苹果准备最早明年发布它的高端 VR 设备，这款计划中的产品售价将会高达 3000 美元。代号为 N301 的 VR 设备使用了两个 8K 显示屏，采用 M1 芯片的继任者，能展示丰富的 3D 图形。苹果将会使用眼球跟踪技术以较低的保真度渲染非用户注视的目标。苹果正在测试的一个版本使用了 10 多个摄像头，从跟踪手运动到提供周围空间的即时动态，可用于混合和增强现实体验，不限于浸入式的 VR。

Example question. Note the "question" tag.

在这里，墙上和桌子上的每一张纸本质上都是Lua编程语言的一个片段。有些纸上印着工作代码。Dynamicland 实际上可以对该代码执行 OCR 并实时运行它，但是通常，它在现实世界中象征性地使用这些代码，并在服务器端存储了自己的数字部分。然而，当一个对象发生变化时，该系统可以在打印出来的纸张上突出显示改变的线条，并能够标记与更新后的数字文件不同步的代码表。

soup = BeautifulSoup('<b class="boldest">Extremely bold</b>', 'html.parser')
tag = soup.b
tag.string
# 'Extremely bold'
type(tag.string)
# <class 'bs4.element.NavigableString'>

What is this an example of? self-referencing? self-presentation? duality?

tags garner traction. When doing makeup reviews, it is wise to use tags such as "review", so people can search the tags in hopes to find a review of a product they are interested in but want outsider opinions on prior to purchasing

ex: https://www.instagram.com/skin.withlove/

^ specifically in posts where she holds makeup/skincare items to her face, the comments has the tag "review" in it. For example, the post of her holding the @nyxcosmetics 'Bare With Me Tinted Skin Veil BB Cream' ⠀

DIZZYING

wtf. you do NOT tag names like this unless there are 2 ppl with the same name or Mr&Ms -> X Family

why so much useless history and naming?

ethical appeal is being used in that the tone of voice and narrative (one which offers constructive criticism and guidance) aids in strengthening this author's credibility. Considering reddit often invites trolls, hypocrites, racist/sexist ideologies etc- as it is clear that this author is someone truly trying to help in answering the main question of this reddit tag: is there an afterlife/proof of it? The author's ethos effected responses in that people were able to consider the questions the author brought forth and formulate their own answers, and- trusting the author due to his tone of voice which makes him credible- post them in a separate thread for the author to see.

How would you even describe this comment?

"just doing my job"? but he is (I assume) answering to be nice not because it's his job

"I won't take it personally"? vote my answer up or down, whichever you please

impartial, dispassionate, and objective, perhaps? "just the facts, ma'am"

---

Separately, what is the "Please don't thank me!" for? Is it that politeness? False modesty? Genuine modesty? Or is it rude? Why not allow someone to thank you??

I love del.icio.us bookmarks, that I used to catalog my web surfings, classify and share them. Upon its demise I went for Keep with good Web & Android client but without easy public sharing. Could hypothes.is be used as I did use del.icio.us? Edit2021: Looking at h. again after two years plus.

Or consider what Hatch had to say on the subject of rail bridges, which number 41 on the disused section of the line:

"The section of track running from Port Hawkesbury to Sydney has been out of service since 2014 and no detailed bridge capacity rating information is available...[I]nspections from 2015 indicate substantial corrosion of principal structural members in a number of steel bridges and general deterioration of concrete on all of the structures. In order to establish exactly what work is required for each structure, it would first be necessary to carry out detailed bridge inspections followed by corroded ratings of all bridges. This is beyond the scope of the current report."

They budget $14 million for structural work on the Grand Narrows swing bridge intended to allow it to operate to Class 1 specifications (with trains traveling at 10MPH). They suggest pulling the swing span open and closed using tug boats, but warn this is “not advisable for regular use given the higher risk of damage.”

Basically, Hatch had a dilemma: it is the job of a consultant to give its client (in this case the Port of Sydney) what it wants, and what the Port wanted was a palatable price tag for refurbishing the rail line.

But consultants have to retain some shred of credibility, so Hatch gave the Port its palatable figure, but added so many caveats that -- as I say in the article -- were the actual cost to be quadruple the estimate, it was covered .

It is interesting to see the tag and the definition of it.

I think this part explains the domino effect. A small proposition might lead to such a big change. There must be a lot of works to do.

I want to write about "The Uberable Lighness of Meaning" and got this by searching for

open market operations destroy price discovery

https://hyp.is/ZaLKPF_WEeuE_T_F-wXBMw/dimartinobooth.com/tag/danielle-dimartino-booth/page/4/

destruction of price discovery

Trabajo Superficie Activa

Why note-taking is so valuable.

• for : TrailHub4Hypothesis

yer it ..

Reviewer #2:

This manuscript interrogates function of Ihog and Boi adhesion molecules in cytoneme-based transport of the Hedgehog morphogen in Drosophila. The cell biology of how cytonemes are regulated to deliver morphogen signals is not yet well understood, so the work addresses an important topic that will be of interest to a broad audience. However, much of the study refines previous work from the same group to provide only a modest advance in understanding of how Ihog impacts cytoneme behavior.

The authors use genetic strategies in Drosophila to investigate how Ihog and Boi influence cytoneme dynamics. They find that the two proteins act differently with regard to cytoneme function. Boi effects are not exhaustively analyzed, but a number of genetic experiments are performed to interrogate Ihog. The authors reveal that the extracellular domains of Ihog interact with the glypicans Dally and Dlp to stabilize cytonemes that originate from Ihog over-expressing cells. Knockdown of Ihog does not alter cytoneme dynamics.

The most novel aspect of the study - that Boi functions differently than Ihog in cytonemes - is, unfortunately, not expanded upon. Some experiments lack controls or are presented in a manner that prevents clear interpretation of results.

Key points to be addressed:

Figure 1: Null alleles and RNAi silencing are used interchangeably to reduce Ihog, Boi, Dally and Dlp function in vivo. Results between methods are directly compared. Oftentimes, controls are not included to confirm the level of knockdown following RNAi. If possible use null alleles due to consistency. However, if this is not possible due to experimental reasons, give an explanation and state impact in the discussion.

Ihog levels decrease following loss of Dally or Dlp and Boi levels appear to increase following knockdown of Ihog, Dally, or Dlp. These stability changes have previously been reported. The mechanism is not clear, so should have been investigated here - especially the increased Boi protein level. How does this occur? Is stabilization occurring at the protein level or is gene expression changing? Is this a compensatory upregulation?

Based upon the supplement for Figure 2, it looks like the Ihog truncation mutants show variable stability. Might this be affecting the extent to which they alter Dally or Dlp stability? The western blot data are presented as crops of single bands adjacent to crops of a molecular weight ladder. Blots should be shown as intact images, preferable with all variants compared across a single gel with a loading control. As presented, relative stability/expression levels are impossible to assess.

Figures 3-4: Ihog mutant transgenes are tagged with either HA or RFP. Best to be consistent with tags when mutant function is being directly compared. Given that the HA tag is a small epitope and the RFP is a protein tag, they may differentially alter protein functionality. To be consistent it would be preferable to use the same tags. However, if this is not possible due to experimental reasons, the technical implication can also be mentioned in the discussion.

