1,318 Matching Annotations
  1. Last 7 days
    1. At 9¢/card these are very expensive in comparison to bulk cards which usually can be found for 1-2¢/card. The difference however is in the luxuriousness of the silky smooth texture. Whether you're writing with your favorite fountain pen or a carefully chosen pencil. I don't know if these are the same brand of Bristol cards that Vladimir Nabokov used for his writing, but one could easily image him using such lovely material.

      These provide a very smooth writing experience for fountain pens, gel pens and pencils. I particularly love the way my Tennessee Reds and Blackwing 602s glide over their surface. In comparison to some Japanese stationery, I'd put these cards somewhere between tsuru tsuru (slippery) and sara sara (smooth). If you're looking for a toothier paper, you'll definitely want to look elsewhere. They take fountain pens pretty well with no feathering or ghosting. My juiciest fountain pen dries in about 15 seconds, while a drier extra fine is dry in about 7 seconds, so it may take some care not to smear ink if you're on the messier end of the spectrum.

      Pencil erases reasonably well, though there may be some minimal residual ghosting here. At 205 gsm, they've got a satisfying thickness unseen in most index cards and one is unlikely to rip or crinkle them when erasing. They're also thick enough that the wettest Sharpie won't bleed much less ghost through. You have to hold a card up to a backlight to see the appearance of any ghosting through it and even then, not well.

      For the sticklers used to using standard 4 x 6" index cards, one should take note that the dimensions of these are slightly shorter in both dimensions—they're closer to 3.94" x 5.91". This means that you might have to take some care that while flipping through mixed company of cards your Exacompta can potentially hide between larger imperial sized cards. They're also close to, but not quite A6 in size either (105 x 148.5 mm or 4.1 x 5.8 inches).

    1. Reviewer #4 (Public Review):

      The authors have collected an impressive array of physiological data and provided some beautiful 3D images of SBCs with dendrites. These are clearly strengths. The computational models for mechanisms of SBC responses, however, are made to fit what may be inadequate anatomical data. Instead of conclusions, perhaps they need to reword their discussions to refer to the anatomy as hypothetical substrates.

  2. May 2023
    1. Reviewer #4 (Public Review):

      In this manuscript, Clary and colleagues use two-photon imaging to visualize the dynamics of Merkel cells and their innervating sensory axons using a combination of transgenic lines, where these parts of the mechanosensory organs of the skin are labelled with distinct fluorescent proteins. It is noteworthy that this study does not stand alone, but should be compared to prior published work cited by the authors, such as Wright et al., Developmental Biology 422 (2017) 4-13.

      The study demonstrates a comparably high degree of remodelling, with a large fraction of Merkel cells (50% in three weeks) and a similar fraction of elaborated (cup-like) axons endings disappearing. It appears by timing and correlation that changes in Merkel cells can clearly drive axonal remodelling, while axons can still remodel even if the Merkel cells remain stable by the parameters measured here. Moreover, changes in Merkel cells partially relate to the hair growth cycle.

      The imaging approach chosen is straightforward and clearly suited in principle to reveal the dynamism of the studied cellular structures. To co-visualize two synaptic partners in a vertebrate sensory organ in vivo - while not unprecedented - certainly remains quite challenging, and represents a strength of the paper. Similarly, understanding how stable structures in the nervous system are under homeostatic (rather than developmental) conditions, remains an understudied topic. I also found some of the correlative analysis in the later parts of the study quite interesting, albeit not always straightforward to interpret.

      My central concern is the very high disappearance rate of Merkel cells. This, in my view is not compatible with a steady state situation in an adult animal - and not with the prior literature (especially the similar study by Wright et al. cited above). Obviously, if this rate were to continue, Merkel cells would all be lost in early adulthood in mice. Whether this is the case in the specific anatomical location was not examined in the study - but it would also imply that the study really addresses a dynamic developmental remodelling situation and should be written up accordingly. I am more suspicious of the depilation agent (plus the shaving). As Wright et al. already show that shaving causes some changes in Merkel cell dynamics (but, as far as I can tell, did not chemically depilate), I would not be surprised that we see an artificially high remodelling rate. Such skin treatment-related biology is probably less relevant in the context of neurobiology (albeit probably quite interesting to other audiences). So, my recommendation to the authors would be to invest some energy to find out, what causes the swift Merkel cell loss.

      Another technical point that warrants discussion is the axonal labelling - first, I do not find the innervation patterns always easy to discern in the images provided, so I am not always sure how reliable this part is. Any artefact here creates the impression of dynamics, as during in vivo imaging stability is more reassuring than change. There are many ways not to see or recognize something, while there are few options to explain by an artefact why something did not change. Additionally, it might be good to explicitly mention that the TrkC mice are knock-in/knock-out (this is how I understood the JAX entry) - so the observations were made under reduced TrkC expression. It would help to explain, why this cannot affect axonal dynamics or Merkel cell-axon interactions.

      Overall, while I feel that the authors performed an interesting in vivo imaging study, I think technical aspects make it difficult to conclude with confidence, whether we are watching a normal and physiological process here or dynamics that are induced by specific interventions. While these interventions might represent conditions that can occur also outside the laboratory, it would be important to clarify how the reader should contextualize this study.

    1. l y a une forme de plaisir masochiste  à surfer sur les sites de rencontres.

      Il s'agit à nouveau d'une opinion de l'auteur et d'un jugement. Premièrement, il suppose que les gens ont de mauvaises expériences et, deuxièmement, qu'ils disposent d'options pour rencontrer de nouvelles personnes.

    2. Mais si on ne séduit pas dans la vraie vie, on ne séduit pas sur les sites de rencontre.

      C'est l'avis de l'auteur sur la base de son expérience des personnes qu'il a rencontrées. Il s'agit d'une extrapolation d'un comportement qu'il ne peut pas prédire.

    1. Reviewer #4 (Public Review):

      This work aims at analyzing the impact of histone variants and histone modifications on chromatin states of the Arabidopsis genome. Authors claim that histone variants are as significant as histone modifications in determining chromatin states. They also study the effect of mutations in the DDM1 gene on the exchange of H2A.Z to H2A.W, which convert the silent state of transposons into a chromatin state normally found on protein coding genes.

      This is an interesting and well done study on the organization of the Arabidopsis genome in different chromatin states, adding to the previous reports on this issue.

    1. Reviewer #4 (Public Review):

      This is an admirable piece of work. The authors build on a previous dataset they assembled, but expand it to include all stages of early development in the nematode Caenorhabditis elegans. Cell collection was done manually, which is very impressive, and is clearly far better than pooled unidentified cells. I will not comment on the specific sequencing and analysis, since this is not my expertise, but will comment on the general conclusions and comparative framework in which the authors place their results.

      While the Introduction and Discussion sections are actually fairly short, much of the presentation of the results is based on a certain comparative framework, which is explicitly a comparison between C. elegans and Drosophila melanogaster. This is an important perspective, but I feel the authors' interpretation is in some places exaggerated and in other places almost trivial.

      Drosophila and C. elegans are two of the main models for developmental biology. However, it has been clear for over two decades that both species are highly derived and specialized and therefore, treating them as representative for their taxa is problematic. Much of the authors' discussion hinges on the question of comparing syncytial and lineage-dependent development. The syncytial early development of Drosophila is very specific and is clearly a recent innovation within a restricted group of flies. The canonical Drosophila segmentation cascade is mostly a novelty and most elements within the cascade are recent (the authors are invited to browse my 2020 review in Curr. Top. Dev. Biol.) Specifically, the expression of gap genes in regional stripes is not found very broadly. Conversely, the polarizing role of Caudal is very ancient and is probably found in all Bilateria. When making comparisons with a distantly related species, it is important to keep this in mind. Not as much is known about development of other nematodes, but the little that is known indicates that C. elegans is also unusual, and specifically, the eutelic development (conserved cell lineages in development) is not found in all nematodes.

      The authors suggest that regional expression of transcription factors in stripes is a conserved characteristic of development. This is true for Hox genes and has been known for decades. The regional expression they show for other genes is not convincing as "stripes". It is no surprise that developmental transcription factors are regionalized, but linking this to the stripes of Drosophila gap genes and even more so to Drosophila pair-rule and segment-polarity genes is a bit far-fetched. Yes, many genes are expressed in restricted domains along the A-P axis, but that is all that can be said based on the data. Calling them "Drosophila-like" is unfounded.

      Beyond these broad homology statements, the rest of the presentation is fine and I have no major comments.

