where there are indications of statistical significance above the bars.

      We have now included a more detailed description of the statistics comparison in the figure legends.

      AAV serotype should be specified.

      The AAV serotype used to label M/T cells was the AAV-PHP.eB. We have added this information in the methods section of the manuscript. 

      Reviewer #2 (Recommendations For The Authors):

      Minor points

      Page 5, para 2: "The decrease in neuronal plasticity with age": it is unclear what "the decrease" refers to.

      We have changed this sentence in the text to make it clear:

      “The decrease in structural plasticity of M/T cells after apical dendrite refinement (Mizrahi and Katz, 2003),….”

      Line 146-148

      Is there a quantification of the effect of Kir2.1 overexpression alone (example shown in Figure 3D)?

      We did an experiment in IDTR animals in which a fraction of M/T cells expressed Kir2.1, and we split these animals in 2 groups: (a) animals that received an injection of DT, and (b) animals that did not receive any DT. We quantified the effect of Kir2.1 on M/T cells from animals that received DT injection (with an ablation of around of 90% of M/T cells) and we did not observe any clear statistically significant differences between cells expressing Kir2.1 or neurons that did not express Kir2.1 from other iDTR animals that also received DT injections. We did not quantify the possible effects of kir2.1 in the group of animals that did not receive DT because on a first inspection we did not observe any clear differences between Kir2.1 cells and neighboring wild type cells. 

      References

      Fujimoto S, Leiwe MN, Aihara S, Sakaguchi R, Muroyama Y, Kobayakawa R, Kobayakawa K, Saito T, Imai T. 2023. Activity-dependent local protection and lateral inhibition control synaptic competition in developing mitral cells in mice. Dev Cell S1534-5807(23)00237-X. doi:10.1016/j.devcel.2023.05.004

      Johnson RE, Tien N-W, Shen N, Pearson JT, Soto F, Kerschensteiner D. 2017. Homeostatic plasticity shapes the visual system’s first synapse. Nat Commun 8:1220. doi:10.1038/s41467-017-01332-7

      Lin DM, Wang F, Lowe G, Gold GH, Axel R, Ngai J, Brunet L. 2000. Formation of precise connections in the olfactory bulb occurs in the absence of odorant-evoked neuronal activity. Neuron 26:69–80. doi:10.1016/s0896-6273(00)81139-3

      Ma L, Wu Y, Qiu Q, Scheerer H, Moran A, Yu CR. 2014. A developmental switch of axon targeting in the continuously regenerating mouse olfactory system. Science 344:194–197. doi:10.1126/science.1248805

      Nishizumi H, Miyashita A, Inoue N, Inokuchi K, Aoki M, Sakano H. 2019. Primary dendrites of mitral cells synapse unto neighboring glomeruli independent of their odorant receptor identity. Commun Biol 2:1–12. doi:10.1038/s42003-018-0252-y

      Richard MB, Taylor SR, Greer CA. 2010. Age-induced disruption of selective olfactory bulb synaptic circuits. Proc Natl Acad Sci U S A 107:15613–15618. doi:10.1073/pnas.1007931107

      Yamaizumi M, Mekada E, Uchida T, Okada Y. 1978. One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell. Cell 15:245–250. doi:10.1016/0092-8674(78)90099-5

    1. eLife Assessment

      This study presents a valuable finding on a potential signaling pathway responsible for the direct effects of nicotine on intestinal stem cell growth and tumorigenesis.  The evidence supporting the claims of the authors is solid. This research will be of interest to medical biologists specializing in intestinal tumors.

    2. Reviewer #1 (Public review):

      Summary:

      In their manuscript, authors Isotani et al used in vivo and ex vivo models to show that nicotine could promote stemness and tumorigenicity in murine model. The authors further provided data supporting that the effects of nicotine on stem cell proliferation and tumor initiation were mediated by the Hippo-YAP/TAZ and Notch signal pathway.

      Strengths and weaknesses:

      The major strength of this study is the using a set of tools, including Lgr5 reporter mice (Lgr5-EGFP-IRES-CreERT2 mice), stem cell-specific Apc knockout mice (Lgr5CreER Apcfl/fl mice), organoids derived from these mice and chemical compounds (agonists and antagonists) to demonstrate nicotine affects stem cells rather than Paneth cells, leading to increased intestinal stemness and tumorigenicity. Whereas, all models are restricted to mice, lacking analysis of human samples or human intestinal organoids to prove the human relevant of these findings. Although the revised manuscript has significantly improved in the quality of pictures, there seems to be still a discrepancy in Figure 2A: quantification result suggested that NIC (1um) treatment increased the number of colonies from 300 to around 450 (1.5 folds), whereas representative picture shown that the difference was 3 to 12 living organoids (4 folds).

      Overall, the presented results could support their conclusions. A previous study reported that nicotine acts through the α2β4 nAChR to enhance Wnt production by Paneth cells, which subsequently affects ISCs. In contrast, this manuscript demonstrated that nicotine directly promotes ISCs through α7-nAChR, independent of Paneth cells. Therefore, this manuscript offers novel insights into the mechanism of nicotine's effects on the mouse intestine.

    3. Reviewer #2 (Public review):

      Summary:

      The manuscript by Isotani et al characterizes the hyperproliferation of intestinal stem cells (ISCs) induced by nicotine treatment in vivo. Employing a range of small molecule inhibitors, the authors systematically investigated potential receptors and downstream pathways associated with nicotine-induced phenotypes through in vitro organoid experiments. Notably, the study specifically highlights a signaling cascade involving α7-nAChR/PKC/YAP/TAZ/Notch as a key driver of nicotine-induced stem cell hyperproliferation. Utilizing a Lgr5CreER Apcfl/fl mouse model, the authors extend their findings to propose a potential role of nicotine in stem cell tumorgenesis. The study posits that Notch signaling is essential during this process.

      Strengths and Weaknesses:

      One noteworthy research highlight in this study is the indication, as shown in Figure 2 and S2, that the trophic effect of nicotine on ISC expansion is independent of Paneth cells. In the Discussion section, the authors propose that this independence may be attributed to distinct expression patterns of nAChRs in different cell types. To further substantiate these findings, the authors provided qPCR analysis of nAchRs in ISCs and Paneth cells from isolated whole small intestine, indicating that α7-nAChR uniquely responds to nicotine treatment among various nAChRs. And the authors further strengthen the clinical relevance of the study by exploring human scRNA-seq dataset, in which α7-nAChR is indeed also expressed in human ISCs and Paneth cells.

      As shown in the same result section, the effect of nicotine on ISC organoid formation appears to be independent of CHIR99021, a Wnt activator. In the Lgr5CreER Apcfl/fl mouse model, it is known that APC loss results in a constitutive stabilization of β-catenin, thus the hyperproliferation of ISCs by nicotine treatment in this mouse model is likely beyond Wnt activation. The authors have included such discussion.

      In Figure 4, the authors investigate ISC organoid formation with a pan-PKC inhibitor, revealing that PKC inhibition blocks nicotine-induced ISC expansion. It's noteworthy that PKC inhibitors have historically been used successfully to isolate and maintain stem cells by promoting self-renewal. Therefore, it is surprising to observe no or reversal effect on ISCs in this context. The authors have now included an additional PKC inhibitor Sotrastaurin to confirm the role of PKC in nicotine-induced ISC expansion.

      Overall, the manuscript has provided sufficient experimental evidence to address my concerns and also significantly enhanced its quality.

    4. Author response:

      The following is the authors’ response to the original reviews.

      Reviewer #1 (Public Review):

      Summary:

      In their manuscript, "Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway", authors Isotani et al claimed that this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggest the use of DBZ as a potential therapeutic strategy for treating intestinal tumors. However, the presented data do not support the primary claims.

      Weaknesses:

      My main reservation is that the quality of the results presented in the manuscript may not fully substantiate their conclusions. For instance, in Figure 2 A and B, it is challenging to discern a healthy organoid. This is significant, as the entirety of Figure 2 and several panels in Figures 3 - 5 are based on these organoid assays. Additionally, there seems to be a discrepancy in the quality of results from the western blot, as the lanes of actin do not align with other proteins (Figure 6B).

      We directly count organoids under microscopy as described previously (Igarashi M et.al., Cell.2016 Igarashi M et.al., Aging Cell.2019). When we count the number of organoids, we exactly can discern which are alive or dead organoids under microscope. Hence, we will detail the method and show which are alive or dead organoids using arrows in our revised version (Figure2A and B).

      Moreover, as reviewer1 pointed out, the number of organoids originated from intestinal or colonic crypts can be affected by dead organoids as in Figure2A and 2B. However, almost all colonies from isolated intestinal stem cells (ISCs) (Figure 2C and D) are alive, so the number of colonies are less affected by dead colonies in those experiments using isolated ISCs. Since all organoid data in Figure 3-5 are based on the same method as that of Figure2C and D, the data quality of Figures 3-5 cannot be affected by dead colonies.