Figure 5: Investigation of histoblast cytonemes reaching into ttv, botv mutant clones: The ability of cytonemes to invade double mutant clones is altered only under the engineered situation of glypican dysfunction combined with Ihog over-expression. From this, it is concluded that Ihog is acting with glypicans to stabilize cytonemes. This may be the case, but they ability to see it only under an engineered situation of compound mutation plus Ihog over-expression leads this review to question the physiological relevance of the observation. Of similar concern is that the authors state the ability of Ihog over-expressing cell cytonemes to cross small vs. large ttv, botv clones differs. The difference is very difficult to appreciate from the results presented.

Figure 6: The apparent functional difference between Ihog and Boi in the ability to stabilize cytonemes is potentially very interesting, but is not investigated, which limits the advance of the current study.

This made me consider how digital annotation could be a fun way for students to enforce their learning of literary devices when physical class time is not a possibility, or as a way to integrate technology into the classroom in new ways.

AAAAA

WWWWW

SSSSS

DDD

Now there's a touchstone for the ages

A dedicated sponge in the blank countenance of empty space and flat time, I'd say.

10 Principles of Accessibilities:

1. Blindness (covers most of accessibility issues through testing)
2. Images (Alt-Text)
3. Tag hamburger menus
4. Don't place important content out of the way
5. Test for accessibility with real users.
6. Don't disable zoom in mobile interfaces.
7. Accessibility is cheaper when done up front.
8. Be aware of visual bias.
9. Check mobile accessibility separately.
10. Embrace all access attitude.

.h2

Reviewer #3:

The authors present a simple model that explains important outstanding controversies in the field of long-range gene regulation. These controversies include the fact that insulation boundaries tend to be weak; that acute inactivation of CTCF or cohesin (that leads to inactivation of insulation boundaries) leads to only minimal gene expression and that in live cells enhancer-promoter contacts appear not correlated with transcriptional bursting. The model involves a futile cycle of tag addition and removal from promoters, stimulation of more tag addition when tag is already present, and stimulation of tag addition by contacts with distal enhancers. The authors show that such a model explains all the above controversies, and indicate that the controversies are not inconsistent with mechanisms where long-range gene activation is driven by physical contacts with distal regulatory elements.

The authors have explained and explored the properties of the model well. I have only minor comments.

1) An alternative explanation for TAD-specific enhancer action is that an E-P interaction within a TAD (between two convergent CTCF sites), one that is brought about by extruding cohesin, is not equivalent to an interaction that occurs between two loci on either side of a CTCF site and that can be a random collision that is not mediated by extruding cohesin. In other words, two interactions can be of the same frequency but can be of a very different molecular nature. I agree that this model would not explain the results of the experiment where cohesin is acutely removed.

2) In the beginning of the introduction the authors introduce TADS. I recommend that the authors present this in a more nuanced way: compartment domains also appear as boxes along the diagonal, an issue that has led some in the chromosome folding field to be confused. This reviewer believes TADS are those domains that strictly depend on cohesin mediated loop extrusion, whereas compartment domains are not. If the authors agree, perhaps they can rewrite this section?

3) If I understand the model correctly, the nonlinearity arises because of the increased rate of tag addition when tag is already present. The authors then speculate histone modifications can be one such tag. However, there are only so many sites of modification at a promoter. Can the authors analyze how the possible range of tag densities affects performance of the model? Is the range required biologically plausible?

4) Can the authors do more analysis to explore how rapid changes in gene expression may occur (e.g. upon signaling a gene may go up within minutes)? How much more frequent does the E-P interaction need to be for rapid switch to the active promoter state? Can the authors do an analysis where they change the rates of the futile cycle upon some signal: at what time scale does transcription then change (keeping E-P frequency the same)?

free text and tag search

label

Dieses Ziel scheint mir etwas nichtssagend bzw. zu generisch zu sein ohne weitere Ausführungen. (Ich versuche z.B. jeden Tag einen positiven (und nicht negativen) Beitrag zum (Welt-)Geschehen zu machen und denke das gilt für viele andere auch.)

Ebenfalls ist mir nicht klar, in welcher Relation dies alles mit der verlinkten Agenda 2030 steht; da sollte m.E. ein expliziter Bezug im Text gemacht werden.

This is where I've felt the same way and the value of integrating support into the product as opposed to making the users go outside the product (e.g., support portal).

Make it easy to get feedback - whether it's an idea or problem the user using our product runs into.

Reviewer #3:

In the manuscript by Kim et al., show that, beyond its roles of preventing somatic differentiation in the germline of embryos, Zn-finger protein PIE-1 also functions in the adult germline, where it is both SUMOylated as well as interacts with the SUMO conjugating machinery and promotes SUMOylation of protein targets. They identify HDA-1 as a target of PIE-1-induced SUMOylation. Here too, I find the claims interesting, however data is sometimes missing or does not fully support the claims.

Main concerns:

1) A key claim of novelty over previously proposed "glue" functions of SUMO is based on the fact that they find that temporally regulated SUMOylation of a very specific residue in a specific protein is affecting protein activity: The observation that "SUMOylation of HDA-1 only appears to regulate its functions in the adult germline" and not in the embryo together with the finding that "other co-factors such as MEP-1 are SUMOylated more broadly, these findings imply that SUMOylation in the context of these chromatin remodeling complexes, does not merely function as a SUMO-glue (Matunis et al., 2006) but rather has specificity depending on which components of the complex are modified and/or when."

I find this claim poorly supported by the data. In fact, I find that the data supports that multiple SUMOylations contribute to formation of larger complexes: The His-SUMO IP (Fig 2B) brings down far more un-SUMOylated HDA-1 than SUMOylated. This argues for the presence of large complexes with different factors being SUMOylated and many bringing down unmodified HDA-1. The chromatography experiments (Fig 3B-C) also provide hits that are in complex and not direct interactors. Finally, HDA-1 SUMOylation is indicated to regulate MEP-1 interaction with numerous factors (Fig 3D). If all these factors are in one complex, it is hard to imagine how a single SUMO residue would mediate all of these simultaneously. It is quite likely (and not tested) that loss of HDA-1 SUMOylation leads to (partial?) dissociation of a large complex, rather than loss of individual interactions with the SUMO residue of HDA-1. Unlike claimed by the authors, there is no evidence that the "activity" of HDA-1 is regulated by SUMO modification.

2) Based on loss of MEP-1/HDA-1 interaction upon pie-1 RNAi and smo-1 RNAi (Fig 4B), the authors conclude that "SUMOylation of PIE-1 promotes the interaction of HDA-1 with MEP-1 in the adult germline".

The evidence that it is PEI-1 SUMOylation that is affecting MEP-1/HDA-1 interaction is fairly weak. In fact, based on Fig 4A, MEP-1 and HDA-1 interact without expression of PIE-1, and in PIE-1 K68R (sumoylation-deficient), although due to poor labeling of the panel it is not clear whether lane 1 and 4 refer to the WT pie-1 locus without tag or lack of pie-1.

In 4B the HDA-1 band that is present in L4440 but not in pie-1 or smo-1 RNAi is very faint, and in our experience such weak signal is not linear i.e., bands can disappear or appear depending on the exposure. Importantly, according to the data, seemingly unmodified HDA-1 immunoprecipitated with MEP-1 (Fig 4B). This data contradicts the authors' claim that "These findings suggest that in the adult germline only a small fraction of the HDA-1 protein pool, likely only those molecules that are SUMOylated, can be recruited by MEP-1 for the assembly of a functional NURD complex".

