rep Inhibition of mitochondrial oxidative metabolism attenuates EMCV replication and protects {beta}-cells from virally mediated lysis [Immunology] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 Viral infection is one environmental factor that may contribute to the initiation of pancreatic β-cell destruction during the development of autoimmune diabetes. Picornaviruses, such as encephalomyocarditis virus (EMCV), induce a pro-inflammatory response in islets leading to local production of cytokines, such as IL-1, by resident islet leukocytes. Furthermore, IL-1 is known to stimulate β-cell expression of iNOS and production of the free radical nitric oxide. The purpose of this study was to determine whether nitric oxide contributes to the β-cell response to viral infection. We show that nitric oxide protects β-cells against virally mediated lysis by limiting EMCV replication. This protection requires low micromolar, or iNOS-derived, levels of nitric oxide. At these concentrations nitric oxide inhibits the Krebs enzyme aconitase and complex IV of the electron transport chain. Like nitric oxide, pharmacological inhibition of mitochondrial oxidative metabolism attenuates EMCV-mediated β-cell lysis by inhibiting viral replication. These findings provide novel evidence that cytokine signaling in β-cells functions to limit viral replication and subsequent β-cell lysis by attenuating mitochondrial oxidative metabolism in a nitric oxide–dependent manner. Full Article
rep Inhibition of oxidative metabolism by nitric oxide restricts EMCV replication selectively in pancreatic beta-cells [Enzymology] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 Environmental factors, such as viral infection, are proposed to play a role in the initiation of autoimmune diabetes. In response to encephalomyocarditis virus (EMCV) infection, resident islet macrophages release the pro-inflammatory cytokine IL-1β, to levels that are sufficient to stimulate inducible nitric oxide synthase (iNOS) expression and production of micromolar levels of the free radical nitric oxide in neighboring β-cells. We have recently shown that nitric oxide inhibits EMCV replication and EMCV-mediated β-cell lysis and that this protection is associated with an inhibition of mitochondrial oxidative metabolism. Here we show that the protective actions of nitric oxide against EMCV infection are selective for β-cells and associated with the metabolic coupling of glycolysis and mitochondrial oxidation that is necessary for insulin secretion. Inhibitors of mitochondrial respiration attenuate EMCV replication in β-cells, and this inhibition is associated with a decrease in ATP levels. In mouse embryonic fibroblasts (MEFs), inhibition of mitochondrial metabolism does not modify EMCV replication or decrease ATP levels. Like most cell types, MEFs have the capacity to uncouple the glycolytic utilization of glucose from mitochondrial respiration, allowing for the maintenance of ATP levels under conditions of impaired mitochondrial respiration. It is only when MEFs are forced to use mitochondrial oxidative metabolism for ATP generation that mitochondrial inhibitors attenuate viral replication. In a β-cell selective manner, these findings indicate that nitric oxide targets the same metabolic pathways necessary for glucose stimulated insulin secretion for protection from viral lysis. Full Article
rep Reply: One Bite from the Apple, One Bite from the Orange in the PRECISE-MDT Study and Limitations of Retrospective Study Design and Potential Bias in the PRECISE-MDT Study By jnm.snmjournals.org Published On :: 2024-10-17T09:03:09-07:00 Full Article
rep Oncologist, Business Leader, and Investor Arie S. Belldegrun Discusses a Career in Innovative Medical Entrepreneurship: A Conversation with Ken Herrmann and Johannes Czernin By jnm.snmjournals.org Published On :: 2024-10-30T08:04:15-07:00 Full Article
rep Problem Notes for SAS®9 - 66535: You might intermittently see the error "RangeError: Maximum call stack exceeded..." when viewing a SAS Visual Analytics report By Published On :: Wed, 26 Aug 2020 15:06:43 EST When viewing a SAS Visual Analytics report, you might intermittently see an error that includes content similar to the following: Error Message: Full Article VISANLYTBNDL+SAS+Visual+Analytics
rep Problem Notes for SAS®9 - 66511: A Russian translation shows the same value for two different variables in the Define Value dialog box for the Reply node in SAS Customer Intelligence Studio By Published On :: Mon, 24 Aug 2020 14:23:55 EST In SAS Customer Intelligence Studio, when you add Reply- node variable values in the Define Value dialog box, you might notice that two identically labeled data-grid variables are Full Article POLICYOFR+SAS+Real-Time+Decision+Manager
rep Problem Notes for SAS®9 - 66401: Using SAS Model Manager to publish a model to SAS Metadata Repository fails and generates an error By Published On :: Fri, 21 Aug 2020 09:34:11 EST When you publish a model to SAS Metadata Repository by using SAS Model Manager, the publishing process fails and the following error is generated: "The model model-name has a function of ';Transformation';, which is not supported for Full Article MMGROFR+SAS+Model+Manager
