2. Worms A worm is similar to a virus; the difference is that worms spread on their own instead of attaching to a program and infecting it and others. A lot of the time, worms spread over a network, exploiting a vulnerability to jump from machine to machine. As they continue to recursively spread, worms infect machines at a faster rate. This wastes the network's bandwidth at a minimum, while nastier worms can spread ransomware or other problems across an entire business network.
AAAAA
10. Exploits and Vulnerabilities While not a form of malware, exploits and vulnerabilities are important terms in online security. Because no programmer or software is perfect, every program, OS, and website has some kind of vulnerability. Malicious actors work to find these flaws so they can exploit them to run malware or similar. advertising function refreshcontentwordcount9(){ if(contentwordcount9Changed == 'false'){ googletag.cmd.push(function(){ googletag.pubads().refresh([contentwordcount9]); googletag.display('div-gpt-ad-1555342976270-7'); }); contentwordcount9Changed = 'true'; }; }; For example, say someone discovered a bug that let you create a new admin account with no password in Windows by following certain steps. Someone could write malware to run these steps on someone's PC, get admin access, and then wreak havoc. The best way to stay safe from these threats is keeping your OS and all software up-to-date. Developers patch these problems as they find them, so staying on the latest version keeps you safe from old and known exploits.
WWWWW
8. Rootkit A rootkit (a term which merges the admin "root" account on Unix systems and the "kit" they use) is a type of malware that gains access to restricted parts of a computer and then disguises or otherwise hides itself. Typically, a rootkit gets installed when the attacker has admin (or root) access to a machine. Once the rootkit is installed, it has privileges to do whatever the owner wants on the system. Rootkits abuse this to hide their intrusion—for example, it might cloak its presence from the installed antivirus app. Obviously, a piece of malware having complete control over your system is quite dangerous. A lot of the time, you'll have to completely reinstall the OS to get rid of a rootkit.
SSSSS
5. Spyware Spyware is another type of malware that can take several forms. It refers to programs that track your computer usage for some purpose and reports it back to an entity. Most programs—and even operating systems like Windows 10—collect data about your usage and report it back to the developer. They use this to improve their tools with real-world data. Proper spyware is distinguished by the fact that it collects this data without letting the user know. advertising function refreshcontentwordcount5(){ if(contentwordcount5Changed == 'false'){ googletag.cmd.push(function(){ googletag.pubads().refresh([contentwordcount5]); googletag.display('div-gpt-ad-1555342976270-3'); }); contentwordcount5Changed = 'true'; }; }; While spyware often collects your data for advertising purposes, nastier spyware can also collect sensitive information like login credentials. Extreme spyware includes keyloggers, which are programs that record every keystroke you make on your machine.
DDD
Utterly encapsulating gapless dark ambient experience.
Now there's a touchstone for the ages
Terrifying in its bleakness, Elegy is a record dedicated to its portrayal of loneliness, telling a story with firm roots in tension contextualised by the title’s disheartening implications.
A dedicated sponge in the blank countenance of empty space and flat time, I'd say.
10 Principles of Accessibilities:
3.4 Tag Decoder Architectures
.h2
Note: your arrow must be an HTMLElement (not an SVGElement). To use an SVG arrow, wrap it in a <div> tag with the data-popper-arrow attribute.
Popper for Svelte with actions, no wrapper components or component bindings required! Other Popper libraries for Svelte (including the official @popperjs/svelte library) use a wrapper component that takes the required DOM elements as props. Not only does this require multiple bind:this, you also have to pollute your script tag with multiple DOM references. We can do better with Svelte actions!
but you'll find that wherever you have an img tag inside a link, the image will have a red border under it.
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
free text and tag search
tag
label
das Ziel, die Weltim Positiven zu verändern (vgl. https://www.biblio2030.de/)
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.
So I think with Dropbox specifically, and I’d say also at Notion now, we’re really looking at what the customer feedback is telling us to drive towards. So Notion has an amazing, what we call a tagging database, where all the conversations that come in, we tag them and have a very robust way of organizing that customer feedback. And that helps us drive our roadmap. So mixed in with customer feedback and a little bit of intuition, helps us determine what type of problems you should be solving that are going to really make the most impact for us long term.
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.
There is a dimension of personal preference to it. I don't like to expose more than strictly necessary to external consumers, because it makes it harder to track usages. If you find a bind:prop in a consumer, you know prop is used (which you already kind of knew since the prop is part of the "public" API of the component). Done. If you find a bind:this, you now need to track all usages of this this.
Wo sind die Produktionsstätten im ganzen Land, die Tag und Nacht laufen, um Leben zu retten und Leben zu ermöglichen? Bundeskanzlerin und Gesundheitsminister wussten lange genug, dass es die brauchen wird. Sie könnten auch jetzt noch eingreifen und die finanzielle und gesetzgeberische Macht des Staates, mit der sie Lockdowns verhängt und wirtschaftlich abgefedert haben, zum Aufbau neuer Produktionsanlagen nutzen.
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.
2.3.1. Mail Objects SMTP transports a mail object. A mail object contains an envelope and content. The SMTP envelope is sent as a series of SMTP protocol units (described in Section 3). It consists of an originator address (to Klensin Standards Track [Page 11] RFC 5321 SMTP October 2008 which error reports should be directed), one or more recipient addresses, and optional protocol extension material
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.)
Check out our new flavors!
This is NOT an H1 tag
RRID:AB_1104231
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
We're born feeling. It's simple response to a stimulus. But it takes years of effort and discipline to subjugate our emotions to our reason, to be more than a dog salivating at the sound of a bell, to become worthy of the tag homo sapiens.
Almost universal education and this is still a large scale problem.
Anti-HA.11 Epitope Tag Antibody
DOI: 10.1016/j.xpro.2020.100231
Resource: (Covance Cat# MMS-101R-1000, RRID:AB_291262)
Curator: @Naa003
SciCrunch record: RRID:AB_291262
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?
Get rich slow
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).
