Electromagnetic Wave Theory and Remote Sensing

Contains reports on eight research projects.Joint Services Electronics Program (Contract DAAG29-83-K-0003)National Science Foundation (Grant ECS82-03390)Schlumberger-Doll Research CenterNational Aeronautics and Space Administration (Contract NAG5-141)National Aeronautics and Space Administration (Contract NAS5-26861)National Aeronautics and Space Administration (Contract NAG5-270)U.S. Navy - Office of Naval Research (Contract N00014-83-K-0258)International Business Machines, Inc

Communications Biophysics

Contains reports on eight research projects split into four sections.National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Grant 5 K04 NS00113)National Institutes of Health (Training Grant 5 T32 NS07047)National Science Foundation (Grant BNS80-06369)National Institutes of Health (Grant 5 ROl NS11153)National Institutes of Health (Fellowship 1 F32 NS06544)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 5 R01 NS10916)National Institutes of Health (Grant 5 RO1 NS12846)National Science Foundation (Grant BNS77-21751)National Institutes of Health (Grant 1 R01 NS14092)National Institutes of Health (Grant 2 R01 NS11680)National Institutes of Health (Grant 5 ROl1 NS11080)National Institutes of Health (Training Grant 5 T32 GM07301

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P <1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P <5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.Peer reviewe

Targeting of cytosolic phospholipase A2α impedes cell cycle re-entry of quiescent prostate cancer cells

Cell cycle re-entry of quiescent cancer cells has been proposed to be involved in cancer progression and recurrence. Cytosolic phospholipase A₂α (cPLA₂α) is an enzyme that hydrolyzes membrane glycerophospholipids to release arachidonic acid and lysophospholipids that are implicated in cancer cell proliferation. The aim of this study was to determine the role of cPLA₂α in cell cycle re-entry of quiescent prostate cancer cells. When PC-3 and LNCaP cells were rendered to a quiescent state, the active form of cPLA₂α with a phosphorylation at Ser⁵⁰⁵ was lower compared to their proliferating state. Conversely, the phosphor-cPLA₂α with Efipladib upon induction of cell cycle re-entry inhibited the re-entry process, as manifested by refrained DNA synthesis, persistent high proportion of cells in G₀/G₁ and low percentage of cells in S and G₂/M phases, together with a stagnant recovery of Ki-67 expression. Simultaneously, Efipladib prohibited the emergence of Skp2 while maintained p27 at a high level in the nuclear compartment during cell cycle re-entry. Inhibition of cPLA₂α also prevented an accumulation of cyclin D1/CDK4, cyclin E/CDK2, phosphor-pRb, pre-replicative complex proteins CDC6, MCM7, ORC6 and DNA synthesis-related protein PCNA during induction of cell cycle re-entry. Moreover, a pre-treatment of the prostate cancer cells with Efipladib during induction of cell cycle re-entry subsequently compromised their tumorigenic capacity in vivo. Hence, cPLA₂α plays an important role in cell cycle re-entry by quiescent prostate cancer cells

Cell-Cycle Reprogramming for PI3K Inhibition Overrides a Relapse-Specific C481S BTK Mutation Revealed by Longitudinal Functional Genomics in Mantle Cell Lymphoma

International audienceDespite the unprecedented clinical activity of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib in mantle cell lymphoma (MCL), acquired resistance is common. By longitudinal integrative whole-exome and whole-transcriptome sequencing and targeted sequencing, we identified the first relapse-specific C481S mutation at the ibrutinib binding site of BTK in MCL cells at progression following a durable response. This mutation enhanced BTK and AKT activation and tissue-specific proliferation of resistant MCL cells driven by CDK4 activation. It was absent, however, in patients with primary resistance or progression following transient response to ibrutinib, suggesting alternative mechanisms of resistance. Through synergistic induction of PIK3IP1 and inhibition of PI3K-AKT activation, prolonged early G1 arrest induced by PD 0332991 (palbociclib) inhibition of CDK4 sensitized resistant lymphoma cells to ibrutinib killing when BTK was unmutated, and to PI3K inhibitors independent of C481S mutation. These data identify a genomic basis for acquired ibrutinib resistance in MCL and suggest a strategy to override both primary and acquired ibrutinib resistance.Significance: We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation. As drug resistance remains a major challenge and CDK4 and PI3K are dysregulated at a high frequency in human cancers, targeting CDK4 in genome-based combination therapy represents a novel approach to lymphoma and cancer therapy

