25 Matching Annotations
  1. Mar 2022
    1. Routes of cell entryEndocytosis is a key mechanism driving EV entry into cells. Mammalian cells depend on a diversity of endocytic mechanisms that occur concurrently, including clathrin-dependent and clathrin–independent mechanisms as well as macropinocytosis. Specialized phagocytic cells are furthermore capable of ingesting other cells and/or particles via phagocytosis. Interestingly, all of these different endocytic mechanisms have been implicated in EV internalization, which is likely a result of the large diversity of EV donor and recipient cell pairs that have been reported, as reviewed in5. The mechanism of internalization may be relevant to the fate of EVs and their cargo. For example, when studying EV-mediated small RNA delivery, a poor correlation between EV/small RNA uptake efficiency and functional small RNA transfer (assessed via target gene knockdown) was observed among different cell types, including phagocytic Kupffer cells75. It is thus tempting to speculate that different EV internalization mechanisms may lead to different functional outcomes: degradation versus functional transfer of EV cargo.Intracellular trafficking and signallingIn general, endocytosis in mammalian cells leads to internalization of cargo from the plasma membrane, and transport from early endosomes to either recycling endosomes through which the cargo is recycled back to the plasma membrane, or to late endosomes and finally lysosomes where it is degraded. EVs seem to follow a similar path, with evidence suggesting that EVs, or at least the dyes or labels that are used to visualize them, eventually end up in lysosomes69,76. Accumulation of EVs in lysosomes may also reflect the final destination of EVs that have signalled at the surface of the recipient cells. While lysosomes are often seen as sites for breaking down biomolecules (and therefore considered non-functional EV destinations), increasing evidence suggests they also function in various cellular processes such as plasma membrane homeostasis, signalling and energy metabolism. Indeed, lysosomal catabolism of EVs by endothelial cells has been suggested to provide these cells with trophic support59. Thus, lysosomes may serve as a site of functionality for EVs, and may not be simply a compartment for their destruction.At the same time, there is overwhelming evidence that EVs are capable of transferring their luminal cargo, including RNA, into the cytosol of recipient cells, which indicates that EVs are capable of escaping the endolysosomal pathway. How EVs induce such endosomal escape is largely unknown, however there is some evidence that this occurs through EVs fusing with late endosomal membranes77,78, potentially triggered by acidification along the endolysosomal axis79,80. Whether there are intrinsic differences in EV subtypes which are destined for lysosomal degradation or cargo release through fusion, or whether EV fate is dictated by the characteristics of the recipient cell remains unknown

      Endocytosis, lysosomes, degradation, lysosomal escape

  2. Jun 2021
  3. May 2021
    1. Build a baseline email experience for subscribers using email apps with limited support for HTML and CSS—such as Outlook and Gmail—before enhancing your email for other clients. Progressive enhancement should not create suboptimal experiences for other users.
    2. An escalator is a great example of progressive enhancement and graceful degradation in real life. The late comedian Mitch Hedberg joked, “An escalator can never break: it can only become stairs. You should never see an Escalator Temporarily Out Of Order sign, just Escalator Temporarily Stairs. Sorry for the convenience.” Regardless of its environment, an escalator maintains its functionality.
    3. The main focus of his talk was on progressive enhancement, which involves providing advanced functionality in environments where its supported. He also emphasized the importance of graceful degradation. Graceful degradation means that if your subscriber’s email client doesn’t support a certain functionality, you’ll still provide them with a pleasant experience.
    1. And that just leaves the Word Outlooks (and their ever-aligning web based equivalents), and a few lesser used (for us) regional clients. Here, our div based layout reverts back to every story being on a new line. For #EmailWeekly, we’re ok with that.
  4. Mar 2021
  5. Feb 2021
    1. There’s an important wrinkle when it comes to animating the menu away. When the user closes the menu, it will always disappear instantly, because the open attribute is, by default, removed immediately when the user clicks that summary element. In order to gracefully animate your menu out when it closes, we need some JavaScript. Here we can listen for clicks on the details element, and call preventDefault() on the click event, then use setTimeout() to determine exactly when that open attribute should be removed. This gives us time to trigger the closing animation with CSS. This click event listener will also fire when a keyboard user hits space or enter while the element is focused, which means no further listeners are needed for keyboard actions!
  6. Jan 2021
    1. JavaScript is more brittle than we care to admit. <a> elements function even if JavaScript breaks. Using anchors for your download means that a person can access what they need, even in suboptimal situations.
  7. Nov 2020
    1. Preserving user privacy is difficult when detectingmore nuanced forms of censorshipSome forms of softcensorship might involve intentional performance degrada-tion or content manipulation. Detecting this type of behav-ior would require comparing performance or content acrossgroups of users, but such a comparison also implies thateach user must reveal their browsing history.

      If you want to investigate whether content for a user was manipulated or performance was degraded, there may be no other way but to access detailed logs of their usage. This might raise privacy concerns.