      Finally, to improve data quality of Figure6B, we repeated this experiments and replaced it by new figures.

      Reviewer #2 (Public Review):

      Summary:

      The manuscript by Isotani et al characterizes the hyperproliferation of intestinal stem cells (ISCs) induced by nicotine treatment in vivo. Employing a range of small molecule inhibitors, the authors systematically investigated potential receptors and downstream pathways associated with nicotine-induced phenotypes through in vitro organoid experiments. Notably, the study specifically highlights a signaling cascade involving α7-nAChR/PKC/YAP/TAZ/Notch as a key driver of nicotine-induced stem cell hyperproliferation. Utilizing a Lgr5CreER Apcfl/fl mouse model, the authors extend their findings to propose a potential role of nicotine in stem cell tumorgenesis. The study posits that Notch signaling is essential during this process.

      Strengths and Weaknesses:

      One noteworthy research highlight in this study is the indication, as shown in Figure 2 and S2, that the trophic effect of nicotine on ISC expansion is independent of Paneth cells. In the Discussion section, the authors propose that this independence may be attributed to distinct expression patterns of nAChRs in different cell types. To further substantiate these findings, it is suggested that the authors perform tissue staining of various nAChRs in the small intestine and colon. This additional analysis would provide more conclusive evidence regarding how stem cells uniquely respond to nicotine. It is also recommended to present the staining of α7-nAChR from different intestinal regions. This will provide insights into the primary target sites of nicotine in the gut tract. Additionally, it is recommended that the authors consider rephrasing the conclusion in this section (lines 123-124). The current statement implies that nicotine does not affect Paneth cells, which may be inaccurate based on the suggestion in line 275 that nicotine might influence Paneth cells through α2β4-nAChR. Providing a more nuanced conclusion would better reflect the complexity of nicotine's potential impact on Paneth cells.

      It was difficult to obtain nAchRs antibodies usable in immunostaining. Hence, we instead performed qPCR of nAchRs in ISCs and Paneth cells from isolated whole small intestine (new Figure3C), although we cannot know the difference of the nAchRs expression in different intestinal regions by this method. Although the comparatively high expression was observed in α7-nAChR and α8nAChR in both ISCs and Paneth cells, the significant difference between ISCs and Paneth cells were not observed (Figure3C). 

      Interestingly, nicotine up-regulated only the expression of α7-nAChR in ISCs, suggesting the specifical response of α7-nAChR to nicotine (Figures 3C and D). We paraphrased the conclusion of the paragraph according to reviewer’s suggestion.

      As shown in the same result section, the effect of nicotine on ISC organoid formation appears to be independent of CHIR99021, a Wnt activator. Despite this, the authors suggest a potential involvement of Wnt/β-catenin activation downstream of nicotine in Figure 4F. In the Lgr5CreER Apcfl/fl mouse model, it is known that APC loss results in a constitutive stabilization of β-catenin, thus the hyperproliferation of ISCs by nicotine treatment in this mouse model is likely beyond Wnt activation. Therefore, it is recommended that the authors reconsider the inclusion of Wnt/β-catenin as a crucial signaling pathway downstream of nicotine, given the experimental evidence provided in this study.

      We appreciate for this important suggestion. Certainly, Wnt/β-catenin was activated in Nicotine treated ISCs. However, as reviewer points out, the hyperproliferation of ISCs by nicotine treatment is likely beyond Wnt activation.  According to the reviewer’s suggestion, we removed Wnt/β-catenin as a crucial signaling pathway downstream of nicotine (Figure 5G).

      In Figure 4, the authors investigate ISC organoid formation with a panPKC inhibitor, revealing that PKC inhibition blocks nicotine-induced ISC expansion. It's noteworthy that PKC inhibitors have historically been used successfully to isolate and maintain stem cells by promoting self-renewal. Therefore, it is surprising to observe no effect or reversal effect on ISCs in this context. A previous study demonstrated that the loss of PKCζ leads to increased ISC activity both in vivo and in vitro (DOI: 10.1016/j.celrep.2015.01.007). Additionally, to strengthen this aspect of the study, it would be beneficial for the authors to present more evidence, possibly using different PKC inhibitors, to reproduce the observed results with Gö 6983. This could help address potential concerns or discrepancies and contribute to a more comprehensive understanding of the role of PKC in nicotine-induced ISC expansion.

      Gö 6983 is a pan-PKC inhibitor against for PKCα, PKCβ, PKCγ, PKCδ and PKCζ with IC50 of 7 nM, 7 nM, 6 nM, 10 nM and 60 nM, respectively. Since we used Gö 6983 at the concentration of 10nM in our experiment, we consider PKCζ may not be possible target of nicotine. Additionally, we treated using 5nM Sotrastaurin, another pan-PKC inhibitor, which is supposed not to affect PKCζ. The observed result with Gö 6983 was reproduced by Sotrastaurin (Supplemental Figure 3E).

      An additional avenue that could enhance the clinical relevance of the study is the exploration of human datasets. Specifically, leveraging scRNA-seq datasets of the human intestinal epithelium (DOI: 10.1038/s41586-021-03852-1) could provide valuable insights. Analyzing the expression patterns of nAChRs across diverse regions and cell types in the human intestine may offer a potential clinical implication.

      We analyzed distribution pattern nAChRs of by scRNA-seq datasets of the human intestinal epithelium (DOI: 10.1038/s41586-021-03852-1). In consistent with mouse data (Figure3C), the expression of human α7-nAChR is higher than that of other nAChRs. The difference of the expression between ISCs and Paneth cells is not clear as in that of mouse (Supplemental Figure4A and B). From mouse and human data, we speculate the induction of specific nAChR by nicotine is essence of ISC response to nicotine, rather than the distribution of nAChRs.

      Reviewer #2 (Recommendations For The Authors):

      The manuscript could benefit from addressing a few minor points to enhance its quality before publication:

      (1) Ensure all images are presented in higher resolution to improve visual clarity.

      We replaced all images by those with higher resolution.

      (2) Quantify Western blot results accurately for rigor and precision in data representation.

      We quantified all blots.

      (3) Include error bars in control groups where missing, particularly in Figures 3C and 4D, to enhance data interpretation.

      We included error bars in control groups in new Figure 3C and 4D.

      (4) The layout of Figure S3B, S4A and S4B should be corrected.

      We corrected the layout of those Figures.

    1. Supermajority requirement: A 60 percent supermajority vote was required for the approval of Amendment 4. Contents 1 Aftermath 1.1 Implementing Amendment 4 1.2 Senate Bill 7066 2 Election results 3 Overview 4 Text of measure 4.1 Ballot title 4.2 Ballot summary 4.3 Constitutional changes 4.4 Readability score 5 Support 5.1 Supporters 5.1.1 Officials 5.1.2 Organizations 5.1.3 Individuals 5.2 Arguments 6 Opposition 6.1 Opponents 6.1.1 Officials 6.1.2 Organizations 6.2 Arguments 7 Media editorials 7.1 Support 7.1.1 Additional editorial endorsements 7.2 Opposition 8 Campaign finance 8.1 Support 8.1.1 Donors 8.2 Methodology 9 Polls 10 Background 10.1 Convicted felons voting laws 10.2 Margin-of-victory in past Florida elections 10.3 Gubernatorial elections 10.3.1 2018 10.3.2 2014 MOV: 1 percent 10.3.3 2010 MOV: 1.2 percent 10.4 Presidential elections in Florida 10.4.1 2016 MOV: 1.2 percent 10.4.2 2012 MOV: 0.9 percent 10.4.3 2008 MOV: 2.8 percent 10.5 History of felon voting laws in Florida 10.6 Johnson v. Bush (2005) 10.7 Hand v. Scott (2018) 10.8 Executive Clemency Board 10.9 Election policy on the ballot in 2018 11 Reports and analyses 11.1 Estimated number of disenfranchised felons 12 Path to the ballot 13 How to cast a vote 13.1 Poll times 13.2 Registration requirements 13.3 Automatic registration 13.4 Online registration 13.5 Same-day registration 13.6 Residency requirements 13.7 Verification of citizenship 13.8 Verifying your registration 13.9 Voter ID requirements 14 See also 15 State overview 15.1 Partisan control 15.1.1 Congressional delegation 15.1.2 State executives 15.1.3 State legislature 15.1.4 Trifecta status 15.2 2018 elections 15.3 Demographics 16 State election history 16.1 Historical elections 16.1.1 Presidential elections 16.1.2 U.S. Senate elections, 2000-2016 16.1.3 Gubernatorial elections, 2000-2016 16.1.4 Congressional delegation, 2000-2016 16.1.5 Trifectas, 1992-2017 17 External links 17.1 Support 17.2 Opposition 18 Footnotes

      Pieces of the article like this show the genuine care of the author to make sure the readers of this page understand the information being relayed. Note: all of the hyper links embedded throughout the text to use as resources.