  3. Apr 2023
    1. strife

      "an act of contention" 爭吵

    2. bewail

      "to express deep sorrow for usually by wailing and lamentation" 悲嘆

    3. repented

      "to feel regret or contrition" 懺悔

    4. indignant

      "feeling or showing anger because of something unjust or unworthy" 憤慨

    5. temperance

      "moderation in action, thought, or feeling" 節制

    6. zeal

      "eagerness and ardent interest in pursuit of something" 熱誠

    7. avarice

      "excessive or insatiable desire for wealth or gain : GREEDINESS, CUPIDITY" 貪心、貪婪

    8. stoop

      "to bend the body or a part of the body forward and downward sometimes simultaneously bending the knees" 彎腰

    9. conjure

      "to charge or entreat earnestly or solemnly" 懇求

    10. toil

      "long strenuous fatiguing labor" 勞苦

    11. jurisdiction

      "the authority of a sovereign power to govern or legislate"; 管轄範圍

    12. drachm’

      "a unit of weight formerly used by apothecaries, equivalent to 60 grains or one eighth of an ounce." 德拉克馬

    13. vengeance

      "punishment inflicted in retaliation for an injury or offense" 報仇

    14. rejoice

      "to feel joy or great delight" 開心

    15. woe

      "a condition of deep suffering from misfortune, affliction, or grief" 悲痛

    16. endorse

      "to approve openly" 認可

    17. vicar

      "an ecclesiastical agent: such as: a Church of England incumbent receiving a stipend but not the tithes of a parish" 牧師

    18. hail

      "precipitation in the form of small balls or lumps usually consisting of concentric layers of clear ice and compact snow" 冰雹

    19. flax

      "any of a genus (Linum of the family Linaceae, the flax family) of herbs especially : a slender erect annual (L. usitatissimum) with blue flowers commonly cultivated for its bast fiber and seed" 亞麻

    20. ample

      "generous or more than adequate in size, scope, or capacity" 寬闊

    21. brethren

      "plural of BROTHER" 弟兄們

    22. boon

      "a timely benefit" 福利

    23. quenched

      "to put out the light or fire of" 熄滅

    24. motionless

      "not moving; stationary" 不動

    25. assailed

      "to attack violently" 攻擊

    26. dew

      "moisture condensed upon the surfaces of cool bodies especially at night" 露水

    27. perforates

      "to make a hole through"; 穿過

    28. tares

      "the seed of a vetch" 稗子

    29. slough

      "a place of deep mud or mire" 泥沼

    30. negligence

      "the quality or state of being negligent" 忽略、忽視

    31. laggard

      "lagging or tending to lag : slow especially compared to others of the same kind" 遲緩的、落後的

    32. courtesy

      "behavior marked by polished manners or respect for others"; 禮節、禮儀

    33. benignity

      "showing kindness and gentleness" 良性

    34. outrage

      "an act of violence or brutality" 暴行

    35. treachery

      "violation of allegiance or of faith and confidence"; 叛變

    36. desist

      "to cease to proceed or act" 斷念

    37. headlong

      "without pause or delay"; 猛然地

    38. astonishment

      "a feeling of great surprise and wonder" 驚愕

    39. pilgrim

      "one who travels to a shrine or holy place as a devotee" 朝聖

    40. brows

      "eyebrow" 眉毛

    41. unwonted

      "being out of the ordinary : RARE, UNUSUAL" 非習常的

    42. agile

      "marked by ready ability to move with quick easy grace" 俐落

    43. scorn

      "open dislike and disrespect or mockery often mixed with indignation" 鄙視、蔑視

    44. bend

      "to constrain or strain to tension by curving" 彎曲

    45. enswathes

      "to enfold or enclose with or as if with a covering"; 包裹住

    46. lingering

      "to move slowly" 逗、留

    47. reproach

      "an expression of rebuke or disapproval"; 批評的話語

    48. vermilion

      "a vivid reddish orange" 珠

    49. slopes

      "to lie or fall in a slant : INCLINE" 傾斜

    50. meridian circle

      "an astronomical transit instrument having its vertical circle very accurately graduated for precise measurements of declination" 經絡圈

    51. forebode

      "to have an inward conviction of (something, such as a coming ill or misfortune)"; 預示、預感

    52. fangs.

      “a long sharp tooth”; 獠牙

    53. hinders

      "to make slow or difficult the progress of";妨礙

    54. stain

      "to suffuse with color" 弄髒

    55. vanquish

      "to overcome in battle : subdue completely" 擊敗、征服

    56. ooze

      "a soft deposit (as of mud, slime, or shells) on the bottom of a body of water" 爛泥

    57. infamy

      “evil reputation brought about by something grossly criminal, shocking, or brutal”; 醜惡的、聲名狼藉的

    58. nape

      "the back of the neck";頸背

  4. Mar 2023
    1. repose

      to rest or lie 休息;憩息;臥眠

    2. Because of that great longing to excel, 80whereon my heart was set, I certainlywould not have been so courteous while I lived.Here is the forfeit paid for pride like this;nor should I be here yet, had it not beenthat, while I still could sin, I turned to God.

      Doing nothing is also a sin. Dante thinks you should stand up for your ideal.

    3. therefrom

      from that or from there; from a thing or place that has been previously mentioned 由此;從那裡;從那一點

    4. I’ve shown him all the people who are guilty;and now I mean those spirits to reveal, 65who ’neath thy jurisdiction cleanse themselves

      Dante gives sinners a second chance, kind of humanism.

    5. thereupon

      on the thing that has been mentioned 關於那,就該事

    6. Great sorrow filled my heart on hearing this,because I knew of people of great worth,who in that Borderland suspended were.

      He still not understand that God is justice itself.

    7. against me this one seemed to be advancingwith head erect and with such raging hunger,that even the air seemed terrified thereby—and of a she-Wolf, which with every lustseemed in her leanness laden, and had caused 50many ere now to lead unhappy lives.

      This imply that lust is the most difficult one for humans to overcome.

    8. Art thou that Virgil, then, that fountain-headwhich poureth forth so broad a stream of speech?”

      Why does Dante choose Virgil?

    9. When half way through the journey of our lifeI found that I was in a gloomy wood,because the path which led aright was lost.

      This is also Dante reminding himself.

    10. I had his hair wrapped round my hand already,and more than one shock had I plucked from him,while he was barking, with his eyes turned down

      Now Dante fully accepted the fact that God is justice. Those people deserve to be punished like this.

    1. Reviewer #4 (Public Review):

      In this manuscript, Tornini and colleagues identify two previously un-characterized micropeptides encoded by linc-mipep and linc-wrb as important modulators of day-time activity in zebrafish larvae. The authors demonstrate that each single mutant shows an increase in day-time activity and that double mutants show a more pronounced effect. Of interest, ubiquitous overexpression of the ORF encoding the linc-mipep-derived peptide can rescue the day-time over-activity phenotype of linc-mipep mutant larvae, establishing that linc-mipep acts indeed as a protein and not at the level of RNA. Using a series of experimental approaches, including ATAC-Seq from double mutant brains and scRNA-Seq and scATAC-seq analyses from linc-mipep mutants as well as linc-mipep and linc-wrb CHIP analyses, the authors furthermore identify differences in chromatin accessibility and gene expression in specific cell types of the larval brain in the absence of linc-mipep (and in case of globale ATAC-Seq, in the absence of both peptides). They conclude that the micropeptides regulate behavior and neuronal states by modulating chromatin accessibility, revealing functional similarities to their known vertebrate homolog HMGN1.

      Overall, the key finding of this paper, namely the identification of two functional microproteins that had previously been misannotated as lincRNAs but have homology to HMGN1 both based on their sequence and function is an exciting discovery since relatively few newly predicted micropeptides have been functionally characterized to date, and because it advances our understanding of the molecular mechanisms underlying vertebrate-specific neuronal function and diversity. The F0 screen leading to the identification of 2 functional micropeptides provides a major advance to the field since so far screens in the F0 generation have not been typically done (rather germline-transmission). Thus, this work provides a major step forward in this regard. In addition, it includes a series of scRNA- and scATAC analyses that are technologically at the forefront and not easy to conduct and analyse.

      The weakest part of the paper in its current form is on the one hand missing the link between the behavioral phenotype in mutants and the molecular phenotypes in the larval brain. It remains unclear how one can reconcile the broad neuronal expression (in the case of linc-mipep preferentially in Purkinje cells) and linc-wrb with the cell-specific effects. Moreover, it is not clear whether both peptides act redundantly or in parallel but distinct pathways since the rescue is only shown for the single linc-mipep mutant by linc-mipep overexpression (and no rescue is shown for linc-wrb or the double mutant). While the authors suggest throughout the manuscript that both peptides have similar functions (act redundantly), no clear data is provided for this, and the use of either single linc-mipep mutants (all single-cell analyses in the last Figure) or double linc-mipep/linc-wrb mutants (global brain ATAC-Seq analyses) for different brain analyses makes the molecular analyses inconsistent and not easy to interpret. While the overall finding(s) of the paper is really interesting, to make this paper really solid, additional controls and analyses will be needed.

    1. 1930s Wilson Memindex Co Index Card Organizer Pre Rolodex Ad Price List Brochure

      archived page: https://web.archive.org/web/20230310010450/https://www.ebay.com/itm/165910049390

      Includes price lists

      List of cards includes: - Dated tab cards for a year from any desired. - Blank tab cards for jottings arranged by subject. - These were sold in 1/2 or 1/3 cut formats - Pocket Alphabets for jottings arranged by letter. - Cash Account Cards [without tabs]. - Extra Record Cards for permanent memoranda. - Monthly Guides for quick reference to future dates. - Blank Guides for filing records by subject.. - Alphabet Guides for filing alphabetically.

      Memindex sales brochures recommended the 3 x 5" cards (which had apparently been standardized by 1930 compared to the 5 1/2" width from earlier versions around 1906) because they could be used with other 3 x 5" index card systems.

      In the 1930s Wilson Memindex Company sold more of their vest pocket sized 2 1/4 x 4 1/2" systems than 3 x 5" systems.

      Some of the difference between the vest sized and regular sized systems choice was based on the size of the particular user's handwriting. It was recommended that those with larger handwriting use the larger cards.