Furthermore, the fact that pie-1 and smo-1 depletion eliminate the interaction between HDA-1/MEP1 doesn't mean that the SUMOylation of pie-1 specifically is required for the interaction: perhaps un-SUMOylated pie1, and SUMOylation of something else, are both necessary for the interaction. The authors show that MEP-1 is also SUMOylated (Fig3C). When IP-ing GFP-MEP-1, they precipitate all its modified forms and associated factors. One alternative possibility for why smo-1 RNAi abolishes MEP-1/HDA-1 interaction is that MEP-1 SUMOylation is needed for interaction with HDA-1 (independently of pie-1). (On a side note, why are the authors not including MEP-1 SUMOylation in the model?)

3) On page 13 the authors write: "These findings suggest that SUMOylation of PIE-1 on K68 enhances its ability to activate HDA-1 in the adult germline" and "We have shown that PIE-1 is also expressed in the adult germline where it engages the Krüppel-type zinc finger protein MEP-1 and the SUMO-conjugating machinery and functions to promote the SUMOylation and activation of the type 1 HDAC, HDA-1 (Figure 6)". Activation of HDA-1 is misleading and was never tested. If not performing in vitro assays for HDAC activity, the authors at least need to look at whether pie loss (degron) leads to acetylation of genomic HDA-1 targets and whether it affects HDA-1 (and/or MEP-1) recruitment to these sites. This could be done by ChIP-seq of HDA-1 and H3K9ac in WT and pie-1 degron animals.

Chemie- und insbesondere Pharmaanlagen werden nicht in Tagen oder Wochen, sondern eher in Jahren gebaut. Dass wir überhaupt jetzt schon impfstoffe haben, ist nur deshalb möglich, weil Anlagen bereits vor der Zulassung gebaut wurden, damit ein Impfstoff dann möglichst schnell zur Verfügung stellt. Das bedeutet aber auch, dass jede dieser Anlagen ein Risiko darstellt. Es wäre halt betriebswirtschaftlich schwachsinnig, die Anlagen so auszulegen, dass innerhalb des ersten Monats eine Produktion durchläuft, die für die Welt reicht und danach die Anlage abzureißen.

The SMTP envelope is sent as a series of SMTP protocol units (described in Section 3). It consists of

• an originator address (to which error reports should be directed),

MAIL FROM that refers to the originator (a.k.a., reverse path, backward-pointing address) of the request

• one or more recipient addresses,

Multiple RCPT TO for each "to:" rfc822 message header in the mail data (see annotation)

• and optional protocol extension material.

DATA (see below)

---

(See also envelope-vs-mail tags.)

This is NOT an H1 tag

DOI: 10.1016/j.celrep.2020.108538

Resource: (Proteintech Cat# 10000-0-AP, RRID:AB_11042316)

Curator: @Naa003

SciCrunch record: RRID:AB_11042316

Curator comments: GST Tag antibody Proteintech Cat# 10000-0-AP

---

What is this?

Almost universal education and this is still a large scale problem.

DOI: 10.1016/j.xpro.2020.100231

Resource: (Covance Cat# MMS-101R-1000, RRID:AB_291262)

Curator: @Naa003

SciCrunch record: RRID:AB_291262

---

What is this?

Reviewer #1:

My general assessment of this work is that it is full of good ideas and presents a novel and general approach to examine lipid remodeling in cells and perhaps subsequent transport of lipids, mainly to mitochondria, but it lacks the scientific rigor necessary to be fully confident that their conclusions firmly support their claims. Often, insufficient information about the methods are provided and the manuscript is hard to follow critically.

More specific comments:

1) I am surprised that acyl-CoAs are transported into cells. I don't know of any precedent for this. Usually fatty acids are imported into cells and then converted to acyl-CoAs as part of the mechanism of import. Could it be that the acyl--CoAs are hydrolysed before uptake only to be reformed inside the cells? I would suggest feeding the NBD-palmitate plus the lysolipids to the cells as a control to see whether this is the case.

2) In fig 1 as an example they choose a region to blow up. As one can see there is a large variation, even in the blowups of mitochondrial labeling and if one looks at the originals the variation is confirmed. How have they chosen these areas? Furthermore, in figure 1 there is quite a bit of label with MLCL outside of the mitochondria, in particular in regions that they did not choose to blow up. What are these structures? Remodeling of MLCL is thought to take place in mitochondria.

3) They speak of transport of lipids from ER to mitochondria, but in fact the demonstration of this is very weak from what they show in the time course in supp fig 1. I am also disturbed by the difference in patterns of the NBD-PA patterns in a and b. They should be the same, but there are problems, maybe focus? I would say anyway that there is no clear evidence that the NBD PA first appears in the ER then goes to mitos. It could be synthesized in both compartments from their data.

4) The product characterization by TLC is insufficient. There are no standards, no characterization. Would they have seen the free NBD-palm by their methods?

5) When they use mutants and find less "transport" the mitochondrial signal as seen by mitotracker is always more diffuse. This indicates to me that there is another problem.

6) In fig 3 the fluorescent pictures do not correspond to what is seen in the quantification. There is more yellow in e than in h.

7) How did they add cholesterol at 50 or 100 micromolar? It is soluble at less than 1 micromolar in aqueous solution. The cholesterol experiments are puzzling. From what we know about StAR protein it recognizes cholesterol not esters. There is no precedent for cholesterol ester transport into mitochondria. Can they rule out that the esters are transported to the surface of the mitochondria and the NBD-Palm cleaved off and transported into the mitochondria?

8) The MAG and DAG experiments are overinterpreted. It could just be a kinetic problem since the MAG gets converted to DAG before TAG

9) They compare to externally added NBD lipids, but we don't know which ones they used. Are they using short chain NBD phospholipids. I could not find this in their manuscript. If they do not have the same NBD-palm in the sn-2 position then the comparison is meaningless.

10) The excitation and emission spectra of their probes are sometimes overlapping. How did they deal with this? Are they sure that they are not seeing FRET?

Good tag line Play on "get rich quick"

There's a bug in Hypothesis (at least the sidebar client) such that it's possible to post annotations with comments to the the public, but if you want to highlight something and make it similarly public, then it's not possible...

I'm using this tag as a workaround. The annotation comment should be a Markdown-style quote (i.e. set off by an ASCII right-pointing angle bracket / less-than sign).

添加 trace 的 build tag

DOI: 10.1016/j.celrep.2020.108490

Resource: (Abcam Cat# ab1874, RRID:AB_302646)

Curator: @Naa003

SciCrunch record: RRID:AB_302646

Curator comments: Rabbit Anti-VSV-G tag Polyclonal Antibody, Unconjugated Abcam Cat# ab1874

---

What is this?

DOI: 10.3390/v12121391

Resource: (MBL International Cat# PM021, RRID:AB_592663)

Curator: @Naa003

SciCrunch record: RRID:AB_592663

Curator comments: S Polyclonal Antibody MBL International Cat# PM021

---

What is this?

