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  1. Last 7 days
    1. "Extensive experience and research show that hydroxychloroquine builds up in the body and continues to work for an average of 40 days even after the last dose is taken. By then, we expect the drug manufacturers to have ramped up production to meet the increased demand. Until then, we are no longer refilling routine prescriptions to ensure we have adequate supply to care for our sickest patients," Gin said.{"adPos":"promo-inline3","adType":"ex","isInfinite":true,"platform":"autodetect","position":3,"renderLookahead":"x0.25","size":[[5,5],[728,90],[300,250],"fluid",[320,50]],"targeting":{"badges":["viral","coronavirus"],"bid":"5376488","brain_tags":["adult-0","crime-30","safe-70","non_profane"],"nbs":0,"nsfw":0,"pos":["promo-inline3"],"sensitive":0,"tag":[],"trending":0,"user":"tanyachen","wid":"212-1","infinite_index":1},"viewability":"high","wid":"212-1","zone1":"bfnews"} Advertisement [tl-ut] { content: ""; } div#BuzzfeedNews_Desktop_inarticle_MPU_Flex_container { position: relative; box-sizing: border-box; margin: 0px auto; display: flex; flex-flow: row nowrap; align-items: initial; max-width: 100%; max-height: none; background-color: rgb(255, 255, 255); border: 1px solid rgba(0, 0, 0, 0.1); width: 100%; height: auto; padding: 0px; font-size: 16px; 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Learn more! Sponsored by Loyola University Chicago See More "Kaiser Permanente physicians and pharmacists are also working together on an evidence-based approach to identify alternative therapies for patients with lupus," Gin added in a follow-up statement.Dale said she immediately called her doctor and has been scheduled for a phone call next week. { "id": "1241213117872234496", "params": { "conversation": "none" } } { "id": 124409135 } Despite thin evidence for the drug’s effectiveness against coronavirus infections, shortages of chloroquine have erupted since Trump called it a “game changer” at a White House news conference late last week. The drug, a derivative of an antimalarial drug, has been added to the regimen for treating COVID-19 infections in China and South Korea and is being tested in clinical trials in the US.However, experts on drug testing have been skeptical of the evidence for its benefits. A frequently cited French study of 20 patients saw several drop out of the trial to instead go into intensive care.{"adPos":"promo-inline4","adType":"ex","isInfinite":true,"platform":"autodetect","position":4,"renderLookahead":"x0.25","size":[[5,5],[728,90],[300,250],"fluid",[320,50]],"targeting":{"badges":["viral","coronavirus"],"bid":"5376488","brain_tags":["adult-0","crime-30","safe-70","non_profane"],"nbs":0,"nsfw":0,"pos":["promo-inline4"],"sensitive":0,"tag":[],"trending":0,"user":"tanyachen","wid":"213-1","infinite_index":1},"viewability":"high","wid":"213-1","zone1":"bfnews"} Advertisement An Arizona man died on Monday after self-medicating with a related drug, chloroquine phosphate, where chloroquine was also touted at White House news conferences.“For many people with lupus there are no alternatives to these medications,” the Lupus Foundation of America said in a statement on Monday, warning of shortages. “Hydroxychloroquine or chloroquine are the only methods of preventing inflammation and disease activity that can lead to pain, disability, organ damage, and other serious illness.”Dale, who's been calling multiple pharmacies in her local area, said, "I have learned that all area pharmacies are completely out of hydroxychloroquine." { "id": 124409399 } <img src="https://img.buzzfeed.com/buzzfeed-static/static/2020-03/25/15/asset/705a16f1d755/sub-buzz-3668-1585151028-3.jpg" alt="" class="xs-block"/> healthy.kaiserpermanente.org { "id": 124409135 } "In their mission statement, Kaiser says that they aim 'to provide high-quality, affordable health care services and to improve the health of our members and the communities we serve,'" Dale said. "How is denying medication for a chronically ill, immunocompromised patient during a pandemic improving my health?""I want Kaiser to follow their own mission statement and reverse the decision to withhold my medication." UPDATE March 25, 2020, at 12:48 p.m. This story has been updated to include a follow-up statement from Kaiser Permanente. More on this Chloroquine Is Being Touted As A Miracle Drug For Coronavirus, But There Are Reasons To Be Wary Dan Vergano · March 23, 2020 A Man Died After Self-Medicating With A Form Of A Drug That Trump Promoted As A Potential Treatment For The Coronavirus Brianna Sacks · March 23, 2020 Trump Said He Wants To Give Coronavirus Patients An Experimental Drug Called Chloroquine Dan Vergano · March 19, 2020 Tanya Chen is a social news reporter for BuzzFeed and is based in Chicago. Contact Tanya Chen at tanya.chen@buzzfeed.com. Got a confidential tip? Submit it here. Dan Vergano is a science reporter for BuzzFeed News and is based in Washington, DC. Contact Dan Vergano at dan.vergano@buzzfeed.com. { "ads": {"density": 1, "placements": [], "skin": "news", "units": [{"companions": [], "is_enabled": true, "programmatic_wireframes": true, "slot": {"adPos": "sidebar1-bp", "adType": "post", "isInfinite": true, "platform": "desktop", "position": null, "renderLookahead": "x0.25", "size": [[300, 250], "fluid", [5, 5], [300, 600]], "targeting": {"badges": ["viral", "coronavirus"], "bid": "5376488", "brain_tags": ["adult-0", "crime-30", "safe-70", "non_profane"], "nbs": 0, "nsfw": 0, "pos": ["sidebar1-bp"], "sensitive": 0, "tag": [], "trending": 0, "user": "tanyachen", "wid": 1301}, "viewability": "high", "wid": 1301, "zone1": "bfnews"}, "template_path": "/adlib/skins/news/sidebar.html", "wireframe_height": 600, "wireframe_width": 300, "with_companions": false}, {"companions": [], "is_enabled": true, "programmatic_wireframes": true, "slot": {"adPos": "sidebar2-bp", "adType": "post", "isInfinite": true, "platform": "desktop", "position": 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      This may be true but I am still confused about how people know this helps fight COVID-19

    1. hypothes.is (use the hashtag/tag #chromosomenomenclature)

      Please add comments directly on the key parts of the commentary you would like to raise any issues with.

    1. But everything’s changed. Notes are stored locally so there is no lag, search is blazing fast, and the search bar provides recommendations and suggestions that are far more accurate and helpful than tags

      I would like less lag time in adjusting and reformulating my searches as I go. The lag time at this point has more to do with how slow Roam is to render things than how slow the process could be, since the sidebar should allow you to pull up many things, explore new threads of thought, and change your question as you go. Thing is, text search with filtration is still powerful as a tag based search if you’re looking at purely functionally, but tagging also gears you towards asking, “when do I want this to resurface?” So you end up coming to more relevant stuff than simply what is written in the base text. This means you're more likely to resurface notes when you take a tagging approach because it gears you to behave differently towards your notes.

      That being said, I don't see this as one or the other. Sometimes I think it's better to just search for a note with text. Only problem is that primarily works for searches where you can clearly formulate your question/goal, you know what you're looking for, and you know where to find it. That essentially turns search into something that requires memory, whereas tag based searches allow for exploratory browsing.

    2. So which behaviors are desired and undesired when it comes to organization? In any organizational system, the constant temptation is to overorganize, i.e. to create too many categories, too many subdivisions that are too specific. As the number of tags grows arithmetically, their complexity grows geometrically, for multiple reasons, both technological and cognitive (see memory fatigue above). This phenomenon is all the more problematic with unlimited digital information that never runs into physical constraints.

      This could be true, it’s a good point. I come back to Conor’s framework of reduce, filter, and map though. If the user is doing behaviors along the way that reduce the amount of information they’ll see when they look in the future, filter to specify what you want, and then map it out to new contexts, then this bug becomes a feature. Progressive summarization helps in that process, and filter specific tags also helps, as well as straight up deleting things or applying an archive tag that you can always filter out.

      This problem also gets reduced when you have aliases and hierarchy abilities along with the tags, because then you’re able to better express what you mean in fewer words/tags. Problem is that Roam doesn't have aliases yet to let the user reduce clutter in their pages and with the different ways that users express the same thing. Tags with bidirectional and unidirectional aliases allow us to express meaning, rather than remember specific words.

    3. Thus the most problematic behavior is implicitly encouraged and enabled. Grrrrrrr. It could be a misspelling. It could be a slip of the finger. It could be a different capitalization, punctuation, or tense, whatever. No warning or indication is given, and a divergent tag is created, for you to hopefully notice and fix later, hopefully before you rely on it.

      Aliases and hierarchy! Would also be helpful if the app suggested aliases to you based on frequent usages together or similar letter combinations.

    4. As good as your brain is at recognizing patterns, it is terrible at storing and recalling multiple patterns precisely, since the patterns of neuronal activation interfere with each other. Yet this is exactly what you’re doing with tags. What a terrifically unnecessary expenditure of mental resources

      See my comment about pattern recognition above. The functionality of tagging can be set up so you have frequent/spaced repetition. Also sort of a feature, not a bug. If something doesn’t get consistently reinforced, then it should sink away. You just need to balance search strategies. Don’t always go in with one predefined query with filters. Let yourself follow train of thoughts, and if it resurfaced, then tag it up more then or build on it. If not, it probably wasn’t too valuable anyway.

      You can also program your attention so some tags never go away by making index pages. I’d say this all just depends on your behavior with notes more than anything, I don’t think about it so much as tags vs. folders.