      By the 1930's at least the Memindex tag line "An Automatic Memory" was being used, which also gave an indication of the ubiquity of automatization of industrialized life.

      The Memindex has proved its success in more than one hundred kinds of business. Highly recommended by men in executive positions, merchants, manufacturers, managers, .... etc.

      Notice the gendering of users specifically as men here.

      Features: - Sunday cards were sold separately and by my reading were full length tabs rather than 1/6 tabs like the other six days of the week - Lids were custom fit to the bases and needed to be ordered together - The Memindex Jr. held 400 cards versus the larger 9 inch standard trays which had space for 800 cards and block (presumably a block to hold them up or at an angle when partially empty).

      The Memindex Jr., according to a price sheet in the 1930s, was used "extensively as an advertising gift".

      The Memindex system had cards available in bundles of 100 that were labeled with the heading "Things to Keep in Sight".

    1. 312 Oak Midget Tray WWeesCoverEquipped same as]No.324,price.55CTohold cards14x3.No.423.Equippedasabove,tohold65Ccards 24x4, priceNo. 533. Standard size.to hold card 3x5, equip-ped as above,price..........No. 7- Nickel ....PrepaidinU. S.onreceiptofpriceNo. 324OakMidgetTraytheCoverWeis75cNo. 644. To hold cards4x6,equipped$1.10(StyleNos.312,423.533and644)asabove......(Style No. 324,213.335and446.)Send for catalog showing many other time-saving office devices. Our goods are soldyour dealer does not carry our line we can supply you direct from the factory.To hold cards 24x4. lengthof tray2%in..equippedwithAtoZindexand100record cards 45cNo. 213. To hold cards 14x3in,, lenght of tray 24in..equipped asabove40cNo.335.Standardsize,tohold3x5 cards.equipped asabove50c80cNo. 446. To hold 4x6 cards,equipped asabove.Any of these trays sent pre-paid in U. S. on receipt ofpriceby stationers everywhere. IfNo. 6 Union St.The WeisManufacturing Co.,Monroe,Mich.,U. S.A.Please mention SYSTEM when writing to advertisers

      Notice the 1 1/4" x 3" cards, 2 1/4 x 4" cards in addition to the 3 x 5" and 4 x 6".

    1. The width of the drawers of both McDowell & Craig and Steelcase desks is just wide enough to accommodate two rows of 4 x 6" index cards side by side with enough space that one might insert a sizeable, but thin divider between them

      I suspect that this is a specific design choice in a world in which card indexes often featured in the office environment of the mid-twenty first century.

      Were other manufacturers so inclined to do this? Is there any evidence that this was by design? Did people use it for this? Was there a standard drawer width?

      The metal inserts to section off the desk drawer area could have also been used for this sort of purpose and had cut outs to allow for expanding and contracting the interior space.

      Keep in mind that some of these tanker desks were also manufactured with specific spaces or areas intended for typewriters or for storing them.

    1. The black line in Fig. 5 shows that redistribution is not enough; if everyone’s emissions are equalized at escape from poverty levels, then we would still overshoot the climate boundaries
      • First stage of characterizing the Safe and Just Corridor
      • The black line in Fig. 5 shows that
      • redistribution is not enough
        • if everyone’s emissions are equalized at escape from poverty levels, then
        • we would STILL overshoot the climate boundaries (annotator's emphasis)
        • hypothetical pressure from 62% of humanity that is lacking humane access to resources is equal to the pressure exerted by 4% of the elits of humanity
    1. Analog Supplies

      I should mention that the Stockroom Plus 4 x 6" cards I got a while back are great with even my juiciest fountain pens. They're some of the least expensive gridded cards I've been able to find and are a fraction of the cost of the Exacompta.

  5. Feb 2023
    1. Every visual creative work is a manifestation of the character of thedesigner.

      This emphasizes the importance of the designer understanding how their work ties into how people determine their level as designers.

    2. The resulting International Style leapt from Europe to the United States, spreading valuesof neutrality, objectivity, and rationality expressed through tightly gridded layouts andrestricted typography.

      The values that this style presented were impactful enough to reach the U.S thus foreshadowing it's importance.

    3. turned revolutIonary avant-garde Ideals Into forMal Method–ologIes, detachIng desIgn froM a dIsruptIve aesthetIc agenda.

      This can relate to their approaches to design and how they may relate to our approaches.

    4. A movementcalled the New Typography emergedfrom the Bauhaus

      This will be important to keep in mind for later in the reading.

    1. ZFIN: ZDB-ALT-150417-4

      DOI: 10.1016/j.cub.2023.01.039

      Resource: RRID:ZFIN_ZDB-ALT-150417-4

      Curator: @evieth

      SciCrunch record: RRID:ZFIN_ZDB-ALT-150417-4

      What is this?

    2. ZFIN: ZDB-ALT-160119-4

      DOI: 10.1016/j.cub.2023.01.039

      Resource: (ZFIN Cat# ZDB-ALT-160119-4,RRID:ZFIN_ZDB-ALT-160119-4)

      Curator: @evieth

      SciCrunch record: RRID:ZFIN_ZDB-ALT-160119-4

      What is this?

    1. People have some control over the timing of their death and can hold on until after important occasions or die quickly after having lost someone important to them

      I thought this was the most interesting fact because it is crazy that as humans we can get to a point in our lives where we literally decide what time is the best to die. It makes sense but also leaves me with so many questions. How is this possible? Can everyone do this? Do you have to be at the point of hospice for the to be possible? I just feel this is crazy that we can control when our time is whether or not we have a will to live. I added a link that goes deeper and adds examples of this subject from the Washington Post.


    1. Signature par le président du conseil régional et le préfet de régiond’une convention régionale pluriannuelle de coordination del’emploi, de l’orientation et de la formation (L6123-4 du code dutravail)
  6. Jan 2023
    1. Lo digital se carateriza por su fragilidad: copias y versiones que se pierden, cambios sin control, ausencia de historia

      cambios controlados y presentes si se hacen necesarios

    1. Reviewer #4 (Public Review):

      In the manuscript the author tried to find the cellular level mechanism that causes sudden cardiac death in elite athletes. They found that there are more ventricular fibrosis, ventricular extrasystole burden, longer action potential duration, higher ventricular fibrillation (VF) inducibility, higher HCN4 expression and decreased Ito in sustained trained dog model.

      The author successfully conducted large animal training model, showed bradycardia and ventricular fibrosis as a finding similar in athletes and demonstrated the increased ventricular arrhythmia susceptibility to electrical stimulation. The finding of increased action potential duration can be postulated to be a factor of sudden cardiac death in these athletes. However, the interpretation of these findings should be cautious just like all the animal studies. Human has a more complex interaction with the environment and individual variabilities. Will the higher susceptibility of VF to electrical stimulation be the same in athletes is still hard to answer.

      Still, it is the first study to provide a large animal model of sustained training mimicking trained athletes and to give insights into the cellular level of change in an athlete's heart. The young death of this special group is a tragedy and the importance of these studies cannot be overemphasized.

    1. Reviewer #4 (Public Review):

      Hu et al introduced the MS2-Suntag system into C. elegans to tag and image the dynamics of individual mRNAs in a live animal. The system involves CRISPR-based integration of 8x MS2 motifs into the target gene, and two transgene constructs (MCP-Suntag; scFv-sfGFP) that can potentially recruit up to 384 GFP molecule to an mRNA to amplify the fluorescent signal. The images show very high signal to background ratio, indicating a large range of optimization to control phototoxicity for live imaging and/or artifacts caused by excessive labeling. The use of epidermal wound repair as a case study provides a simplified temporal context to interpret the results, such as the initiation of transcription upon wounding. The preliminary results also reveal potentially novel biology such as localization of mRNAs and dynamic RNP complexes in wound response and repair. On the other hand, the system recruits a large protein complex to an mRNA molecule, an immediate question is to what extent it may interfere with in vivo regulation. Phenotypic assays, e.g., in development and wound repair, would have been a powerful argument but are not explored. In all, C. elegans is powerful system for live imaging, and the genome is rich in RNA binding proteins as well as miRNAs and other small RNAs for rich posttranscriptional regulation. The manuscript provides an important technical progress and valuable resource for the field to study posttranscriptional regulation in vivo.

    1. May 19, 2004 #1 Hello everyone here at the forum. I want to thank everyone here for all of the helpful and informative advice on GTD. I am a beginner in the field of GTD and wish to give back some of what I have received. What is posted below is not much of tips-and-tricks I found it very helpful in understanding GTD. The paragraphs posted below are from the book Lila, by Robert Pirsig. Some of you may have read the book and some may have not. It’s an outstanding read on philosophy. Robert Pirsig wrote his philosophy using what David Allen does, basically getting everything out of his head. I found Robert Pirsigs writing on it fascinating and it gave me a wider perspective in using GTD. I hope you all enjoy it, and by all means check out the book, Lila: An Inquiry Into Morals. Thanks everyone. arthur

      Arthur introduces the topic of Robert Pirsig and slips into the GTD conversation on 2004-05-19.

      Was this a precursor link to the Pile of Index Cards in 2006?

      Note that there doesn't seem to be any discussion of any of the methods with respect to direct knowledge management until the very end in which arthur returns almost four months later to describe a 4 x 6" card index with various topics he's using for filing away his knowledge on cards. He's essentially recreated the index card based commonplace book suggested by Robert Pirsig in Lila.