// +build trace
添加 trace 的 build tag
Rabbit polyclonal anti-VSV-G 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
S tag
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
Tg(C3-1-TAg)cJeg/JegJ
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
In fact, even <svelte:slot /> feels a bit confusing because it introduces a new kind of slot, where the concept is already a bit crowded (there the <slot /> in the parent component, and the target slot="name" for the slot content).
tag?: crowded (how do we disambiguate, make it not ambiguous?)
Some devs prefer Svelte’s minimal approach that defers problems to userland, encouraging more innovation, choice, and fragmentation, and other devs prefer a more fully integrated toolkit with a well-supported happy path.
tag?: what scope of provided features / recommended happy path is needed?
It’s worth mentioning that Svelte limits its scope to being only a UI component framework. Like React, it provides the view layer, but it has more batteries included with its component-scoped CSS and extensible stores for state management. Others like Angular and Vue provide a more all-in-one solution with official routers, opinionated state management, CLIs, and more. Sapper is Svelte’s official app framework that adds routing, server-side rendering, code splitting, and some other essential app features, but it has no opinions about state management and beyond. Some devs prefer Svelte’s minimal approach that defers problems to userland, encouraging more innovation, choice, and fragmentation, and other devs prefer a more fully integrated toolkit with a well-supported happy path.
tag?: what scope of provided features / recommended happy path is needed?
With the caveat that hero worship can be gross, distorting, and unhelpful to everyone involved, Svelte author Rich Harris (@rich_harris on Twitter) is one of my favorite open source developers. In the JS community he’s well-known among tool authors for spreading interesting ideas. He’s the creator of many open source projects including Rollup, the bundler of choice for many libraries including React and Vue.
Svelte is its own language, not plain HTML+CSS+JS
its own _
The compiler architecture moves complexity from the runtime and source code to buildtime and tools. Behind Svelte’s simple APIs sits a beefy compiler. Frontend web development has become very tool heavy in the webapp era, so in practice this adds little cost beyond what developers like myself already pay, but increased build complexity is important to acknowledge.
tool-heavy dependence on build tools / heavy/complex build-time
A preferred medium is the price tag: in New Orleans, where he currently lives, he once ran a lunch cart that asked white patrons to pay more than double what he charged people of color, reflecting the city’s racial income disparities. In Nashville, he hosted a series of dinners where hot chicken was free for the neighborhood’s black residents, while white diners were asked to pledge a hundred dollars for one piece, a thousand dollars for four, and the deed to a property for a whole bird plus sides.
I absolutely love this concept that he did
First, I'll tag each idea with the book I got it from
给每个想法以 书名 为标签
我也是这么想的:)
streptavidin-HRP
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
RRID:AB_2798161
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
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?
some common metadata
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.
communication
skill tag 1
Remora Communiqué
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…
In Python, every object has a unique identification tag
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.
Image-based memes involve, primarily, an image created by somebody. Sometimes the meme creator is also the image creator, but often, when involving movie stills or images of celebrities, the image’s copyright is owned by someone else. American copyright law gives creators the exclusive rights of reproduction, modification, distribution, performance, and display. The viral spread of a meme infringes on theses protections as the original image is modified and then displayed, distributed and reproduced when posted and reposted.
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.
None
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:
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
Allow me to tag books instead of placing them into static lists (think clusters or tag clouds).
Have your tried Roam Research?
Mouse monoclonal anti-V5
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
We’re now 100% powered by renewable and sustainable energy which is great in further minimizing our impact on the planet. Plausible Analytics script weights less than 1 KB which is more than 45 times smaller than the recommended Google Analytics Global Site Tag implementation.
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.
There's a huge area of seemingly obvious user-centric products that don't exist simply because there isn't a working business model to support it.
500 iPad-Koffer mit insgesamt 8000 Geräten
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 also find that a lot of the complexity of Flutter can be avoided, and I mostly use it to define the UI as a more app-centric alternative to HTML/CSS.
I mostly use it to define the UI as a more app-centric alternative to HTML/CSS.
Anthony Tattersal
I suggest to add a link to his biography or any other link that tells the reader who he is