    1. This type of source is known as a feature piece. Feature pieces combine journalism and storytelling. The New York times is known for journalistic integrity , but this source may reflect the bias of the perspective of the writer on this political issue. As a result, there may be some bias in this source.

    1. They more frequently turn out to vote, engage in political discussions, attend campaign events, contribute money, contact public officials, and the like (Verba, Schlozman, & Brady 1995; Schlozman, Verba, & Brady, 2012)

      These citations are fairly old, and it would be likely to find more recent studies if they exist. The newest citation is over a decade old, while this does not mean the information is invalid, it could be helpful to find newer sources that have since built on this principle.

    1. carrying off numbers of the whites and blacks.

      Seems like hes starting to accept that it takes both white and black people

    2. What the San Dominick wanted was, what the emigrant ship has, stern superior officers. But on these decks not so much as a fourth-mate was to be seen.

      Usually slave ships are well kept and have a good hierarchy, this one is very different from that.

    3. The San Dominick was in the condition of a transatlantic emigrant ship

      So like bad?

    4. Wonted

      The usual

    5. nvoluntary victim of mental disorder

      The captain is mute, also I dont think its ever voluntary to be mentaly ill

    1. (15%), the

      (like 15% for example), even though the

    2. the sensor will only down to

      the sensor will only see down to

    1. eLife Assessment

      This study provides an important re-evaluation of modality-specific information processing in the thalamus of trained mice. Using an elegant task design that probes competing tactile and visual stimuli, the authors present compelling evidence that behavioral training reshapes the sensitivity of higher-order thalamic nuclei. Despite the powerful task design and the significance of the main findings, the origin of the cross-modal responses remains an open question and requires future investigation.

    2. Reviewer #1 (Public review):

      Petty and Bruno investigate how response characteristics in the higher-order thalamic nuclei POm (typically somatosensory) and LP (typically visual) change when a stimulus (whisker air puff or visual drifting grating) of one or the other modality is conditioned to a reward. Using a two-step training procedure, they developed an elegant paradigm, where the distractor stimulus is completely uninformative about the reward, which is reflected in licking behavior of trained mice. While the animals seem to take on to the tactile stimulus more readily, they can also associate reward with the visual stimulus, ignoring tactile stimuli. In trained mice, the authors recorded single unit responses in both POm and LP while presenting the same stimuli. The authors first focused on POm recordings, finding that in animals with tactile conditioning POm units specifically responded to the air puff stimulus but not the visual grating. Unexpectedly, in visually conditioned animals, POm units also responded to the visual grating, suggesting that the responses are not modality-specific but more related to behavioral relevance. These effects seem not not be homogeneously distributed across POm, whereas lateral units maintain tactile specificity and medial units respond more flexibly. The authors further ask if the unexpected cross-modal responses might result from behavioral activity signatures. By regressing behavior-coupled activity out of the responses, they show that late activity indeed can be related to whisking, licking and pupil size measures. However, cross-modal short latency responses are not clearly related to animal behavior. Finally, LP neurons also seem to change their modality-specificity dependent on conditioning, whereas tactile responses are attenuated in LP if the animal is conditioned to visual stimuli.

      The authors make a compelling case that POm neurons are less modality specific than typically assumed. The training paradigm, employed methods and analyses are to the point, well supporting the conclusions. The findings importantly widen our understanding of higher-order thalamus processing features with flexibility to encode multiple modalities and behavioral relevance. The results raise many important questions on the brain-wide representation of conditioned stimuli. E.g. how specific are the responses to the conditioned stimuli? Are thalamic cross-modal neurons recruited for the specific conditioned stimulus or do their responses reflect a more global shift of attention from one modality to another? Are these cross-modal responses tracking global arousal/attention features, or actually encoding a different stimulus?

      The authors clarified a number of points in the updated version of the manuscript and expanded analyses and methods descriptions, which substantially improved the paper. The different time periods around the stimuli are more clearly assigned now and make the conclusions stronger.

      Especially the discussion is now well rounded and addresses the major points.

      To ask if the cross-modal activity is in some way functional for task performance I would like to see if (population) activity in the classical vs. cross-modal nucleus is predictive of lick latency or frequency on a trial-to-trial basis.

      I accept that the authors cannot differentiate between bottom-up "raw" sensory responses and top-down context/attention/etc signals and thus support the decision to restrict the analyses to either the likely sensory early part following stimulus onset or the (as shown here mostly movement-driven) offset period after cessation of the stimulus. However, the composite responses over different stimuli and conditioning types seem triphasic to me. I find the "ongoing" activity differences (~100-2000 ms) depending on conditioning type quite interesting and would welcome a more specific discussion on the different response periods.

      Overall a very elegant and well-presented study.

    3. Reviewer #2 (Public review):

      This manuscript by Petty and Bruno delves into the still poorly understood role of higher-order thalamic nuclei in the encoding of sensory information by examining the activity in the Pom and LP cells in mice performing an associative learning task. They developed an elegant paradigm in which they conditioned head-fixed mice to attend to a stimulus of one sensory modality (visual or tactile) and ignore a second stimulus of the other modality. They recorded simultaneously from POm and LP, using 64-channels electrode arrays, to reveal the context-dependency of the firing activity of cells in higher-order thalamic nuclei. They concluded that behavioral training reshapes activity in these secondary thalamic nuclei. The authors brought new analyses and figures which greatly improve their manuscript and support their conclusion. The manuscript benefits now from a better communication about both the methodology and the results. I have no more major concerns, but I feel that the readability of the manuscript could be improved with the following revisions.

      Strengths

      The authors developed an original and elegant paradigm in which they conditioned head-fixed mice to attend to a stimulus of one sensory modality, either visual or tactile and ignore a second stimulus of the other modality. As a tactile stimulus, they applied gentle air puffs on the distal part of the vibrissae, ensuring that the stimulus was innocuous and therefore none aversive which is crucial in their study.

      It is commonly viewed that first-order thalamus performs filtering and re-encoding of the sensory flow; in contrast the computations taking place in high-order nuclei are poorly understood. They may contribute to cognitive functions. By integrating top-down control, high-order nuclei may participate in generating update models of the environment based on sensory activity; how this can take place is a key question that Petty and Bruno addressed in the present study.

      Weaknesses

      (1) It's difficult when reading the text to understand which results were quantified and which were not, in part because mean data as well as (s.e.m. or S.D.) do not appear either in the main text nor in the legends of the figures. Only vague and unquantified data are given in the main text. I understand that the authors may want to make the main text less heavy, but having these data fully written somewhere (i.e., main text, summary table, figure legends) rather than having to estimate through looking at a graph (especially when the data are constraint in the first 20% of the graph (Figure 4c)), would greatly improve the text's clarity and precision.

      For instance, Line #173, "At the population level, POm cells in both conditioning groups had a peak of activity 40ms after air puff onset (Figure 4a)." Is this 40 ms a result of quantified data, then a s.e.m. would be informative, or a reading measurement on the Figure 4a graphs? As it stands, it is too vague a value.

      (2) The authors give clearer definition of what they analyzed, which greatly improved the readability of the manuscript. The clarity of the manuscript could still be improved by solving remaining ambiguities about sensory- versus non-sensory-responses to the applied stimuli throughout the manuscript, in order to better convey the authors' conclusion that behavioral training reshapes activity in these secondary thalamic nuclei which then may participate in generating update models of the context in which the animal is performing the task.

      Line #24 in the abstract "In mice trained to respond to tactile stimuli and ignore visual stimuli, POm was robustly activated by touch and largely unresponsive to visual stimuli". The abstract would better reflect the manuscript conclusions indicating that POm was robustly activated during tactile stimuli.

      (3) The new analysis of the "early" responses in Pom cells pointed out, Line #173, that "At the population level, POm cells in both conditioning groups had a peak of activity 40ms after air puff onset (Figure 4a)." Previous works cited by the authors, Diamond et al. (1992), described tactile responses in Pom cells at 15-20ms latency which were suppressed by the barrel cortex inactivation.

      The 40ms-latency responses described in this manuscript therefore do not fit with "purely sensory" and barely with S1-feedbacks, as proposed on line #168 "Such responses could be "purely sensory" (i.e. driven by ascending brainstem inputs)" or line #334 "It is likely that the observed activity in lateral dorsal POm is driven by true whisker responses in SpVi and S1."

      In the same way, Line #315 "we observed POm cells that responded to the onset of the air puff in both conditioning groups". This conclusion should be dampened, to better fit the results, by "we observed POm cells that responded 40 ms after the onset of the air puff in both conditioning groups."

    4. Reviewer #3 (Public review):

      Petty and Bruno ask whether activity in secondary thalamic nuclei depends on the behavioral relevance of stimulus modality. They recorded from POm and LP, but the weight of the paper is skewed toward POm. They use two cohorts of mice (N=11 and 12), recorded in both nuclei using multi-electrode arrays, while being trained to lick to either a tactile stimulus (air puff against whiskers, first cohort) or a visual stimulus (drifting grating, second cohort), and ignore the respective other. They find that both nuclei, while primarily responsive to their 'home' modality, are more responsive to the relevant modality (i.e. the modality predicting reward).

