{"id":3210,"date":"2023-01-22T17:09:59","date_gmt":"2023-01-22T23:09:59","guid":{"rendered":"https:\/\/kermitmurray.com\/msblog\/?page_id=3210"},"modified":"2023-01-22T17:09:59","modified_gmt":"2023-01-22T23:09:59","slug":"science-in-the-pipeline","status":"publish","type":"page","link":"https:\/\/kermitmurray.com\/msblog\/links\/journal-feeds\/science-journals\/science-journal\/science-in-the-pipeline\/","title":{"rendered":"Science in the Pipeline"},"content":{"rendered":"\n<div class=\"wp-block-caxton-grid relative\"><div class=\"absolute absolute--fill\"><div class=\"absolute absolute--fill cover bg-center\" style=\"background-color:;background-image:linear-gradient( );\"><\/div><div class=\"absolute absolute--fill\" style=\"background-color:;background-image:linear-gradient( );opacity:1;\"><\/div><\/div><div class=\"relative caxton-columns caxton-grid-block\" style=\"padding-top:0;padding-left:0;padding-bottom:0;padding-right:0;grid-template-columns:repeat(12, 1fr)\" data-tablet-css=\"padding-left:em;padding-right:em;\" data-mobile-css=\"padding-left:em;padding-right:em;\">\n<div class=\"wp-block-caxton-section relative\" style=\"grid-area:span 1\/span 8\"><div class=\"absolute absolute--fill\"><div class=\"absolute absolute--fill cover bg-center\" style=\"background-color:;background-image:linear-gradient( );\"><\/div><div class=\"absolute absolute--fill\" style=\"background-color:;background-image:linear-gradient( );opacity:1;\"><\/div><\/div><div class=\"relative caxton-section-block\" style=\"padding-top:5px;padding-left:5px;padding-bottom:5px;padding-right:5px\" data-mobile-css=\"padding-left:1em;padding-right:1em;\" data-tablet-css=\"padding-left:1em;padding-right:1em;\">\n<p><strong><a href=\"https:\/\/www.science.org\/content\/page\/email-alerts-and-rss-feeds\" target=\"_blank\" rel=\"noreferrer noopener\">Journal Home<\/a><\/strong><\/p>\n<\/div><\/div>\n\n\n\n<div class=\"wp-block-caxton-section relative\" style=\"grid-area:span 1\/span 4\"><div class=\"absolute absolute--fill\"><div class=\"absolute absolute--fill cover bg-center\" style=\"background-color:;background-image:linear-gradient( );\"><\/div><div class=\"absolute absolute--fill\" style=\"background-color:;background-image:linear-gradient( );opacity:1;\"><\/div><\/div><div class=\"relative caxton-section-block\" style=\"padding-top:5px;padding-left:5px;padding-bottom:5px;padding-right:5px\" data-mobile-css=\"padding-left:1em;padding-right:1em;\" data-tablet-css=\"padding-left:1em;padding-right:1em;\">\n<p><strong><a href=\"https:\/\/www.science.org\/blogs\/pipeline\/feed\" target=\"_blank\" rel=\"noreferrer noopener\">RSS<\/a><\/strong><\/p>\n<\/div><\/div>\n<\/div><\/div>\n\n\n<ul class=\"has-dates has-authors has-excerpts wp-block-rss\"><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/machine-learning-mass-spec-data-hmmm'>Machine-Learning Mass Spec Data: Hmmm<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">For someone with a reputation as an AI skeptic, I actually have a lot of time for machine learning approaches, at least when pursued with due humility and attention to detail. Science is a vast sea of data, full of currents, seamounts, hidden reefs, archipelagos, and shorelines, and we need all the help we can get in navigating it. And successes in protein structure prediction are evidence enough that if you have a large enough data set, well-curated and covering [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/covid-19-vaccinations-and-heart'>Covid-19 Vaccinations and the Heart<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">First off, a note that posting will be a bit irregular this week, but I wanted to let people know that I&#039;m definitely still around! So here&#039;s something to talk about: There&#039;s a good new paper in JAMA Internal Medicine looking at a large recent data set in Covid-19 vaccinations in an older population. It&#039;s from the Veterans Administration, looking at about one million veterans who got a flu vaccine in 2024, and over three hundred thousand of them also [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/hydroxyl-radicals-water-droplets-doesn-t-look-it'>Hydroxyl Radicals In Water Droplets? Doesn&#039;t Look Like It.<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">I\u2019ve written more than once here (most recently last year) about the long-running controversy about what\u2019s happening with very small droplets of water. There have been numerous reports of unusual chemistry under these situations, and I think it\u2019s safe to say that one of the marquee candidates is the reported production of hydrogen peroxide, which is often based on mass spectral evidence. It has to be noted that further investigations did not support hydrogen peroxide generation per se, but numerous [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/new-antibiotic-idea-old-source'>A New Antibiotic Idea From An Old Source<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">As longtime readers will know, I am always ready to celebrate advances in antibiotic research. That\u2019s for several good reasons, not least of which is that such advances are notoriously hard to come by. And of course they\u2019re also extremely important from a public health perspective: we are under constant threat from pathogenic infections, and the organisms that cause them are getting steadily more resistant to our existing treatments. At this point the only people in the industrialized world who [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/insights-idiopathic-pulmonary-fibrosis'>Insights Into Idiopathic Pulmonary Fibrosis<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">Idiopathic pulmonary fibrosis (IPF) is a terrible disease, made worse by the fact that biomedical science can do so little about it. The lung tissue (particularly around the air sacs gradually becomes thicker and stiffer as scar