    1. Reviewer #4 (Public Review):

      This is an extraordinary study that will serve as key resource for all researchers in the field of Drosophila testis development. The lineages that derive from the germline stem cells and somatic stem cells are described in a detail that has not been previously achieved. The RNAseq approaches have permitted the description of cell states that have not been inferred from morphological analyses, although it is the combination of RNAseq and morphological studies that makes this study exceptional. The field will now have a good understanding of interactions between specific cell states in the somatic lineage with specific states in the germ cell lineage. This resource will permit future studies on precise mechanisms of communication between these lineages during the differentiation process, and will serve as a model for studies of co-differentiation in other stem cell systems. The combination of snRNAseq and scRNAseq has conclusively shown differences in transcriptional activation and RNA storage at specific stages of germ cell differentiation and is a unique study that will inform other studies of cell differentiation.

      Could the authors please describe whether genes on the Y chromosome are expressed outside of the male germline. For example, what is represented by the spots of expression within the seminal vesicle observed in Figure 3D?

      I would appreciate some discussion of the "somatic factors" that are observed to be upregulated in spermatocytes (e.g. Mhc, Hml, grh, Syt1). Is there any indication of functional significance of any of these factors in spermatocytes?

      In the discussion of cyst cell lineage differentiation following cluster 74 the authors state that neither the HCC or TCC lineages were enriched for eya (Figure 6V). It seems in this panel that cluster 57 shows some enrichment for eya - is this regarded as too low expression to be considered enriched?

    1. Ai Ebihara is the kind of character that you expect to hate from the get-go, but her struggle surprisingly becomes one of the better links in the game. Ai is pretty and rich, and she knows it – something that makes her insufferable at the start. She is always stroking her own ego, keeping up appearances, and spends her time being generally self-centered. But it takes a form of rejection to show Ai is dealing with some heavy feelings, even suicidal thoughts. What I loved so much about Ai’s social link is that it’s unpredictable – a rollercoaster of uncertainty. Every time you think you know where you stand with the girl and make progress, you get slapped in the face with an unsettling event or revelation. The question the link poses: Is there a redeeming quality about her? Can a kind soul be all it takes to save someone? Watching it all unfold is beautiful.  

      "The question the link poses: Is there a redeeming quality about [Ai Ebihara]? Can a kind soul be all it takes to save someone?"

      This is a beautiful write-up of the Ai Ebihara social link in Persona 4. I would be curious what the author thinks the answers are to the two questions presented. In my view, Ai's redeeming quality -- that is the quality she uses to redeem her character in the end -- is the same quality that drove her unpleasant personality early in the arc -- introspection. The player "saves" Ai by giving Ai the courage to save herself. Part of the beauty of the link is that the rest is for Ai to figure out as she goes forward.

  7. Dec 2022
    1. (Joshua 4:20).

      connect this to:

      The helps whereof by this art memorative, they would prove to be as effectual, by these conceived fictions in the eye of the mind,12 as those we remember by the visible eye of the body, for example whereof say they, concerning the latter we read in the holy Scriptures of 12 stones, that were erected in the river Jordan in memory of the wonderful transpassage of the Israelites, Josh. 24.27.—The Memory Arts in Renaissance England by William E. Engel, Rory Loughnane, and Grant Williams

    1. The drawers are jammed with jokes typed on 4-by-6-inch cards — 52 drawers, stacked waist-high, like a card catalog of a certain comedian’s life’s work, a library of laughs.

      Joan Rivers had an index card catalog with 52 drawers of 4-by-6-inch index cards containing jokes she'd accumulated over her lifetime of work. She had 18 2 drawer stackable steel files that were common during the mid-1900s. Rather than using paper inserts with the label frames on the card catalogs, she used a tape-based label maker to designate her drawers.

      Scott Currie, who worked with Melissa Rivers on a book about her mother, Joan Rivers, at the comedian’s former Manhattan office. Many of her papers are stored there.Credit...Hiroko Masuike/The New York Times

      Note carefully that the article says 52 drawers, but the image in the article shows a portion of what can be surmised to be 18 2-drawer cabinets for a total of 36 drawers. (14 2-drawer cabinets are pictured, but based on size and perspective, there's one row of 4 2-drawer boxes not shown.)

    1. Reviewer #4 (Public Review):

      The study employs a number of methods, including TEM morphometric analysis, immunochemistry, western blotting, genomics, genetically modified models, whole heart measurements.

      However, the manuscript seems to be a collection of two unfinished works: one on the transition p20-p60 in post-natal development of the heart, second about the role of ephrinB1 in the maturation of the crests of the sarcolemma. Otherwise, it is not clear why in the first figure there is no staining for ephB1, and why there is staining for claudin 5 instead.<br /> The authors are trying to defend the idea that development of the heart in rats doesn't finish on postnatal day 20 and goes on for up to day 60. However, it is not convincing.<br /> It is no surprise transcription profile is different between day 20 and day 60, I am sure as life goes on development continues into aging and any comparison of samples collected with sufficient time lapse will give transcriptional differences. Whether these differences represent a truly separate development stage is not a clear-cut story.<br /> Most of the argument is based on morphometric study of TEM images. However, the method is not described at all. There is reference to another paper by the authors, but this paper doesn't provide a concise description of the morphometry either. It is unclear how randomisation of images and fields of view has been achieved and what statistical methods has been implemented. In TEM it is often possible to find all sorts of oddities depending on how you choose the images.<br /> Why didn't the authors use microscopy of live isolated cells, which may be more relevant to study crest hight?<br /> Both claudin5 and EphrinB1 seem to be expressed highly after p5, which doesn't correlate with the proposed maturation of crests at days 20 to 60.<br /> There is no causative relationship between the lack of ephrinb1 and crest maturing, at least to my mind.

    1. Reviewer #4 (Public Review):

      This retrospective study addresses an important aspect of breast cancer treatment for prolonging survival and minimizing adverse events. Moreover, the findings could improve the treatment response of HR+ DCIS patients, which is very promising for the treatment. The article is mostly well-written and supported by encouraging data. The major strength of the study is the finding that ET after mastectomy should not be used for the treatment of HR+ DCIS patients. Nevertheless, only the Chinese population was analyzed, and that is the only limitation. This study would greatly help in the management of HR+ DCIS patients and in clinical decision-making.

    1. what Marvin Harris said was the most important thing projecting the viability of a historical cultures is infrastructure, which is your expertise. But before we get into the infrastructure part, how do you envision society at the higher levels of belief, motivation, institutions? 00:25:09 Have you thought about that? Simon Michaux: Yes. So I believe society will shift into four parallel groups based on paradigm

      !- transition : for cultural / social groups / paradigms

    1. Reviewer #4 (Public Review):

      In this paper, Zhou et al. propose a polarization microscope for measuring the emission polarization of bifunctional rhodamine molecules attached to AdiC transporters. The polarization is used to resolve the orientation of the fluorophores, which allows the authors to successfully resolve the four conformations of AdiC at a temporal resolution of tens of milliseconds. The measured orientation for each conformation is validated with the results using crystallography.

      Overall, I believe the paper is well written and demonstrates a great application for orientation imaging using polarized microscopes. Detailed experimental procedures, calibrations, and mathematical frameworks are included. I have the following recommendations to improve the manuscript.

      1) On page 20, the authors note that they set a threshold to filter out molecules whose total intensity varies during the measurements. The statement that "while fluorescence intensity is expected to vary among different polarization directions, the total intensity should be essentially invariant" is not true. Since the authors use TIRF illumination to excite the molecules, the excitation polarization component along the tilting direction (e.g., along the y-axis) of the excitation is 0, i.e., molecules oriented along that direction (e.g., y-oriented) will be excited less effectively compared to other orientations.

      2) Could the authors provide more details regarding how the clusters are ranked? The authors note that C1-C4 are "ranked according to the values of both angles". It is not clear to me how this is done. Also, what is the range of the measured theta_L and phi_L? And how is the warping of the spherical coordinates handled in the ranking process, e.g., a change from 350 deg to 10 deg is +20 deg or -340 deg.

      3) Is the k-means clustering also based on the distance in the Cartesian space, similar to the state identification?

    1. Reviewer #4 (Public Review):

      This manuscript investigates the process of neurotransmitter release from hair cell synapses using electron microscopy of tissue rapidly frozen after optogenetic stimulation. The primary finding is that in the absence of a stimulus very few vesicles appear docked at the membrane, but upon stimulation vesicles rapidly associate with the membrane. In contrast, the number of vesicles associated with the ribbon and within 50 nm of the membrane remains unchanged. Additionally, the authors find no changes in vesicle size that might be predicted if vesicles fuse to one-another prior to fusing with the membrane. The paper claims that these findings argue for rapid replenishment and against a mechanism of multi-vesicular release, but neither argument is that convincing. Nonetheless, the work is of high quality, the results are intriguing, and will be of interest to the field.

      1) The abstract states that their results "argue against synchronized multiquantal release". While I might agree that the lack of larger structures is suggestive that homotypic fusion may not be common, this is far from an argument against any mechanisms of multi-quantal release. At least one definition of synchronized multiquantal release posits that multiple vesicles are fusing at the same time through some coordinated mechanism. Given that they do not report evidence of fusion itself, I fail to see how these results inform us one way or the other.