      Strengths:

      The paper asks an important question, it is timely and is very well executed. The behavioral method using a delayed lick index (excluding impulsive responses) is well worked out. Electrophysiology methods are state-of-the-art with information about spike quality in Fig. S1. The main result is novel and important, convincingly conveying the point that encoding of secondary thalamic nuclei is flexible and clearly includes aspects of the behavioral relevance of a stimulus. The paper explores the mapping of responses within POm, pointing to a complex functional structure, something that has been reported/suggested in earlier studies.

      Weaknesses:

      Coding: It does not become clear to which aspect of the task POm/LP are responding. There is a motor-related response (whisking, licking, pupil), which, however, after regressing it out leaves a remaining response that the authors speculate could be sensory.

      Learning: The paper talks a lot about 'learning', although it is only indirectly addressed. The authors use two differently (over-)trained mice cohorts rather than studying e.g. a rule switch in one and the same mouse, which would allow to directly assess whether it is the same neurons that undergo rule-dependent encoding

      Mapping: The authors present electrode tracks with marked selectivity indices of recordings in POm and LP. This is a great start, but to finally understand the functional composition of POm and LP, a more detailed and systematic mapping effort is needed in the future.

    5. Author response:

      The following is the authors’ response to the original reviews.

      Reviewer #1 (Public Review): 

      Petty and Bruno investigate how response characteristics in the higher-order thalamic nuclei POm (typically somatosensory) and LP (typically visual) change when a stimulus (whisker air puff or visual drifting grating) of one or the other modality is conditioned to a reward. Using a two-step training procedure, they developed an elegant paradigm, where the distractor stimulus is completely uninformative about the reward, which is reflected in the licking behavior of trained mice. While the animals seem to take on to the tactile stimulus more readily, they can also associate the reward with the visual stimulus, ignoring tactile stimuli. In trained mice, the authors recorded single-unit responses in both POm and LP while presenting the same stimuli. The authors first focused on POm recordings, finding that in animals with tactile conditioning POm units specifically responded to the air puff stimulus but not the visual grating. Unexpectedly, in visually conditioned animals, POm units also responded to the visual grating, suggesting that the responses are not modality-specific but more related to behavioral relevance. These effects seem not be homogeneously distributed across POm, whereas lateral units maintain tactile specificity and medial units respond more flexibly. The authors further ask if the unexpected cross-modal responses might result from behavioral activity signatures. By regressing behavior-coupled activity out of the responses, they show that late activity indeed can be related to whisking, licking, and pupil size measures. However, cross-modal short latency responses are not clearly related to animal behavior. Finally, LP neurons also seem to change their modality-specificity dependent on conditioning, whereas tactile responses are attenuated in LP if the animal is conditioned to visual stimuli.

      The authors make a compelling case that POm neurons are less modality-specific than typically assumed. The training paradigm, employed methods, and analyses are mostly to the point, well supporting the conclusions. The findings importantly widen our understanding of higher-order thalamus processing features with the flexibility to encode multiple modalities and behavioral relevance. The results raise many important questions on the brain-wide representation of conditioned stimuli. E.g. how specific are the responses to the conditioned stimuli? Are thalamic cross-modal neurons recruited for the specific conditioned stimulus or do their responses reflect a more global shift of attention from one modality to another? 

      To elaborate on higher-order thalamic activity in relationship to conditioned behavior, a trialby-trial analysis would be very useful. Is neuronal activity predictive of licking and at which relative timing? 

      To elaborate on the relationship between neuronal activity and licking, we have created a new supplementary figure (Figure S1), where we present the lick latency of each mouse on the day of recording. We also perform more in-depth analysis of neural activity that occurs before lick onset, which is presented in a new main figure (new Figure 4). 

      Furthermore, I wonder why the (in my mind) major and from the data obvious take-away, "POm neurons respond more strongly to visual stimuli if visually conditioned", is not directly tested in the summary statistics in Figure 3h.

      We have added a summary statistic to Figure 3h and to the Results section (lines 156-157) comparing the drifting grating responses in visually and tactilely conditioned mice.  

      The remaining early visual responses in POm in visually conditioned mice after removing behavior-linked activity are very convincing (Figure 5d). It would help, however, to see a representation of this on a single-neuron basis side-by-side. Are individual neurons just coupled to behavior while others are independent, or is behaviorally coupled activity a homogeneous effect on all neurons on top of sensory activity?

      In lieu of a new figure, we have performed a new analysis of individual neurons to classify them as “stimulus tuned” and/or “movement tuned.” We find that nearly all POm cells encode movement and arousal regardless of whether they also respond to stimuli. This is presented in the Results under the heading “POm correlates with arousal and movement regardless of conditioning” (Lines 219-231).

      The conclusions on flexible response characteristics in LP in general are less strongly supported than those in POm. First, the differentiation between POm and LP relies heavily on the histological alignment of labeled probe depth and recording channel, possibly allowing for wrong assignment. 

      We appreciate the importance in differentiating between POm, LP, and surrounding regions to accurately assign a putative cell to a brain region. The method we employed (aligning an electrode track to a common reference atlas) is widely used in rodent neuroscience, especially in regions like POm and LP which are difficult to differentiate molecularly (for example, see Sibille, Nature Communications, 2022; and Schröder, Neuron, 2020). 

      Furthermore, it seems surprising, but is not discussed, that putative LP neurons have such strong responses to the air puff stimuli, in both conditioning cases. In tactile conditioning, LP air puff responses seem to be even faster and stronger than POm. In visual conditioning, drifting grating responses paradoxically seem to be later than in tactile conditioning (Fig S2e). These differences in response changes between POm and LP should be discussed in more detail and statements of "similar phenomena" in POm and LP (abstract) should be qualified.  

      We have further developed our analysis and discussion of LP activity. Our analysis of LP stimulus response latencies are now presented in greater detail in Figure S3, and we have expanded the results section accordingly (lines 266-275). We have also expanded the discussion section to both address these new analyses and speculate on what might drive these surprising “tactile responses” in LP.

      Reviewer #2 (Public Review): 

      Summary  

      This manuscript by Petty and Bruno delves into the still poorly understood role of higherorder thalamic nuclei in the encoding of sensory information by examining the activity in the Pom and LP cells in mice performing an associative learning task. They developed an elegant paradigm in which they conditioned head-fixed mice to attend to a stimulus of one sensory modality (visual or tactile) and ignore a second stimulus of the other modality. They recorded simultaneously from POm and LP, using 64-channel electrode arrays, to reveal the contextdependency of the firing activity of cells in higher-order thalamic nuclei. They concluded that behavioral training reshapes activity in these secondary thalamic nuclei. I have no major concerns with the manuscript's conclusions, but some important methodological details are lacking and I feel the manuscript could be improved with the following revisions.

      Strengths 

      The authors developed an original and elegant paradigm in which they conditioned headfixed mice to attend to a stimulus of one sensory modality, either visual or tactile, and ignore a second stimulus of the other modality. As a tactile stimulus, they applied gentle air puffs on the distal part of the vibrissae, ensuring that the stimulus was innocuous and therefore none aversive which is crucial in their study. 

      It is commonly viewed that the first-order thalamus performs filtering and re-encoding of the sensory flow; in contrast, the computations taking place in high-order nuclei are poorly understood. They may contribute to cognitive functions. By integrating top-down control, high-order nuclei may participate in generating updated models of the environment based on sensory activity; how this can take place is a key question that Petty and Bruno addressed in the present study.

      Weaknesses  

      (1) Overall, methods, results, and discussion, involving sensory responses, especially for the Pom, are confusing. I have the feeling that throughout the manuscript, the authors are dealing with the sensory and non-sensory aspects of the modulation of the firing activity in the Pom and LP, without a clear definition of what they examined. Making subsections in the results, or a better naming of what is analyzed could convey the authors' message in a clearer way, e.g., baseline, stim-on, reward.  

      We thank Reviewer 2 for this suggestion. We have adjusted the language throughout the paper to more clearly state which portions of a given trial we analyzed. We now consistently refer to “baseline,” “stimulus onset,” and “stimulus offset” periods. 

      In line #502 in Methods, the authors defined "Sensory Responses. We examined each cell's putative sensory response by comparing its firing rate during a "stimulus period" to its baseline firing rate. We first excluded overlapping stimuli, defined as any stimulus occurring within 6 seconds of a stimulus of a different type. We then counted the number of spikes that occurred within 1 second prior to the onset of each stimulus (baseline period) and within one second of the stimulus onset (stimulus period). The period within +/-50ms of the stimulus was considered ambiguous and excluded from analysis." 