      However, I would totally say that you need to behave a certain way with your notes or it does become unnecessary expenditure. If you aren’t searching your notes and conversing with them, you won’t see the benefits.

    1. Using + to trace Spam Some site collect your information to sell to other people. To detect this, you can use a custom tag in your email address for every site you sign up for. For instance, if you were joining the Washington Post email list, you could sign up with your_username+washingtonpost@protonmail.com. This will deliver the email into your account, while allowing you to identify where you inputted the email address. If you receive email to this address from anyone other than the Washington Post you will know they either sold your data or experienced a data breach. To learn more about using + in your email address, please see: Addresses and Aliases.
  2. Mar 2020
    1. DEM.Encrypt(K, L, M)

      Here, in contrast to the DEM used in the Tag-KEM paper, we have a label (additional data).

    1. Theorem 3.1[Tag-KEM/DEM Composition Theorem] If the Tag-KEM is CCA secure and theDEM is one-time secure then the Hybrid PKE scheme in Section3is CCA secure. In particular,²pke<2²tkem+²dem.

      Could we reuse this theorem? Or at least replicate this proof in CryptoVerif?

    2. Notethat, in the above syntactic definition,τis not included inψand explicitly given toTKEM.Dec

      If we change DHKEM to use a context when deriving zz, does this make DHKEM a Tag-KEM?

    1. You can tag public or shared resources, but the tags you assign are available only to your AWS account and not to the other accounts sharing the resource.

      tags on AMI cannot be used for search across accounts

    1. Lydia Sigourney

      You could, if you wanted, tag all of the Connecticut authors or locations in a document.

    Tags

    Annotators

    1. sometimes called

      The HTML5 audio broken for several reasons: you can't use the same name for a class and ID ('audio'), and you can't use an already reserved tag name (<audio> and 'audio'). Also, it looks like the path to the audio file is wrong, or the file is missing.

    1. Cookies may not be detected by scanner if the related tag is triggered by actions such as form submission, scroll depth, timing delay, etc. These tags will need to be controlled by manual methods.

      With all these caveats listed, it makes me wonder for which tags auto-blocking does work. Only script tags inside of head?

      They are a bit vague in their "how it works" description...

    1. Note: This rebuttal was posted by the corresponding author to Review Commons. Content has not been altered except for formatting.

      Learn more at Review Commons


      Reply to the reviewers

      __Reviewer #1 (Evidence, reproducibility and clarity (Required)):


      In this article, the authors characterize a complex formed by sec22b-stx1-Esyt2. They investigate how such interactions are involved in the modulation of dynamics of the plasma membrane in the context of neuritogenesis. They conclude that the contact sites between the ER and the plasma membrane, mediated by the afore-mentioned complex, contribute the expansion of the plasma membrane.

      **Major comments:**

      Overall, the article clearly shows that in mammalian cells there is an interaction between sec22b-stx1-Esyt2 which appears to be important for filopodia formation and possibly neuritogenesis in neurons. However, performing additional experiments to better clarify some links and assumptions made by authors could strengthen the article.

      The manuscript relies on work performed either on cell lines (HeLA, PC12) or primary neuronal cultures. Although it is clear the value of the findings obtained using cell lines, they should be seen as a complementary rather than an exclusive approach. This is particularly important as the authors often make claim about neuron-related cellular biology.

      For instance, the biochemistry-based findings on the interaction and characterization of the protein complex (Figure 1) are all derived from experiments perfomed in Hela or PC12. As the authors have the capacity to culture and manipulate primary neuronal cultures, such findings should be validates in neuronal cells. The authors could also consider performing biochemical experiments (i.e. co-ip) of the endogenous proteins in neuronal cultures or brain tissue.*

      ->Endogenous Co-IP has been tried in E18 brain tissue. One experiment using brain tissue demonstrated co-immunoprecipitation of endogenous Sec22b and E-Syt2. Unfortunately, repetitions of this experiment failed due to high background in negative control (naïve Rabbit IgG). We agree with the reviewer that this data is worth trying again. We will carry out this co-immunoprecipitation experiment from cultured neurons to answer the reviewer’s request.

      The authors do show some evidence regarding the complex in neuronal cells using PLA (proximity ligation assay, figure 2) or super resolution microscopy, however, these findings should be corroborated by stronger findings targeting interaction and not based on simple proximity.

      ->We agree with this reviewer that PLA is limited in demonstrating the occurrence of a protein complex. We would like to stress that we have used PLA complementarily to immunoprecipitation and that we already have shown STED super-resolution data (Figure 3). In order to strengthen the STED data, we will include more details in the figure, as a supplementary movie and a supplementary spreadsheet with the quantification of the distance between the E-Syt2/Sec22b clusters to the plasma membrane stained using WGA. The STED data demonstrate that 50% of the clusters are closer than 33.6nm to the plasma membrane, a distance in the range of ER-PM contact sites.

      A similar critique regards the experiments using RNA-interference of Figure 4. Performing loss-of-function experiments in neuronal cultures would strengthen and complement the results obtained via over-expression approaches shown in Figure 5.

      ->The loss-of-function experiments in neuronal cultures using siRNA were attempted unsuccessfully. The three E-Syts have largely different cDNA sequences thus three distinct siRNAs must be transfected in order to silence all three simultaneously. This is quite challenging in neuronal cultures and we were never able to get strong silencing of the three E-Syts. In the following points, we plan to carry out further experiments using expression of a fragment of Sec22b (Longin domain). We are confident that this is a better approach to demonstrate the importance of Sec22b/E-Syt interaction.


      *Given that the authors have already in place all the necessary technology for the suggested biochemical and morphological-related experiments, these could be carried out swiftly within 3-4 months.

      **Minor comments:**

      The manuscript is really technical and at times tough to follow; it could benefit from key sentences to better guide the reader, particularly if not coming from the specialist field, in the appreciation of the experiments and results.

      Authors should submit the manuscript to a severe round of proofreading. There are several inconsistencies and sometimes what looks like internal comments: i.e. in the methods "STED Missing" or the fact that "LTP" is used everywhere but not defined and considering that the targeted audience is most likely neuroscience-based could easily lead to confusion.

      *

      ->We fully agree with this reviewer and apologize for leaving behind such errors. We will carefully proofread the revised ms.

      *The experiments appear to have been repeated a sufficient number of times and the statistics seem adequate. It would be advisable to show in dot-plots the findings rather than in bar graphs all findings and not just the morphometrics-relative ones.

      *

      ->We will modify the figures according to this reviewer’s suggestion.

      Reviewer #1 (Significance (Required)):

      *This work closely follows the excellent previous work from the Galli laboratory. As such, it is mostly incremental from a technical perspective and does not present particularly novel findings. An interesting aspect would be in addressing directly the influence of the described interactions in the lipid transfer between ER and the plasma membrane but in that sense the manuscript falls short. Although it is to be appreciated the functional readouts in terms of neuritogenesis, in the present state the manuscript features findings suitable for a very specific audience.

      I believe that the appropriate audience for the present manuscript lies within the neuroscientific community interested in development, specifically neuritogenesis, and/or membrane dynamics. Additionally, it might be interesting also for researchers outside of the neuroscience community and interested in the dynamics between ER and plasma membrane.

      *

      ->We are happy to read the comments of this reviewer. Nevertheless, we would like to stress the importance of deciphering precise molecular mechanisms in any biological process. Here, we are the first to demonstrate an interaction between lipid-transfer proteins E-Syts and ER v-SNARE Sec22b. As an example, the molecular mechanism connecting synaptic SNAREs and synaptotagmin has been the topic of more than 500 publications since seminal articles in the early 1990’s. We think that the first article linking E-Syts to SNAREs cannot be considered as a mere increment from our previous work.

      The activity of E-Syts to transfer lipids in vitro has been well established __(1–3) In addition, recent work by the De Camilli lab using Origami showed that reducing the distance between liposomes enhanced the lipid transfer mediated by E-Syt2 (3). Therefore, we did not carry out experiments such as combining SNAREs and E-Syt2 in artificial membranes in vitro because we considered that there would not be much more to demonstrate than what has already been done. Furthermore, we considered the experiments in cells, particularly neurons, much more critical at this point. Demonstrating transfer of glycerophospholipid between ER and PM in cells cannot be performed like other lipids’ transfer at other membrane interfaces for the following reasons: phospholipids are very abundant (4) and they are not modified upon transfer (1)__, there are no specific dyes to detect glycerophospholipids (unlike phosphoinositides), and ER and PM are too close to distinguish if a glycerophospholipid is in one or the other membrane. Such a challenging experiment would require the ability to setup a specific biochemical assay circumventing these constraints. We think that this is out of the scope of the present study focused on the role of E-Syt/Sec22b complex.

      Nevertheless, in order to get further insights on this question, we will express WT and mutant E-Syt2, purify the PM using the protocol of Figure 4 in Saheki et al __(1)__, followed by lipidomics analysis. We hope that this approach further supports our idea that E-Syts mediate an important lipid transfer mechanism towards the PM.

      * Keywords regarding my expertise: Molecular and Cellular Neuroscience, Morphometrics, Dendrite, Neurons, Dendritogenesis, Biochemistry, Imaging, Microscopy.


      __

      Reviewer #2 (Evidence, reproducibility and clarity (Required)): *This manuscript identifies and characterises a novel interaction between E-Syts and Sec22b and demonstrates that lipid transfer between the ER and PM contributes to the development of filopodia and neuronal expansion. This interaction with E-Syt2 occurs through the Longin domain of Sec22b Sec22b association. The authors suggest a continuum with further interactions with syntaxin1, that mediates neurite outgrowth. Overall I find this study very interesting and convincing. The experimental analysis is well carried out and the claims are well aligned with their results.