tissue builds up around them, and this naturally causes a decline in lung function. As you can tell from the name, the actual cause of the disease is not understood, but the effects certainly are: average life expectancy after diagnosis is about four [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/unusual-toxicity-protein-degrader-molecule'>Unusual Toxicity With a Protein Degrader Molecule<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">Those of you who lived through the worst of the \u201cRule of Five\u201d era in medicinal chemistry will well appreciate that we are working with a lot of compounds now that cheerfully violate some of those strictures. Molecular weight might be the first on the list, thanks to the number of large bifunctional molecules (for targeted protein degradation and other ideas) that have been in development. In retrospect, there were people (and departments, and whole companies) that put blinders on [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/causes-long-covid'>The Causes of Long Covid<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">There are two really interesting papers that have come out that give us some very badly needed insights into \u201cLong Covid\u201d, which we can define as a constellation of symptoms that persist many weeks after a coronavirus infection. Most people recover quite well &#8211; I\u2019ve had the damn virus more than once myself and haven\u2019t noticed any particular long-term effects. But not everyone is so fortunate! Estimates are fuzzy, but there are millions of people worldwide who are dealing with [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/action-action-now'>Action! Action Now.<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">So I wrote the other day about the severe damage the Trump administration has done to US federally funded science, and mentioned the even more severe damage they are planning. This is contained in an irritatingly lengthy and gassy Office of Management and Budget proposal, which boils down to some key horrible ideas (summarized, for example, by Elizabeth Ginexi here) and at BioCentury here (free link). Section 200.205 will require that political appointees (and not professional staffers at any granting [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/current-crisis-what-s-happening-science-america'>The Current Crisis: What&#039;s Happening to Science in America<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">I have written a number of times about what\u2019s happening to federal funding of scientific research in the US, but I have some updates, and they are grim. Let\u2019s first consider the policies reported here at Science on collaboration with scientists and institutions outside the US. It appears that the NIH and NASA (so far) want permission in advance for any such proposal, with grantees also saying that they have been directed to remove papers with foreign co-authors from their [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/evaluating-co-scientist-new-ai-science-system'>Evaluating &quot;Co-Scientist&quot;, a New AI Science System<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">There are a couple of very interesting AI-assisted-chemistry paper out this week, and I have been trying to find the time to take them on. Let\u2019s do this one first. It\u2019s a report on \u201cCo-Scientist\u201d, a system to help propose hypotheses, potential mechanisms, et al. for biomedical discovery. The authors first applied this in what I think is a good test bed for it: drug repurposing. Let\u2019s put aside the not-all-that-high success rates seen in these efforts, because nothing in [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/methyl-methacrylate-tank'>That Methyl Methacrylate Tank<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">I wasn\u2019t posting over the long weekend, so I missed the saga of the Garden Grove methyl methacrylate tank. The immediate danger seems to abated, fortunately, but let\u2019s talk about it to illustrate some widely applicable chemistry. People wrote to me to ask if methyl methacrylate itself is on my \u201cThings I Won\u2019t Work With\u201d list, but it\u2019s a long way from being in that category, to be honest. I\u2019ve worked with it, as well as related compounds like methyl [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/reading-labels-mutant-mice'>Reading the Labels on Mutant Mice<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">I\u2019m working on a big post or two, but I did want to get something up today. Have a look at this rather disturbing news from the mouse model world, published here at Science. The authors went to the trouble of genotyping 611 mice tissue samples representing 341 strains at the MMRRC (Mutant Mouse Resource and Research Centers), and as the paper notes, rather dryly and through pursed lips, \u201cUsers\u2019 expectations for congenic strains based on nomenclature are not consistently [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/cya'>CYA<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">Working in any sort of large organization, you quickly come to recognize the signs of people trying to avoid blame or to just plain old scurry for cover. There\u2019s one I always remember from my early days in the industry when we had a pretty useful fire in a fume hood across the hall. This was about 1990, in a building that doesn\u2019t even exist any more, with a company that doesn\u2019t exist either! I\u2019m not sure how it got [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/stemming-ai-preprint-flood'>Stemming the AI Preprint Flood<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">The arXiv preprint server has become essential to several scientific fields, and has inspired similar services like BioRxiv and ChemRxiv. But the generative AI age has been hard on these