Benardou, Agiatis, Panos Constantopoulos, Costis Dallas, et Dimitris Gavrilis. 2010. « Understanding the information requirements of arts and humanities scholarship ». International Journal of Digital Curation 5 (1):18‑33. « British Museum Collection ». 2015. https://old.datahub.io/dataset/british-museum-collection. Brown, Susan. 2011. « Don’t Mind the Gap: Evolving Digital Modes of Scholarly Production across the Digital-Humanities Divide ». In Retooling the humanities: The culture of research in Canadian universities, édité par Daniel Coleman et Smaro Kamboureli, 203‑31. Edmonton: University of Alberta Press. http://hdl.handle.net/10402/era.25382. Brown, Susan, et John Simpson. 2013. « The curious identity of Michael Field and its implications for humanities research with the semantic web ». In 2013 IEEE International Conference on Big Data, 77‑85. IEEE. http://ieeexplore.ieee.org/xpls/abs_all.jsp?arnumber=6691674&tag=1. Bulger, M, E Meyer, G De la Flor, M Terras, S Wyatt, M Jirotka, K Eccles, et others. 2011. « Reinventing research? Information practices in the humanities ». Information Practices in the Humanities (March 2011). A Research Information Network Report. Crane, Gregory. 2006. « What do you do with a million books? » D-Lib magazine 12 (3). Corporation for National Research Initiatives. « DBpedia ». 2015. https://wiki.dbpedia.org/. « Digital Environmental Humanities ». 2015. https://dig-eh.org/. « Dublin Core Metada Initiative ». 2015. https://www.dublincore.org/. Egerton, Frank N. 2013. « History of ecological sciences, part 47: Ernst Haeckel’s ecology ». The Bulletin of the Ecological Society of America 94 (3). JSTOR:222‑44. « eMOP: Early Modern OCR Project ». 2015. https://emop.tamu.edu/. Europeana. 2014. « Linked Open Data ». Europeana Pro. https://pro.europeana.eu/page/linked-open-data. Fons, Ted. 2014. « Transforming bibliographic records into linked open data (LOD) ». Panel presentation at the Coalition for Networked Information Fall 2014. https://www.cni.org/topics/information-access-retrieval/exposing-library-collections-on-the-web-challenges-and-lessons-learned. Godby, Jean, Karen Smith-Yoshimura, Bruce Washburn, Kalan Knudson Davis, Karen Detling, Christine Fernsebner Eslao, Steven Folsom, et al. 2019. « Creating Library Linked Data with Wikibase: Lessons Learned from Project Passage ». OCLC Research Report. https://www.oclc.org/content/dam/research/publications/2019/oclcresearch-creating-library-linked-data-with-wikibase-project-passage.pdf. Hegde, Medha. 2012. « Ecotones: the transitional zones ». Biotech Articles, nᵒ 12. http://www.biotecharticles.com/Biology-Article/Ecotones-The-Transitional-Zones-2191.html. Hendler, Jim, et others. 2011. « Why the Semantic Web will never work ». In 7th Extended Semantic Web Conference (ESWC 2011), Crete, Greece. http://videolectures.net/eswc2011_hendler_work/. Internet Philosophy Ontology (InPhO) Project. s. d. « The InPhO Project ». Consulté le 19 juin 2020. https://www.inphoproject.org/. Jaeger, Paul T, Jimmy Lin, Justin M Grimes, et Shannon N Simmons. 2009. « Where is the cloud? Geography, economics, environment, and jurisdiction in cloud computing ». First Monday 14 (5). Klein, Max. 2012. « VIAFbot Debriefing ». OCLC Research. https://hangingtogether.org/?p=2306. Krafft, Dean, et Tom Cramer. 2014. « Video: Linked Data For Libraries (LD4L) Project Update ». Coalition for Networked Information. https://www.cni.org/news/video-linked-data-for-libraries-ld4l-project-update. Lam, Dominic. 2014. « Big Data Challenges in Social Sciences & Humanities Research ». Datanami. https://www.datanami.com/2014/09/08/big-data-challenges-social-sciences-humanities-research/. « Linked Data for Libraries (LD4L) ». 2014. https://wiki.lyrasis.org/pages/viewpage.action?pageId=41354028. LODE: Linked Open Data Enhancer. s. d. « Gihub Linkedhumanities/lode ». Consulté le 19 juin 2020. https://github.com/linkedhumanities/lode. McCarty, William. 2005. Humanities Computing. Palgrave Macmillan UK. Nardi, Bonnie, et Vicki O’Day. 1999. « Information Ecologies: Using Technology with Heart-Chapter Four ». First Monday 4 (5). Valauskas, Edward J. http://firstmonday.org/ojs/index.php/fm/article/view/672/582. OCLC Research. 2014. « Scholars’ Contributions to VIAF ». https://www.oclc.org/research/areas/data-science/viaf-scholars.html. « Open Annotation Data Model ». 2013. http://www.openannotation.org/spec/core/. Pan-Canadian Documentary Heritage Network. s. d. « Linked Open Data (LOD) Visualization “Proof-of-Concept.” ». Canadiana. Consulté le 13 septembre 2015. http://www.canadiana.ca/sites/pub.canadiana.ca/files/PCDHN\%20Proof-of-concept\_Final-Report-ENG\_0.pdf. Price, Gary. 2012. « Video: “Out of the Trenches: A Linked Open Data Project” From the Pan-Canadian Documentary Heritage Network ». LJ infoDOCKET. https://www.infodocket.com/2012/10/25/video-out-of-the-trenches-a-linked-open-data-project-from-pan-canadian-documentary-heritage-network/. Risser, Paul G. 1990. « The ecological importance of land-water ecotones ». In The ecology and management of aquatic-terrestrial ecotones, édité par H Décamps et Naiman R J, 7‑21. Paris: UNESCO. « Schema.org ». 2015. https://schema.org/. Searle, John R. 1995. The construction of social reality. New York: Simon; Schuster. Simpson, John Edward, Susan Brown, et Lisa Goddard. 2013. « A Humanist Perspective on Building Ontologies in Theory and Practice. » In Digital Humanities Conference Abstracts 2013, édité par University of Nebraska, 403‑5. Lincoln. http://dh2013.unl.edu/abstracts/ab-413.html. Smith-Yoshimura, Karen, David Michelson, et Beth Mardutho. 2013. « Irreconcilable differences? Name authority control & humanities scholarship ». OCLC Research. http://hangingtogether.org/?p=2621. « The Muninn Project ». 2015. http://blog.muninn-project.org/. The Stanford Natural Language Processing Group. s. d. « Software > Stanford Named Entity Recognizer (NER) ». Consulté le 19 juin 2020. https://nlp.stanford.edu/software/CRF-NER.html. Uddin, Mueen, et Azizah Abdul Rahman. 2011. « Techniques to implement in green data centres to achieve energy efficiency and reduce global warming effects ». International Journal of Global Warming 3 (4). Inderscience Publishers:372‑89. « VIAF ». 2015. https://viaf.org/. « VIVO Open Research Networking Community Group ». 2015. https://www.w3.org/community/vivo/. Warren, Robert. 2012. « Creating specialized ontologies using Wikipedia: The Muninn experience ». Proceedings of Wikipedia Academy: Research and Free Knowledge (WPAC2012). Berlin. https://wikipedia-academy.wikimedia.de/w/images.wikipedia-academy-2012/0/0f/21_Paper_Robert_Warren.pdf. Widmer, Rolf, Heidi Oswald-Krapf, Deepali Sinha-Khetriwal, Max Schnellmann, et Heinz Böni. 2005. « Global perspectives on e-waste ». Environmental impact assessment review 25 (5). Elsevier:436‑58. « WorldCat Entities ». 2015. OCLC Developer Network. https://www.oclc.org/developer/develop/linked-data/worldcat-entities.en.html. Wuppleman, William. 2012. « Out of the trenches: A linked open data project ». Canadiana. https://www.canadiana.ca.
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.