rep Problem Notes for SAS®9 - 66504: Clicking a link to pass a group break value to a SAS Web Report Studio report returns an HTTP 400 error By Published On :: Thu, 20 Aug 2020 14:07:26 EST SAS Web Report Studio enables you to link reports based on a group break value. However, when you click the link, it might fail with an HTTP 400 error. The exact message you see depends on which browser you are u Full Article CITATIONWEB+SAS+Web+Report+Studio
rep Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures [Special Reports] By www.jlr.org Published On :: 2020-12-01T00:05:39-08:00 A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation. Full Article
rep The Neuroproteomic Basis of Enhanced Perception and Processing of Brood Signals That Trigger Increased Reproductive Investment in Honeybee (Apis mellifera) Workers [Research] By www.mcponline.org Published On :: 2020-10-01T00:05:25-07:00 The neuronal basis of complex social behavior is still poorly understood. In honeybees, reproductive investment decisions are made at the colony-level. Queens develop from female-destined larvae that receive alloparental care from nurse bees in the form of ad-libitum royal jelly (RJ) secretions. Typically, the number of raised new queens is limited but genetic breeding of "royal jelly bees" (RJBs) for enhanced RJ production over decades has led to a dramatic increase of reproductive investment in queens. Here, we compare RJBs to unselected Italian bees (ITBs) to investigate how their cognitive processing of larval signals in the mushroom bodies (MBs) and antennal lobes (ALs) may contribute to their behavioral differences. A cross-fostering experiment confirms that the RJB syndrome is mainly due to a shift in nurse bee alloparental care behavior. Using olfactory conditioning of the proboscis extension reflex, we show that the RJB nurses spontaneously respond more often to larval odors compared with ITB nurses but their subsequent learning occurs at similar rates. These phenotypic findings are corroborated by our demonstration that the proteome of the brain, particularly of the ALs differs between RJBs and ITBs. Notably, in the ALs of RJB newly emerged bees and nurses compared with ITBs, processes of energy and nutrient metabolism, signal transduction are up-regulated, priming the ALs for receiving and processing the brood signals from the antennae. Moreover, highly abundant major royal jelly proteins and hexamerins in RJBs compared with ITBs during early life when the nervous system still develops suggest crucial new neurobiological roles for these well-characterized proteins. Altogether, our findings reveal that RJBs have evolved a strong olfactory response to larvae, enabled by numerous neurophysiological adaptations that increase the nurse bees' alloparental care behavior. Full Article
rep Serum Protein Profiling Reveals a Landscape of Inflammation and Immune Signaling in Early-stage COVID-19 Infection [Report] By www.mcponline.org Published On :: 2020-11-01T00:05:37-07:00 Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy. Full Article
rep CIITA-transduced glioblastoma cells uncover a rich repertoire of clinically relevant tumor-associated HLA-II antigens [Research] By www.mcponline.org Published On :: 2020-09-22T12:35:16-07:00 CD4+ T cell responses are crucial for inducing and maintaining effective anti-cancer immunity, and the identification of human leukocyte antigen class II (HLA-II) cancer-specific epitopes is key to the development of potent cancer immunotherapies. In many tumor types, and especially in glioblastoma (GBM), HLA-II complexes are hardly ever naturally expressed. Hence, little is known about immunogenic HLA-II epitopes in GBM. With stable expression of the class II major histocompatibility complex transactivator (CIITA) coupled to a detailed and sensitive mass spectrometry based immunopeptidomics analysis, we here uncovered a remarkable breadth of the HLA-ligandome in HROG02, HROG17 and RA GBM cell lines. The effect of CIITA expression on the induction of the HLA-II presentation machinery was striking in each of the three cell lines, and it was significantly higher compared to interferon gamma (IFN) treatment. In total, we identified 16,123 unique HLA-I peptides and 32,690 unique HLA-II peptides. In order to genuinely define the identified peptides as true HLA ligands, we carefully characterized their association with the different HLA allotypes. In addition, we identified 138 and 279 HLA-I and HLA-II ligands, respectively, most of which are novel in GBM, derived from known GBM-associated tumor-antigens that have been used as source proteins for a variety of GBM vaccines. Our data further indicate that CIITA-expressing GBM cells acquired an antigen presenting cell-like phenotype as we found that they directly present external proteins as HLA-II ligands. Not only that CIITA-expressing GBM cells are attractive models for antigen discovery endeavors, but also such engineered cells have great therapeutic potential through massive presentation of a diverse antigenic repertoire. Full Article