      2) The complete lack of docked vesicles in the absence of a stimulus followed by their appearance with a stimulus is a fascinating result. However, since there are no docked vesicles prior to a stimulus, it is really unclear what these docked vesicles represent - clearly not the RRP. Are these vesicles that are fusing or recently fused or are they ones preparing to fuse? It is fine that it is unknown, but it complicates their interpretation that the vesicles are "rapidly replenished". How does one replenish a pool of docked vesicles that didn't exist prior to the stimulus?

    1. Oxidation Method


    2. Balancing Basic Redox Reactions Balance as if it was acidic, and then add OH- to both sides to neutralize H+ (converting it to H2O) Split Skeletal Eq. into 1/2 Reactions For Each Hal- Reaction Balance all Elements Except O and H Balance O by adding water Balance H by adding H+. Balance Charge by adding e-. Multiply 1/2 rxns by appropriate integer so electrons lost = electrons gained. Add half-reactions, cancelling electrons lost and gained, and check work Add OH- to both sides to neutralize H+ (converting it to H2O) (only the last step is different from balancing acidic reactions)


    3. Balancing Acidic Redox Reactions The following steps allow you to balance a redox reaction and you often do not even have to identify the oxidation state of the various species. Split Skeletal Eq. into 1/2 Reactions For Each Half-Reaction Balance all Elements Except O and H Balance O by adding water Balance H by adding H+. Balance Charge by adding e-. Multiply 1/2 rxns by appropriate integer so electrons lost = electrons gained. Add half-reactions, cancelling electrons lost and gained, and check work

      Know these steps and know how to do the equations

    4. oxidationreduction=loss of electrons=gain of electrons

      Remember where oxidation and reduction occurs

    5. Zinc is losing electrons in the reaction and is thus oxidized to the zinc cation, while sulfur is gaining electrons and is thus reduced to the sulfide anion.

      While my instinct is that reduction = less electrons, in reality it's the charge that's being reduced, which means more electrons

    1. https://www.youtube.com/watch?v=b-Wp0sLpnMY

      PVA Glue used in bookbinding, but isn't inexpensive.

      • Tacky glue - okay
      • rubber cement - not great
      • elmer's glue - not great, tears esp. for 2 layers
      • Mod podge - pulls nicely and strong
      • mod podge hard shell - cracks, not great
      • PVA Glue - the best of the group

      Recommendations in order: PVA, Tacky Glue, Mod Podge (regular)

      Brush on top edge and do two coats. Don't get it down between sheets.

  8. Nov 2022
    1. Benefícios da nossa plataforma de legalização

      Também acho que é uma oportunidade em copiar o formato da seção "Para quem a Company Hero é feita" na homepage.

    1. a basic type of chemical reaction involving the transfer of electrons from one atom or chemical entity to another, or more accurately, from one type of orbital to another, that results in new bonds being formed

      Redox reaction definition

    1. https://www.instagram.com/p/CeWV6xBuZUN/?hl=en

      Ryan Holiday in the past has made custom 4 x 6" index cards for taking notes for his individual projects.

      Pictured: A custom slip with 11 light gray lines, small margins all around, and at the top the printed words: "Courage. Temperance. Justice. Wisdom."

      <small><cite class='h-cite via'> <span class='p-author h-card'>Billy Oppenheimer, research assistant to Ryan Holiday</span> in The Notecard System: Capture, Organize, and Use Everything You Read, Watch, and Listen To - Billy Oppenheimer (<time class='dt-published'>11/03/2022 16:53:44</time>)</cite></small>

      <div style="padding:16px;"> <div style=" display: flex; flex-direction: row; align-items: center;"> <div style="background-color: #F4F4F4; border-radius: 50%; flex-grow: 0; height: 40px; margin-right: 14px; width: 40px;"></div> <div style="display: flex; flex-direction: column; flex-grow: 1; justify-content: center;"> <div style=" background-color: #F4F4F4; border-radius: 4px; flex-grow: 0; height: 14px; margin-bottom: 6px; width: 100px;"></div> <div style=" background-color: #F4F4F4; border-radius: 4px; flex-grow: 0; height: 14px; width: 60px;"></div></div></div><div style="padding: 19% 0;"></div> <div style="display:block; height:50px; margin:0 auto 12px; width:50px;"><svg width="50px" height="50px" viewBox="0 0 60 60" version="1.1" xmlns="https://www.w3.org/2000/svg" xmlns:xlink="https://www.w3.org/1999/xlink"><g stroke="none" stroke-width="1" fill="none" fill-rule="evenodd"><g transform="translate(-511.000000, -20.000000)" fill="#000000"><g><path d="M556.869,30.41 C554.814,30.41 553.148,32.076 553.148,34.131 C553.148,36.186 554.814,37.852 556.869,37.852 C558.924,37.852 560.59,36.186 560.59,34.131 C560.59,32.076 558.924,30.41 556.869,30.41 M541,60.657 C535.114,60.657 530.342,55.887 530.342,50 C530.342,44.114 535.114,39.342 541,39.342 C546.887,39.342 551.658,44.114 551.658,50 C551.658,55.887 546.887,60.657 541,60.657 M541,33.886 C532.1,33.886 524.886,41.1 524.886,50 C524.886,58.899 532.1,66.113 541,66.113 C549.9,66.113 557.115,58.899 557.115,50 C557.115,41.1 549.9,33.886 541,33.886 M565.378,62.101 C565.244,65.022 564.756,66.606 564.346,67.663 C563.803,69.06 563.154,70.057 562.106,71.106 C561.058,72.155 560.06,72.803 558.662,73.347 C557.607,73.757 556.021,74.244 553.102,74.378 C549.944,74.521 548.997,74.552 541,74.552 C533.003,74.552 532.056,74.521 528.898,74.378 C525.979,74.244 524.393,73.757 523.338,73.347 C521.94,72.803 520.942,72.155 519.894,71.106 C518.846,70.057 518.197,69.06 517.654,67.663 C517.244,66.606 516.755,65.022 516.623,62.101 C516.479,58.943 516.448,57.996 516.448,50 C516.448,42.003 516.479,41.056 516.623,37.899 C516.755,34.978 517.244,33.391 517.654,32.338 C518.197,30.938 518.846,29.942 519.894,28.894 C520.942,27.846 521.94,27.196 523.338,26.654 C524.393,26.244 525.979,25.756 528.898,25.623 C532.057,25.479 533.004,25.448 541,25.448 C548.997,25.448 549.943,25.479 553.102,25.623 C556.021,25.756 557.607,26.244 558.662,26.654 C560.06,27.196 561.058,27.846 562.106,28.894 C563.154,29.942 563.803,30.938 564.346,32.338 C564.756,33.391 565.244,34.978 565.378,37.899 C565.522,41.056 565.552,42.003 565.552,50 C565.552,57.996 565.522,58.943 565.378,62.101 M570.82,37.631 C570.674,34.438 570.167,32.258 569.425,30.349 C568.659,28.377 567.633,26.702 565.965,25.035 C564.297,23.368 562.623,22.342 560.652,21.575 C558.743,20.834 556.562,20.326 553.369,20.18 C550.169,20.033 549.148,20 541,20 C532.853,20 531.831,20.033 528.631,20.18 C525.438,20.326 523.257,20.834 521.349,21.575 C519.376,22.342 517.703,23.368 516.035,25.035 C514.368,26.702 513.342,28.377 512.574,30.349 C511.834,32.258 511.326,34.438 511.181,37.631 C511.035,40.831 511,41.851 511,50 C511,58.147 511.035,59.17 511.181,62.369 C511.326,65.562 511.834,67.743 512.574,69.651 C513.342,71.625 514.368,73.296 516.035,74.965 C517.703,76.634 519.376,77.658 521.349,78.425 C523.257,79.167 525.438,79.673 528.631,79.82 C531.831,79.965 532.853,80.001 541,80.001 C549.148,80.001 550.169,79.965 553.369,79.82 C556.562,79.673 558.743,79.167 560.652,78.425 C562.623,77.658 564.297,76.634 565.965,74.965 C567.633,73.296 568.659,71.625 569.425,69.651 C570.167,67.743 570.674,65.562 570.82,62.369 C570.966,59.17 571,58.147 571,50 C571,41.851 570.966,40.831 570.82,37.631"></path></g></g></g></svg></div><div style="padding-top: 8px;"> <div style=" color:#3897f0; 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      A post shared by Ryan Holiday (@ryanholiday)

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      I used to do this sort of practice before, but I used buckslips instead.

  9. Oct 2022
    1. Reviewer #4 (Public Review):

      This manuscript reports combining recently developed and described in the accompanying paper nanobodies against Sallimus and Projectin with DNA-Paint technology that allows super-resolution imaging. Presented data prove that such a combination provides a powerful system for imaging at a nano-scale the large and protein-dense structures such as Drosophila flight muscle. The main outcome is the observation that in flight muscle sarcomeres Salimus and Projectin overlap at the I/A band border. This was elegantly achieved using double color DNA-Paint with Sls and Projectin nanobodies.