A Wikipedia kifogása az iTA szócikkel kapcsolatban
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.
am 17. April 1967, einen Tag vor seinem Tod
Welche Relevanz haben Datum und Zeitpunkt der Verabreichung?
(15x) ENJOYMENT: Forgettable Outstanding(10x) DEPTH (IN RELATION TO COMPLEXITY): Lacking Meaty (5x) LUCK FACTOR: All Luck All Skill (3x) REPLAYABILITY: Nil Limitless(10x) MECHANICS: Boring Interesting (4x) PLAYER INTERACTION: Low High (4x) PLAYER COUNT PERFORMANCE: Not Balanced Balanced (2x) GAME LENGTH: Too Short/Long Just Right (2x) CLARITY OF RULES: Mud Crystal (5x) COMPONENT QUALITY: Cheap World ClassINITIAL RATING (sum(Criteria Rating x Criteria Weight)/Total Weight) = 7.7
rating scale evaluation
mouse monoclonal anti-myc
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
The FBI said it has stopped using the "Black Identity Extremist" tag and acknowledged that white supremacist violence is the biggest terrorist threat this country faces.
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.
adatlapja
hozzáadtam (2020.11.15)
l’aboutissement de la V1
git tag V1
l’aboutissement de la V1
git tag V1
Digitális Irodalmi Akadémia tagja
Alapító tag
Luckily, Tinder offers a variety of additional signal amplifiers that help you to stand out. The sole purpose of features like Tinder Boost and Super Likes is to outcompete status rivals by giving you preferential signaling treatment. And guess what – they come with a price tag.
Julian claims Tinder is monetizing on signal amplifiers like Boost and Super Like.
Another point of evidence is the lack of luxury software products. People spend absurd amounts of money on jewellery, handbags and cars, but I can’t think of a piece of software with an even remotely similar price tag. Sure, people have tried to sell $999 apps but those never took off.
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.
添加标签（tag）
测试tags
It isn't really compatible with HTML5's input "required" attribute. If an input has the required tag, and you press the submit buton, and the field is empty the browser will fire the "Please fill out this field" message, BUT, you also just disabled that submit button. So in effect, the form can no longer be submitted.
This whole system is much, much better than having to manually update some CRM like in Airtable. Since you're naturally tagging people as you interact with them, you can create an easy record of your relationship with them and compile any useful notes on them as you go.
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".
This removes all the decision making about where to put things that you frequently run into with Evernote, Notion, etc. When everything can be everywhere, you don’t have to worry about the filing structure. You just keep adding links.
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.
By structuring information in this way, Roam makes it super easy to move laterally across your information, while retaining vertical references. The book Emergency by Neil Strauss can live in my Book Notes page, my Prepping page, and my Neil Strauss page, without having to be moved.
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.
This also highlights a big difference between Roam and other note taking tools: tags are both everything and nothing. Every page is a tag, and every tag is a page.
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.
By keeping the price of ebooks high, publishers keep paperbacks as a valid option for readers. That way, the world of physical books isn't under threat of becoming extinct due to ebooks.
Do you like this reason?
If you're an avid reader, you may know the pain of losing or damaging your books. Ebooks, however, don't share this problem.
How long do ebooks last?
Has one of your ebooks ever become damaged?
Have you ever lost an ebook?
On top of this, ebooks are very convenient for the readers buying them. Buying a physical book involves going to a bookstore and hoping they have it in stock, or ordering it online and waiting for it to arrive. For ebooks, you go to a website, click the "Buy" button, and download the book to your PC or reader.
Are people willing to pay for convenience?
This constraint is the reason ebooks sometimes cost more than paperbacks. For example, a publisher can list the price of their physical book at $27.95 and the ebook at $20, which is a reasonable 30 percent markdown.
Explain why ebooks sometimes cost more than physical books.
Unlike with physical books, Amazon has no control over the price of ebooks. If someone has performed the steps required to publish an ebook via Kindle Direct Publishing, they set the price as they please, with no exceptions.
Do you think this is true for authors who don't have a following?
However, ebooks utilize the agency model when sold. Instead of letting the retailer choose the price, the publisher states what they're selling for. The publisher gets 70 percent of each transaction, and the retailer gets the remaining 30 percent.
How is the pricing system for ebooks different from the one for physical books?
Everything makes sense when you imagine all of the people who helped make the book who need paying. For one, the author has to get their agreed royalty cut from every sale. From there, the editors, proofreaders, cover artists, and marketers all need to be paid. These obligations don't leave the publisher with a lot of money for themselves.
Who else needs to be paid besides just the author?
a physical book takes around $1-2 to produce. If this is true, however, then why are they priced a lot more than that?
Does this surprise you?
Great list! Some things we didn't think about until we needed them are:
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.
címkefelhő
tag cloud
Címkefelhő
tag cloud
tag cloud
Jelentése: kulcsszavak vizuális ábrázolása
(tag cloud
kulcsszavak vizuális ábrázolása
Oh, and from a language/design perspective, you can actually turn regular words in a sentence into channels, just as many people do with @replies. For example: I’m coming to #barcamp later today.
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.
It also enforces actual use in the wild of tags, since no evidence of a tag will exist without it first being used in conversation. This means that representing channels in tagclouds across the site that grow and fade over time, and are contextual to all of Twitter or to a single user, is the ideal interface for displaying this information.
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.
I also like that the folksonomic approach (as in, there are no “pre-established groups”) allows for a great deal of expression, of negotiation (I imagine that #barcamp will be a common tag between events, but that’s fine, since if there is a collision, say between two separate BarCamps on the same day, they’ll just have to socially engineer a solution and probably pick a new tag, like #barcampblock) and of decay (that is, over time, as tags are used less frequently, other people can reuse them — no domain squatting!).
The folksonomic approach (user-generated tagging) is beneficial because it allows complexity to emerge bottom-up.
Every time someone uses a channel tag to mark a status, not only do we know something specific about that status, but others can eavesdrop on the context of it and then join in the channel and contribute as well. Rather than trying to ping-pong discussion between one or more individuals with daisy-chained @replies, using a simple #reply means that people not in the @reply queue will be able to follow along, as people do with Flickr or Delicious tags. Furthermore, topics that enter into existing channels will become visible to those who have previously joined in the discussion. And, perhaps best of all, anyone can choose to leave or remove topics that don’t interest them.