Sage-Bionetworks/synapsePythonClient: v4.0.0-rc

&lt;h2&gt;Highlights&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;&lt;strong&gt;Only authentication through Personal Access Token&lt;/strong&gt; &lt;strong&gt;(aka: Authentication bearer token) is supported&lt;/strong&gt;. Review the &lt;a href="https://python-docs.synapse.org/tutorials/authentication/"&gt;Authentication document&lt;/a&gt; for information on setting up your usage of a Personal Access Token to authenticate with Synapse.&lt;/li&gt; &lt;li&gt;&lt;strong&gt;Date type Annotations on Synapse entities are now timezone aware&lt;/strong&gt;. Review our &lt;a href="https://python-docs.synapse.org/reference/annotations/"&gt;reference documentation for Annotations&lt;/a&gt;. The &lt;a href="https://pypi.org/project/pytz/"&gt;&lt;code&gt;pytz&lt;/code&gt; package&lt;/a&gt; is reccomended if you regularly work with data across time zones.&lt;ul&gt; &lt;li&gt;If you do not set the &lt;code&gt;tzinfo&lt;/code&gt; field on a date or datetime instance we will use the timezone of the machine where the code is executing.&lt;/li&gt; &lt;li&gt;If you are using the &lt;a href="https://python-docs.synapse.org/explanations/manifest_tsv/#annotations"&gt;Manifest TSV&lt;/a&gt; for bulk actions on your projects you'll now see that [synapseutils.sync.syncFromSynapse][] will store dates as &lt;code&gt;YYYY-MM-DDTHH:MM:SSZ&lt;/code&gt;. Review our documentation for an &lt;a href="https://python-docs.synapse.org/explanations/manifest_tsv/#example-manifest-file"&gt;example manifest file&lt;/a&gt;. Additionally, if you'd like to upload an annotation in a specific timezone please make sure that it is in &lt;a href="https://en.wikipedia.org/wiki/ISO_8601"&gt;ISO 8601 format&lt;/a&gt;. If you do not specify a timezone it is assumed to use the timezone of the machine where the code is executing.&lt;/li&gt; &lt;/ul&gt; &lt;/li&gt; &lt;li&gt;&lt;strong&gt;Support for annotations with multiple values through the&lt;/strong&gt; &lt;a href="https://python-docs.synapse.org/explanations/manifest_tsv/#multiple-values-of-annotations-per-key"&gt;&lt;strong&gt;Manifest TSV&lt;/strong&gt;&lt;/a&gt; with the usage of a comma delimited bracket wrapped list. Any manifest files wishing to take advantage of multi-value annotations need to match this format. Examples:&lt;ul&gt; &lt;li&gt;&lt;code&gt;[&quot;Annotation, with a comma&quot;, another annotation]&lt;/code&gt;&lt;/li&gt; &lt;li&gt;&lt;code&gt;[1,2,3]&lt;/code&gt;&lt;/li&gt; &lt;li&gt;&lt;code&gt;[2023-12-04T07:00:00Z,2000-01-01T07:00:00Z]&lt;/code&gt;&lt;/li&gt; &lt;/ul&gt; &lt;/li&gt; &lt;li&gt;Migration and expansion of the docs site! You'll see that the look, feel, and flow of all of the information on this site has been touched. As we move forward we hope that you'll &lt;a href="https://sagebionetworks.jira.com/servicedesk/customer/portal/5/group/7"&gt;provide the Data Processing and Engineering team feedback on areas we can improve&lt;/a&gt;.&lt;/li&gt; &lt;li&gt;Expansion of the available Python Tutorials can be found &lt;a href="https://python-docs.synapse.org/tutorials/python_client/"&gt;starting here&lt;/a&gt;.&lt;/li&gt; &lt;/ul&gt; &lt;h2&gt;What's Changed&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;Adding a label to the dockerfile to automatically label it for this repo by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1018&lt;/li&gt; &lt;li&gt;Updates Dockerfile to Correctly Install Dependencies by @BWMac in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1019&lt;/li&gt; &lt;li&gt;[SYNPY-1358] Correction of timestamp in annotations from manifest file by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1020&lt;/li&gt; &lt;li&gt;[SYNPY-1336] Benchmarking upload with annotations by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1021&lt;/li&gt; &lt;li&gt;[SYNPY-1321] Download benchmark results by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1024&lt;/li&gt; &lt;li&gt;[SYNPY-1360] Migrating to mkdocstrings by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1025&lt;/li&gt; &lt;li&gt;[SYNPY-1366] Add code coverage by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1029&lt;/li&gt; &lt;li&gt;[SYNPY-1362] High level best practices for project structure by @thomasyu888 in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1028&lt;/li&gt; &lt;li&gt;[SYNPY-1371] Migrate to Google Style by @BWMac in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1033&lt;/li&gt; &lt;li&gt;[SYNPY-1302] Replace getPermission with get_acl and add new get_permissions by @danlu1 in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1037&lt;/li&gt; &lt;li&gt;[SYNPY-1334] Revamp getting started docs by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1036&lt;/li&gt; &lt;li&gt;[SYNPY-1332] Pypi deployment strategy by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1038&lt;/li&gt; &lt;li&gt;[SYNPY-1370] Documentation Upgrade by @jaymedina in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1032&lt;/li&gt; &lt;li&gt;[SYNPY-1370] Minor formatting fixes by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1039&lt;/li&gt; &lt;li&gt;[SYNPY-1371] Doc fixes by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1040&lt;/li&gt; &lt;li&gt;[SYNPY-1225] Support authToken only by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1041&lt;/li&gt; &lt;li&gt;[SYNPY-1392] Remove some deprecated pieces by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1043&lt;/li&gt; &lt;li&gt;[Synpy 1369] Migrate to Google style by @danlu1 in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1042&lt;/li&gt; &lt;li&gt;[SYNPY-1387] Update Structure Project doc by @danlu1 in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1044&lt;/li&gt; &lt;li&gt;[SYNPY-1357] Allow multiple values in manifest TSV by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1030&lt;/li&gt; &lt;/ul&gt; &lt;h2&gt;New Contributors&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;@jaymedina made their first contribution in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/1032&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;&lt;strong&gt;Full Changelog&lt;/strong&gt;: https://github.com/Sage-Bionetworks/synapsePythonClient/compare/v3.2.0...v4.0.0-rc&lt;/p&gt