DOI: 10.1016/j.devcel.2020.10.004

Resource: (IMSR Cat# JAX_013591,RRID:IMSR_JAX:013591)

Curator: @Naa003

SciCrunch record: RRID:IMSR_JAX:013591

Curator comments: FVB-Tg(C3-1-TAg)cJeg/JegJ Mus musculus IMSR Cat# JAX:013591

---

What is this?

tag?: crowded (how do we disambiguate, make it not ambiguous?)

tag?: what scope of provided features / recommended happy path is needed?

tag?: what scope of provided features / recommended happy path is needed?

its own _

tool-heavy dependence on build tools / heavy/complex build-time

I absolutely love this concept that he did

给每个想法以 书名 为标签

我也是这么想的:)

DOI: 10.1007/s11120-020-00806-y

Resource: (Thermo Fisher Scientific Cat# R960-25, RRID:AB_2556564)

Curator: @Naa003

SciCrunch record: RRID:AB_2556564

Curator comments: V5 Tag Monoclonal Antibody Thermo Fisher Scientific Cat# R960-25

---

What is this?

DOI: 10.1111/bph.15060

Resource: (Cell Signaling Technology Cat# 13246, RRID:AB_2798161)

Curator: @Naa003

SciCrunch record: RRID:AB_2798161

Curator comments: T7-Tag (D9E1X) XP® Rabbit mAb antibody Cell Signaling Technology Cat# 13246

---

What is this?

testing page note for image

Hi Collin, nice project! So these results would be useful for reliable sources to write articles in a way that will increase shares. Do you think social media could also benefit from these results in order to find and tag misleading articles perhaps?

添加阅读的起始时间和结束时间，一方面是表明是否读完，另一方面则是 measure。

添加 推荐人 也是个好想法，增加更多的 connection，无论是书还是人都有更多的 context

但是需要构建一个 tag system，不光是个不同的 source，甚至还可以通用于非 Roam Research 之外，比如 raindrop

Reviewer #3:

In this manuscript, Naetar et al. investigate the role of LAP2α binding to A-type lamins in the nucleoplasm. LAP2α was already thought to be important for maintaining the nucleoplasmic pool of soluble A-type lamins, because knockout of LAP2α has previously been shown to reduce nucleoplasmic signal from an antibody that recognizes the lamin-A/C amino terminus. However, by directly tagging A-type lamins with fluorescent proteins and by using an alternative antibody to stain them, Naetar et al. find that the presence of LAP2α does not appreciably affect the pool of soluble lamins in the nucleoplasm. Instead, they find that LAP2α affects the assembly state of soluble lamins within the nucleoplasm, preventing formation of higher order A-type lamin structures that impede the mobility of telomeres within the nucleus.

There is a lot to like about this paper. I admire the author's mechanistic approach to studying lamin assembly state. The complementary cell biology/microscopy approaches paired with the biochemical approaches in figure 5 lead to an overall convincing story. And finally, I appreciate the efforts the authors made to "show their work," including their genome editing quality control measures.

Major comments:

1) Although I appreciate the transparency of the authors in demonstrating their workflow and quality control measures (see above), some of the terminology makes the manuscript difficult to read. At times it feels more like reading a lab notebook than reading a manuscript. For example, The manuscript would be easier to understand if cell lines were given descriptive names (eg: LAP2α KO, or mEos3.2-lmna instead of "WT#21") rather than continuing to refer to them by the small guide RNA that was used to generate them. A second example: it is nice to show biological replicate data as in figure 1, but it took me a while to figure out that the second and third columns in panels A and B were biological replicates; I spent some time trying to determine which experimental condition was different. Perhaps one biological replicate could be displayed in the main text and the second could be moved to the supplement, especially considering that it appears that only one of the clones was used for the quantifications shown in the bottom panels.

2) Why was the choice made to disrupt LAP2α at the beginning of exon 4? How large are exons 1 and 2, which are not shown in the schematic in the supplemental figures? What percentage of the LAP2α peptide primary sequence is affected by a frameshift mutation at the start of exon 4? Why was this approach preferable to introducing a frameshift mutation closer to the 5' end of the gene? I am concerned that the "LAP2α KO" cells used in the experiments may have some partially functional truncated LAP2α protein.

3) On page 16, the authors describe a set of experiments that are meant to demonstrate that their failure to see a difference in nucleoplasmic A-type lamins in LAP2α mutants is not due to the fluorescent protein tag used, however, instead of looking at untagged lamins, they elect to look at a cell line that has all lmna alleles tagged. Wouldn't it be better to use the LAP2α KO cells from figure 1 and stain with both the 3A6 antibody and the N18 antibody to determine whether untagged lamins behave the same way as tagged lamins? Perhaps this experiment could be added along with the current data, as it would be nice to compare directly between a cell line with all lmna alleles tagged and a cell line with no lmna alleles tagged.

This experiment would also give the authors a chance to compare morphology and overall fitness of cells with all untagged lmna with cells with all tagged lmna, to determine whether the tagged proteins are fully functional. Even if the tagged protein is fully functional, it would be appropriate to add a brief discussion of the possibility that fluorescent tags do perturb lamin-A/C function. After all, many lamin mutations do not cause obvious phenotypes in tissue culture cells, but defects can still emerge during development and aging in the context of an animal.

4) The authors build a convincing case that binding to A-type lamins by LAP2α influences their ability to assemble. But how do cells leverage this relationship for biological functions? Do cells tune the amount of fully soluble vs. partially assembled A-type lamins in the nucleoplasm in order to control nuclear structure or function in response to certain stimuli? Have the A-type lamins in the nucleoplasm been found to be in a different assembly state in different cell types? As the study is currently written, it presents an interesting molecular mechanism but no biological mechanism.

skill tag 1

The Remora Communiqué

Issued by No Spectator Left, December 2020

1

I heard the voice

Of the Remora speak –

Slowly, all in silence,

To wake me from my sleep.

2

I heard the voice

Of its silence say,

‘A Plague Ship has been

Stopped today.’

3

‘Did you even know

You were at sea?

Did you ever stop

To think of me?’

4

‘Know you’d left

The world behind,

Or what on Earth

You hoped to find?’

5

‘Have you heard the whales

Now have to yell?

You think they’re singing –

You can’t tell!’

6

‘It was the droning on & on

Of your Dread-Nought Destroyer

That made me sound my calm alarm

In the ear of your Employer.’

7

‘The Strain & Refrain

From onboard seemed familiar,

An updated version of

“Long Live Caligula!”’

8

‘I stopped his progress, ah

The hutzpah of karma!

Rome outweighed

By the scales of Remora... ’

9

‘Mark Antony

I scuppered too,

Underthrown before

He knew…’

10

‘But today, you thought,

What need to worry?

What voodoo-glue can now undo

Your ship’s world-beating hurry!’

11

‘So I downsized, to fill the role

I was unborn to play:

Remember, as the Show Goes On,

You recast me this way!’

12

‘You even gave new me a name

(With hollow ring, it’s true):

Corona-Virus, The Sick Crown,

Sitting right with you…’

13

‘If you should miss this hint now –

Heaven knows, I tried! –

The next ring at the doorbell?

No more Mr. Nice Guy!’

14

‘For tho’ the story of l’il ole me

Is soon & simply told

(N.B., I’m only as little

As you made the world),

15

Perchance in the Grand Scheme

There’s ‘small’ & then there’s small,

And your friend the atom

May do for us all!’