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.
This is how it works in IRC, and how it needed to work in Twitter.
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.
Now, in thinking about implementing channels, it was imperative that I not introduce any significant changes into the way that I currently use Twitter any more than I have for other features that have been added to Twitter (for example, @replies or direct messages). Channels would need to be a command-line-friendly addition, and one that would require absolutely zero web-based management to make the most of it (to draw a distinction, Pownce fails this test with its Friend Sets, since it requires use of their website to take advantage of this feature).
The requirements [[Joe Messina]] laid out for a concept of "channels" on Twitter was that:
Twitter of 2020 satisfies these requirements. You just type #something, and you can click on that hash or search for it to see results.
Jaiku comes closest with their channels implementation, making it extremely easy to create new channels (simply post a message that begins with a hash (#) and your intended channel name — and if the channel doesn’t exist, it’ll be created for you):
[[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.
I’m more interested in simply having a better eavesdropping experience on Twitter.
[[Joe Messina]]'s reason for suggesting the hashtag was his interest in having "better eavesdropping experience on Twitter"
SGML
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).
anti-HA
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
Nutrition
practicing
Schulprogramm (wird überarbeitet)
Muss vor dem Tag der offenen Tür auf jeden Fall da hin ;-). (Note to myself)
Did you look at it and decide not, or not look at it?
This isn't written to hype a battle in the holy war.
It looks like you just deleted our lovely crafted issue template. It was there for good reasons. Please help us solving your issue by answering the questions asked in this template. I'm closing this. Please either update the issue with the template and reopen, or open a new issue.
Ignoring official advice
See: https://github.com/sveltejs/svelte/issues/5158
I also tried to use
<!-- svelte-ignore unused-export-let -->before thescripttag but still no chance.
I also tried to use <!-- svelte-ignore unused-export-let --> before the script tag but still no chance.
As of version 3.5.2 and #3013, attributes that are set to null or undefined won't be added to the tag.
group: Ariel Methodology Group Narrow your search: user: search by username tag: search for annotations with a tag url: search by URLfor domain level search add trailing /* eg. example.com/* group: show annotations associated with a group Danfff1
test note
test note
And that’s because to treat graphic design like it’s a service, where it makes sense to optimize time and labor for maximum efficiency, undermines the aura of indispensability, superiority, and yes, authenticity that institutions such as design schools and “professional associations” rely on in order to justify the massive dollar signs they place on themselves via tuition, and member fees.
I'm assuming Libby means that Rob Giampietro is on the other side of the argument where viewing design as something to be optimized for efficiency undermines that high dollar price tag that institutions have marketed as only possible by studying with them. But she is on the side that, that thinking is irrelevant to how design ought to progress.
http://jonudell.info/h/tag-rename-02.mp4
Most people would embed a YouTube video. Nice to see no dependency on 3rd-party service here.
The submission system required students to manually enter all ‘‘tags’’ (rele-vant topic keywords) for their letters, entering up to five tags per letter; thesystem did not provide a menu list of common issues for students to choosefrom.
I like that the tags were student generated. Personally, when given a list to choose a tag from sometimes I don't feel the tag is listed that is most appropriate. I enjoy that students were able to create their own tags to summarize the main issue of their letter.
For example, Samuel H. chose a "classroom" tag that peaked my interest. I was curious to explore what issues in the classroom he believed should be addressed. This is one of the aspects that stood out to me.
Looking at all those bearing, heading, orientation, navigation, position, direction, etc. I think we have a bigger problem here. Someone has decided how to use tag (e.g. orientation is about page orientation), but there are 100 other cases. Imho, to disallow misusing there should be no "heading", but rather "html-heading", "gps-heading", "whatelse-heading", which make mistakes impossible. So yes, "heading" should go.
Retagging the HTML/CSS questions to use html-heading seems the right thing to do. For the other uses, I don't have enough grounding in the geographic area to know whether the direction and bearing are replacements for heading. But the tag information for heading should be created and should firmly point at the other tags — at least until it is expunged.
Wurde beispielsweise ein Algorithmus zur Erkennung von Hautkrankheiten an Bildern isländischer Patienten trainiert, wäre das eine wichtige Information, da der Algorithmus womöglich bei australischen Ureinwohnern eine völlige andere Trefferquote an den Tag legt.
Welche Rolle spielt das Training von Algorithmen? Wie funktioniert es?
H3K14ub is a histone modification that facilitates deposition of H3K9me on heterochromatin in fission yeast, but the mechanism by which this modification stimulates Clr4 was unknown. Using mutants and HDX, the authors identified the interaction surface of Clr4 for H3K14ub, which they used to design mutants that responded poorly to H3K14ub stimulation. In vivo, these mutations resulted in loss of heterochromatin marks and defects in heterochromatin-based silencing, suggesting that H3K14ub stimulation is essential to K9me-mediated silencing. Finally, the authors show that human SUV39H2 but not G9a or Arabidopsis SUVH4 can be stimulated by H3K14ub in a similar manner.
The authors provided biochemical and structural insights into the mechanism that increases the H3K9-specific methyltransferase activity of Clr4 by H3K14ub. Although H3K14ub-mediated promotion of H3K9 methylation is shown in Oya et al. EMBO Rep 2019, this study further characterizes the potential mechanism. However, there are some issues with the results that need to be resolved.
1) Similarity and difference with the previous study. As the authors acknowledge, this manuscript builds on a previous study by Oya et al. 2019, however I think the similarities and the differences need to be made even more explicit and better addressed.
a) The authors should clearly state that Figure 1B and 1C are basically a confirmation of Oya et al. 2019.
b) I am more puzzled by the difference in the mapping of the region required for H3K14ub stimulation. The authors suggest that a difference in the preparation of the recombinant proteins might be responsible. This can and should be tested as it would seemingly be a simple experiment (compare with and without GST tag).
c) Possibly to reconcile their findings with the previous report the authors state in the description of Fig. 1 that "the N-terminus plays a regulatory role in the sensing of H3K14ub by the catalytic domain" but I don't see this reflected in the data show in Fig. 1C, given that the degree of stimulation is very similar for KMT and FL.