      I only have minor issues:

      Figure 1. Some of the western blots have several bands and it is difficult to know which band is the relevant one. They should be indicated in the fig panel. Further panel E and F are barely readable and should be redrawn with the appropriate line and font size.*

      ->We will make the changes requested by this reviewer in Figure 1.

      • *

      Figure 2: is there a difference between the number of dots in axons and dendrites? Can the author elaborate on this aspect as it is not clear from the image presented.

      ->We could not combine PLA with further staining of MAP2 and TAU. Indeed, to perform PLA, neurons are already double labelled to detect the proteins of interest. At the stage of the neurons used in this study, both axons and dendrites are growing. Therefore, we did not invest in distinguishing between axons and dendrites. Because growth cones are known to be the major sites of membrane growth, we instead distinguished dots within neurites and in growth cones. We will make the other changes requested by this reviewer in Figure 2.

      Figure 7: statistical analysis should be indicated from the BoNT/A and BoNT/C as BoNT/A represent an appropriate control cleaving SNAP25 but not Syntaxin.

      ->We agree with this request and we will add statistical analysis as suggested, using BoNT/A as an additional control.

      On top of controlling fusion and neuronal outgrowth, syntaxin has a role in survival and its cleavage leads to neuronal death. Is this pathway mediated by E-Syts interactions?

      ->We have stated in the ms: “Since exposure to BoNT/C1 at high concentrations and for long incubation periods causes degeneration of neurons in culture __(5,6)__, various concentrations and incubation times were tested, and a 4-hour treatment of neurons with 1nM BoNTs was chosen to avoid such deleterious effects.” Accordingly, we did not see any degeneration in our experimental conditions.__ __


      Reviewer #2 (Significance (Required)): This papers identifies the molecular mechanism of neuronal outgrowth. It is highly significant. ->We are very grateful to this reviewer for pointing out the high significance of our article.


      __Reviewer #3 (Evidence, reproducibility and clarity (Required)):

      __*1. The evidence for the claim that the Sec22b/Stx1 complex and E-Syts colocalize in native cells (neurons) and bind in heterologous cells is strong (3 independent lines of evidence: co-immunoprecipitation, Proximity Ligation (PLA) and STED super-resolution microscopy) However, the current title of the paper makes a claim beyond this interaction/proximity, based on evidence that is obtained with E-Syt over-expression in wildtype cells. The physiological relevance of the effects remain elusive with over-expression in wildtype cells only.

      Furthermore, it is plausible that overexpression of membrane binding/bending C2-domains promotes neurite outgrowth and ramifications by a non-specific effect (as shown for copine C2 domains, PMID:25450385 and indirect evidence for synaptotagmins1,2,7).*

      * This issue is especially relevant in the light of the fact that loss of all 3 Extended Synaptotagmins does not affect normal mouse development and viability (PMID: 27399837)

      It would be more appropriate to choose a more descriptive title*

      • *

      ->We agree with this reviewer that the original title may be too strong and are now proposing the following, more descriptive title:

      Role of the Sec22b/E-Syt complex in neurite growth and ramification

      We are fully aware that proteins harbouring C2 domains could potentially promote non-specific effects when overexpressed. However, we do not think this is the case here because none of the morphological effects of E-Syt2 expression in neurons and HeLa cells were reproduced by mutants lacking the SMP or the membrane-anchoring domains. Based on work on Copine __(7)__, a cytosolic protein, E-Syt2 still containing 3xC2 domains but lacking the membrane-anchoring domain should have shown a morphological effect if non-specific binding to phosphoinositides was the mechanism of action. We will discuss this point in the ms.


      • The evidence for the working model that the morphological effects of E-Syt2 depends on the Sec22b/Stx1 complex is not strong. Although plausible, the positive effect on neurite outgrowth (E-Syt2 overexpression) and the negative effects (inhibition by Stx1 cleaveage, Sec22b-Longin or Sec22b extended linker expression) may in fact be independent

        The evidence could be strengthened by PLA measurements in neurons over-expressing Myc-E-Syt2 and Sec22b to assess MSC density. It is predicted that in both conditions, MCS density increases. MCS density by PLA measurements could also be performed in Sec22b-P33 and DLongin overexpressed and BoNT/C1 treated neurons. According to the model, the number of MCS should go down. This is of special interest for BoNT/C1 treatment, as it is important to show that the altered morphology is not purely caused by a pre-state of degeneration that is known to be induced by BoNT/C1. In addition, EM measurements of ER-PM distances might provide an independent line of evidence.*

      ->We agree with this reviewer that additional experiments could strengthen the description of the molecular mechanism. To this end, we will carry out the following experiments:

      1/Co-immunoprecipitation experiments of endogenous Syntaxin, Sec22b and E-Syt2 in cells expressing GFP as control or Longin-GFP to demonstrate that expression of the Longin domain perturbs the association of Sec22b with E-Syt2 and Syntaxin.

      2/PLA measuring the association between E-Syt2 and Syntaxin in cells expressing GFP as control or Longin-GFP to demonstrate that expression of the Longin domain perturbs the association between E-Syt2 and Syntaxin using a complementary approach.


      Unfortunately, membrane-associated, BoNTC1-cleaved syntaxin corresponds to a short fragment undetectable by available antibodies whereas the fragment detected by the antibody after BoNTC1 cleavage lacks the transmembrane domain (Figure 7a). Therefore, we cannot perform PLA in BoNTC1-treated neurons.


      We are confident that further exploring the mechanism of action of the Longin domain, together with the data already in the ms, will make it very clear that the morphological effects of E-Syt2 depends on the Sec22b/Stx1 complex.



        • Link between neurite outgrowth and lipid transfer is weak. The authors argue that functional E-syt/Sec22b/Stx interaction is important for neurite outgrowth by mediating lipid transfer. The only line of evidence they provide is the absence of outgrowth effects in E-syt mutants lacking SMP or membrane spanning domains. However, from the data it is unclear whether these mutants are correctly folded, expressed and/or localized. Additional ICC stainings of the mutants in neurons are necessary to drive this point home. *
      • *

      ->The mutants and siRNA have been already used and validated in Giordano et al. 2013 __(8)__, therefore we did not carry out experiments aiming at basic characterization of these reagents. To answer this request, we will show images of the subcellular localization by ICC of WT and mutant E-Syt2 in the revised Figure 6 or in a Supplementary Figure.


      In addition, the authors might make the link between neurite outgrowth and lipid transfer stronger by examining PM lipid levels and distribution in control, Myc-E-Syt2 and E-Syt2 mutant neurons.

      ->We agree with this reviewer that this question is of high relevance. In order to answer this request, we will express WT and mutant E-Syt2, purify the PM using the protocol of Figure 4 in Saheki et al __(1)__, followed by lipidomics analysis. We hope that this approach further supports our idea that E-Syts mediate an important lipid transfer mechanism towards the PM.

        • There is no clear evidence that E-syt first binds to Sec22b, after which Stx1 leaves SNAP25 and joins the interaction. This should be indicated as speculation.

        * ->We will make it clear that our model in Figure 9 is a hypothetical model.

      • An apparent discrepancy exists between the TKD E-syts effects (i.e. reduced MSC density, Fig 4) and the lack of neurite outgrowth defects in TKO E-syts. According to the proposed model, the levels of E-syt correlate with the number of MSCs and thereby neurite outgrowth. Furthermore, to knock down E-Syts, single siRNAs against the three E-syts were used in Fig4. Off-target effects are not controlled in this approach. Using multiple siRNAs and/or siRNA resistant rescues would be required for robust conclusions.

        *

      ->The mutants and siRNA have already been used and validated in Giordano et al. 2013 __(8)__, therefore we did not carry out experiments aiming at basic characterization of these reagents. In addition, we would like to stress the complexity of carrying out a rescue experiment of a triple KD of proteins.

      Statistical analysis is incomplete. It is not clear whether statistical assumptions (e.g. normal distribution) were checked before performing the tests, and whether non-parametric alternatives where used if assumptions were not met.


      ->We thank this reviewer for making this important alert. We would like to stress that we have always checked whether samples followed the normal distribution and made non-parametric tests__. We will include this comment in the methods.__

      In Fig4, a T-test is used between multiple groups. This test can only be used when comparing two groups. Number of (independent) measurements is not clear in Fig1, 2, 4

      ->In all the figure legends the number of repetitions is specified


      All figures: display all individual data points in all bar graphs (as shown in 5c)

      *

      *

      \*Minor comments:**

      1. Inconsistencies on distances in model. Syts are enlongated proteins and thought to be found in MSCs of ~20 nm (Fernandez-Busnadiego, 2015). Trans-SNARE complexes start to interact when the distance between membranes is ~8 nm (Liu, 2007). In the introduction, the authors suggest that incomplete zippering might occur between Stx and Sec22b, resulting in a distance between 10 and 20 nm, which would allow E-Syt localization. In the discussion, however, the authors suggest a model where Sec22b/Stx interaction is important to bring the membranes in ~10 nm distance to enhance LTP activity. Proof for either model is lacking. Please clarify.*

      Fig1A: Please clarify the multiple bands? for Stx3 (anti-eGFP).

      • *

      ->These additional bands are recognised by the anti-GFP antibody, the tag being N-terminal, thus they represent proteolytic fragments. We consistently observe these in our experiments.

      Fig2: There is no size marker for panels C1-C6

      • *

      ->We will make the appropriate correction.