16

‘Fat Man’s little boy

For purpose trained fit:

The crack that splits open

The hull of the ship!’

17

‘Yes, that’s the thing (you’ll see too late),

It All cracks from inside:

Nothing in the world left ‘out’

Now you’ve grown worldwide.’

18

‘So while we’ve a moment –

And if not now, when? –

Pray, pay me best attention:

We may not meet again.’

19

‘And it’s hard to imagine

But sadly safe to say, you

May yet remember me

Fondly one day!’

20

‘For it’s not just the overlooked

Pit of the Bomb, the

Abyss that’s grown tired from

Yawning so long,’

21

‘There’s now – just in case! –

As the Atomic Clock ticks,

A new kid on the Doomsday Block,

A spare Apocalypse!’

22

‘And with two caps melting

The Dunce is warming to his task,

Facing down his Mother,

Preparing Her Death-Mask.’

23

‘But what does Her life matter

(& who’ll be left to grieve?),

The Old Girl in the Chokehold

Croaking “I Can’t Breathe!”’

24

‘O you wring your hands & ring your bells

While skies & forests fall,

But “capitalism will adapt!” no doubt:

It has to, after all!’

25

‘The trusty greenwashed reset button,

Point missed without fail –

“Sustainable development”…

Of the Fairy Tale!’

26

‘And to “listen to the science”

Isn’t all you need to do:

If you want to really heal thyself,

Listen to my silence too!’

27

‘It really is a killer,

The racket y’all make:

What kind of f** bully

Wants to make his Mother Quake?’

28

‘It is what it is,

Boys will be boys,

In their noisome

Kingdom of Noise?’

29

‘Well, until my little finger

Touched the spinning top,

Ripped you from the driver’s seat

Of the Roaring Chariot.’

30

‘But I cannot now take the helm

Lay in a course that’s true,

Back to safely grounded land –

That’s up to all the Crew.’

31

‘For in this emergency,

All hands on the (burning) deck:

Check your destiny’s manifest, there

Are no passengers left!’

32

‘It’s time to call a midnight strike,

Make love to Mutiny –

Go overboard, throw overboard

This plaguey, illthy Bounty!’

33

‘What exactly should you do? You

Crave a detailed scheme?

I’m not a power-point, you know,

Just your own fever-dream!’

34

I started when the silence stopped,

So badly missed its voice:

Left all alone, onboard to make

The choice that is no choice –

35

To put away so many

Very foolish things,

While we can still remember

What being human means,

36

Remember that the question

‘To be or not to be?’

Isn’t just a question

Of or for humanity,

37

Though it wouldn’t be an issue

Without the threats we pose,

The constant hammering it takes

To crucify Life’s Rose,

38

To pulverize the Earth that is

Our only common wealth,

To tame and tag, gas & gag

The good wild life of health.

39

I cried, ‘my God, I have to rush,

Right now alert the crew;

Not those who know they slave & serve –

The rest, without a clue,

40

Who buckle up,

Enjoy the ride,

Let those “in the

Know” decide

41

Their fate: “Awake!,” I’d cry,

“Discern!, deride

The course laid in

For Omnicide!”’

42

But my voice would

Not be the Dream’s,

And I must wake

To what It means –

43

So first things first,

Some silence, pray:

High Time to issue

The Remora Communiqué…

在Python中，每个对象都有一个唯一的标识标签

每个object 在堆内存里都有一个id 空间

Author Response

Summary: A major tenet of plant pathogen effector biology has been that effectors from very different pathogens converge on a small number of host targets with central roles in plant immunity. The current work reports that effectors from two very different pathogens, an insect and an oomycete, interact with the same plant protein, SIZ1, previously shown to have a role in plant immunity. Unfortunately, apart from some technical concerns regarding the strength of the data that the effectors and SIZ1 interact in plants, a major limitation of the work is that it is not demonstrated that the effectors alter SIZ1 activity in a meaningful way, nor that SIZ1 is specifically required for action of the effects.

We thank the editor and reviewers for their time to review our manuscript and their helpful and constructive comments. The reviews have helped us focus our attention on additional experiments to test the hypothesis that effectors Mp64 (from an aphid) and CRN83-152 (from an oomycete) indeed alter SIZ1 activity or function. We have revised our manuscript and added the following data:

1) Mp64, but not CRN83-152, stabilizes SIZ1 in planta. (Figure 1 in the revised manuscript).

2) AtSIZ1 ectopic expression in Nicotiana benthamiana triggers cell death from 3-4 days after agroinfiltration. Interestingly CRN83-152_6D10 (a mutant of CRN83-152 that has no cell death activity), but not Mp64, enhances the cell death triggered by AtSIZ1 (Figure 2 in the revised manuscript).

For 1) we have added the following panel to Figure 1 as well as three biological replicates of the stabilisation assays in the Supplementary data (Fig S3):

Figure 1 panel C. Stabilisation of SIZ1 by Mp64. Western blot analyses of protein extracts from agroinfiltrated leaves expressing combinations of GFP-GUS, GFP Mp64 and GFP-CRN83_152_6D10 with AtSIZ1-myc or NbSIZ1-myc. Protein size markers are indicated in kD, and equal protein amounts upon transfer is shown upon ponceau staining (PS) of membranes. Blot is representative of three biological replicates , which are all shown in supplementary Fig. S3. The selected panels shown here are cropped from Rep 1 in supplementary Fig. S3.

For 2) we have added the folllowing new figure (Fig. 2 in the revised manuscript):

Fig. 2. SIZ1-triggered cell death in N. benthamiana is enhanced by CRN83_152_6D10 but not Mp64. (A) Scoring overview of infiltration sites for SIZ1 triggered cell death. Infiltration site were scored for no symptoms (score 0), chlorosis with localized cell death (score 1), less than 50% of the site showing visible cell death (score 2), more than 50% of the site showing cell death (score 3). (B) Bar graph showing the proportions of infiltration sites showing different levels of cell death upon expression of AtSIZ1, NbSIZ1 (both with a C-terminal RFP tag) and an RFP control. Graph represents data from a combination of 3 biological replicates of 11-12 infiltration sites per experiment (n=35). (C) Bar graph showing the proportions of infiltration sites showing different levels of cell death upon expression of SIZ1 (with C-terminal RFP tag) either alone or in combination with aphid effector Mp64 or Phytophthora capsica effector CRN83_152_6D10 (both effectors with GFP tag), or a GFP control. Graph represent data from a combination of 3 biological replicates of 11-12 infiltration sites per experiment (n=35).

Our new data provide further evidence that SIZ1 function is affected by effectors Mp64 (aphid) and CRN83-152 (oomycete), and that SIZ1 likely is a vital virulence target. Our latest results also provide further support for distinct effector activities towards SIZ1 and its variants in other species. SIZ1 is a key immune regulator to biotic stresses (aphids, oomycetes, bacteria and nematodes), on which distinct virulence strategies seem to converge. The mechanism(s) underlying the stabilisation of SIZ1 by Mp64 is yet unclear. However, we hypothesize that increased stability of SIZ1, which functions as an E3 SUMO ligase, leads to increased SUMOylation activity towards its substrates. We surmise that SIZ1 complex formation with other key regulators of plant immunity may underpin these changes. Whether the cell death, triggered by AtSIZ1 upon transient expression in Nicotiana benthamiana, is linked to E3 SUMO ligase activity remains to be investigated. Expression of AtSIZ1 in a plant species other than Arabidopsis may lead to mistargeting of substrates, and subsequent activation of cell death. Dissecting the mechanistic basis of SIZ1 targeting by distinct pathogens and pests will be an important next step in addressing these hypotheses towards understanding plant immunity.