2) Stimulation-defective mutants. The authors should carefully discuss the stimulation-defective mutants, which should be premised on the retention of their methyltransferase activity on unmodified H3. The authors claim that 30% loss of activity of the Clr4 KMT mutants on unmodified H3 is observed in Figure S3C (Pg 11 line 15), but this cannot be determined from the graph provided, which is normalized to unmodified H3. The authors should (1) make another graph to show the 30% loss and (2) compare Clr4 KMT mutants with catalytic-dead Clr4 KMT or dissolution buffer (no protein). It is still possible that GS253 and F3A mutations simply reduce MTase activity, thus displaying lower activity than WT in the presence of H3K14ub, which would also suggest a different interpretation for the results in vivo.
3) Heterochromatin localization of Clr4 mutants. The FLAG ChIP results in Fig. 4E is not very informative, as with the loss of heterochromatin a loss of Clr4 is predicted. If the authors want to test whether the localization activity of Clr4 mutants is intact, (1) FLAG ChIP in the clr4+, Flag-Clr4GS253/F3A background (i.e., two clr4 alleles exist) or (2) in vitro H3K9me2/3 binding assay should be performed. Since Clr4 N-terminus might regulate MTase activity as discussed in Pg 18 line 19, it is also possible that amino acid substitutions in the KMT region affect the function of N-terminus, including CD. The co-IP in Fig. 4C is not sufficient to clarify this point as Clr4 directly binds heterochromatin via its CD, in addition to the CLRC-mediated mechanism, and it is unclear if this is affected in the mutants.
4) Allosteric vs. binding regulation. On Pg. 11, the authors suggest that an allosteric mechanism is at play, but this is not supported by the data. In fact the observation that providing ubiquitin in trans does not stimulate and rather inhibits the activity on H3K14ub would suggest that the ubiquitin just increases binding affinity. To clarify this the authors should measure binding affinity of WT and mutants to the H3 peptide with and without ubiquitin.
This manuscript further characterizes the role of HILPDA/HIG2 in TAG/LD biology. The major finding is that HILPDA interacts with and promotes DGAT activity and TAG synthesis, which is novel given that HILPDA has largely been thought to regulate TAG turnover as a lipolytic inhibitor.
Characterization of the interaction between HILPDA and DGAT1 (and to a lesser extent DGAT2) is the major strength of this paper and an important advancement in the field. The early parts of the paper are not particularly novel (Fig. 1) or well-designed (Fig 2. - poor NAFLD/NASH model showing almost no effects) and the study is a bit on the thin side for data.
1) The data shown in Figure 1 is not particularly striking given that HILPDA is a known target gene of PPAR-alpha, which is activated by FAs. Showing that HILPDA expression tracks with PLIN2 is also pretty obvious as PLIN2 tracks with LD accumulation. I really don't see the need/relevance of this figure.
2) The MCD diet is widely regarded as a poor model for NAFLD/NASH since it doesn't replicate human NASH in so many regards. As a result, the use of this model makes these studies less relevant. Also, it is referenced that HILPDA was found to be up in a MCD study, but why not look at the plethora of human and mouse studies of NAFLD that have done RNAseq or arrays to provide a more physiological assessment of its expression in NAFLD/NASH?
3) The conclusion that effects are independent of ATGL are not overly convincing. Since ATGListatin is not specific for ATGL (Quiroga et al. 2018), a more thorough and quantitative analysis of TAG turnover with ATGL knockdown/out is warranted if these claims are to be made.
4) Since DGAT1 mRNA is unchanged but protein goes up, it would be assumed that HILPDA is affecting DGAT1 stability/turnover. This should be considered.
This study dissects the role of LD associated protein HILPDA in triglyceride and LD homeostasis in hepatic tissue. Using a mouse tissue-specific HILPDA KO, live cell imaging, and lipid analysis, it proposes that HILPDA promotes TAG storage in LDs independently of ATGL regulation. Instead, HILPDA is proposed to interact with DGAT1 and promote TAG synthesis/storage.
This is an interesting and potentially exciting study that provides a new insight for HILPDA in liver fat storage. The proposed model differs from previous literature that proposes HILPDA regulates lipolysis via ATGL. Unfortunately, while the data presented support a potential role for HILPDA in DGAT regulation, a clear mechanism is not identified. The first half of the paper that phenotypes loss and over-expression of HILPDA is thorough and conclusive. The latter half of the paper, investigating the interplay between HILPDA and DGAT1, appears more preliminary.
The critical issue in this study is that the nature of the HILPDA-DGAT1 interaction is not well defined. HILPDA over-expression is shown to increase DGAT1 protein levels, but the specific mechanism underlying this is not further dissected. Furthermore, it is still unclear whether this interaction is direct, or merely stochastic due to the fact that both DGAT1 and HILPDA reside on the same LDs in the experiments presented. More biochemical investigation as to whether these proteins physically interact in their native states, and if so whether that interaction affects DGAT1 enzymatic activity directly or allosterically, is required. Without this the study is mainly descriptive.
Major concerns:
1) Fig 4: overnight and acute fatty acid addition experiment: The authors propose that HILPDA enriches at sites where new fatty acids are being processed. Can you demonstrate that both these fluorescent FA species are even being incorporated into TAG during the time periods associated with the microscopy? An alternative explanation is simply that HILPDA localizes to regions of the cell where FA esterification or incorporation into other lipid species is occurring. TAG is potentially only one of many fates for these FAs. Can DGAT1/2 be colocalized with HILPDA in these experiments? Alternatively, what happens in these experiments if DGAT inhibitors are co-added with the FAs?