      Considering that the responses to whisker deflection, while weak and delayed, were shown to occur, when present, before 50 ms in the Pom (Diamond et al., 1992), it is not clear what the authors mean and consider as "Sensory Responses"? 

      We have addressed this important concern in three ways. First, we have reanalyzed our data to include the 50ms pre- and post-stimulus time windows that were previously excluded. This did not qualitatively change our results, but updated statistical measurements are reflected in the Results and the legends of figures 3 and 7. Second, we have created a new figure (new Figure 4) which provides a more detailed analysis of early POm stimulus responses at a finer time scale. Third, we have amended the language throughout the paper to refer to “stimulus responses” rather than “sensory responses” to reflect how we cannot disambiguate between bottom-up sensory input and top-down input into POm and LP with our experimental setup. We refer only to “putative sensory responses” when discussing lowlatency (<100ms) stimulus responses.

      Precise wording may help to clarify the message. For instance, line #134: "Of cells from tactilely conditioned mice, 175 (50.4%) significantly responded to the air puff, as defined by having a firing rate significantly different from baseline within one second from air puff onset (Figure 3d, bottom)", could be written "significantly responded to the air puff" should be written "significantly increased (or modified if some decreased) their firing rate within one second after the air puff onset (baseline: ...)". This will avoid any confusion with the sensory responses per se.

      We have made this specific change suggested by the reviewer (lines 145-146) and made similar adjustments to the language throughout the manuscript to better communicate our analysis methods. 

      (2) To extend the previous concern, the latency of the modulation of the firing rate of the Pom cells for each modality and each conditioning may be an issue. This latency, given in Figure S2, is rather long, i.e. particularly late latencies for the whisker system, which is completely in favor of non-sensory "responses" per se and the authors' hypothesis that sensory-, arousal-, and movement-evoked activity in Pom are shaped by associative learning. Latency is a key point in this study. 

      Therefore, 

      - latencies should be given in the main text, and Figure S2 could be considered for a main figure, at least panels c, d, and e, could be part of Figure 3. 

      - the Figure S2b points out rather short latency responses to the air puff, at least in some cells, in addition to late ones. The manuscript would highly benefit from an analysis of both early and late latency components of the "responses" to air puffs and drafting grating in both conditions. This analysis may definitely help to clarify the authors' message. Since the authors performed unit recordings, these data are accessible.

      - it would be highly instructive to examine the latency of the modulation of Pom cells firing rate in parallel with the onset of each behavior, i.e. modification of pupil radius, whisking amplitude, lick rate (Figures 1e, g and 3a, b). The Figure 1 does not provide the latency of the licks in conditioned mice.

      - the authors mention in the discussion low-latency responses, e.g., line #299: "In both tactilely and visually conditioned mice, movement could not explain the increased firing rate at air puff onset. These low-latency responses across conditioning groups is likely due in part to "true" sensory responses driven by S1 and SpVi."; line #306: "Like POm, LP displayed varied stimulus-evoked activity that was heavily dependent on conditioning. LP responded to the air puff robustly and with low latency, despite lacking direct somatosensory inputs."  But which low-latency responses do the authors refer to? Again, this points out that a robust analysis of these latencies is missing in the manuscript but would be helpful to conclude.

      We have moved our analysis of stimulus response latency in POm to new Figure 4 in the main text and have expanded both the Results and Discussion sections accordingly. We have also analyzed the lick latency on the day of recording, included in a new supplemental Figure S1. 

      (3) Anatomical locations of recordings in the dorsal part of the thalamus. Line #122 "Our recordings covered most of the volume of POm but were clustered primarily in the anterior and medial portions of LP (Figure 2d-f). Cells that were within 50 µm of a region border were excluded from analysis." 

      How did the authors distinguish the anterior boundary of the LP with the LD nucleus just more anterior to the LP, another higher-order nucleus, where whisker-responsive cells have been isolated (Bezdudnaya and Keller, 2008)? 

      Cells within 50µm of any region boundary were excluded, including those at the border of LP and LD. We also reviewed our histology images by eye and believe that our recordings were all made posterior of LD. 

      (4) The mention in the Methods about the approval by an ethics committee is missing.  All the surgery (line #381), i.e., for the implant, the craniotomy, as well as the perfusion, are performed under isoflurane. But isoflurane induces narcosis only and not proper anesthesia. The mention of the use of analgesia is missing. 

      We thank Reviewer 2 for drawing our attention to this oversight. All experiments were conducted under the approval of the Columbia University IACUC. Mice were treated with the global analgesics buprenorphine and carprofen, the local analgesic bupivacaine, and anesthetized with isoflurane during all surgical procedures. We have amended the Methods section to include this information (Lines 458-470).

      Reviewer #3 (Public Review): 

      Petty and Bruno ask whether activity in secondary thalamic nuclei depends on the behavioral relevance of stimulus modality. They recorded from POm and LP, but the weight of the paper is skewed toward POm. They use two cohorts of mice (N=11 and 12), recorded in both nuclei using multi-electrode arrays, while being trained to lick to either a tactile stimulus (air puff against whiskers, first cohort) or a visual stimulus (drifting grating, second cohort), and ignore the respective other. They find that both nuclei, while primarily responsive to their 'home' modality, are more responsive to the relevant modality (i.e. the modality predicting reward). 

      Strengths: 

      The paper asks an important question, it is timely and is very well executed. The behavioral method using a delayed lick index (excluding impulsive responses) is well worked out. Electrophysiology methods are state-of-the-art with information about spike quality in Figure S1. The main result is novel and important, convincingly conveying the point that encoding of secondary thalamic nuclei is flexible and clearly includes aspects of the behavioral relevance of a stimulus. The paper explores the mapping of responses within POm, pointing to a complex functional structure, something that has been reported/suggested in earlier studies. 

      Weaknesses: 

      Coding: It does not become clear to which aspect of the task POm/LP is responding. There is a motor-related response (whisking, licking, pupil), which, however, after regressing it out leaves a remaining response that the authors speculate could be sensory.

      Learning: The paper talks a lot about 'learning', although it is only indirectly addressed. The authors use two differently (over-)trained mice cohorts rather than studying e.g. a rule switch in one and the same mouse, which would allow us to directly assess whether it is the same neurons that undergo rule-dependent encoding. 

      We disagree that our animals are “overtrained,” as every mouse was fully trained within 13 days. We agree that it would be interesting to study a rule-switch type experiment, but such an experiment is not necessary to reveal the profound effect that conditioning has on stimulus responses in POm and LP. 

      Mapping: The authors treat and interpret the two nuclei very much in the same vein, although there are clear differences. I would think these differences are mentioned in passing but could be discussed in more depth. Mapping using responses on electrode tracks is done in POm but not LP.

      The mapping of LP responses by anatomical location is presented in the supplemental Figure S4 (previously S3). We have expanded our discussion of LP and how it might differ from POm.

      Reviewer #1 (Recommendations For The Authors):  

      Minor writing issues: 

      122 ...67 >LP< cells?

      301 plural "are”

      We have fixed these typos.

      Figure issues

      *  3a,b time ticks are misaligned and the grey bar (bottom) seems not to align with the visual/tactile stimulus shadings.

      *  legend to Figure 3b refers to Figure 1c which is a scheme, but if 1g is meant, this mouse does not seem to have a session 12? 

      *  3c,e time ticks slightly misaligned. 

      *  5e misses shading for the relevant box plots, assuming it should be like Figure 3h.  

      We thank Reviewer 1 for pointing out these errors. We have adjusted Figures 1, 3, and 5 accordingly.

      Analyses 

      I am missing a similar summary statistics for LP as in Figure 3h 

      We have added a summary box chart of LP stimulus responses (Figure 7g), similar to that of POm in Figure 3. We have also performed similar statistical analyses, the results of which are presented in the legend for Figure 7. 

      Reviewer #2 (Recommendations For The Authors): 

      More precisions are required for the following points: 

      (1) The mention of the use of analgesia is missing and this is not a minor concern. Even if the recordings are performed 24 hours after the surgery for the craniotomy and screw insertion and several days after the main surgery for the implant, taking into account the pain of the animals during surgeries is crucial first for ethical reasons, and second because it may affect the data, especially in Pom cells: pain during surgery may induce the development of allodynia and/or hyperalgesia phenomenae and Pom responses to sensory stimuli were shown to be more robust in behavioral hyperalgesia (Masri et al., 2009).  

      We neglected to include details on the analgesics used during surgery and post-operation recovery in our original manuscript. Mice were administered buprenorphine, carprofen, and bupivacaine immediately prior to the head plate surgery and were treated with additional carprofen during recovery. Mice were similarly treated with analgesics for the craniotomy procedure. Mice were carefully observed after craniotomy, and we saw no evidence of pain or discomfort. Furthermore, mice performed the behavior at the same level pre- and postcraniotomy (now presented in Figure 1j), which also indicates that they were not in any pain. 

      (2) The head-fixed preparation is only poorly described.