rep Impact report 2020–21 By www.chathamhouse.org Published On :: Wed, 14 Jul 2021 15:44:51 +0000 Impact report 2020–21 Other resource dora.popova 14 July 2021 Explore our policy impact in the past year, including through our research, convening and next generation initiatives, in a revised format annual review. Chair’s statement It has been an extraordinary year of change for us all. The COVID-19 pandemic is the greatest challenge to the world for generations. Millions have lost their lives or suffered devastating impacts on their health, both from COVID-19 itself and because health systems have been unable to deliver treatments for other conditions. The pandemic has also caused the greatest shock to the global economy since the 1930s, setting back the progress of recent years in eliminating poverty, getting more children into education and improving global health. This means Chatham House is needed more than ever. Our world-leading convening and cutting-edge research on the major challenges facing the world, from building more sustainable economic growth and tackling climate change to easing geopolitical tensions, has continued despite the challenges of lockdown. For that I pay tribute to the resilience and ingenuity of the staff who have found innovative solutions to the obstacles presented by the pandemic, all while working largely from home. This year I am also delighted to note the exceptional gift of £10 million from the MAVA Foundation to enable us to launch the Sustainability Accelerator. This initiative builds on the Hoffmann Centre’s last five years of innovative convening and activity. And it puts sustainability at the core of the institute’s work in this critical year for addressing climate change and biodiversity. So, as I prepare to step down from my three years as chair of the institute, I would like to thank my fellow Council members and Robin Niblett and his team for their hard work and ambition to deliver on Chatham House’s mission. I have also been especially pleased to see how we are engaging younger, more diverse audiences through the next generation initiatives, including our Panel of Young Advisers, the Common Futures Conversations project, the QEII Academy Ambassadors, our Internship Programme and the Chatham House-SNF CoLab. I am particularly pleased about the Chatham House Summer School, where 16–18-year-olds can now engage with experts on international affairs and get an insight into careers within the charity and not-for-profit sector. It has been an honour to lead this extraordinary institution and I look forward to continuing my involvement with Chatham House in new ways. Lord Jim O’Neill Impact Report 2020-21 (PDF) Full Article
rep Mycobacteria excise DNA damage in 12- or 13-nucleotide-long oligomers by prokaryotic-type dual incisions and performs transcription-coupled repair [Genomics and Proteomics] By www.jbc.org Published On :: 2020-12-11T00:06:21-08:00 In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli. Full Article
rep Nonspecific DNA binding by P1 ParA determines the distribution of plasmid partition and repressor activities [Microbiology] By www.jbc.org Published On :: 2020-12-11T00:06:21-08:00 The faithful segregation, or “partition,” of many low-copy number bacterial plasmids is driven by plasmid-encoded ATPases that are represented by the P1 plasmid ParA protein. ParA binds to the bacterial nucleoid via an ATP-dependent nonspecific DNA (nsDNA)-binding activity, which is essential for partition. ParA also has a site-specific DNA-binding activity to the par operator (parOP), which requires either ATP or ADP, and which is essential for it to act as a transcriptional repressor but is dispensable for partition. Here we examine how DNA binding by ParA contributes to the relative distribution of its plasmid partition and repressor activities, using a ParA with an alanine substitution at Arg351, a residue previously predicted to participate in site-specific DNA binding. In vivo, the parAR351A allele is compromised for partition, but its repressor activity is dramatically improved so that it behaves as a “super-repressor.” In vitro, ParAR351A binds and hydrolyzes ATP, and undergoes a specific conformational change required for nsDNA binding, but its nsDNA-binding activity is significantly damaged. This defect in turn significantly reduces the assembly and stability of partition complexes formed by the interaction of ParA with ParB, the centromere-binding protein, and DNA. In contrast, the R351A change shows only a mild defect in site-specific DNA binding. We conclude that the partition defect is due to altered nsDNA binding kinetics and affinity for the bacterial chromosome. Furthermore, the super-repressor phenotype is explained by an increased pool of non-nucleoid bound ParA that is competent to bind parOP and repress transcription. Full Article
rep Optimized incorporation of an unnatural fluorescent amino acid affords measurement of conformational dynamics governing high-fidelity DNA replication [DNA and Chromosomes] By www.jbc.org Published On :: 2020-12-11T00:06:21-08:00 DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication. Full Article