      Fig3: Both proteins seem to show a diffuse pattern. Please specify the validity of measuring average distance. A higher magnification zoom of staining pattern in the growth cone and visualization of the calculation could benefit interpretation.

      • *

      ->We agree with this reviewer that Figure 3 was not optimal to show all the extent of our STED data. In order to strengthen this part, we will include more details in both the figure and as a supplementary movie and supplementary spreadsheet with the quantification of the distance between the E-Syt2/Sec22b clusters to the plasma membrane stained using WGA. The STED data demonstrate that 50% of the clusters are closer than 33.6nm to the plasma membrane, a distance in the range of ER-PM contact sites.

      • E-Syt2 and E-Syt3 are used interchangeably throughout the manuscript and E-Syt1 is left out completely. It would help the reader if the authors could elaborate on their interpretation on the similarities and differences in structure and functionality between the three E-Syts.
      1. Why is there a red line in Fig 7b?*

      __->We added the red line to highlight the shift of SNAP25 band in BoNTA samples. If misleading, it can be removed

      Reviewer #3 (Significance (Required)):__

      A growing body of literature recognizes the importance of close proximities between membranes, facilitating direct interaction between organelles (Scorrano et al., 2019). Membrane Contact Sites (MCSs) are shown to be important for a wide range of cellular functions, such as lipid and calcium transfer. E-Syts have been recognized as one of the key players in neuronal MCSs, mediating lipid transport (Fernández-Busnadiego et al., 2015). A study published in 2014 by the authors of the current study revealed another two proteins important for MSCs in neurons (Petkovic et al., 2014). ER protein Sec22b and PM SNARE Syntaxin1 were shown to form a non-fusogenic trans-SNARE complex, important for lipid-transfer mediated neurite outgrowth. Gallo and colleagues have now provided important new evidence that these two components (E-Syts and Stx1/Sec22b) are together and may work together at MSCs.

      ->We thank this reviewer for stressing the importance of our article and agree with the conclusion of __Fernández-Busnadiego et al. (9) on E-Syts being one of the key players in neuronal MCSs, mediating lipid transport. We think that our work is a further key piece of evidence in the demonstration of the importance of E-Syts in neuronal development.__

      Bibliography

      Saheki Y, Bian X, Schauder CM, Sawaki Y, Surma MA, Klose C, et al. Control of plasma membrane lipid homeostasis by the extended synaptotagmins. Nat Cell Biol. 2016 Apr 11;18(5):504–515. Yu H, Liu Y, Gulbranson DR, Paine A, Rathore SS, Shen J. Extended synaptotagmins are Ca2+-dependent lipid transfer proteins at membrane contact sites. Proc Natl Acad Sci USA. 2016 Apr 19;113(16):4362–4367. Bian X, Zhang Z, Xiong Q, De Camilli P, Lin C. A programmable DNA-origami platform for studying lipid transfer between bilayers. Nat Chem Biol. 2019 Jul 18;15(8):830–837. Alberts B, Johnson A, Lewis J, Raff M. The lipid bilayer. Molecular Biology of …. 2002; Osen-Sand A, Staple JK, Naldi E, Schiavo G, Rossetto O, Petitpierre S, et al. Common and distinct fusion proteins in axonal growth and transmitter release. J Comp Neurol. 1996 Apr 1;367(2):222–234. Igarashi M, Kozaki S, Terakawa S, Kawano S, Ide C, Komiya Y. Growth cone collapse and inhibition of neurite growth by Botulinum neurotoxin C1: a t-SNARE is involved in axonal growth. J Cell Biol. 1996 Jul;134(1):205–215. Park N, Yoo JC, Lee Y-S, Choi HY, Hong S-G, Hwang EM, et al. Copine1 C2 domains have a critical calcium-independent role in the neuronal differentiation of hippocampal progenitor HiB5 cells. Biochem Biophys Res Commun. 2014 Nov 7;454(1):228–233. Giordano F, Saheki Y, Idevall-Hagren O, Colombo SF. PI (4, 5) P2-dependent and Ca2+-regulated ER-PM interactions mediated by the extended synaptotagmins. Cell. 2013; Fernández-Busnadiego R, Saheki Y, De Camilli P. Three-dimensional architecture of extended synaptotagmin-mediated endoplasmic reticulum-plasma membrane contact sites. Proc Natl Acad Sci USA. 2015 Apr 21;112(16):E2004–13.

    1. vec des articles de presse, des textes scientifiques, des textes d’histoire ou des commentaires d’œuvres

      Dommage, je ne peux pas choisir la couleur du surlignage, mais je peux mettre un tag

    1. To be fully compliant with GDPR, you would also need to enable Show Reject All Button setting.
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    5. if you are using some tools/scripts on your website that are used to identify individuals and their data is processed by you or 3rd parties), that can be done only when a person gives consent
    1. Where will we tag this?remind me.Where will we tag this?And with what?remind me 
    1. Use JSDOC https://jsdoc.app/about-getting-started.html format.

      Standardise your JavaScript comments:

      1. Use block comment
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    1. accomplish
    2. More generally, teaching a subject forces its evaluation from different perspectives and can provide a deeper understanding.

      Let's try some tags

    1. As explained by Flanders, “An element has three core constituent parts: the start tag, the end tag, and the content, which is whatever lies between the start tag and the end tag” (Flanders 106).

      This is a great quote fro Julia Flanders, I came upon this text as well and really helped me understand the reason behind encoding.

    1. Tags in the digital marketing and analytics context are similar to, but distinct from, the standard HTML tags that developers will use to code web pages. The analytics version of the word "tag" is derived from the fact that the tags provided by vendors are often encapsulated by HTML <script> or <img> tags. When we speak of tags in an HTML context, we refer to tags such as <body>, <p>, <li>, <blockquote>, and so on. When we refer to tags used in the analytics and marketing industry, we refer to code that an organization provides to install the desired product or functionality on your website or mobile app.
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    1. Create a Git repository for every new project. Learn more about what a Git repo is in this beginner Learning Git with GitKraken tutorial. Always create a new branch for every new feature and bug. Regularly commit and push changes to the remote branch to avoid loss of work. Include a gitignore file in your project to avoid unwanted files being committed. Always commit changes with a concise and useful commit message.  Utilize git-submodule for large projects. Keep your branch up to date with development branches. Follow a workflow like Gitflow. There are many workflows available, so choose the one that best suits your needs. Always create a pull request for merging changes from one branch to another. Learn more about what a pull request is and how to create them in this intermediate Learning Git with GitKraken tutorial. Always create one pull request addressing one issue. Always review your code once by yourself before creating a pull request. Have more than one person review a pull request. It’s not necessary, but is a best practice. Enforce standards by using pull request templates and adding continuous integrations. Learn more about enhancing the pull request process with templates.  Merge changes from the release branch to master after each release. Tag the master sources after every release. Delete branches if a feature or bug fix is merged to its intended branches and the branch is no longer required. Automate general workflow checks using Git hooks. Learn more about how to trigger Git hooks in this intermediate Learning Git with GitKraken tutorial. Include read/write permission access control to repositories to prevent unauthorized access. Add protection for special branches like master and development to safeguard against accidental deletion.

      Git Dos

    1. Throughout the process, there were situations where I was torn between different ways to tag certain words or phrases.

      From class discussion and personal experience, this problem was common for the entirety of the assignment. In regards to your encounter with the dog, by identifying if the dog contains human traits would allow you to label him as a person versus an object. In this case, the dog is compared to a person, ensuring why the dog should be tagged as a person.

    2. I found this quote to be very true because although it was harder to do the semantic encoding because I had to make certain decisions about what to tag, I found it more interesting. The structural encoding was very tedious because I had to go line by line giving the same tags over and over again.

      I agree. The structural encoding was repetitive, tedious, and boring. Whereas the semantic encoding differed in regards to tagging objects, people, places, and concepts. However, both are required to acquire a PDF document comprised with color coded words in relationship to their specific tagging.

    1. The <meta name="robots" content="noindex" /> tag or directive applies to search engine crawlers. To block non-search crawlers, such as AdsBot-Google, you might need to add directives targeted to the specific crawler
    1. Learning will not happen quickly and it will be a good journey to further educate myself in the space.

      I think you did a great job, but maybe for the module assignment talk about your experience collaborating with the class about how to tag specific words.

    2. . I felt that finishing this before the rest of the encoding made things simpler because once we started encoding different parts of the songs,

      I followed the same process to my encoding as you because I felt that it also made it easier to tag specific words after encoding the lines, speakers, speech, and title.