      Line #414: "Prior to conditioning, mice were habituated to head fixation and given ad libitum water in the behavior apparatus for 15-25 minutes." 

      And line #425 "Mice were trained for one session per day, with each session consisting of an equal number of visual stimuli and air puffs. Sessions ranged from 20-60 minutes and about 40-120 of each stimulus. " 

      More details should be given about the head-fixation training protocol. Are 15-25 minutes the session time duration, 60 minutes, or other time duration? How long does it take to get mice well trained to the head fixation, and on which criteria?  

      Line #389: "Mice were then allowed to recover for 24 hours, after which the sealant was removed and recordings were performed. At the end of experiments,"

      The timeline is not clear: is there one day or several days of recordings? 

      We have expanded on our description of the head fixation protocol in the Methods. We describe in more detail how mice were habituated to head fixation, the timing of water restriction, and the start of conditioning/training (Habituation and Conditioning, lines 492-500).

      (4) Line #411: "Mice were deprived of water 3 days prior to the start of conditioning" followed by line #414 "Prior to conditioning, mice were habituated to head fixation and given ad libitum water in the behavior apparatus for 15-25 minutes".

      If I understood correctly, the mice were then not fully water-deprived for 3 days since they received water while head-fixed. This point may be clarified. 

      We addressed these concerns in the changes to the Methods section mentioned in the preceding point (3).

      (5) Line #157: "Modality selectivity varies with anatomical location in Pom" while the end of the previous paragraph is "This suggests that POm encoding of reward and/or licking is insensitive to task type, an observation we examine further below."

      The authors then come to anatomical concerns before coming back to what the Pom may encode in the following section. This makes the story quite confusing and hard to follow even though pretty interesting.  

      We have reordered our Figures and Results to improve the flow of the paper and remove this point of confusion. We now present results on the encoding of movement before analyzing the relationship between POm stimulus responses and anatomical location. What was old Figure 5 now precedes what was old Figure 4.

      (6) Licks Analysis. Line #99 "However, this mouse also learned that the air puff predicted a lack of reward in the shaping task, as evidenced by withholding licking upon the onset of the air puff. The mouse thus displayed a positive visual lick index and a negative tactile lick index, suggesting that it attended to both the tactile and visual stimuli (Figure 1f, middle arrow)."

      Line #105 "All visually conditioned mice exhibited a similar learning trajectory (Figure 1i left, 1j left)". 

      Interestingly, the authors revealed that mice withheld licking upon the onset of the air puff in the visual conditioning, which they did not do at the onset of the drifting grating in the tactile conditioning. This withholding was extinguished after the 8th session, which the authors interpret as the mice finally ignoring the air puff. Is this effect significant, is there a significant withholding licking upon the onset of the air puff on the 12 tested mice? 

      The withholding of licking was significant (assessed with a sign-rank test) in visually conditioned mice prior to switching to the full version of the task. Indeed, it was the abolishment of this effect after conditioning with the full version of the task that was our criterion for when a mouse was fully trained. We have elaborated on this in the Habituation and Conditioning section in the Methods.

      (1) Throughout the manuscript "Touch" is used instead of passive whisker deflection, and may be confusing with "active touch" for the whisker community readers. I recommend avoiding using "touch" instead of "passive whisker deflection".

      We appreciate that “touch” can be an ambiguous term in some contexts. However, we have limited our use of the word to refer to the percept of whisker deflection; we do not describe the air puff stimulus as a “touch.” We respectfully would like to retain the use of the word, as it is useful for comparing somatosensory stimuli to visual stimuli.

      (2) Line #395: "Air puffs (0.5-1 PSI) were delivered through a nozzle (cut p1000 pipet tip, approximately 3.5mm diameter aperture)".

      Are air puffs of <1 PSI applied, not <1 bar?  

      We thank Reviewer 3 for pointing out this inaccuracy. The air puffs were indeed between 0.5 and 1 bar, not PSI. We have addressed this in the Methods.

      (3) Line #441: "In the full task, the stimuli and reward were identical, but stimuli were presented at uncorrelated and less predictable intervals."  Do the authors mean that all stimuli are rewarded?  

      The stimuli and reward were identical between the shaping and full versions of the task. In the full version of the task, the unrewarded stimulus was truly uncorrelated with reward, rather than anticorrelated. 

      (4) Line #445 "for a mean ISI of 20 msec." ISI is not defined, I guess that it means interstimulus interval. Even if pretty obvious, to avoid any confusion for future readers, I would recommend using another acronym, especially in a manuscript about electrophysiology, since ISI is a dedicated acronym for inter-spike interval. 

      We have defined the acronym ISI as “inter-stimulus interval” when first introduced in the results (Line 82) and in the Methods (Line 511).

      (5) Line #416 "In the first phase of conditioning ("shaping"), mice were separated into two cohorts: a "tactile" cohort and a "visual" cohort. Mice were presented with tactile stimuli (a two-second air puff delivered to the distal whisker field) and visual stimuli (vertical drifting grating on a monitor). Throughout conditioning, mice were monitored via webcam to ensure that the air puff only contacted the whiskers and did not disturb the facial fur nor cause the mouse to blink, flinch, or otherwise react - ensuring the stimulus was innocuous. The stimulus types were randomly ordered. In the visual conditioning cohort, the visual stimulus was paired with a water reward (8-16µL) delivered at the time of stimulus offset. In the tactile conditioning cohort, the reward was instead paired with the offset of the air puff. Regardless of the type of conditioning, stimulus type was a balanced 50:50 with an inter-stimulus interval of 8-12 seconds (uniform distribution)." 

      The mention of the "full version of the task" will be welcome in this paragraph to clarify what the task is for the mouse in the Methods part.

      We have more clearly defined the full version of the task in a later paragraph (line 506). We believe this addresses the potential confusion caused by the original description of the conditioning paradigm. 

      (6) Line #467: "Units were assigned to the array channel on which its mean waveform was largest". 

      Should it read mean waveform "amplitude"? 

      This is correct, we have adjusted the statement accordingly. 

      (7) Line #482 "The eye camera was positioned on the right side of the face and recorded at 60 fps." Then line #487 "The trace of pupil radius over time was smoothed over 5 frames (8.3 msec).” 5 frames, with a 60fps, represent then 83 ms and not 8.3 ms.

      We have corrected this error.  

      (8) Line #121: "257 POm cells and 67 cells from 12 visually conditioned mice" 

      67 LP cells, LP is missing 

      We have corrected this error. 

      (9) Line #354: "A consistent result of attention studies in humans and nonhuman primates is the enhancement of cortical and thalamic sensory responses to an attended visual stimuli. Here, we show not just enhancement of sensory responses to stimuli within a single modality, but also across modalities. It is worth investigating further how secondary thalamus and high-order sensory cortex encode attention to stimuli outside of their respective modalities. Our surprising conclusion that the nuclei are equivalently activated by behaviorally relevant stimuli is nevertheless compatible with these previous studies."  Since higher-order thalamic nuclei are integrative centers of many cortical and subcortical inputs, they cannot be viewed simply as relay nuclei, and there is therefore no "surprising" conclusion in these results. Not surprising, but still an elegant demonstration of the contextdependent activity/responses of the Pom/LP cells. 

      We disagree. Visual stimuli activating strong POm responses and tactile stimuli activating strong LP responses - however they do it - is a surprising result. We agree that higher-order thalamic nuclei are integrative centers, but exactly what they integrate and what the integrated output means is still poorly understood.

    1. whose mode of travel proclaimed their poverty and therefore the greater probability of their being wanderers with some illicit or economically disruptive motive.

      would this count

    2. purpose—was traditionally criminal, and English laws fostered the perception of travellers as potential wanderers whose character and motives should properly fall under suspicion.

      This happens in De Quincey's narrative as Betty is warned by the bishop

    3. hat unrestricted travel leads to unrestricted work, and that people's labour should be directed toward specific and known ends controlled by the authorities.

      This is basically the lack of control causing an anxiety of the strange

    4. n 1572, for instance, an ‘Acte for the punishment of Vacabondes’ stated:

      Traveling causing the surveillance of the government

  4. www.accessengineeringlibrary.com www.accessengineeringlibrary.com
    1. mal-neutron reactors 233U has an important advantage over 235U or 239Pu in that the number of neutrons produced per thermal neutron absorbed, η, is higher for 233U than for the other fissile

      cjwejcfwejfjwejfdwejfdjwedfwe

    1. As a landmark moment in American history, Brown’s significance perhaps lies less in immediate tangible changes—which were slow, partial, and inseparable from a much longer chain of events—than in the idealism it expressed and the momentum it created. The nation’s highest court had attacked one of the fundamental supports of Jim Crow segregation and offered constitutional cover for the creation of one of the greatest social movements in American history.

      The nation attack of fundamental supports of Jim Crow segregation creating the greatest social movement in this nations history.