Sage-Bionetworks/synapsePythonClient: v3.1.0-rc

&lt;h2&gt;What's Changed&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;[SYNPY-49] Aggregate acl based on groups by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/979&lt;/li&gt; &lt;li&gt;[SYNPY-967] deprecated memoize and added @lru_cache by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/983&lt;/li&gt; &lt;li&gt;SYNPY-1285: Create pipfile by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/984&lt;/li&gt; &lt;li&gt;[SYNPY-1282] Adds Type Hinting to &lt;code&gt;client.py&lt;/code&gt; by @BWMac in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/987&lt;/li&gt; &lt;li&gt;[SYNPY-1293] Update urllib3 version dependency by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/988&lt;/li&gt; &lt;li&gt;[SYNPY-1283] Replace Broken Link URL by @BWMac in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/989&lt;/li&gt; &lt;li&gt;[SYNPY-1296] Config client error with api key or PAT by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/990&lt;/li&gt; &lt;/ul&gt; &lt;h2&gt;New Contributors&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;@BryanFauble made their first contribution in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/979&lt;/li&gt; &lt;li&gt;@BWMac made their first contribution in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/987&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;&lt;strong&gt;Full Changelog&lt;/strong&gt;: https://github.com/Sage-Bionetworks/synapsePythonClient/compare/v3.0.0...v3.1.0-rc&lt;/p&gt

Sage-Bionetworks/synapsePythonClient: v3.1.0

&lt;h2&gt;What's Changed&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;[SYNPY-49] Aggregate acl based on groups by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/979&lt;/li&gt; &lt;li&gt;[SYNPY-967] deprecated memoize and added @lru_cache by @BryanFauble, @linglp in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/983&lt;/li&gt; &lt;li&gt;SYNPY-1285: Create pipfile by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/984&lt;/li&gt; &lt;li&gt;[SYNPY-1282] Adds Type Hinting to &lt;code&gt;client.py&lt;/code&gt; by @BWMac in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/987&lt;/li&gt; &lt;li&gt;[SYNPY-1293] Update urllib3 version dependency by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/988&lt;/li&gt; &lt;li&gt;[SYNPY-1283] Replace Broken Link URL by @BWMac in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/989&lt;/li&gt; &lt;li&gt;[SYNPY-1296] Config client error with api key or PAT by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/990* * [SYNPY-1283] Adds Missing Trailing Space (Broken Link Fix) by @BWMac in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/991&lt;/li&gt; &lt;li&gt;[SYNPY-1295] Adding to the credentials.rst doc by @BryanFauble in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/992&lt;/li&gt; &lt;/ul&gt; &lt;h2&gt;New Contributors&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;@BryanFauble made their first contribution in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/979&lt;/li&gt; &lt;li&gt;@BWMac made their first contribution in https://github.com/Sage-Bionetworks/synapsePythonClient/pull/987&lt;/li&gt; &lt;/ul&gt; &lt;p&gt;&lt;strong&gt;Full Changelog&lt;/strong&gt;: https://github.com/Sage-Bionetworks/synapsePythonClient/compare/v3.0.0...v3.1.0-rc&lt;/p&gt