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'active' : '' }}} {{{ ( part.errors ) ? 'errors' : '' }}}"> <a href="#" class="nf-breadcrumb" data-index="{{{ index }}}">{{{ ( part.errors ) ? '' : '' }}} {{{ part.title }}}</a> </li> <# } ); #> </ul> <div class="nf-progress-container"> <div class="nf-progress" style="width: {{{ data.percent }}}%;"></div> </div> <nf-fields></nf-fields> <nf-cells></nf-cells> Formular schließen Wer profitiert von yuuvis® RAD? Rapid Application Development – für starke Anwendungen <img loading="lazy" class='avia_image' src='https://bp387lpw.myraidbox.de/wp-content/uploads/2020/02/illu-startup-01.svg' alt='Die Abbildung zeigt einen Mann, der vor einem Desktop steht' title='illu-startup-01' height="500" width="489" itemprop="thumbnailUrl" /> Systemintegratoren, die Tools in einem Bruchteil der Zeit und mit geringeren Kosten integrieren <img loading="lazy" class='avia_image' src='https://bp387lpw.myraidbox.de/wp-content/uploads/2020/02/illu-data_analysis-01.svg' alt='Die Abbildung zeigt drei Personen, die um einen Tisch herum stehen.' title='illustration-drei-personen-arbeiten-erfolgreich-an-tisch' height="500" width="458" itemprop="thumbnailUrl" /> Anwendungsdesigner, die leistungsstarke, inhaltsbasierte Applikationen erstellen <img loading="lazy" class='avia_image' src='https://bp387lpw.myraidbox.de/wp-content/uploads/2020/02/illu-web-hosting-01.svg' alt='Die Abbildung zeigt einen Mann, der vor 4 Servern steht mit grauem Schatten' title='illu-web-hosting-01' height="428" width="500" itemprop="thumbnailUrl" /> IT-Abteilungen, die kundenspezifische Anwendungen auf webbasierter IT-Ebene betreiben Das yuuvis® RAD Framework ist die ideale Lösung für kleinere bis mittelständische Unternehmen, die on-premise hoch performante Plattformen betreiben wollen.  Außerdem ist es optimal, um bestehende Anwendungen um ein Archiv zu erweitern. Die mit yuuvis® RAD implementierten Applikationen skalieren dank des modernen Microservices-Stack und des responsiven Web-Clients (Angular/HTML5) auch in mittelgroßen, weltweit verteilten Firmennetzen. Finden Sie heraus, wer von yuuvis® RAD profitieren kann Warum yuuvis® RAD? Schnelle Anwendungsentwicklung – die Vorteile auf einen Blick State of the ArtHigh-End-ECM auf dem neuesten Stand der Technik. Perfekt für content-zentrische Anwendungen. Offene ArchitekturREST-API gewährleistet einfache Integration in bestehende Systemlandschaften. Low CodeWeniger Code bedeutet weniger potenzielle Fehle, einfachere Wartung und geringere Kosten. ZukunftssicherHoher Investitionsschutz durch ein nachhaltiges Konzept gegen zukünftige disruptive Technologien. Einfaches HandlingGemeinsame Benutzerverwaltung mit sehr gut integriertem Workflow und Datenmanagement. Custom MicroservicesKomplexe Anwendungs­szenarien können mit eigenen passenden Erweiterungen im Client ergänzt werden. Erfahren Sie mehr über die Vorzüge von yuuvis® RAD Sie wollen mit yuuvis® RAD arbeiten? Kontaktieren Sie uns! Wie funktioniert yuuvis® RAD? Die Technik hinter unserer Rapid Application Development-Anwendung Offene Technologie yuuvis® RAD basiert auf offenen Stan­dard­tech­nologien. Alle server­seitigen Kom­po­nen­ten sind java-ba­siert und im­ple­men­tieren eine sau­bere, skalier­bare und leicht­gewichtige Micro­services-Archi­tektur. Diese wird von Spring Cloud Netflix or­ches­triert. Kommu­nikation und Pro­to­koll basieren auf HTTP(S). Der Web­client ist eine hun­dert­pro­zentige HTML5 Angular (Typeskript) An­wen­dung. Die server­sei­tige API ist rein REST­basiert. Neueste Standards Die strikte An­wen­dung neu­es­ter Stan­dards er­mög­licht den so­for­ti­gen Zu­griff auf das grö­ßte Netz­werk von Soft­ware-Ex­per­ten der Welt. Pro­prie­tär ist ein Fremd­wort in yuuvis® RAD. Es bie­tet damit die schnells­te und si­cherste Ar­chi­tek­tur, die heu­te ver­fügbar ist. Rechenzentrumsfreundlich Dank des Webclients ist der Rollout auf End­be­nutz­er­ar­beits­plät­zen ein­fach und un­kom­pliziert, ohne lo­kalen In­stal­lations­auf­wand. Das HTTP(S)/REST-Pro­to­koll zwi­schen dem Web­client und dem Ser­ver ent­spricht voll­ständig den Stan­dard-Fire­wall-Tech­no­logien. Microservices-basiert Der Microservices-Stack bietet eine um­fas­sende In­te­gra­tion von War­tung, Last­aus­gleich, Fail­over und Health-Check in die Man­age­ment- und Über­wach­ungs­werk­zeuge von Rech­en­zen­­tren. yuuvis® RAD be­dient so­wohl die S3-Schnitt­stelle, den De-facto-Stan­dard der Da­ten­speich­erung als auch OAuth 2.0 zur stan­dar­disier­ten, si­che­ren API-Au­to­risie­rung für Desk­top-, Web- und Mo­bile-An­wen­dungen. <img loading="lazy" class='avia_image ' src='https://bp387lpw.myraidbox.de/wp-content/uploads/2020/02/yuuvis-rad-framework-infografik.jpg' alt='Infografik zeigt das yuuvis® RAD Framework' title='yuuvis-rad-framework-Konzept' itemprop="thumbnailUrl" /> Das Rahmenkonzept der yuuvis® RAD Plattform Lesen Sie mehr über die Technologie von yuuvis® RAD Wer nutzt yuuvis® RAD? Diese Unternehmen vertrauen auf schnelle Anwendungsentwicklung Sie wollen mehr erfahren? Wir sind für Sie da! <img loading="lazy" class='avia_image' src='https://bp387lpw.myraidbox.de/wp-content/uploads/2020/02/yuuvis-photo-frank-dembach.jpg' alt='Foto Senior Key Account Manager yuuvis®' title='yuuvis-foto-frank-dembach-quer' height="694" width="1000" itemprop="thumbnailUrl" /> Frank Dembach Team Leader Sales – yuuvis® +49 (0)30 – 895 70 80 info@yuuvis.com Hinweis: Für diesen Inhalt ist JavaScript erforderlich. Felder mit einem * sind Pflichtfelder. Bitte Anrede auswählen: * Sehr geehrte Frau Sehr geehrter Herr Guten Tag Vorname Nachname * Email * Ihre Nachricht an uns 160 von 160 Zeichen übrig Divider HTML Erleben Sie yuuvis® live! Die Einführung der Software-Lösung ist geplant. Ich bin an einer Software-Präsentation interessiert. Trennung HTML Felder mit * sind Pflichtfelder. 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<div class="nf-mp-header"></div> <div class="nf-mp-body"></div> <div class="nf-mp-footer"></div> {{{ data.renderProgressBar() }}} {{{ data.renderBreadcrumbs() }}} {{{ data.renderPartTitle() }}} <h3> {{{ data.title }}} </h3> {{{ data.renderNextPrevious() }}} <ul class="nf-next-previous"> <# if ( data.showPrevious ) { #> <li class="nf-previous-item"> <input type="button" class="nf-previous" value="{{{ data.prevLabel }}}" /> </li> <# } #> <# if ( data.showNext ) { #> <li class="nf-next-item"> <input type="button" class="nf-next" value="{{{ data.nextLabel }}}" /> </li> <# } #> </ul> <ul class="nf-breadcrumbs"> <# _.each( data.parts, function( part, index ) { #> <li class="{{{ ( data.currentIndex == index ) ? 'active' : '' }}} {{{ ( part.errors ) ? 'errors' : '' }}}"> <a href="#" class="nf-breadcrumb" data-index="{{{ index }}}">{{{ ( part.errors ) ? '' : '' }}} {{{ part.title }}}</a> </li> <# } ); #> </ul> <div class="nf-progress-container"> <div class="nf-progress" style="width: {{{ data.percent }}}%;"></div> </div> <nf-fields></nf-fields> <nf-cells></nf-cells> Q&A

      Hier wird die Q&A Seite direkt geladen und nicht in einem neuen TAB

    1. Tag-teaming vocalists Eaddy and theOGM don’t emerge in wedding dresses, smashing all equipment in sight like they did on 2015’s Warped Tour, causing their removal.

      This is a prepostion its the how it tell how the arrived in 2015

  3. Feb 2020
    1. The biggest drawback of algorithmic feeds is that you might be looking at irrelevant content. When you see something on your timeline and want to comment, you will have to check the timestamp to see if your comment is still relevant or not.
    1. Use google image search or the website site used last class to find illustrations to pair with a THREE quotes from the book.  Briefly explain your choices. Categorize: Reading Response; tag your post: class10

      I totally forgot how to use this

    1. When a consumer (subscription) is registered, messages will be delivered (pushed) by RabbitMQ using the basic.deliver method. The method carries a delivery tag, which uniquely identifies the delivery on a channel.

      Messages are delivered with Unique Identifiers as delivery tag

    1. From Rain RFID Tag IC point of view it is therefore of highest importance to ensure correctness of these data.

      **Delete

    1. Entrepreneurship Defined

      TIP for OERu LEARNERS: Remember to add the course code tag in the tag field when annotating with Hypothes.is. Eg BMAN111 or IENT101. (Hit the enter key after typing the tag.)