    2. Builders created sprawling neighborhoods of single-family homes on the outskirts of American cities

      This helped America recover economically because they gave builders work with these new neighborhoods and gave them better income to pay taxes.

    1. Well, look, I think what it means to be American is the perception is really about life, liberty, and the pursuit of happiness. It’s the ability to bring one up from their own bootstraps, to have the ability to maximize the American Dream, and firmly participate in the political process and civic process, raise their family, and go throughout their life relatively unencumbered.

      Traditional understanding of what it means to be an American.

    1. nited States detonated the first thermonuclear weapon, or hydrogen bomb (using fusion explosions of theoretically limitless power) on November 1, 1952. The blast measured over ten megatons and generated an inferno five miles wide with a mushroom cloud twenty-five miles high and a hundred miles across. The irradiated debris—fallout—from the blast circled the earth, occasioning international alarm about the effects of nuclear testing on human health and the environment.

      The United States gets more involved in atomic bombs and nuclear testing which lead to many health issues and environmental impact.

    2. The European Recovery Program (ERP), popularly known as the Marshall Plan, pumped enormous sums of capital into Western Europe.

      Marshall's plan must have been a big relief for Americans as it gave us allies if the Soviet Union attacks the US.

    3. The world was never the same after the United States leveled Hiroshima and Nagasaki in August 1945 with atomic bombs. Not only had perhaps 180,000 civilians been killed, the nature of warfare was forever changed.

      How would the nature of warfare be different today if the U.S. hadn't launched the attack at Hiroshima and Nagasaki?

    1. The United States entered the war in a crippling economic depression and exited at the beginning of an unparalleled economic boom. The war had been won, the United States was stronger than ever, and Americans looked forward to a prosperous future. And yet new problems loomed. Stalin’s Soviet Union and the proliferation of nuclear weapons would disrupt postwar dreams of global harmony.

      America entered war in a unfit state of economic depression. America grew strong but stalin's Soviet unions and the threat of use of nuclear weapons would stop this quickly

    2. Germany was conquered

      In America, this must have been great news as it was one of the biggest issues during the war and used most of our resources.

    1. His process for creating posts, he told me, is pretty simple and AI intensive: “I use ChatGPT to ask for the best images that can generate a lot of popularity and engagement on Facebook,” focusing on topics like the Bible, God, the U.S. Army, wildlife, and Manchester United. “WRITE ME 10 PROMPT picture OF JESUS WHICH WILLING BRING HIGH ENGAGEMENT ON FACEBOOK,” read the ChatGPT prompt in one screenshot he shared with me. You then take the prompts to the image-generation programs Leonardo.ai and Midjourney. Voilà: slop.

      lol

    1. 𝑖 attends to token 𝑗

      In the 3B1B video, Grant Sanderson uses this language in the opposite senses (he talk about adjectives, keys, attending to nouns, queries). As far as we can tell, this is incorrect (there was some discussion about it in the comments.

    2. 𝑄⁢𝐾⊤.

      Note that the way the matrices are shown in the video is consistent with is compatible with K^\top Q (rather than Q K^\top)

    1. Another way of managing disabilities is assistive technology, which is something that helps a disabled person act as though they were not disabled

      Looking at how the technology has evolved and where it's headed, I always loved looking at assistive technology. Although I did not understand that assistive technology could include things like glasses or stimulants because of how normalized they are compared to other technology like electronic prosthetics.

    1. Most humans are trichromats, meaning they can see three base colors (red, green, and blue), along with all combinations of those three colors. Human societies often assume that people will be trichromats. So people who can’t see as many colors are considered to be color blind, a disability. But there are also a small number of people who are tetrachromats and can see four base colors2 and all combinations of those four colors. In comparison to tetrachromats, trichromats (the majority of people), lack the ability to see some colors. But our society doesn’t build things for tetrachromats, so their extra ability to see color doesn’t help them much. And trichromats’ relative reduction in seeing color doesn’t cause them difficulty, so being a trichromat isn’t considered to be a disability.

      It is actually interesting to know that there are different ways of seeing more colors outside of being color blind. I wonder what type of sight I have and whether I'm a tetrochromat or trichromat.

    1. Zippo Lighter Fluid (Naphtha)

      While Zippo lighter fluid (Naphtha) is a bit more expensive per ounce than other solvents (mineral spirits, lacquer thinner, et al), it does usually come packaged in a dispensing container that may make it easier to dispense in a directed method into the internals of typewriters for cleaning them out.

      The other benefit is that some may have it on hand for general household use without needing to make a separate trip to the hardware store.


      via, but not really directly suggested by https://old.reddit.com/r/typewriters/comments/1g9ntnj/lubricant_reccomendations/

    1. Further, wolves are opportunistic, flexible hunters with dietsdepending on availability and vulnerability of prey (Huggard 1993,Cressman and Garay 2011, Morehouse and Boyce 2011, Metz etal. 2012), and livestock depredation by wolves is common in manyareas of the world (e.g., Rigg et al. 2011, Li et al. 2015, Ali et al.2016, Fernández-Gil et al. 2016).

      Wolves are highly adaptable predators, meaning their hunting strategies can shift based on environmental conditions and prey availability. What factors contribute to the opportunistic hunting behavior of wolves, and how does this flexibility impact their predation on livestock? How do the predator-avoidance strategies of wild prey compare to those of cattle, and what implications does this have for their vulnerability to wolves?

    1. eLife Assessment

      This paper addresses an important topic (normative trajectory modelling), seeking to provide a method aiming to accurately reflect the individual deviation of longitudinal/temporal change compared to the normal temporal change characterized based on a pre-trained population normative model. The evidence provided for the new methods is, however, incomplete, with the simulations validating the method needing to be extended.

    2. Reviewer #1 (Public review):

      Summary:

      In this manuscript, the authors provide a method aiming to accurately reflect the individual deviation of longitudinal/temporal change compared to the normal temporal change characterized based on pre-trained population normative model (i.e., a Bayesian linear regression normative model), which was built based on cross-sectional data. This manuscript aims at solving a recently identified problem of using normative models based on cross-sectional data to make inferences about longitudinal change.

      Strengths:

      The efforts of this work make a good contribution to addressing an important question of normative modeling. With the greater availability of cross-sectional studies for normative modeling than longitudinal studies, and the inappropriateness of making inferences about longitudinal subject-specific changes using these cross-sectional data-based normative models, it's meaningful to try to address this gap from the aspect of methodological development.

      In the 1st revision, the authors added a simulation study to show how the performance of the classification based on z-diff scores relatively changes with different disruptions (and autocorrelation). Unfortunately, in my view this is insufficient as it only shows how the performance of using z-diff score relatively changes in different scenarios. I would suggest adding the comparison of performance to using the naïve difference in two simple z-scores to first show its better performance, which should also further highlight the inappropriate use of simple z-scores in inferring within-subject longitudinal changes. Additionally, Figure 1 is hard to read and obtain the actual values of the performance measure. I would suggest reducing it to several 2-dimensional figures. For example, for several fixed values of rho, how the performance changes with different values of the true disruption (and also adding the comparison to the naïve method (difference in two z-scores)).

      I would also suggest changing the title to reflect that the evaluation of "intra-subject" longitudinal change is the method's focus.

    3. Author response:

      The following is the authors’ response to the original reviews.

      Reviewer #1 (Public Review):

      The models described are not fundamentally novel, essentially a random intercept model (with a warping function), and some flexible covariate effects using splines (i.e., additive models).

      We respectfully but strongly disagree with the reviewer’s assessment of the novelty of our work. The models referred to by the reviewer as “random intercept models … and some flexible covariate effects” seem to relate to the estimation of normative models derived cross-sectionally as developed in and adopted from previous work, not to the work presented here. To be clear, the contributions of this work are: (i) a principled methodology to make statistical predictions for individual subjects in longitudinal studies based on a novel z-diff score, (ii) an approach to transfer information large scale normative models estimated on large scale cross-sectional data to longitudinal studies (iii) an extensive theoretical analysis of the properties of this approach and (iv) empirical evaluation on an unpublished psychosis dataset. Put simply, we provide the ability to estimate within subject change in normative models which until now only provide the ability to show a subject's position in the normative range at a given timepoint. With the exception of the reference [13] cited in the main text, we are not aware of any methods available that can achieve this. Based on this feedback combined with the feedback of the Reviewer 2, we now improved our introduction and clearly state our contribution right from the outset of the manuscript whilst also shortening the introduction to make it more concise. In this work, we are trying to be very transparent in showing to the reader that our method builds on a previously peer-reviewed model.

      The assumption of constant quantiles is very strong, and limits the utility of the model to very short term data.

      We now provide an extensive theoretical analysis of our approach (section 2.1.3), where we show that this assumption is actually not strictly necessary and that our approach yields valid inferences even under much milder assumptions. More specifically, we first provide a mathematical grounding for the assumption we made in the initial submission, then generalise our method to a wider class of residual processes and show that our original assumption of constant quantiles is not too restrictive. We also provide a simulation study to show how the practitioner can evaluate the validity and implications of this assumption on a case-by-case basis. This generalisation is described in depth in section 2.1.3.