      Overall, as it stands, this manuscript even if of high technological value, remains entirely descriptive and short in providing new insights into muscle structure and architecture.<br /> The main finding, an overlap between short Sls isoform and Proj in flight muscle sarcomeres, is redundant with the author's observation (described in the companion paper "A nanobody toolbox to investigate localisation and dynamics of Drosophila titins") that in larval muscles expressing a long Sls isoform, Sls and Proj overlap as well.<br /> Alternatively, combination of Sls and Proj nanobodies with DNA-Paint represents an interesting example of technological development that could strengthen the accompanying nanobodies toolkit manuscript.

    1. Reviewer #4 (Public Review):

      This study revealed the structure of TMEM87A for the first time. Unexpectedly, the authors found that TMEM87A shared high structural similarity with WLS that mediates Wnt secretion and trafficking. Particularly, these two proteins share a similar extracellular GOLD domain and a large cavity that is accessible from both the extracellular side and the membrane. Through structural comparison, the authors have also identified a few other membrane proteins that share similar architecture with TMEM87A/WLS. These findings define a new membrane protein family that may play important roles in membrane-associated protein trafficking.

      The authors also provided structural analyses and functional characterizations that suggest TMEM87A might function differently from GPCRs or ion channels. This proposal is reasonable. More experimental evidence is needed in either this study or future studies.

      Overall, the findings from this study are highly interesting. This work provides a molecular framework for future elucidation of TMEM87A's functional roles and provides important and novel insights into this newly defined family of membrane proteins, and more broadly protein trafficking process.

    1. Reviewer #4 (Public Review):

      In "A Toxin-Antidote Selfish Element Increases Fitness of its Host", Long et al. attempt to address an outstanding question in the evolution of toxin-antidote (TA) systems in primarily selfing species: How do TA systems escape drift and spread in a primarily selfing species? The authors use simulations to show that at outcrossing rates similar to that observed in C. elegans a TA element, like the peel-1/zeel-1 element, has a high probability of being lost to genetic drift. However, the authors show that the peel-1 gene provides a fitness advantage to strains harboring it, providing evidence for a dual role for this gene and insights into how this element might have escaped being lost to genetic drift.


      The experiments in this paper are well-framed. The authors use simulations to show that the observed frequency of the peel-1/zeel-1 TA element in the C. elegans population is highly unlikely given the inferred outcrossing rates of species.

      The authors clearly show that the 140-370kb CB4856 introgression into N2 lowers relative fitness, number of eggs laid, and animal size, relative to N2.

      The authors generated null alleles of peel-1 and zeel-1 and showed that a truncated version of PEEL-1 confers a detrimental fitness effect when compared to N2. Furthermore, the authors show that the fitness effect associated with peel-1 is independent of the antidote (zeel-1) component of this TA element.


      1) The reference N2 strain has been cultivated in the lab for decades and many different versions of this strain exist. The different versions of N2, which might have slightly different genomes, are likely to have different fitness in laboratory conditions. It is unclear whether the N2 strain used to construct QX1198 is the same N2 strain used to construct CX12311, PTM229, and PTM377 (and others derived from these). The potential difference in the N2 strain used for the construction of these strains might contribute to the large discrepancy between the relative fitness shown in Figure 2A (~0.25) and Figure 3E-F (~0.07). Alternatively, the other CB4856-specific variants present in the 140-370 kb introgression in the QX1198 strain might cause this large discrepancy.<br /> Regardless of the potential discrepancy among N2 strains used as the genetic background, the claim that the presence of peel-1 confers higher relative fitness is supported by Figure 3E because PTM377/409 were presumably derived from the same N2 strain.

      2) For Figures 2B and 3C, the authors report the number of eggs laid per animal. C. elegans strains can lay embryos that do not hatch and therefore fail to develop into reproductive adults. Does the difference between N2 and N2(peel-1(0)) remain when considering the number of reproductively mature progeny? Presumably, eggs laid translate to reproductive adults because a relative fitness increase is observed when peel-1 is present.

      3) The authors did not perform whole-genome sequencing of the peel-1 and zeel-1 CRISPR edited strains or mention any backcrossing done to eliminate potential off-target editing events. Therefore it is difficult to conclude whether off-target effects might influence the quantified traits presented in Figure 3. This concern is somewhat alleviated by the reciprocal competition assay presented in Figure 3E (4th boxplot), but a potential off-target editing event that lowers fitness could have segregated with the silent dpy-10 and peel-1 edits.<br /> The same concern is present with the zeel-1-independence experiment, however, this experiment does not have reciprocal competition experiments.

      4) In Figure 3C-D, the authors show that a homozygous truncated version of PEEL-1 confers a reduction in eggs laid per animal (proxy for brood size) and animal length (proxy for developmental speed). However, the authors do not show whether a heterozygous truncated PEEL-1 strain (N2 peel-1/peel-1(kah126)) confers the same reduction in eggs laid or animal size. Would the allele frequency dynamics derived from the simulations be affected by a fitness advantage only being conferred by the presence of two copies of peel-1?

      5) The authors show a fitness advantage associated with peel-1 in laboratory conditions. It is obviously extremely difficult to extend these observations to the wild, however, the authors do not take their observations that peel-1 confers a fitness advantage in the lab and apply their empirical observations to the simulation framework. If the laboratory fitness advantage of peel-1 did extend to the wild, one might expect the element would fix in the population in the simulation framework.

      6) It seems possible that a truncated version of the PEEL-1 protein might have unknown deleterious fitness consequences that are independent of any beneficial effect the full-length protein might have. The same is true for the truncated ZEEL-1 protein, though potentially less concerning because there are only 5 amino acids.

    1. It does not follow, because our difficulties are stupendous, because there are some souls timorous enough to doubt the validity and effectiveness of our ideals and our system, that we must turn to a State-controlled or State-directed social or economic system in order to cure our troubles.  That is not liberalism; it is tyranny.  It is the regimentation of men under autocratic bureaucracy with all its extinction of liberty, or hope, and of opportunity.  Of course, no man of understanding says that our system works perfectly.  It does not.  The human race is not perfect.  Nevertheless, the movement of a true civilization is toward freedom rather than regimentation.  This is our ideal

      hoover's big thing is to avoid the federal government from being too involved

    2. Instead, we met the situation with proposals to private business and the Congress of the most gigantic program of economic defense and counter attack ever evolved in the history of the Republic.  We put it into action.

      hoover legitimately believes he did all he could

    3. The countries of Europe proved unable to withstand the stress of the depression.  The memories of the world had ignored the fact that the insidious diseases left by the Great War had not been cured.  The skill and intelligence of millions in Europe had been blotted out by battle, disease and starvation.  Stupendous burdens of national debts had been built up.  Poisoned springs of political instability lay in the treaties which closed the war.  Fears and hates held armaments to double those before the war.  Governments were fallaciously seeking to build back by enlarged borrowing, by subsidizing industry and employment with taxes that slowly sapped the savings upon which industry must be rejuvenated and commerce solidly built.  Under these strains the financial systems of many foreign countries crashed one by one.

      Hoover is still blaming other countries

    1. To meet our domestic emergencies in credit and banking arising from the reaction to acute crisis abroad the National Credit Association was set up by the banks with resources of $500,000,000 to support sound banks against the frightened withdrawals and hoarding. It is giving aid to reopen solvent banks which have been closed. Federal officials have brought about many beneficial unions of banks and have employed other means which have prevented many bank closings. As a result of these measures the hoarding withdrawals which had risen to over $250,000,000 per week after the British crisis have substantially ceased.

      Hoover provided support for the banks in crisis, trying to stabalize the withdraws and panic

    2. The emergencies of unemployment have been met by action in many directions. The appropriations for the continued speeding up of the great Federal construction program have provided direct and indirect aid to employment upon a large scale.

      But not enough aid

    1. expanded we must also contend with the implica-tions that algorithmically tailored digital environments pose for historical interpretation

      Algorithms are becoming more and more sophisticated, with that said it is plausible to arrive at the conclusion that algorithms pose threat to historical interpretions. However, I think as we move into the future this potential for error will become more and more minute as our data management and data storage will improve as well as the standards governing data. It will likely become harder to find gaps in digital history.

    2. How does this interaction change when you have a digitized copy of a letter? Similarly, how does it change when you are looking at an e-mail message?

      I feel that email has the ability to be impersonal, and the time spent reading an email cannot be equivocated to reading a letter. I think that we take more notice to a letter because someone took the time to write and mail this information.

    1. As to the mechanics of research, I take notes on four-by-six indexcards, reminding myself about once an hour of a rule I read long agoin a research manual, “Never write on the back of anything.”

      Barbara Tuchman took her notes on four-by-six inch index cards.

      She repeated the oft-advised mantra to only write on one side of a sheet.

      What manual did she read this in? She specifically puts quotes on "Never write on the back of anything." so perhaps it might be something that could be tracked down?

      Who was the earliest version of this quote? And was it always towards the idea of cutting up slips or pages and not wanting to lose material on the back? or did it also (later? when?) include ease-of-use and user interface features even when not cutting things up?

      At what point did double sided become a thing for personal printed materials? Certainly out of a duty to minimize materials, but it also needed the ability to duplex print pages or photocopy them that way.

    1. Dwyer, Edward J. “File Card Efficiency.” Journal of Reading 26, no. 2 (1982): 171–171.

      Ease of use in writing and grading with short assignments by using 4 x 6" index cards in classrooms.

      This sounds like some of the articles from 1912 and 1917 about efficiency of card indexes for teaching.