Reviewer #1:

In this manuscript, the authors suggest that SIZ1, an E3 SUMO ligase, is the target of both an aphid effector (Mp64 form M. persicae) and an oomycete effector (CRN83_152 from Phytophthora capsica), based on interaction between SIZ1 and the two effectors in yeast, co-IP from plant cells and colocalization in the nucleus of plant cells. To support their proposal, the authors investigate the effects of SIZ1 inactivation on resistance to aphids and oomycetes in Arabidopsis and N. benthamiana. Surprisingly, resistance is enhanced, which would suggest that the two effectors increase SIZ1 activity.

Unfortunately, not only do we not learn how the effectors might alter SIZ1 activity, there is also no formal demonstration that the effects of the effectors are mediated by SIZ1, such as investigating the effects of Mp64 overexpression in a siz1 mutant. We note, however, that even this experiment might not be entirely conclusive, since SIZ1 is known to regulate many processes, including immunity. Specifically, siz1 mutants present autoimmune phenotype, and general activation of immunity might be sufficient to attenuate the enhanced aphid susceptibility seen in Mp64 overexpressers.

To demonstrate unambiguously that SIZ1 is a bona fide target of Mp64 and CRN83_152 would require assays that demonstrate either enhanced SIZ1 accumulation or altered SIZ1 activity in the presence of Mp64 and CRN83_152.

The enhanced resistance upon knock-down/out of SIZ1 suggests pathogen and pest susceptibility requires SIZ1. We hypothesize that the effectors either enhance SIZ1 activity or that the effectors alter SIZ1 specificity towards substrates rather than enzyme activity itself. To investigate how effectors coopt SIZ1 function would require a comprehensive set of approaches and will be part of our future work. While we agree that this aspect requires further investigation, we think the proposed experiments go beyond the scope of this study.

After receiving reviewer comments, including on the quality of Figure 1, which shows western blots of co-immunoprecipitation experiments, we re-analyzed independent replicates of effector-SIZ1 coexpression/ co-immunoprecipitation experiments. The reviewer rightly pointed out that in the presence of Mp64, SIZ1 protein levels increase when compared to samples in which either the vector control or CRN83-152_6D10 are co-infiltrated. Through carefully designed experiments, we can now affirm that Mp64 co-expression leads to increased SIZ1 protein levels (Figure 1C and Supplementary Figure S3, revised manuscript). Our results offer both an explanation of different SIZ1 levels in the input samples (original submission, Figure 1A/B) as well as tantalizing new clues to the nature of distinct effector activities.

Besides, we were able to confirm a previous preliminary finding not included in the original submission that ectopic expression of AtSIZ1 in Nicotiana benthamiana triggers cell death (3/4 days after infiltration) and that CRN83-152_6D10 (which itself does not trigger cell death) enhances this phenotype.

We have considered overexpression of Mp64 in the siz1 mutant, but share the view that the outcome of such experiments will be far from conclusive.

In summary, we have added new data that further support that SIZ1 is a bonafide target of Mp64 and CRN83-152 (i.e. increased accumulation of SIZ1 in the presence of Mp64, and enhanced SIZ cell death activation in the presence of CRN83-152_6D10).

Reviewer #2:

The study provides evidence that an aphid effector Mp64 and a Phytophthora capsici effector CRN83_152 can both interact with the SIZ1 E3 SUMO-ligase. The authors further show that overexpression of Mp64 in Arabidopsis can enhance susceptibility to aphids and that a loss-of-function mutation in Arabidopsis SIZ1 or silencing of SIZ1 in N. benthamiana plants lead to increased resistance to aphids and P. capsici. On siz1 plants the aphids show altered feeding patterns on phloem, suggestive of increased phloem resistance. While the finding is potentially interesting, the experiments are preliminary and the main conclusions are not supported by the data.

Specific comments:

The suggestion that SIZ1 is a virulence target is an overstatement. Preferable would be knockouts of effector genes in the aphid or oomycete, but even with transgenic overexpression approaches, there are no direct data that the biological function of the effectors requires SIZ1. For example, is SIZ1 required for the enhanced susceptibility to aphid infestation seen when Mp64 is overexpressed? Or does overexpression of SIZ1 enhance Mp64-mediated susceptibility?

What do the effectors do to SIZ1? Do they alter SUMO-ligase activity? Or are perhaps the effectors SUMOylated by SIZ1, changing effector activity?

We agree that having effector gene knock-outs in aphids and oomycetes would be ideal for dissecting effector mediated targeting of SIZ1. Unfortunately, there is no gene knock-out system established in Myzus persicae (our aphid of interest), and CAS9 mediated knock-out of genes in Phytophthora capsici has not been successful in our lab as yet, despite published reports. Moreover, repeated attempts to silence Mp64, other effector and non-effector coding genes, in aphids (both in planta and in vitro) have not been successful thus far, in our hands. As detailed in our response to Reviewer 1, we considered the use of transgenic approaches not appropriate as data interpretation would become muddied by the strong immunity phenotype seen in the siz1-2 mutant.

As stated before, we hypothesize that the effectors either enhance SIZ1 activity or alter SIZ1 substrate specificity. Mp64-induced accumulation of SIZ1 could form the basis of an increase in overall SIZ1 activity. This hypothesis, however, requires testing. The same applies to the enhanced SIZ1 cell death activation in the presence of CRN83-152_6D10.

Whilst our new data support our hypothesis that effectors Mp64 and CRN83-152 affect SIZ1 function, how exactly these effectors trigger susceptibility, requires significant work. Given the substantial effort needed and the research questions involved, we argue that findings emanating from such experiments warrant standalone publication.

While stable transgenic Mp64 overexpressing lines in Arabidopsis showed increased susceptibility to aphids, transient overexpression of Mp64 in N. benthamiana plants did not affect P. capsici susceptibility. The authors conclude that while the aphid and P. capsici effectors both target SIZ1, their activities are distinct. However, not only is it difficult to compare transient expression experiments in N. benthamiana with stable transgenic Arabidopsis plants, but without knowing whether Mp64 has the same effects on SIZ1 in both systems, to claim a difference in activities remains speculative.

We agree that we cannot compare effector activities between different plant species. We carefully considered every statement regarding results obtained on SIZ1 in Arabidopsis and Nicotiana benthamiana. We can, however, compare activities of the two effectors when expressed side by side in the same plant species. In our original submission, we show that expression of CRN83 152 but not Mp64 in Nicotiana benthamiana enhances susceptibility to Phytophthora capsici. In our revised manuscript, we present new data showing distinct effector activities towards SIZ1 with regards to 1) enhanced SIZ1 stability and 2) enhanced SIZ1 triggered cell death. These findings raise questions as to how enhanced SIZ1 stability and cell death activation is relevant to immunity. We aim to address these critical questions by addressing the mechanistic basis of effector-SIZ1 interactions.