2) Fig 5H: The DGAT activity assays indicate that HILPDA over-expression increases the incorporation of fluorescent FA and DAG into TAG, but it is unclear as written whether these assays are normalizing for DGAT1 protein amount. Does HILPDA over-expression enhance DGAT enzymatic activity in this panel, or merely promote TAG synthesis here by the increased total DGAT protein level noted later in the study? This is a clear distinction in mechanism, and needs to be dissected further.
3) Fig 6/7: DGAT1-HILPDA interaction. The data presented in Fig 7 indicate that DGAT1 and HILPDA co-localize in cells and potentially are in very close proximity with one another. However, the data as presented are not enough to indicate whether these proteins directly interact. Do these proteins immunoprecipitate with one another? Some biochemical evidence for their interaction is necessary
4) Fig 7: relatedly, the mechanism by which DGAT1 is increased in protein level from HILPDA is also unclear. Is the protein more long-lived, or stabilized in the ER when HILPDA is over-expressed? Again, protein biochemical analysis would be helpful.
This preprint was reviewed using eLife’s Preprint Review service, which provides public peer reviews of manuscripts posted on bioRxiv for the benefit of the authors, readers, potential readers, and others interested in our assessment of the work. This review applies only to version 2 of the manuscript.
This study further characterizes the role of lipid droplet (LD) associated protein HILPDA in LD biology. The authors propose that HILPDA promotes triglyceride (TAG) storage in LDs by a mechanism independent of ATGL, through activation of DGAT. This is a potentially interesting finding, however, as detailed by the reviewers below, the data presented do not identify a mechanism for how HILPDA affects DGAT.
We could broadcast a warning if we find the variable to be set in the environment, but that is more likely than not to annoy people who intentionally set it.
New tag?: warnings that may annoy people who intentionally do something. (Need a way to selectively silence certain warnings?)
Malicious code pushed to your .gitlab-ci.yml file could compromise your variables and send them to a third party server regardless of the masked setting. If the pipeline runs on a protected branch or protected tag, it could also compromise protected variables.
With over 1,500 dating apps on the market, many have come to the conclusion that the romance of courtship has been replaced with fantasy and heavily-edited Instagram photos. Along with driving this increase in dating apps, the millennial generation is also delaying marriage and moving away from conventional religious practices. Because of this, many popular magazines and TV shows suggest that hook-up culture dominates contemporary pursuits of love. Right-swiping, label free, highly educated, and technologically savvy, today’s young people appear to pursue sex frequently and do so on their own terms. There also appears to be much more equal footing between genders than ever before.
This is true, young generation does not want to bound themselves in a permanent relationship tag because now they have lots of options due to dating apps.
Although Madisyn applied only one tag of ‘‘Race’’ and did nottag her letter with ‘‘Police,’’ ‘‘Violence,’’ or anything else, her letter speaksto students’ deep and related concerns around discrimination, violence,and specifically the role of police.
This is observed in two of my letters too. Although the students tag their letters to one topic, they talk about other related issues. For example, in Vivian's letter "Problems in education", she talks about equity in education, standardized testing, and teacher pay. Her letter speaks to deeper and broader issues in education. - Anitha
BIO
gold data: IOB(inside-outside-beginning) format or BIO
quote from this link https://towardsdatascience.com/named-entity-recognition-and-classification-with-scikit-learn-f05372f07ba2
The IOB (short for inside, outside, beginning) is a common tagging format for tagging tokens. I- prefix before a tag indicates that the tag is inside a chunk. B- prefix before a tag indicates that the tag is the beginning of a chunk. An O tag indicates that a token belongs to no chunk (outside).
THE BOOK OF TEA By Kakuzo Okakura
Hi Bob!! 👋
Storyboard_cursoID
mouse anti‐DDDDK‐tag
DOI: 10.1111/acel.13251
Resource: (MBL International Cat# M185-3, RRID:AB_10950447)
Curator: @Naa003
SciCrunch record: RRID:AB_10950447
Curator comments: anti-DDDDK-tag antibody MBL International Cat# M185-3
I expected that the param being passed by reference to have the same reactivity of the variable being created in the script tag.
Kit_wikicite
nach der ein Schwangerschaftsabbruch (SSA) bis zur 12. Woche nach dem 1. Tag der
Sicher? Ich dachte 14 Wochen ab menstruation und 12 ab Empfängnis?
https://www.profamilia.de/themen/schwangerschaftsabbruch.html
Paths are traversed in the order they occur in the search path. By default, this means the files in app/assets take precedence, and will mask corresponding paths in lib and vendor.
Doing so also means adding empty import statements to guarantee correct order of evaluation of modules (in ES modules, evaluation order is determined statically by the order of import declarations, whereas in CommonJS – and environments that simulate CommonJS by shipping a module loader, i.e. Browserify and Webpack – evaluation order is determined at runtime by the order in which require statements are encountered).
Here: dynamic loading (libraries/functions) meaning: at run time
We then made our way to the scanner. After removing all metal objects —including a belt and a stray dry-cleaning tag with a staple
Everythingmetal need yo be removed?
Kit_doaj
Someadolescents also create personal sites because their friends have
Some create their online presence as a communication tool because their friends have it and its the easiest way to reach them, texting can go as far as gifs , voice notes and more but the online precence brings you closer to their online precense as you can tag your friends in funny memes, videos or the coolest trip to plan next , it builds togetherness and interaction without seeing that person face to face but as a means of interaction
In some cases, I could also create a component without any <script> tag at all. So in that way, I could actually bulk up the logic in one place if I could get some help from the #with block.