      I'm reminded of some programmed learning texts that were card-based (or really strip-based since they were published in book form) in the 1960s and 1970s. Thse books had small strips with lessons or questions on the front with the answers on the reverse. One would read in strips through the book from front to back and then start the book all over again on page one on the second row of strips and so on.

  10. Sep 2022
    1. Reviewer #4 (Public Review):

      The manuscript reports an experiment testing how the distribution of rewards and costs influences perceived reward value in ants. Using a bundling manipulation where rewards and costs were presented either in small separated amounts (segregated) or together in a larger amount (bundled), the results show that ants deposited a greater quantity of pheromones (which was used as an index of "liking") when rewards were segregated and costs bundled compared to when both rewards and costs were bundled (although that difference was statistically significant only in ants experiencing the segregated reward condition first during training) and when both rewards and costs were segregated. By contrast, no evidence was found for a bundling effect in terms of choice behaviour (which was used as an index of "wanting"). The authors suggest that these findings demonstrate a bundling effect and a dissociation between "wanting" and "liking" in ants.

      Overall, the experiment provides a worthy contribution to the study of the biases that affect the perceived value of rewards in a translational perspective from humans to invertebrate animals. The experimental manipulation is clever, and the results clearly indicate that manipulating bundling affected pheromone deposition in ants. However, the data reported do not appear to fully support the conclusions of an increased "liking" of the segregated rewards and bundled costs compared to bundled rewards and costs. In addition, more evidence (along with stronger justifications) would be needed to establish that choice behaviour and pheromone deposition are appropriate and sensitive measures of "wanting" and "liking", respectively. This aspect renders any claim of a dissociation between "wanting" and "liking" in ants somewhat premature and speculative at this stage. I describe these concerns in more detail below.

      1) The main hypothesis tested is that segregated rewards with bundled costs should be the most "liked" option relative to bundled rewards and costs and segregated rewards and costs. The results are interpreted as fully in line with this hypothesis. However, the data reported do not suggest this is the case: The difference between the 'segregated rewards' condition and the 'bundled' condition is not statistically significant when all ants are considered (that difference being statistically significant only for ants that first experienced the 'segregated rewards' condition during training). Although this point is briefly acknowledged in the discussion, more nuance and extra caution are needed in the overall interpretation of the findings, so that this statistically nonsignificant result does not appear as being treated as if it were statistically significant.

      2) An important requirement to adequately evaluate the findings from the choice behaviour test is to ensure that ants did learn the associations between the reward conditions and the runway scents. Ruling out potential learning confounds is in fact essential to interpret the results as reflecting the operation of motivational processes such as "wanting". Whereas the results from the pilot experiment suggest that ants learned the contingencies between the runway length and its associated scent, the pilot experiment and the main experiment differ in significant ways. Therefore, it is unclear whether the ants learned the contingencies in the main experiment, which could be advanced as an alternative explanation for the lack of preferences between the two scented arms of the Y-maze during the choice test. Another important aspect to consider is that the reward still has to be valued by the organism to appropriately assess "wanting" processes. Indeed, "wanting" is generally conceptualised as conjointly determined by the associative history between the cue or context (scent) and the reward (sucrose solution) on one hand, and the organism's homeostatic or physiological needs such as hunger on the other hand (e.g., Zhang et al., 2009. https://doi.org/10.1371/journal.pcbi.1000437). In the main experiment, the question arises as to whether reward devaluation could have occurred-resulting in the reward having a diminished value as the ants were able to consume the sucrose solution to satiation multiple times across the experiment. For these reasons, it would be important to provide information showing that (a) the ants learned with which condition the scent was associated and (b) that the reward was still valued during the choice test. These points are key preconditions that need to be fulfilled for ruling out potential confounds that could explain the findings of the choice test as well as for suggesting a dissociation between "wanting" and "liking".

      3) Relatedly, a strong justification needs to be formulated to substantiate that the choice test provides a reliable indicator of "wanting". This is critical to conclude that the results can be interpreted as reflecting a dissociation between "wanting" and "liking". In rodents and humans, "wanting" is typically measured as an increased effort mobilisation during the presentation of a cue associated with a reward (e.g., Pool et al., 2016. https://doi.org/10.1016/j.neubiorev.2016.01.006). It remains however unclear how choice can capture such effects. This questions the extent to which choice represents an adequate operationalisation and measure of "wanting" as described in the incentive salience hypothesis (Berridge & Robinson, 2016. https://doi.org/10.1037/amp0000059). Moreover, it should be clearly explained and motivated whether, and if so how, choice purely measures "wanting" without being contaminated or influenced by liking-based processes, such as preferences or expected pleasantness for instance.

      4) Little information is provided on how pheromone deposition was measured and on the specificities of this measure, such as its physiological bases, timing properties, and granularity. However, detailed information about this measure is of high relevance to be able to assess if pheromone deposition represents a sensitive measure of "liking". "Liking" is typically measured as hedonic reactions during reward consumption across the rodent and human literature (e.g., Pool et al., 2016. https://doi.org/10.1016/j.neubiorev.2016.01.006). Accordingly, a good index of "liking" should be specifically responsive to reward consumption. By extension, an increased pheromone deposition should be particularly evident after the ants consumed the sucrose drop. As it stands, it is unclear whether this is the case as the pilot experiment showed no statistically significant difference in pheromone deposition between the way towards the sucrose drop or back. If the measure of pheromone deposition allows for distinguishing between pheromones deposited on the way towards the drop and pheromones deposited on the way back in the main experiment, a further test that could be run would be to compare the pheromone deposition on the way towards the drop in the 'segregated all' condition versus the 'segregated rewards' and 'bundled' conditions. A higher pheromone deposition on the way towards the sucrose drop in the 'segregated all' condition could provide converging evidence that pheromone deposition is a sensitive indicator of "liking".

    1. Reviewer #4 (Public Review):

      Overall the paper is clear and well-written. The experimental design is elegant and powerful, and it's a stimulating read. Most QTL mapping has focused on directly measurable phenotypes such as expression or drug response; I really like this paper's distinctive approach of placing bespoke functional assays for a specific molecular mechanism into the classical QTL framework.

    1. GWAS genetic association

      A genome-wide association study (abbreviated GWAS) is a research approach used to identify genomic variants that are statistically associated with a risk for a disease or a particular trait. The method involves surveying the genomes of many people, looking for genomic variants that occur more frequently in those with a specific disease or trait compared to those without the disease or trait. Once such genomic variants are identified, they are typically used to search for nearby variants that contribute directly to the disease or trait.

      source: https://www.genome.gov/genetics-glossary/Genome-Wide-Association-Studies

      this is more like a medical definition... what about plants?

    1. Above all, a fresh and original intellectual approach is needed, avoid-ing all standard solutions.

      This relates to the increasing difficulty of being originial with the rapid advances in productivity today.

    2. A striving for order can, and must, also be expressed inasymmetrical form.

      This relates to sticking to past foundations that are somewhat indispensable.

    3. Thetypographer must take the greatest care to study how his work is read andought to be read.

      Today, this is foundational since there are constantly advances in works of typography making documentation and research important to giving future credit.

    4. Evenin good central-axis composition the contents are subordinated to “beautifulline arrangement.”

      Clarity becomes less important due the focus on the composition being centralized as it relates to improving the visual appeal of the artistic, "arrangement."

    5. the rigidity of central-axis setting hardly allows work tobe carried out with the degree of logic we now demand.

      The central axis in art relates to a somewhat balanced distribution of space on an art piece.

      “ARTTALK Chapter 10 Balance - Ppt Google Img.” SlidePlayer, https://slideplayer.com/slide/10709291/.

    6. This utmost clarity is necessarytoday because of the manifold claims for our attention made by the extraor-dinary amount of print, which demands the greatest economy of expression.

      This emphasizes that having clear communication is made crucially important due to the difficulty of communicating to those who are surrounded by countless other "prints."

    1. Posted byu/jackbaty4 hours agoCard sizes .t3_xib133._2FCtq-QzlfuN-SwVMUZMM3 { --postTitle-VisitedLinkColor: #9b9b9b; --postTitleLink-VisitedLinkColor: #9b9b9b; --postBodyLink-VisitedLinkColor: #989898; } I've been on-again/off-again with paper for PKM, but one thing remains consistent each time: I don't enjoy using 4x6 index cards. I much prefer 3x5-inch cards. I realize that it's irrational, but there it is.My question is if I dive into building an antinet, will I regret using 3x5 cards? I already have hundreds of them. I have dividers, holders, and storage boxes for them. I just prefer how they _feel_, as weird as that sounds.I'd like to hear if people are using 3x5 cards successfully or if you've come to regret it.

      While it may be slightly more difficult to find larger metal/wood cases for the 4x6 or 5x8 cards, it's a minor nuisance and anyone who wants them will eventually find the right thing for them. Beyond this, choose the card size that feels right to you.

      If you don't have an idea of what you need or like, try things out for 10-20 cards and see how it works for you, your handwriting size, and general needs. People have been using 3x5, 4x6, and even larger for hundreds of years without complaining about any major issues. If Carl Linnaeus managed to be okay with 3x5, which he hand cut by the way, I suspect you'll manage too.