      Not only is personalization difficult to disambiguate from manipulation and censorship, personalization also makes it more costly to compare the personalized experience to some baseline value to determine if manipulation or performance degradation has taken place.

  8. Sep 2020
  9. Jun 2020
    1. We do know that, just like iMessage, this new approach will failover to SMS/MMS if a user cannot receive the encrypted variant or if bandwidth is insufficient on either end.
    2. A couple of years after WhatsApp, Apple jumped into the game with iMessage—its obvious drawback, that senders and recipients had to be using iPhones, was overcome by integration with the standard SMS platform on those phones. If a recipient was not on iMessage or was offline, the message would revert to SMS.
  10. May 2020
    1. Adopting TypeScript is not a binary choice, you can start by annotating existing JavaScript with JSDoc, then switch a few files to be checked by TypeScript and over time prepare your codebase to convert completely.
    1. First proposed as a somewhat less unwieldy catchall phrase to describe the delicate art of "separating document structure and contents from semantics, presentation, and behavior"
    2. In progressive enhancement (PE) the strategy is deliberately reversed: a basic markup document is created, geared towards the lowest common denominator of browser software functionality, and then the designer adds in functionality or enhancements to the presentation and behavior of the page, using modern technologies such as Cascading Style Sheets, Scalable Vector Graphics (SVG), or JavaScript.
    3. graceful degradation
  11. May 2017
    1. thermal degradation of the permafrost

      Thermal degradation is the process of the breaking of molecules due to heating (Zeus). In Arctic regions, thermal degradation can occur to permafrost. This can lead to uneven snowmelt and ground instability (Grandpre). The ground instability affects any infrastructure built on permafrost, including roads, buildings, or piping systems. Uneven melting of the permafrost can create holes or indentations in roadways. A study by the Canadian Journal of Earth Sciences in 2011 showed that heat transfer from groundwater movement can increase the rate of thermal degradation of permafrost. In areas where wildfires are prevalent, thermal degradation of permafrost is an even greater issue (Jafarov). Climate change effects change the patterns and prevalence of forest fires. A study performed for Environmental Research Letters found that under conditions of severe fire in an upland forest where no other climate change effects are present, 18 meters of permafrost can degrade in 120 years. In lowland forests, permafrost is more resilient to thermal degradation and these effects were not found. Wildfires affect permafrost because they burn the organic layer of soil and the rate of permafrost melt is directly impacted by how much of the organic layer is burned. If a thick organic soil layer is present and the fire is short-lived, the permafrost may not melt. Climate change also increases the rate of thermal degradation in permafrost. Temperatures in northern high latitude regions are expected to rise by 2.5 to 7 degrees Celsius. The thermal degradation of permafrost is important not only due to increased carbon emissions in the air and oceans, but also for its negative effects of infrastructure.

      References: Grandpré, Isabelle De, Daniel Fortier, and Eva Stephani. "Degradation of permafrost beneath a road embankment enhanced by heat advected in groundwater." Canadian Journal of Earth Sciences. August 01, 2012. Accessed May 06, 2017. http://cjes.geoscienceworld.org/content/49/8/953.

      Jafarov, E. E., V. E. Romanovsky, H. Genet, A. D. McGuire, and S. S. Marchenko. "The effects of fire on the thermal stability of permafrost in lowland and upland black spruce forests of interior Alaska in a changing climate." Environmental Research Letters 8, no. 3 (August 27, 2013). Accessed May 06, 2017. http://iopscience.iop.org/article/10.1088/1748-9326/8/3/035030/pdf.

      "Thermal Degradation of Plastics." Zeus Industrial Products Inc. 2005. Accessed May 06, 2017.

  12. Oct 2016
    1. But what about the pleasures of the world and all the myriad pursuits that are undertaken to acquire them, to keep them and to ward off their dissipation? What of these? Clearly, given the excesses that you see about you, the pursuit of pleasure can be seen as utterly destructive and demeaning. Examples of this are so common and take so many forms that you need but look at human life around you to see their many expressions.
  13. Jun 2015
    1. If you want a DIY version of this, try ImageMagick's compare command: compare bag_frame1.gif bag_frame2.gif compare.gif Documentation: http://www.imagemagick.org/Usage/compare/ reply no_gravity 2 hours ago Interesting. And to render the html you can use cutycapt. Which is in the Debian repos too. I just tried it, and this rendered a nice diff of two pages for me: cutycapt --url=http://www.xyz.com/1 --out=1.png cutycapt --url=http://www.xyz.com/2 --out=2.png compare 1.png 2.png diff.png reply easytiger 2 hours ago Now make it a webservice and charge $200/month! reply programmernews3 1 hour ago First part already done: http://archive.is/ reply prottmann 1 hour ago apt-get install the services and use them on my server ;-) reply

      Plain and simple way to report visual degradation of website or webapp

  14. Jan 2015