I'm more inclined towards an {@ tag than a {# tag because the indentation could quickly get out of control
Contrast with: https://hyp.is/U_7sXhGREeumDJvbgTImjQ/github.com/sveltejs/svelte/pull/4601
create catalog manifest and CASE files
In this stage we create + upload the ibm-appconnect-operator.tar.gz archive.
unstashes 'repo', 'operatormanifestinfo' 'bundlemanifestinfo' 'csv' So that we have access to operator, operator-init, and bundle fat manifest digests. Also access to csv and operator.yaml file.
run the scrpt create-operator-archive.sh which in turn runs the create-catalog-manifest.sh script, which in turn does:
Downland cp4i-operator-bundle-tools.tar.gz from Artifactory and extract it jenkins-build-scripts/cp4i-operator-bundle-tools, that's so to use the push-images-to-er.sh script later on.
call the create-manifest-image-from-platform-images.sh script, which in turn creates the appconnect-operator-catalog fat manifest with the tag ${VERSION}-${BUILD_TIMESTAMP} and pushes it up to appconnect artifactory. it also creates the OperatorCatalogDigest file.
returning back to create-catalog-manifest.sh, update the deploy/catalogsource.yaml file with the new appconnect-operator-catalog fat manifest's digest value
calls the script push-images-to-er.sh in order to copy appconnect-operator-catalog fat manifest to staging Entitled Registry. copied across using tag->digests, then copied across digest->tags. then copied across arch-specific-tags->arch-digests (to enable va scanning).
back in create-catalog-manifest.sh script, in staging ER, assign "latest" to the newly uploaded catalog fat manifest, ${VERSION}-${BUILD_TIMESTAMP}->latest
Returning back to create-operator-archive.sh,
feed the stashed goodimages.json to create-resources-yaml.sh script. This in turn generates the resource.yaml file under the "case" folder.
Curl the cp4i-operator-bundle-tools.tar.gz from artifactory and put it in the jenkins-build-scripts folder. This folder will get ignrore a bit later.
Download cp4i-deploy-operator.tar.gz from artifactory and extract it in the stable/ibm-appconnect-bundle/tests folder
copy the airgap.sh and put it in the stable/ibm-appconnect-bundle/operators/ibm-appconnect/scripts/ folder
copy all "PROD" goodimages.json images into staging ER.
update "latest" tag to now point to the new uploaded gooimages.json images in staging ER.
Also copy some "dev" goodimages.json images into staging ER. That's so that developers can requests images get pull from dockerhub, but actually get pulled from staging ER thanks to openshift registry redirect.
copy the dev images above the /appc bit. so dockerhub urls don't have to specify /appc. Also retag to latest.
Create ibm-appconnect-operator.tar.gz archive. but exclude:
--exclude "${APP_NAME}/jenkins-build-scripts"
--exclude "${APP_NAME}/.travis.yml"
--exclude "${APP_NAME}/.git"
back in jenkinsfile, upload this archive to artifactory in the "latest" folder, this will overwrite what is already there.
Update jenkins job description with info about what has been built.
triggers the job - test-and-promote-cp4i-demo-system. but it doesn't wait for it to succeed.
resulting files:
create operator manifest image
runs the create-operator-manifests.sh script:
2.1 pulls down each arch image using ${VERSION}-${BUILD_TIMESTAMP}-${arch} tags
2.2 create docker manifest with tag - ${VERSION}-${BUILD_TIMESTAMP}. And add both entries.
2.3 push up operator manifest to appconnect artifactory
2.4 Create the OperatorImageDigest file
Update the operator.yaml file with the fat manifest digests of both appconnect-operator and init image.
create new stash called operatormanifestinfo. This specifically specifies the 2 new top level digest files and the changes made to operator.yaml (with the same digests)
Tagging
I have found that tagging is really helpful. It might be interesting to see what are common themes.
It is important to note here that the flow does not need to begin with a user interaction. With the rise of asynchronous middleware like redux-saga and redux-observable, the ability to trigger any code on a component anywhere is very useful.
This tag doesn't quite fit: can be used independently (fine-grained/decoupled)
Resulting articles met inclusion criteria for review if they addressed psychiatric side effects of isotretinoin treatment or the neurobehavioral teratology of isotretinoin.
Could I do a search like this where I look up mass articles and make sure that they have the same tag words
acknowledges that high priced textbooks are a barrier to learning because many students do not purchase expensive textbooks
I suspect students also make value judgments--this book is too expensive because that number on the price tag is too high, rather than my financial aid doesn't cover it.
hyperscript is more concise because it's just a function call and doesn't require a closing tag. Using it will greatly simplify your tooling chain.
I suppose this is also an argument that Python tries to make? That other languages have this con:
end or } ?The primary motivation behind virtual-dom is to allow us to write code independent of previous state. So when our application state changes we will generate a new VTree. The diff function creates a set of DOM patches that, based on the difference between the previous VTree and the current VTree, will update the previous DOM tree to match the new VTree.
annotation meta: may need new tag: for: "code independent of previous state."
annotation meta: may need new tag: for: diffs other than source/text code diffs (in this case diffs between virtual DOM trees)
7 blog post data science
Kit_datos_ligados
Kit_semantica
Tag your bestie in the comments!
I wrote this caption so that it tempts people to tag other people. I posted a funny quote about best friends and asked people to “tag their besties” so they can see the post as well and engage with it further. Here’s an example: https://www.instagram.com/p/CGGacUoHq2p/
@quoteoftheday
I also tagged a successful account that wrote in their bio, “Tag @quoteoftheday to be featured on our page!” If they feature my post on their account, it could bring a lot of engagement to my own page. Here’s the account: https://www.instagram.com/quoteoftheday/.
Tag your bestie in the comments!
I wrote this caption so that it tempts people to tag other people. I posted a funny quote about best friends and asked people to “tag their besties” so they can see the post as well and engage with it further. Here’s an example: https://www.instagram.com/p/CGGacUoHq2p/
@quoteoftheday
I also tagged a successful account that wrote in their bio, “Tag @quoteoftheday to be featured on our page!” If they feature my post on their account, it could bring a lot of engagement to my own page. Here’s the account: https://www.instagram.com/quoteoftheday/.
Here, when x is a Boolean value then the section tag acts like an if conditional, but when x is an array then it acts like a foreach loop.
Kit_editoriales
Kit_dimensions
Kit_literatura
fewer faithful supports
(see tag)
Kit_altmetria
Kit_spar
Kit_altmetric
spar/biro/BibliographicCollection
spar/fabio/Ontology
Descripción: la liga corresponde a una etiqueta de Twitter
FACULTAD DE CIENCIAS, UNAM
Layla Michán
Kit_wos