      Of course I won't mention to the Americans the cleverness of the A6, A5, A4 paper standards which allows you to fold the larger sizes in half to get the exact next smaller size down. Then you might get the benefit of the smaller size as well as the larger which could be folded into your collection of smaller cards, you just have to watch out for accidentally wrapping ("taco-ing") a smaller card inside of a larger one and losing it. I suppose you could hand cut your own 5" x 6" larger cards to do this if you found that you occasionally needed them.

      For the pocketbook conscious, 3x5 does have the benefit of lower cost as well as many more options and flexibility than larger sizes.

      At least commercial card sizes are now largely standardized, so you don't have deal with changing sizes the way Roland Barthes did over his lifetime.

      My personal experience and a long history of so many manuals on the topic saying "cards of the same size" indicates that you assuredly won't have fun mixing different sized slips together. I personally use 3x5" cards in a waste book sense, but my main/permanent collection is in 4x6" format. Sometimes I think I should have done 3 x 5, but it's more like jealousy than regret, particularly when it comes to the potential of a restored fine furniture card catalog. But then again...

  11. Aug 2022
    1. day-length profoundly affects growth responses with stronger impact on root elongation under SD conditions

      SD has a stronger impact on root elongation...

    1. Forcertainlyagreatervarietyofcards,clippings,andsuchlikecan befiledbehind 4x6slipsthan behind3x5's.

      A benefit of 4 x 6" cards is that clippings and other items can often be more easily filed along with them as opposed to the smaller 3 x 5" cards.

    2. shall I adopt the 3x5 slip or the 4x61

      Dow indicates in 1924 that 3 x 5" and 4 x 6" are both commonly had in a range of materials the US as well as boxes or cases to keep them in. He does mention that one can also cut their own paper, indicating that this is a possibility.

    1. How do publishers design and organize content for their audience and purpose?

      I will just say this: there are both tried and true and normed audiences and purposes as well as dynamic and non-evergreen contents. This is vague I understand but the kinds of content in social media is always changing. When the algorithm changes so, too, does the shape and style of content. I don't know if the larger values, audience and purpose, change, but I suspect the even larger ones like empathy are super evergreen. Sorry. I wish I had more time to make this shorter.

  12. Jul 2022
    1. Reviewer #4 (Public Review):

      Yao and Ochoa conducted a systematic examination of the association study using PCA and LMM with both simulated and empirical datasets. The overall finding is that LMM should be used and generally there is no need to include a few PCs in LMM. While similar studies have been conducted earlier with the comparison goal, the authors made additional effort to conduct this extensive study. Many scenarios were considered, and the results were clearly presented. This paper is interesting to researchers in statistical genetics.

    1. 1. Focus on items that occur with high frequency in the language as awhole (see Table 3.1 for examples). Such items will occur often inmany different texts.2. Focus on strategies that can be used with most texts (see Table 3.1for examples).


    1. there's a crucial distinction between what barney called three and four that's what uh captured me so 01:08:55 if you take the mind as fundamental as existing the only existing thing where where the the movie of the world is reflected into i am not happy 01:09:08 my my culture uh rejects then as a useless point of view to do science that's what but there is an alternative much more interesting and i find much more 01:09:21 deep in which which i read in a garage you know which is what uh barry seems to be is calling the fourth alternative in which the mind is not the fundamental thing in which everything is it's 01:09:32 reflected it's just one part of this uh uh uh interdependence now namely it's not the things that not intrinsic existence but mind has intrinsic existence that's not the 01:09:45 the the there's a more interesting answer namely that mind itself has no intrinsic uh uh existence uh and so it's just uh uh 01:09:57 it has an existence but is is it of course it's an existence my mind exists and i exist but uh and and and and if i think in terms of groups to say i mean all sentience being or all 01:10:10 human beings whatever um together uh which is an ideal also some some some some western philosophy that you know um it's collectively that through language and 01:10:22 that would create a vision of the world but i want to think of this as one aspect of the ensemble of things which is existence where uh uh nothing of that has um 01:10:36 uh has intrinsic existence so i want to think about my mind it's my brain my sensation my all my my my love people loving me the the image that people have of me my instead of the set 01:10:48 of processes uh uh which part of the world and it seems to me that the belgian allows me to think at me as part of the world at the same sense of the same ground as the world being 01:11:01 reflected in my consciousness without having to choose one of the two perspective to be the true one the intrinsic existence um 01:11:12 all all perspectives are uh uh empty they're all good but they are um they are not the the one on which the rest is ground they 01:11:24 each of one i can understand dependently on something else so marios you read a a verse or two from the third chapter of nagarjuna and uh let me comment on that

      Carlo points out the view he now holds, influenced by Nagarjuna's philosophy, that the mind exists, but does not intrinsically exist.

      So he argues on one (conventional) level, his mind and all other minds exist.

      Agreeing with Barry's fourth suggested alternative. The mind is not the fundamental thing, but is just ONE PART of this interdependency. Each view, whether of any human or even non-human is empty but conventional exists in interdependence of many causes and conditions.

      From Stop Reset Go perspective and the Indyweb, a web3 technology that can embody each indivdiual's perspectival knowing through the establishment of their the individuals unique and privately owned data repository can enhance the discovery of the process of emptiness. How? By theoretically having all one's (digital) interactions of the world, one can begin to see in granular detail how one learns about the world and begin to sense the flow of the mind. Through repeated use of the Indyweb and witnessing how one forms new ideas or reforms old ones, the indyvidual becomes increasingly aware of oneself as a process, not a thing. Furthermore, one begins to see self knowledge as hopelessly entangled with cultural and social learning. One begins to sense the 4Ps of propositional, perspectival, participatory and procedural learning, also entangled with each other and with individual/social learning.

      https://docdrop.org/video/Gyx5tyFttfA/#annotations:vkOUgv8rEeypE39kg2ckCw https://hyp.is/go?

      Quick John Varvaeke interview on 4P: url=http%3A%2F%2Fdocdrop.org%2Fvideo%2FERdJDVdbkcY%2F&group=world

      One especially begins to sense perspectival knowing and situatedness and that causes and conditions unique to one's own worldview constructs one's relative reality.

    1. it's a how we know it in some way so it's different forms of how yes it's not based on the content of it so there's different ways you can do taxonomies and people often want to monkey with the taxonomy they said no no like you can make a 00:00:50 taxonomy however you want like if you make the taxonomy on the basis of content you're going to have like you're going to have like you know knowledge about australia knowledge about the solar system and right right now that you're right this is much more about the 00:01:03 manner and the mechanisms of knowing than it is about the content

      The 4 P's is concerned with the "how" of knowing rather than content of knowledge.

    1. Dogen can be very difficult to read or understand. That’s why we often need a commentary or teacher to introduce his way of writing and the underlying teaching. I often say he’s a thirteenth century cubist. Just like Picasso or in the writing world, Gertrude Stein, he tries to show all sides of the story in one paragraph or even one sentence. That is why he repeats himself and contradicts himself all in the same paragraph. If you are looking for the “right” understanding, you become confused and lost in his prism of various interpretations or views. Dogen’s “right” understanding is that there is none.   No one point of view is “right”. According to conditions, any view can be the right view in the right circumstance. Dogen really wants to take away our solid idea of a fixed ground of reality. It is not form or emptiness. It is not both or neither. There is no one right, fixed view. That is our “clinging”.

      Dogen contradicts himself because he tries to show "all sides of the story". His teaching is a "pointing out" instruction that ANY viewpoint is simply that, perspectival knowing.

      An important question then, is this, if Dogen (and Nagarjuna) are claiming that there is no objective reality in our constructed world of concepts and language, is science being denied? Is fake news ok? Is this a position that basically accepts post modernism? No, I would say no to all of these. It's pointing out the LIMITATIONS of concepts and language. They are incomplete and always leave with a sense of wanting more. And since Post Modernism is also one point of view, it is also thrown out by Dogen and Nagarjuna. Remember, ALL points of views are points of view. Fake news is also a point of view so those who practice it can also not justify it.

      What Dogen and Nagarjuna are saying is that as soon as one enters the world of concepts and language, any concept and anything side is inherently one sided. It is inherently perspectival and situated in an inherently incomplete conceptual space.

      As Tibetan doctor/monk Barry Kerzin points out in this conversation with physicist Carlo Rovelli, there is a critical difference between "existence" and "intrinsic existence". The first is not being denied by Nagarjuna, but the second, intrinsic existence, the existence of concepts and the words that represent them, is. If these two are confused, it can lead straight to nihilism.


      This also aligns with John Vervaeke's perspectival and propositional knowing in his 4 P ways of knowing about reality: Propositional, Perspectival, Participatory and Procedural. A good explanation of Vervaeke's 4Ps is here: https://hyp.is/go?url=http%3A%2F%2Fdocdrop.org%2Fvideo%2FGyx5tyFttfA%2F&group=world

    1. we often have too narrow an appreciation of   knowing focusing too much on one or two kinds  of knowing but to live well in a complex world   we need to effectively engage with four kinds  of knowing and perfectly they all begin with a P

      Title: Four Kinds of Knowing Author: Rich Watkins Date


  13. Apr 2022
    1. Siemens (2002) notes that learner-learner interactions in an e-learning course can be viewed as a four stage continuum:

      Communication People ‘talking,’ discussing Collaboration People sharing ideas and working together (occasionally sharing resources) in a loose environment Cooperation People doing things together, but each with his or her own purpose Community People striving for a common purpose

  14. Mar 2022