rep A human cancer cell line initiates DNA replication normally in the absence of ORC5 and ORC2 proteins [DNA and Chromosomes] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 The origin recognition complex (ORC), composed of six subunits, ORC1–6, binds to origins of replication as a ring-shaped heterohexameric ATPase that is believed to be essential to recruit and load MCM2–7, the minichromosome maintenance protein complex, around DNA and initiate DNA replication. We previously reported the creation of viable cancer cell lines that lacked detectable ORC1 or ORC2 protein without a reduction in the number of origins firing. Here, using CRISPR-Cas9–mediated mutations, we report that human HCT116 colon cancer cells also survive when ORC5 protein expression is abolished via a mutation in the initiator ATG of the ORC5 gene. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2–7 and initiate replication from a similar number of origins as WT cells. In addition, we introduced a second mutation in ORC2 in the ORC5 mutant cells, rendering both ORC5 and ORC2 proteins undetectable in the same cells and destabilizing the ORC1, ORC3, and ORC4 proteins. Yet the double mutant cells grow, recruit MCM2–7 normally to chromatin, and initiate DNA replication with normal number of origins. Thus, in these selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels on the chromatin can recruit and load enough MCM2–7 to initiate DNA replication, or human cell lines can sometimes recruit MCM2–7 to origins independent of ORC. Full Article
rep Polymerase {gamma} efficiently replicates through many natural template barriers but stalls at the HSP1 quadruplex [Enzymology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Faithful replication of the mitochondrial genome is carried out by a set of key nuclear-encoded proteins. DNA polymerase γ is a core component of the mtDNA replisome and the only replicative DNA polymerase localized to mitochondria. The asynchronous mechanism of mtDNA replication predicts that the replication machinery encounters dsDNA and unique physical barriers such as structured genes, G-quadruplexes, and other obstacles. In vitro experiments here provide evidence that the polymerase γ heterotrimer is well-adapted to efficiently synthesize DNA, despite the presence of many naturally occurring roadblocks. However, we identified a specific G-quadruplex–forming sequence at the heavy-strand promoter (HSP1) that has the potential to cause significant stalling of mtDNA replication. Furthermore, this structured region of DNA corresponds to the break site for a large (3,895 bp) deletion observed in mitochondrial disease patients. The presence of this deletion in humans correlates with UV exposure, and we have found that efficiency of polymerase γ DNA synthesis is reduced after this quadruplex is exposed to UV in vitro. Full Article
rep Genetic evidence for the involvement of mismatch repair proteins, PMS2 and MLH3, in a late step of homologous recombination [Cell Biology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Homologous recombination (HR) repairs DNA double-strand breaks using intact homologous sequences as template DNA. Broken DNA and intact homologous sequences form joint molecules (JMs), including Holliday junctions (HJs), as HR intermediates. HJs are resolved to form crossover and noncrossover products. A mismatch repair factor, MLH3 endonuclease, produces the majority of crossovers during meiotic HR, but it remains elusive whether mismatch repair factors promote HR in nonmeiotic cells. We disrupted genes encoding the MLH3 and PMS2 endonucleases in the human B cell line, TK6, generating null MLH3−/− and PMS2−/− mutant cells. We also inserted point mutations into the endonuclease motif of MLH3 and PMS2 genes, generating endonuclease death MLH3DN/DN and PMS2EK/EK cells. MLH3−/− and MLH3DN/DN cells showed a very similar phenotype, a 2.5-fold decrease in the frequency of heteroallelic HR-dependent repair of restriction enzyme–induced double-strand breaks. PMS2−/− and PMS2EK/EK cells showed a phenotype very similar to that of the MLH3 mutants. These data indicate that MLH3 and PMS2 promote HR as an endonuclease. The MLH3DN/DN and PMS2EK/EK mutations had an additive effect on the heteroallelic HR. MLH3DN/DN/PMS2EK/EK cells showed normal kinetics of γ-irradiation–induced Rad51 foci but a significant delay in the resolution of Rad51 foci and a 3-fold decrease in the number of cisplatin-induced sister chromatid exchanges. The ectopic expression of the Gen1 HJ re-solvase partially reversed the defective heteroallelic HR of MLH3DN/DN/PMS2EK/EK cells. Taken together, we propose that MLH3 and PMS2 promote HR as endonucleases, most likely by processing JMs in mammalian somatic cells. Full Article
rep Politicians are failing to prepare for next pandemic, warns head of European health agency By www.bmj.com Published On :: Thursday, September 26, 2024 - 11:21 Full Article