    1. four-component instructional design (4C/ID)

      4C/ID tag might be one of the models I want to look into as I might use it for the Art Modules Class

    1. Top 10 Important Online Marketing Tools for Entrepreneurs 4.0 Thank you for your rating! Why not leave a message? Any additional feedback or questions are welcome below. Your Name Your Email Address Phone Number Message the Author Cancel By Shiv | Contact Author less than a minute ago Marketing tools are like a helping hand for many entrepreneurs. As time is money using online marketing tools make your job easy and fast and also saves money. Marketing tools are like a helping hand that makes your job so easy. These tools are designed in such a way that it saves you time, effort and money. Apart from finding customers, one of the most difficult problems faced by entrepreneurs is to save time and manage cash flow. Using tools for marketing your business ensures you meet your goal on time. Here are the top 10 most important online marketing tools for entrepreneurs- Hubspot- Inbound Marketing Tool If you want to buy one tool to grow your business exponentially, this is the tool you should buy. Hubspot offers an inbound marketing tool that promises you with attracting leads, converting them and closing the deal. This tool acts as a funnel for your business that narrows downs your audience into your customers and finally generates revenue out of them. You can get started using the Hubspot tool with just $113 per month. You can also get online tutorials on how to use Hubspot tools online or you can always call or email their support team to help you out. Freelancing Graphic Design Platform by EveryDesigns Marketing is impossible without good designs. In marketing, we have a lot of promotional content that uses heavy design work to attract customers. We, humans, are visual animals and it is easier to influence us visually rather than any other means. You can use the EveryDesigns platform to get designs for your business. It is a one-stop destination for your business to get any graphic design services. The innovation that they offer in their services is by organizing a contest for your designs where multiple designers work from around the world. You choose the best design submitted by designers and pay for only that design. You get multiple design options to choose from, along with a 100% money-back guarantee. MailChimp- Email Marketing MailChimp is the best tool when it comes to email marketing. As an entrepreneur, you know how important email marketing is. If you strategize your email marketing outreach, you can attract very valuable customers to your business website. The best part is that it provides some of its features for free, which is enough for a startup or small business to get started and if you want to buy the paid version, then it is as low as $10 per month. Zoom- Conference Meeting Tool Zoom is a web as well as an app-based conference meeting organization tool that helps you in connecting with different team members throughout the world. You can also use this tool to organize a webinar and post it on youtube by recording it. You can pretty much do anything, it is a better version of skype where you can whiteboard as well. The basic version can be used for free and the paid version with pro features starets at $20 for each member. Klusster- Publication Community Kluster is a tool used by digital marketers to spread content and attract customers to their website. Kluster offers a platform to publish content written by you and promote business. As an entrepreneur, you should understand the importance of the backlink for your website. Klusster is one such platform providing quality publications for businesses. The best part it's free. Grammarly-Content Optimization Tool As a marketer or entrepreneur, you know the power of content marketing. It is the most powerful way of branding your business. Creating content can be tough but, the most important thing is creating grammatically correct content. That’s where Grammarly comes and saves the day. It automatically suggests your corrections for every mistake you made. The basic version is free and the paid version with advanced features is $30. You can really see the difference in your writing after using Grammarly. Zoho Social-Social Media Marketing Tool Social media is a platform that has numerous potential and if you are not using social media then you are missing out on a huge opportunity. There are around 4.3 billion social media users and the primary rule of business is where there are people, there is business. Zoho Social is a social media management tool that helps you in promoting your business on multiple social media channels. You can use different channels like Facebook, Twitter Instagram, etc. and post your content, images using one app. UberSuggest- Digital Marketing Tool UberSuggest is a free digital marketing tool provided by Neil Patel Digital. This tool is best for a digital marketer who does not want to spend a big amount of money on buying digital marketing tools. This tool is very easy to use and offers many features that are enough for you to get started with your website’s SEO. Yoast SEO- WordPress Plugin for SEO Yoast SEO is a plugin that you can install on your WordPress site. This tool is a well-researched tool that recommends you SEO corrections that you should make in order to rank your website for specific keywords. It is the best on-page SEO management tool and comes with a one-time price tag of $89 for one website. You can also subscribe to their service starting from $19 per month where you get all the premium features with multiple plugins in one. If you do not want to buy Yoast SEO Plugin then you can also use the free version of the plugin but it is recommended that you should use the premium version if you want to stay ahead off of your competitors. Google- Search Engine & Other Tools You heard it right. Google is a tool that everyone uses and earlier in this post, I’ve said where there are people there is business, therefore, you should also use it. Google's market share when it comes to search engines is 80-90%. As an entrepreneur, you should aim for ranking your website higher in the high volume search keywords. To do that, you would need your website to be optimized according to the Google guidelines and recommendations. Google Offers multiple tools like search console, analytics, tag manager, etc to manage and optimize your website. You should use these tools to make your website better. Conclusion You can use these tools to have leverage over your competitors and quickly increase sales for your business. You are an entrepreneur and time is money for you, therefore, you should use these tools to save time and money. Comment below, what tool are you using to manage your business along with pricing and if you are using any of the above-mentioned tools, tell us your experience. Tags marketing tools / List of best marketing tools

      Marketing tools are like a helping hand for many entrepreneurs. As time is money using online marketing tools make your job easy and fast and also saves money. Top 10 Important Online Marketing Tools for Entrepreneurs

    1. dieses Mal führte uns Google Maps über einen anderen Weg. Zu Beginn bemerkten wir es gar nicht, aber hier und dort fuhren wir plötzlich Landstraße, wo wir bisher immer auf die Autobahn gelenkt worden waren. Da es keine größeren Umwege waren, dachte ich mir nichts dabei und folgte stur den Anweisungen des Gerätes. Kurz vor dem Ziel wollten wir noch mal ein Stück Autobahn fahren, wichen von der vorgeschlagenen Route ab und steckten plötzlich fest – eine offenbar eben erst errichtete Straßenblockade einiger Bauern versperrte uns den Weg. Google Maps hielt kurz inne und schlug schnell eine Umfahrung vor. Dann hörte ich im Radio, dass französische Bauern schon den ganzen Tag über landesweit für höhere Lebensmittelpreise streikten, viele Auffahrten und Kreuzungen seien von den wütenden Bauern blockiert worden. Da erst wurde mir klar, dass Google uns den ganzen Tag um die Blockaden herumgelenkt hatte

      Staus waren Demos, Google ersparte den Kontakt mit einer schwierigen und unbequemen Wirklichkeit. Was zeigt das Beispiel wirklich? Wo ist hier das Problem? Was ist anders als sonst in der urban-technischen "realen Welt"?

    1. In this volume in the MIT Press Essential Knowledge series, Richard Cytowic, the expert who returned synesthesia to mainstream science after decades of oblivion, offers a concise, accessible primer on this fascinating human experience.

      This would be a great gift! I add a tag for the event and a tag for the person the gift might be great for. Sometimes, when a site is dynamic (so I might not be able to get all the way back) I include an image and enough info to identify the gift.! Back to the 100K blog for another adventure?

    1. uld argue the text is most guilty of exoticism as it reflects a sense of wonder about different groups of people without any reference to respective racial superiority or inferi

      guilty of exoticism - wonder, "otherness"

    2. “the Anglo-Saxon readers and viewers of these texts probably considered them true”

      early english readers probably considered the wonders real

    1. CRM means greater efficiency for multiple teams. Automatically stored communication allows you to view emails, calendar, and phone call details in one easily accessible place. Add that to the ability for multiple teams to access the same information, and the amount of achievable progress simply skyrockets. Sales, marketing, and customer service teams can share valuable information about clients to continue to funnel them down the pipeline to get the desired result of closing a sale, knowledge of new products, or excellent customer service. Every department can now tag team to get the right information to the right individual. With this new found ease, teams can seamlessly work together to improve the bottom line.

      Good CRM can help people to focus on high value activities. And it is very important to avoid duplicating tasks among different groups.

  4. Jan 2020
    1. m Bereich der Theorie.

      Das stimmt nicht ganz, alljährlich herrscht in Moskau bei der Parade über Nazi-Deutschland Sonnenschein, nur möglich mit sogenannter "Wolkenimpfung":

      Einen Tag vor der großen Militärparade regnet es kräftig in Moskau. Auch für Dienstag ist Schneeregen angekündigt. Doch voraussichtlich wird die Sonne scheinen. Wie geht das?

      https://www.dw.com/de/wolkenimpfung-sch%C3%B6nes-wetter-auf-bestellung/a-38751024

    1. For whatever be the knowledge which we are able to obtain of God, either by perception or reflection, we must of necessity believe that He is by many degrees far better than what we perceive Him to be.

      tag: interesting

    1. It’s worth noting that first line of the script starts with #!. It is a special directive which Unix treats differently.

      Term hash tag at top of bash scripts are NOT comments... they are important

    1. spielerischer Überwachung keineswegs nur in Fernost, sondern auch im Westen angewandt werden, treffen Berichte über das chinesische SCS hierzulande meist auf großes Befremden.

      In der spielerischen Überwachung liegt eine der großen Gefahren für die westlich sozialisierte Welt. Da China durch seine autoritäre Regierungsform und das zensierte Internet eine Sonderrolle einnimmt, die für Europäer weit entfernt von ihrem Alltag erscheint, werden SCS für ebenfalls befremdlich und genauso weit entfernt gehalten.

      Dabei schleichen sich diese immer weiter ein. Neben den seit langem geläufigen Bonitätsprüfungen für Kreditnehmer versuchen viele Teile der digitalen Welt Nutzerverhalten durch Belohnungen zu steuern.

      Dies beginnt bei in der Freizeit verwendeten Diensten und Videospielen, die für tägliches Einloggen und Nutzen bzw. das Erledigen kleiner banaler Aufgaben einen Bonus vergeben - z.T. sogar für kumulierte Zeiträume, die dann die Notwendigkeit erzeugen, keinen Tag verpassen zu dürfen.

      Andererseits eröffnen sich ähnliche Systeme auch schon außerhalb der rein hobbymäßigen Tätigkeiten. Die meisten der Krankenkassen in Deutschland arbeiten bereits mit Scoring-Systemen (Bonus-Programmen), die einem bei ausreichender Teilnahme an Sportveranstaltungen und gesundheitlicher Vorsorge Prämien auszahlen.