sites, and you can see it by their steady imposition of new rules. Last November, arXiv announced that it was clamping down on the submission of review articles, particularly in computer science. These were becoming alarmingly easy to put together (often as not padded out with references that didn\u2019t even [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/futuristic-synthesis-indeed'>A Futuristic Synthesis Indeed<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">I definitely need to cover this recent work from Merck, because (1) it\u2019s very interesting scientifically and (2) it has over 130 authors on the paper (!) It details the industrial synthesis of enlicitide, which is a beast of a macrocyclic peptide (see below!) Just looking at the structure tells you that this must be a ferociously active molecule with huge commercial potential, because there is just no way that anyone is going to make this on scale &#8211; or [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/what-success-can-look-darn-it'>What Success Can Look Like, Darn It<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">I wrote here last year about the clinical trial results for the first \u201cbifunctional degrader\u201d molecule to make it that far, vepdegestrant from Arvinas and Pfizer. That post will send you to some background information about this class of molecule, but suffice it to say that they represent a completely new mode of action (destruction of a target protein in the living cell as opposed to chemical inhibition of it). As such, this program has been watched closely, and the [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/more-vague-more-useful'>More Vague, But More Useful<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">I think that many synthetic organic chemists will be able to relate to the approach described in this paper, on software-aided route design. Its authors are trying to make such software take a viewpoint from higher over the synthesis, rather than working out every reaction. As noted in this commentary, for larger molecules that can leave you with a forest of rather-similar routes that differ in choice of protecting groups, relative oxidation states, order of reactions and other details that [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/those-pesky-post-translational-modifications'>Those Pesky Post Translational Modifications<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">I\u2019ve written here many times about various post-translational protein modifications. That\u2019s a huge field of study, because it has become more and more clear over the years that it\u2019s not so much that living cells have huge numbers of different protein sequences in them (although they have plenty!) it\u2019s that every protein seems to be modifiable by a long list of add-ons. These include (but are absolutely guaranteed not to be limited to!) phosphorylation, ubiquitination, farnesylation, glycosylation, acetylation, palmitoylation and [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/latest-news-vaccine-obstruction'>The Latest News in Vaccine Obstruction<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">Well, I know by now what happens when I bring up vaccines, but I\u2019m going to do it anyway because we have a lot of news. As many will have heard, news broke recently of several large-scale studies of safety for the coronavirus and shingles vaccines. Here\u2019s the New York Times on the story, and here\u2019s the Guardian. These were done by evaluating millions of patient records, and seem to have concluded that these vaccines are in fact safe, with [&hellip;]<\/div><\/li><li class='wp-block-rss__item'><div class='wp-block-rss__item-title'><a href='https:\/\/www.science.org\/content\/blog-post\/ubiquitin-rides-again'>Ubiquitin Rides Again<\/a><\/div><div class=\"wp-block-rss__item-excerpt\">When appropriate I usually wait until the end of one of these posts to draw attention to the way that its subject dovetails (or not) with the current fashion for AI\/ML techniques. For one thing, I find it helpful to remember that really new results cannot generally be obtained by asking an LLM system that is trained on piles of existing text which it has blended and chopped and extruded back to you. That\u2019s because those new results were not [&hellip;]<\/div><\/li><\/ul>\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity is-style-wide\"\/>\n\n\n\n<h4 class=\"wp-block-heading\">Related Journals<\/h4>\n\n\n<ul class=\"su-siblings\"><li class=\"page_item page-item-3212\"><a href=\"https:\/\/kermitmurray.com\/msblog\/links\/journal-feeds\/science-journals\/science-journal\/science-first-release\/\">Science First Release<\/a><\/li>\n<li class=\"page_item page-item-3208\"><a href=\"https:\/\/kermitmurray.com\/msblog\/links\/journal-feeds\/science-journals\/science-journal\/science-podcast\/\">Science Podcast<\/a><\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Related Journals<\/p>\n","protected":false},"author":1,"featured_media":3202,"parent":3204,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-3210","page","type-page","status-publish","has-post-thumbnail","hentry","entry"],"_links":{"self":[{"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/pages\/3210","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/comments?post=3210"}],"version-history":[{"count":1,"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/pages\/3210\/revisions"}],"predecessor-version":[{"id":3211,"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/pages\/3210\/revisions\/3211"}],"up":[{"embeddable":true,"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/pages\/3204"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/media\/3202"}],"wp:attachment":[{"href":"https:\/\/kermitmurray.com\/msblog\/wp-json\/wp\/v2\/media?parent=3210"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}