The authors emphasize that the increased resistance to aphids and P. capsici in siz1 mutants or SIZ1 silenced plants are independent of SA. This seems to contradict the evidence from the NahG experiments. In Fig. 5B, the effects of siz1 are suppressed by NahG, indicating that the resistance seen in siz1 plants is completely dependent on SA. In Fig 5A, the effects of siz1 are not completely suppressed by NahG, but greatly attenuated. It has been shown before that SIZ1 acts only partly through SNC1, and the results from the double mutant analyses might simply indicate redundancy, also for the combinations with eds1 and pad4 mutants.

We emphasized that siz1-2 increased resistance to aphids is independent of SA, which is supported by our data (Figure 5A). Still, we did not conclude that the same applies to increased resistance to Phytophthora capsici (Figure 5B). In contrast, the siz1-2 enhanced resistance to P. capsici appears entirely dependent on SA levels, with the level of infection on the siz1-2/NahG mutants even slightly higher than on the NahG line and Col-0 plants. We exercise caution in the interpretation of this data given the significant impact SA signalling appears to have on Phytophthora capsici infection.

The reviewer commented on the potential for functional redundancy in the siz1-2 double mutants. Unfortunately, we are unsure what redundancy s/he is referring to. SNC1, EDS1, and PAD4 all are components required for immunity, and their removal from the immune signalling network (using the mutations in the lines we used here) impairs immunity to various plant pathogens. The siz1-2 snc1-11, siz1-2 eds1-2, and siz1-2 pad4-1 double mutants have similar levels of susceptibility to the bacterial pathogen Pseudomonas syringae when compared to the corresponding snc1-11, eds1-2 and pad4-1 controls (at 22oC). These previous observations indicate that siz1 enhanced resistance is dependent on these signalling components (Hammoudi et al., 2018, Plos Genetics).

In contrast to this, we observed a strong siz1 enhanced resistance phenotype in the absence of snc1- 11, eds1 2 and pad4-1. Notably, the siz1-2 snc1-11 mutant does not appear immuno-compromised when compared to siz1-2 in fecundity assays, indicating that the siz1-2 phenotype is independent of SNC1. In our view, these data suggest that signalling components/pathways other than those mediated by SNC1, EDS1, and PAD4 are involved. We consider this to be an exciting finding as our data points to an as of yet unknown SIZ1-dependent signalling pathway that governs immunity to aphids.

How do NahG or Mp64 overexpression affect aphid phloem ingestion? Is it the opposite of the behavior on siz1 mutants?

We have not performed further EPG experiments on additional transgenic lines used in the aphid assay. These experiments are quite challenging and time consuming. Moreover, accommodating an experimental set-up that allows us to compare multiple lines at the same time is not straightforward. Considering that NahG did not affect aphid performance (Figure 5A), we do not expect to see an effect on phloem ingestion.

Memes are basically just ways of making fun of certain pictures, a lot of the time, they happen to be real people caught at a weird or funny moment and the catchy tag you put on the picture is what makes it funny.

I am surprised to see no honorable mention here, because a "book log" sounds a lot like a reference manager. The best free/open-source one I know of is Zotero: https://www.zotero.org

From your list of desired features above, it can do:

• tagging of items (automatically when collecting items with the browser button, manually, or a mix of both automatic tags and your own tags)
• notes as attachments to an item
• bookmarks as an URL attached to an item (and actually, most item types collected with the browser button have the URL saved by default)
• making items and their annotations public on your profile on zotero.org
• shareable format: you can export in many formats, from simple printout kind of formats (HTML) to formats fully re-importable into another instance of Zotero
• query: not sure it has all the capabilities of a relational database, but you can search based on any piece of metadata found in your items, you can build arbitrarily complex search queries, you can save searches (they will materialize in the interface as "dynamic folders" containing the search results automatically as new items added to your library match the query)

For dealing with prioritization, you would have to come up with your own system. The workflow described here uses the tag system for this (with custom tags to mark status "to read", "read", etc.): https://incenp.org/notes/2019/managing-academic-literature.html

Have your tried Roam Research?

DOI: 10.1016/j.cub.2020.10.061

Resource: (Thermo Fisher Scientific Cat# R960-25, RRID:AB_2556564)

Curator: @Naa003

SciCrunch record: RRID:AB_2556564

Curator comments: V5 Tag Monoclonal Antibody Thermo Fisher Scientific Cat# R960-25

---

What is this?

After speaking to the folks at Plausible they pointed me to this page on the digital ocean community forums:

https://www.digitalocean.com/community/questions/what-kind-of-electricity-do-you-run-on

And this one here:

https://www.interxion.com/why-interxion/sustainability

The TLDR version is that the servers they are using are run by Digital Ocean, who lease from Interxion, who source the power for the datacentre from renewables.

Interxion themselves are owned by Digital Realty, who do release figures, but not at a granularity to confirm.

Once there is info from Interxion, it's possible to confirm this.

Ich bin ein großer iPad-Fan und nutze meines jeden Tag für Handschriftliches.

Dieser Aktion ist bestimmt eine gründliche Evaluierung der Optionen vorausgegangen und es ist toll, dass unsere Schulen jetzt besser ausgestattet werden, gar keine Frage.

Trotzdem nagt die Erkenntnis an mir, dass ein iPad doch in erster Linie ein Konsum- und Kommunikationsgerät und weniger ein Kreativwerkzeug ist. Ich frage mich deshalb, ob die iPads nicht zumindest um günstige Laptops mit Tastatur ergänzt werden sollten.

Ich schreibe diesen Kommentar übrigens gerade auf einem RaspberryPi für 100€. Davon bekommt man so etwa vier Stück für den Preis eines iPads. Und unglaublich viel mehr Möglichkeiten.

I mostly use it to define the UI as a more app-centric alternative to HTML/CSS.

I suggest to add a link to his biography or any other link that tells the reader who he is

Pour la bibliographie issue d'internet, il faut uniformiser dans un sens où dans l'autre : certains sites portent la mention "Consulté le", d'autres non.

Mint Wikipedia szerkesztésért "felelős" jelzem: ne törődj ezzel! Nem számít túlzottan, ha majd az "supervisor"-ok mégis jeleznek (amit nekem fognak), teszek valamit. A tag törölhető - szerintem.

Welche Relevanz haben Datum und Zeitpunkt der Verabreichung?

rating scale evaluation

DOI: 10.1016/j.ajhg.2020.10.012

Resource: (Millipore Cat# 05-724, RRID:AB_309938)

Curator: @Naa003

SciCrunch record: RRID:AB_309938

Curator comments: Anti-Myc Tag, clone 4A6 antibody Millipore Cat# 05-724

---

What is this?

Look at her face, its kinda the face like oh you guys are finally noticing this. I think it's really good that they are noticing these things and working to stop it. It's really good that people are still talking about this because if they dont I feel that some may start to forget.

hozzáadtam (2020.11.15)

git tag V1

git tag V1

Alapító tag

Julian claims Tinder is monetizing on signal amplifiers like Boost and Super Like.

Julian Lehr posits that because software purchases are less visible, their signalling power is reduced. This is why, for instance, you don't see any luxury software products: Because you cannot signal you're in on it.

测试tags

If you use Roam as a CRM, in your daily note you can simply tag a person you just had a meeting with and log some notes. Those notes will then show up under that person in the linked references under a block for the current date.