      Die genannten Beispiele finden natürlich alle auf freiwilliger Basis statt und sind bisher ohne Negativ-Folgen bei Missachtung , produzieren trotzdem gleichzeit wieder Daten über das Nutzerverhalten. Sollten solche Systeme in Zukunft spontan in Pflichtprogramme verwandelt werden, kann sich am Beispiel der Krankenversicherung eine freiwillige Zusatzprämie schnell in eine nicht genehmigte Kassenleistung verwandeln, da die erforderlichen Punkte nicht erbracht wurden.

      Dass bei einigen Krankenversicherungen beispielsweise eine Zahnreinigung im Jahr kostenlos ist, bei anderen wiederum erst Punkte dafür gesammelt werden müssen, ist bereits jetzt schon Realität.

    1. [mp4 @ 0x7fe98400dc00] track 1: could not find tag, codec not currently supported in container This means that pcm_mulaw is not allowed in the MP4 output container format. Your choices are: Use a different output container format ffmpeg -i input -codec copy output.mkv Or re-encode the audio ffmpeg -i input -c:v copy -c:a aac output.mp4
    1. p-value=PH0[|¯¯¯¯Y−μY,0|>|¯¯¯¯Yact−μY,0|](3.2)(3.2)p-value=PH0[|Y¯−μY,0|>|Y¯act−μY,0|]\begin{equation} p \text{-value} = P_{H_0}\left[ \lvert \overline{Y} - \mu_{Y,0} \rvert > \lvert \overline{Y}^{act} - \mu_{Y,0} \rvert \right] \tag{3.2} \end{equation} In (3.2), ¯¯¯¯YactY¯act\overline{Y}^{act} is the mean of the sample actually computed. Consequently, in order to compute the ppp-value as in (3.2), knowledge about the sampling distribution of ¯¯¯¯YY¯\overline{Y} when the null hypothesis is true is required. However in most cases the sampling distribution of ¯¯¯¯YY¯\overline{Y} is unknown. Fortunately, as stated by the CLT (see Key Concept 2.7), the large-sample approximation ¯¯¯¯Y≈N(μY,0,σ2¯¯¯¯Y)  ,  σ2¯¯¯¯Y=σ2YnY¯≈N(μY,0,σY¯2)  ,  σY¯2=σY2n \overline{Y} \approx \mathcal{N}(\mu_{Y,0}, \, \sigma^2_{\overline{Y}}) \ \ , \ \ \sigma^2_{\overline{Y}} = \frac{\sigma_Y^2}{n} can be made under the null. Thus, ¯¯¯¯Y−μY,0σY/√n∼N(0,1).Y¯−μY,0σY/n∼N(0,1). \frac{\overline{Y} - \mu_{Y,0}}{\sigma_Y/\sqrt{n}} \sim \mathcal{N}(0,1). So in large samples, the ppp-value can be computed without knowledge of the exact sampling distribution of ¯¯¯¯YY¯\overline{Y}. Calculating the p-Value when the Standard Deviation is Known For now, let us assume that σ¯¯¯¯YσY¯\sigma_{\overline{Y}} is known. Then, we can rewrite (3.2) as p-value=PH0⎡⎢⎣∣∣ ∣∣¯¯¯¯Y−μY,0σ¯¯¯¯Y∣∣ ∣∣>∣∣ ∣∣¯¯¯¯Yact−μY,0σ¯¯¯¯Y∣∣ ∣∣⎤⎥⎦=2⋅Φ⎡⎢⎣−∣∣ ∣∣¯¯¯¯Yact−μY,0σ¯¯¯¯Y∣∣ ∣∣⎤⎥⎦.(3.3)p-value=PH0[|Y¯−μY,0σY¯|>|Y¯act−μY,0σY¯|](3.3)=2⋅Φ[−|Y¯act−μY,0σY¯|].\begin{align} p \text{-value} =& \, P_{H_0}\left[ \left\lvert \frac{\overline{Y} - \mu_{Y,0}}{\sigma_{\overline{Y}}} \right\rvert > \left\lvert \frac{\overline{Y}^{act} - \mu_{Y,0}}{\sigma_{\overline{Y}}} \right\rvert \right] \\ =& \, 2 \cdot \Phi \left[ - \left\lvert \frac{\overline{Y}^{act} - \mu_{Y,0}}{\sigma_{\overline{Y}}} \right\rvert\right]. \tag{3.3} \end{align} The ppp-value can be seen as the area in the tails of the N(0,1)N(0,1)\mathcal{N}(0,1) distribution that lies beyond ±∣∣ ∣∣¯¯¯¯Yact−μY,0σ¯¯¯¯Y∣∣ ∣∣

      This part is very confusing

  5. Dec 2019
    1. Alternatively, you can use the Explore function to ask Google Sheets any number of questions about your to do list. It'll give you suggestions like "Most frequent Task" or "What percentage of Tag is [tag name]" and so on. This can give you insight into what you're working on the most and how you're spending your time, which can help you plan your workdays more productively.
    1. As neither microautophagy, which involves direct uptake ofbulk cargo by lysosomes [10], nor CMA, which degrades a small subset of proteins via recognitionof a specific protein tag [11], have been implicated in host-pathogen defense against noroviruses,macroautophagy will primarily be discussed here

      Microautophagy: direct bulk uptake by lysosomes Chaperone-mediated autophagy: requires protein tag recognition to degrade small subset of proteins Macroautophagy: involved in host-pathogen interactions

    Annotators

    1. What is telling is the list of blogs that have refereed traffic to my blog are all written by men. I am not sure what – or if – there is anything to make out of that fact, but anytime I see a list of people that is exclusively male it does make me pause and go hmmmm.

      As another white male sending traffic back to your blog, I am left thinking.

    2. And I am planning on cutting back on my personal use of social media (easier said than done) and want to try to return to using my blog more than Twitter for sharing.

      certainly a laudable goal!

      It helped me a lot to simply delete most of the social media apps off of my phone. I scribbled a bit about the beginning of the process back in November and there's a link there to a post by Ben doing the same thing on his own website.

      More people are leaving social feeds for RSS feeds lately. I've recently started following Jeremy Felt who is taking this same sort of journey himself. See: https://jeremyfelt.com/tag/people-still-blog/

      Kudos as well to making the jump here:

      Taking a bit of a Twitter break. I'm going to try to stay off until the new year, but likely lack the willpower to stay off for more than a few hours. Wish me luck!<br><br>....but silently. Not via reply to to this tweet. Cause that'll just suck me back into the vortext.

      — Clint Lalonde (he/him) (@edtechfactotum) December 19, 2019
      <script async src="https://platform.twitter.com/widgets.js" charset="utf-8"></script>

      In part, it's what prompted me to visit your site to write a comment. (Sorry for upping your cis-gendered white male count, but 2019 was a bad year, and hopefully we can all make 2020 better as you've indicated.)

    1. Classes encapsulate code into instantiable units. Namespaces group functions, classes, and constants into spaces where their name is unique.The namespace declaration must occur straight after the opening <?php tag and no other statements may precede it.Namespaces affect constants, but you must declare them with the const keyword and not with define()

      Rule of using Namespaces

    1. Types of questions and where to ask: How do I? -- ask on Server Fault (tell them what tags to use -- your product tag at minimum) I got this error, why? -- ask on Server Fault I got this error and I'm sure it's a bug -- report it on your own site I have an idea/request -- report it on your own site Why do you? -- ask in your own community (support forum, etc) When will you? -- ask in your own community
    1. Since the time of Henry I, it has been used by the reigning monarch and is the longest-occupied palace in Europe

      Make an note.

    1. Archiving and downloading annotations Annotation viewing and export, from Hypothesis Labs Link: https://jonudell.info/h/facet Screencast: https://jonudell.net/h/facet.mp4 Description:  View annotations by user, group, URL, or tag. Export results to HTML, CSV, text, or Markdown.

      Did anyone tried to use this to feed mind/concept-mapping tools like Tinderbox or Cmap?

    1. Leo: Stephen in Glasgow, Scotland shares his recent NFC experience: I think I know of a problem with NFC. When I first got my Galaxy S3 it would quite often beep for no apparent reason. Every time I put it in my jacket pocket or on my table, it would beep. Then I noticed it was when I put it on my table resting on my wallet that it was beeping. I felt like an idiot for not figuring it out. Some of my newer credit cards have RFID chips inside for the new contactless payment systems. We don't have these in the U.S. yet; or, if we do, they're in very limited areas.Steve: Yes.Leo: One of the problems I had, when you go to Europe it's hard to buy gas because our credit cards are dumb, and you need a smart credit card to buy gas. And the Galaxy S3's reader was shouting out, "Hey, I found a tag." And sure enough, when I downloaded an NFC app from the Android store, the beep would then be accompanied by the card info displayed on the screen when I put my S3 near my wallet. If these phones are going to go crazy when we put them near a wallet with RFID cards, no wonder Apple is holding back. As far as I can see, there is no way to tell Android to ignore a tag. And even if you could, would that use battery as the RFID tag in your wallet was constantly shouting out, "Hey, hey, I'm here," and your phone listened to the details before ignoring it again? Love the show. That's a great question.

      Highlight

    1. Alexander Samuel reflects on tagging and its origins as a backbone to the social web. Along with RSS, tags allowed users to connect and collate content using such tools as feed readers. This all changed with the advent of social media and the algorithmically curated news feed.

      Tags were used for discovery of specific types of content. Who needs that now that our new overlords of artificial intelligence and algorithmic feeds can tell us what we want to see?!