      The schizophrenia example leads to a counter-intuitive normalization of trajectories, which leads to suspicions that this is driven by some artifact of the data modeling/imaging pipelines.

      We understand that the observed normalisation effects might appear surprising. As we outlined in our provisional response, we would like to emphasise that there is increasing evidence that the old neurodegenerative view of psychosis is an oversimplification and that trajectories of cortical thickness are highly variable across different individuals after the first psychotic episode. More specifically, we have shown in an independent sample and with different methodology that individuals treated with second-generation antipsychotics and with careful clinical follow-up can show normalisation of cortical thickness atypicalities after the first episode (https://www.medrxiv.org/content/10.1101/2024.04.19.24306008v2, now accepted in Schizophrenia Bulletin). These results are well-aligned with the results we show in this manuscript. We now added remarks on this topic into the discussion. We would also like to re-emphasise that the data were processed with the utmost rigour using state of the art processing pipelines including quality control, which we have reported as transparently as possible. The confidence that the results are not ‘driven by some artifact of the data modeling/imaging pipelines’ is also supported by the fact that analysis of a group of healthy controls did not show any significant z-diffs (see Discussion section), neither frontally nor elsewhere. If the reviewer believes there are additional quality control checks that would further increase confidence in our findings, we would welcome the reviewer to provide specific details.

      The method also assumes that the cross-sectional data is from a "healthy population" without describing what this population is (there is certainly every chance of ascertainment bias in large scale studies as well as small scale studies). This issue is completely elided over in the manuscript.

      Indeed, we do not describe the cross-sectional population used for training the models, as these models were already trained and published with in-depth description of the datasets used for the training (https://elifesciences.org/articles/72904). We now make this more explicit in the section 2.1.1. of the manuscript (page 7), and also more explicitly acknowledge the possibility of ascertainment bias in the simulation section 2.1.4. However, we would like to emphasise that such ascertainment bias is not in any way specific to the analyses we report. In fact it is present in all studies that utilise large scale cohorts such as UK Biobank. Indeed, we are currently working on another manuscript to address this question in detail, but given the complexity of this problem and the fact that many publicly available legacy studies simply do not record sufficient demographic information, e.g. to assess racial bias properly, we believe that this is beyond the scope of the current work.

      Reviewer #2 (Public Review):

      The organization and clarity of this manuscript need enhancement for better comprehension and flow. For example, in the first few paragraphs of the introduction, the wording is quite vague. A lot of information was scattered and repeated in the latter part of the introduction, and the actual challenges/motivation of this work were not introduced until the 5th paragraph.

      As noted above in our response to Reviewer 1, we significantly pruned the introduction, stating our objective in the first paragraph and elaborating on the topic later in the text. We hope that it is now less repetitive and easier to follow.

      There are no simulation studies to evaluate whether the adjustment of the crosssectional normative model to longitudinal data can make accurate estimations and inferences regarding the longitudinal changes. Also, there are some assumptions involved in the modeling procedure, for example, the deviation of a healthy control from the population over time is purely caused by noise and constant variability of error/noise across x_n, and these seem to be quite strong assumptions. The presentation of this work's method development would be strengthened if the authors can conduct a formal simulation study to evaluate the method's performance when such assumptions are violated, and, ideally, propose some methods to check these assumptions before performing the analyses.

      This comment encouraged us to zoom out from our original assumption and generalise our method to a wider class of residual processes (stationary Gaussian processes) in section 2.1.3. We now present a theoretical analysis of our model to show that our original assumption (of stable quantiles plus noise) is actually not necessary for valid inference in our method, which broadens the applicability of our method. Of course, we also discuss in what way the original assumption is restrictive and how it aligns with the more general dynamics. We also include a simulation study to evaluate the method's performance and elucidate the role of the more general dynamics in section 2.1.4.

      The proposed "z-diff score" still falls in the common form of z-score to describe the individual deviation from the population/reference level, but now is just specifically used to quantify the deviation of individual temporal change from the population level. The authors need to further highlight the difference between the "z-score" and "z-diff score", ideally at its first mention, in case readers get confused (I was confused at first until I reached the latter part of the manuscript). The z-score can also be called a measure of "standardized difference" which kind of collides with what "z-diff" implies by its name.

      We added the mention of the difference between z-score and z-diff score into the last paragraph of introduction.

      Explaining that one component of the variance is related to the estimation of the model and the other is due to prediction would be helpful for non-statistical readers.

      We now added an interpretation of the z-score in the original model below equation 7.

      It would be easier for the non-statistical reader if the authors consistently used precision or variance for all variance parameters. Probably variance would be more accessible.

      This was a very useful observation, we unified the notation and now only use variance.

      The functions psi were never explicitly described. This would be helpful to have in the supplement with a reference to that in the paper.

      Indeed, while describing the original model we had to make choices about how to condense the necessary information from the original model so that we can build upon it. As the phi function is only used for data transformation in the original model, we did not further elaborate on it, however, we now refer to the specific section of the original paper of Fraza et al. 2021 where it is described more in detail (https://www.sciencedirect.com/science/article/pii/S1053811921009873).

      What is the goal of equations (13) and (14)? The authors should clarify what the point of writing these equations is prior to showing the math. It seems like it is to obtain an estimate of \sigma_{\ksi}^2, which the reader only learns at the end.

      We corrected the formatting.

      What is the definition of "adaption" as used to describe equation (15)? In this equation, I think norm on subsample was not defined.

      We added a more detailed description of the adaptation after equation 15.

      "(the sandwich part with A)" - maybe call this an inner product so that it is not confused with a sandwich variance estimator. This is a bit unclear. Equation (8) does have the inner product involving A and \beta^{-1} does include variability of \eta. It seems like you mean that equation (8) incorrectly includes variability of \eta and does not have the right term vector component of the inner product involving A, but this needs clarifying.

      We now changed the formulation to be less confusing and also explicitly clarified the caveat regarding the difference of z-scores.

      One challenge with the z-diff score is that it does not account for whether a person sits above or below zero at the first time point. It might make it difficult to interpret the results, as the results for a particular pathology could change depending on what stage of the lifespan a person is in. I am not sure how the authors would address those challenges.

      We agree with the outlined limitation in interpretation of overall trends when the position in the visit one is different between the subjects. However, this is a much broader challenge and is not specific to our approach. This effect is generally independent of the lifespan, but may further interact with the typical lifespan of disease. rWhen the z scores are taken in the context of the cross-sectional normative models, it does make it possible to identify what the overall trend of an illness is across the lifespan, and individual patient’s z-diffs not in line (with what would this typical group trajectory predicts) may e.g. correspond to early/late onset of their individual atrophy. We now make these considerations explicitly in the discussion section.

      Reviewer #2 (Recommendations For The Authors):

      Other minor suggestions to help improve the text:...

      We thank Reviewer #2 for the list of minor suggestions to improve the text, which we all implemented in the manuscript.

    1. January the 1st. Capt. Hannears died here in the night before in which the year ended 1759, and now the year begins; but God only knows who will see the end, for death spares not any.

      There are clear signals that he is starting to lose hope

    2. Mrs. Treawoue

      Where are the voices of the women in the war?

    3. vollies

      Volle: The firing of a gun or weapon at the same time.

    4. January 28th. A drummer belonging to Warburton’s Regiment was shot for breaking into a house and stealing a box of Soap,

      the soldiers were so desperate that they resorted to stealing soap.

    5. Care and as there had been war between the Crown of England and France by which reason men was very hard for to be raised in New England, I then willingly enlisted in the service of my King and Country in the then intended expedition against Canada, in Capt. Andrew Giddings Company in a provincial Regiment Commanded by Coll Jonathan Bagley Esqr in the year 1759…

      Gibson Clough grew up being educated and he decided to enlist on his own.

    1. I'm skeptical that that is what will happen

      Expression of skepticism about the inevitability of a societal bifurcation due to AI.

    2. I think I'm as optimistic as you in terms of the things that it will do for us

      Expression of optimism about the potential benefits of AI.

    3. you can give these robots voices they can talk they can listen

      Discussion on the capabilities of robots to communicate and interact with humans.

    4. software is the big challenge um I think

      Highlighting software as the major challenge in robotics.

    5. there's basically I would say three big categories

      Introduction to the three major categories of challenges in robotics.

    6. the theory of humanoid robots which I believe is the the great thing about humanoid robots

      Discussion on the theory and potential of humanoid robots.

    7. we have two Chinese robot dogs at home

      Personal anecdote about owning Chinese robot dogs, illustrating the advancements in robotics.

    8. self-driving cars that are now a thing and that now now work really well

      Discussion on the advancements and current state of self-driving cars.

    9. probably the single biggest question I'm asking right now is robotics

      Highlighting robotics as a major area of interest and inquiry.