So in one sentence, with using only your keyboard, you've created a meeting note linked to a person and linked to a specific date.

With any other solution you'd have to navigate to a person, create an entry, set a date and write the note.

This "decide where to put it" step is completely replaced with "what entities does this pertain to".

Nat's conclusion is correct, but his reason for arriving at that conclusion is wrong.

You're not faced with the question of where to put things with Roam because you can do the following:

(1) You can tag a new entry on the fly, in-line, CLI style. (2) If the tag exists, it will autocomplete, if it doesn't you can create it with no extra effort (3) Any tags you add are links to their respective pages, which allows you to (a) navigate their as soon as you've typed the tag/page name and (b) it creates a backlink on those pages so your new entry is automatically linked to from there.

I think Nat touches on an important use case here, but I wouldn't call it "moving laterally while retaining vertical references."

He's referring to a link to the book Emergency, not some content of the book itself. So each page can link to the book, that's not novel.

What is novel is that when entering in the book into your Roam database you can tag it with Prepping and Neil Strauss and it will show up under those pages automatically.

Nat says that tags are everything and nothing, but I don't agree with that.

Pages consist of blocks.

A reference to a page is treated in the exact same way as a tag.

A block is not treated in the same way. A block is not a tag.

Do you like this reason?

How long do ebooks last?

Has one of your ebooks ever become damaged?

Have you ever lost an ebook?

Are people willing to pay for convenience?

Explain why ebooks sometimes cost more than physical books.

Do you think this is true for authors who don't have a following?

How is the pricing system for ebooks different from the one for physical books?

Who else needs to be paid besides just the author?

Does this surprise you?

Great list! Some things we didn't think about until we needed them are:

• stroller organizer
• teethers
• crinkly books
• pacifier holders but ones that could probably hold other things too like teethers or wubba nubs
• baby sunglasses
• Milkies trays - you'll want 1oz milk cubes for putting in the boon silicone thing when she's teething and in the beginning you'll bag and freeze less oz so as not to waste but then she'll grow and need just one oz more so you can defrost 1oz at a time.
• If you are going to try to breastfeed have emergency formula on hand in case it doesn't go well or an emergency where Rob will have to feed. These single packets are great because you can put some in the diaper bag for just in case & I found out that once you open a tin of formula you must use w/in 30 days so if it's just for emergencies the tin is a waste.
• A very Extra purchase but we LOVE it: a baby cam for the car instead of the stupid mirrors that really don't work--it also has night vision so you can see them at night whereas you can't see them with a mirror. We have the Yada and love it but it looks like there are now some cheaper ones that are highly reviewed.
• diaper caddy so you can change diapers in any room
• these washable portable changing pads-one in the caddy, one in the car, one in your diaper bag
• reusable swim diaper
• a brush, we obviously knew our kid would have hair, maybe a toss up with your kid
• this is the baby sunscreen we got thinkbaby) & Babo
• a giant play mat to roll out and away
• spray oxy clean or the powder to soak all the dirty stuff
• if you are up for (evidence-based, because I'm a researcher nerd) pregnancy and parenting book recs I LOVE Emily Oster
• a foot stool for your glider while nursing
• socks, are the worst so we love the booties with snaps: zutano
• Baby tylenol
• Baby saline drops
• baby vitamin D drops
• a giant water bottle (insulated if you prefer cold water) with a STRAW -- you don't have two hands ever again to unscrew a top and you'll be thirsty all the time while breastfeeding
• a nightstand next to your glider stocked with more water and granola bars, protein bars, (or in my case, poptarts). You'll be so hungry at 2am
• BLACKOUT curtains! These travel ones are great because you can put them up wherever for naps.
• a giant basket to hold toys/books/blankets

Why do we need this proprietary service?

So they can track us when we go to: http://svelte-autocomplete.surge.sh/?ref=madewithsvelte.com ?

Rather than bookmark/use https://madewithsvelte.com/svelte-autocomplete I would prefer to just use https://github.com/elcobvg/svelte-autocomplete as the canonical URL for this project.

tag cloud

tag cloud

Jelentése: kulcsszavak vizuális ábrázolása

kulcsszavak vizuális ábrázolása

Because the use of hashtags is inline and you can turn regular words into hashtags (and therefor channels), there is no friction to do so.

Hashtags have the added benefit that they won't show up for others if they're not used.

If you look at which hashtags are being used (trending), you get a taxonomy of micro-contexts, ranked by popularity, with which you can navigate Twitter. All from the bottom up.

The folksonomic approach (user-generated tagging) is beneficial because it allows complexity to emerge bottom-up.

Twitter's hashtags form a dual purpose. They label a status with a certain tag, telling us something about the intended context of that Tweet.

The ease of which makes it frictionless for anyone to jump into the conversation.

But they also equip an interested eavesdropper with the ability to follow along with a conversation. This idea (at the time this was being discussed at Twitter) was already happening with Flickr and Delicious tags.

The idea of:

When you use a hastag and the channel with that name doesn't exist, it gets created, is an idea that came from IRC.

The requirements [[Joe Messina]] laid out for a concept of "channels" on Twitter was that:

1. It shouldn't add any friction to his current use
2. It shouldn't require any web-based management to make the most of

Twitter of 2020 satisfies these requirements. You just type #something, and you can click on that hash or search for it to see results.

[[Joe Messina]] details an example from [[Jaiku]] where you can create a channel by simply posting a message that starts with a hash (#). If the channel doesn't exist, it will be created for you.

[[Joe Messina]]'s reason for suggesting the hashtag was his interest in having "better eavesdropping experience on Twitter"

Az SGML (Standard Generalized Markup Language, szabványos általános jelölőnyelv) egy ISO szabványos jelölőnyelv dokumentumformátumok leírására. Az SGML elődjét, a GML-t (Generalized Markup Language) az 1960-as években fejlesztette ki az IBM-nél Charles Goldfarb, Edward Mosher és Raymond Lorie (családnevük kezdőbetűi alapján találta ki Goldfarb a GML nevet). Ennek leszármazottja az SGML, ami 1986-ban lett ISO ( International Organization for Standardization) szabvány.[1]

Az SGML egy absztrakt szintaxist biztosít, amit sokféle alkalmazásban használhatunk. A szabványos szintaktika lehetővé teszi, hogy az ilyen formátumú dokumentumokat egy általános célú értelmezővel (parser) könnyen beolvashassuk, írhassuk vagy formailag ellenőrizhessük. SGML-ben a jelölések (tag) jelentése nincs meghatározva, ez mindig az SGML-t használó alkalmazás feladata (például a HTML-ben, ami az egyik legismertebb SGML alkalmazás, a jelöléseknek már konkrét jelentésük van, és a jelölések értékkészlete véges).

DOI: 10.1016/j.celrep.2020.108332

Resource: (Cell Signaling Technology Cat# 3724, RRID:AB_1549585)

Curator: @Naa003

SciCrunch record: RRID:AB_1549585

Curator comments: Rabbit Anti-HA-Tag Monoclonal Antibody, Unconjugated, Clone C29F4 Cell Signaling Technology Cat# 3724

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What is this?

practicing

Muss vor dem Tag der offenen Tür auf jeden Fall da hin ;-). (Note to myself)

Ignoring official advice