      Of course we still need tags!!! How are you going to know serendipitously that you need more poetry in your life until you run into the tag on a service like IndieWeb.xyz? An algorithmic feed is unlikely to notice--or at least in my decade of living with them I've yet to run into poetry in one.

    1. function flow(bytes32 ilk) external note { require(debt != 0, "End/debt-zero"); require(fix[ilk] == 0, "End/fix-ilk-already-defined"); (, uint rate,,,) = vat.ilks(ilk); uint256 wad = rmul(rmul(Art[ilk], rate), tag[ilk]); fix[ilk] = rdiv(mul(sub(wad, gap[ilk]), RAY), debt); }
      • Important notes
        • fix[ilk] is the exchange ratio between collateral and Dai. This is where the haircut could be applied to dai holders. The gap[ilk] is the aggregation of insolvency across all under water CDPs
    2. function skim(bytes32 ilk, address urn) external note { require(tag[ilk] != 0, "End/tag-ilk-not-defined"); (, uint rate,,,) = vat.ilks(ilk); (uint ink, uint art) = vat.urns(ilk, urn); uint owe = rmul(rmul(art, rate), tag[ilk]); uint wad = min(ink, owe); gap[ilk] = add(gap[ilk], sub(owe, wad)); require(wad <= 2**255 && art <= 2**255, "End/overflow"); vat.grab(ilk, urn, address(this), address(vow), -int(wad), -int(art)); }
      • Important notes to consider
        • Vow is empty → dai holders
        • Surplus in the vow → then it will eventually be canceled (or "burned") with the incoming sin. And since the every collateral's art (and thus DCS debt) is unaltered, then this dai burning is distributing the surplus to dai holders in the form of greater share of the pie
          • e.g. 10 MM Dai claims 1 MM eth. If 1 MM Dai is in the form of surplus and is subsequently burned, then each Dai now has a great claim on eth when only 9 MM Dai is remaining)
        • Bad debt in the vow → increases the ending balance of Sin within the Vow. This bad debt would otherwise be covered by MKR holders, but now, it is actually covered by Dai holders
        • Undercollateralized CDPs → more sin is accrued in the vow than ink accrued in the End
          • These are present when CDPs have not yet been bitten when ES is initiated. They are unfortunately not penalized if they're not bitten.
        • Overcollateralized CDPs → exact amount of sin is accrued in the vow as ink value in End
    3. function skip(bytes32 ilk, uint256 id) external note { require(tag[ilk] != 0, "End/tag-ilk-not-defined"); (address flipV,,) = cat.ilks(ilk); Flippy flip = Flippy(flipV); (, uint rate,,,) = vat.ilks(ilk); (uint bid, uint lot,,,, address usr,, uint tab) = flip.bids(id); vat.suck(address(vow), address(vow), tab); vat.suck(address(vow), address(this), bid); vat.hope(address(flip)); flip.yank(id); uint art = tab / rate; Art[ilk] = add(Art[ilk], art); require(int(lot) >= 0 && int(art) >= 0, "End/overflow"); vat.grab(ilk, usr, address(this), address(vow), int(lot), int(art)); }
      • Important notes
        • First vow.suck used to accrue (TODO - still not entirely sure, but I think it has something to do with refunding the last bidder with their Dai bid)
        • Second vow.suck accrues the amount of dai in End from the last bid to be returned to the bid.usr(which is the bitten urn) in the form of art
        • The final vat.grab returns dai and collateral from End to bid.usr. This same process decreases the amount of sin that was accrued in the second vow. Now the CDP is an over/undercollateralized and can be skim'ed
        • Skip doesn't have a material impact on the auction or vow accounting. For more gas, it simply stops the tend auctions, returns the dai bid to the last bidder and transfers the collateral from the flip auction to End and finally back to the bid.usr. In other words, it pulls a CDP back into a state that can be skim'ed
    1. A UMD build will let people use your module via a global variable by dropping it into a <script> tag - this makes it easier to try without any build tooling in an HTML file, and in tools like JS Bin and CodePen.
  6. Nov 2019
    1. ”,

      needs a tag (p#).<br> The quotation needs more integration to show how "industry norms" fit in with the complex layers you're pointing to in "Dawn"

    1. The narrative is a hypertext story that changes every time the reader interacts with it, to create the sense of an unreliable narrator and stand as an allegory for the process of memory.

      you are closely summarizing the editor's and author's introductions to the work on the ELC3. You even use many of the same words.

      Without a citation, this is plagiarism. Please revise to include citations either with the lead in format or all in the tag (cite)

    1. For this option to work we will need to: * work through a way to tag the landing page in a consistent way

      • Add titles and captions to tagged images that help with navigation
      • provide introductory and instructional text to help users understand how to navigate content

      Questions:

      • Do we want just one structured media gallery or a structured media gallery for each seminar path?
    1. Let's ditch the Civil Engineers, Surveyors and Planners part for this logo. It makes our tag line repetitive.

    1. Jacqueline knew better than to interrupt her sister when she was this heated; you don’t get to be the richest woman in the tech industry without a ruthless reputation. 

      Maybe add another dialogue tag for Lizzie; she should probably be mentioned since these are her words.

    2. Jacqueline fired back at her sister.

      MY BAD, there is a tag here lol; possibly shift it up earlier in the dialogue though.

    3. Lizzie said, still shouting.

      Take out this dialogue tag, but add one for Jacqueline in the next paragraph.

    1. Zuhause

      Hier ploppt einem doch zwingend der Hype-Begriff Smart-Home auf, oder? Gerade, wenn einer der größten Global Player des Daten(Überwachung)Kapitalismus – Google – an vorderster Front mitspielt. Mit der Google Home Reihe gab's schon drei Lautsprechergrößen mit Mikrofonen, die zu erst zum abrufen allgemeiner Daten benutzt wurden und sich dann Stück für Stück über User-Profile individualisieren lassen. Sprich: Benutze ich das Google Home mit meinem privaten Account, kann ich mir meine Mails vorlesen lassen, meine Musik hören (über mein verbundenes Streamingkonto), kann auf Nachrichten antworten und und und. Und das halt immer zurückverfolgbar auf genau mein Konto. Man stelle sich den Funnel jetzt so vor: Mein Tag lief doof. Ich komme nach Hause, stelle mein Licht, dass ich ins Google Home integriert habe auf die hälfte der Heiligkeit ein und lasse Google traurige Musik spielen. Google weiß also, mir gehts nicht so gut. Und kann das a) in das Werbeprofil, das über mich angelegt wurde eintragen. Langfristig heißt es dann womöglich: Student, männlich, vor 3 Wochen getrennt. Mit der mittelbaren Folge: Dem kann man jetzt zugeschnitten darauf Werbung ausspielen. Bei Amazon läuft's mit Alexa genauso und Apple hat wohl bis jetzt einen ganz guten Schnitt, wenn es um Datenschutz geht. Dabei kann man über dieses Datensammeln nicht nur ein Profil von Menschen erstellen, um ihnen effizient Produkte zu verkaufen, sondern dieses eben auch nutzen, um Ideen zu verkaufen.

    1. Anything inside the <FancyBorder> JSX tag gets passed into the FancyBorder component as a children prop. Since FancyBorder renders {props.children} inside a <div>, the passed elements appear in the final output.

      key point - the 'magic' of 'children'

    1. America the safe haven and America the self-absorbed, even the self-righteous America that assumes the right to impose enlightenment on foreign nations

      America was the place you ran to. We were base in a life or death game of tag. We have also been the country with the biggest "stick" for so long that it almost seems laughable that someone would try to take over our country. Americans have this hero mentality and a good guy complex.

    Annotators

    1. a man is rich in proportion to the number of things which he can afford to let alone

      Good example of one of his quotable quotes. If you can picture it on a mug, calendar, or tea tag, he wins (but so does capitalism).

    1. comment trouver les principes ?

      Ah! La belle question épistémologique des principes de l’architecture.

      (Une piste : Principes universels du Design, ouvrage publié chez Eyerolles, réunit de nombreux principes applicables notamment en architecture, reposant sur des textes fondateurs et des études en psychologie : organisation de l'espace urbain, environnement et sécurité, mais aussi des effets a posteriori, après la construction, comme les boucles de rétroaction).

    1. decoding and deterritorialization

      As noted before, capitalism "deterritorializes" by kicking things out of their meaningful place and putting a price on them, allowing them to be traded utterly out of their context.

      "Decoding" is the same idea. Perhaps a better word is "de-symbolizing". Consider the crucifix. It is a sacred symbol for Christians. Now slap a price tag on it. The symbolism is lost. 1 Crucifix = 1 Subway Sandwich.

    1. result.

      Corollary tag missing.

    Annotators

  7. Oct 2019
    1. uint owe = rmul(rmul(u.art, i.rate), tag[ilk]);

      owe is the amount of debt in CDP (urn) in units of collateral (ink)

    2. tag[ilk] = wdiv(spot.par(), uint(spot.ilks(ilk).pip.read()));

      Determine the cage price, which is tag[ilk] = ilk/usd in math notation ($200 for ETH/USD would lead to a tag[eth] of 1/200).

    3. mapping (bytes32 => uint256) public tag; // cage price [ray]

      Cage price / price per collateral type at time of settlement.

    1. type FindByTag<Union, Tag> = Union extends { tag: Tag } ? Union : never; function cast<A extends Foo["tag"]>(foo: Foo, expectedTag: A): FindByTag<Foo, A> { if (foo.tag !== expectedTag) throw Error(`expected tag ${expectedTag} but was ${foo.tag}`) return foo as FindByTag<Foo, A>; }