rep Pandemics are no longer “rare” and now pose constant threat, global preparedness board warns By www.bmj.com Published On :: Tuesday, October 15, 2024 - 14:51 Full Article
rep UK reports two further cases of clade Ib mpox By www.bmj.com Published On :: Tuesday, November 5, 2024 - 14:26 Full Article
rep Business Development in Madagascar: How to Enable Entrepreneurialism By www.chathamhouse.org Published On :: Thu, 09 Nov 2017 10:30:00 +0000 Business Development in Madagascar: How to Enable Entrepreneurialism 15 November 2017 — 12:00PM TO 1:00PM Anonymous (not verified) 9 November 2017 Chatham House, London Madagascar’s business environment has improved in a period of stability ushered in with elections in 2013, which brought an end to the political crisis that had started in 2009. SME development has been constrained by poor access to credit and financial services, weak definition of property titles, and skills gaps and human capital shortfalls that have impeded the development of a managerial talent pool. However, the government has prioritized reform for company creation, granting construction permits and cross-border trade, in support of entrepreneurialism and business development. At this event, Erick Rajaonary, the CEO of the GuanoMad Group and president of the association of the Madagascar entrepreneurs, will discuss the how to create space for entrepreneurialism and prospects for broad based business development in Madagascar. Full Article
rep Clinical Factors That Influence Repeat 68Ga-PSMA-11 PET/CT Scan Positivity in Patients with Recurrent Prostate Cancer Under Observation After a Negative 68Ga-PSMA-11 PET/CT Scan: A Single-Center Retrospective Study By jnm.snmjournals.org Published On :: 2024-10-01T04:08:08-07:00 This analysis aimed to identify clinical factors associated with positivity on repeat 68Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann–Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2–1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9–3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative 68Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat 68Ga-PSMA-11 PET/CT. Full Article
rep Development of 18F-Fluoromisonidazole Hypoxia PET/CT Diagnostic Interpretation Criteria and Validation of Interreader Reliability, Reproducibility, and Performance By jnm.snmjournals.org Published On :: 2024-10-01T04:08:08-07:00 Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with 18F-fluoromisonidazole (18F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret 18F-FMISO hypoxia PET. Methods: We randomly selected 123 patients with human papillomavirus–positive oropharyngeal cancer enrolled in a phase II trial who underwent 123 18F-FDG PET/CT and 134 18F-FMISO PET/CT scans. Four independent nuclear medicine physicians with no 18F-FMISO experience read the scans. Interpretation by a fifth nuclear medicine physician with over 2 decades of 18F-FMISO experience was the reference standard. Performance was evaluated after initial instruction and subsequent dedicated training. Scans were considered positive for hypoxia by visual assessment if 18F-FMISO uptake was greater than floor-of-mouth uptake. Additionally, SUVmax was determined to evaluate whether quantitative assessment using tumor-to-background ratios could be helpful to define hypoxia positivity. Results: Visual assessment produced a mean sensitivity and specificity of 77.3% and 80.9%, with fair interreader agreement ( = 0.34), after initial instruction. After dedicated training, mean sensitivity and specificity improved to 97.6% and 86.9%, with almost perfect agreement ( = 0.86). Quantitative assessment with an estimated best SUVmax ratio threshold of more than 1.2 to define hypoxia positivity produced a mean sensitivity and specificity of 56.8% and 95.9%, respectively, with substantial interreader agreement ( = 0.66), after initial instruction. After dedicated training, mean sensitivity improved to 89.6% whereas mean specificity remained high at 95.3%, with near-perfect interreader agreement ( = 0.86). Conclusion: Nuclear medicine physicians without 18F-FMISO hypoxia PET reading experience demonstrate much improved interreader agreement with dedicated training using specific interpretation criteria. Full Article
rep Report: SpaceX signs battery deal with South Korea-based LG Energy Solution to power Starship By www.upi.com Published On :: Mon, 11 Nov 2024 17:29:20 -0500 SpaceX has reportedly struck a deal with LG Energy Solution Ltd. to supply cylindrical lithium-ion batteries for Elon Musk's Starship rocket, expected to launch early next year, according to industry sources. Full Article
rep Pentagon asks employees to report cases of strange, sudden sickness By www.upi.com Published On :: Thu, 16 Sep 2021 14:17:38 -0400 U.S. Defense Secretary Lloyd Austin has pledged to get to the bottom of reports of military personnel experiencing mysterious illnesses while overseas. Full Article
rep TSMC Releases October 2024 Revenue Report By www.hpcwire.com Published On :: Fri, 08 Nov 2024 16:43:48 +0000 HSINCHU, Taiwan, Nov. 8, 2024 – TSMC (TWSE: 2330, NYSE: TSM) today announced its net revenue for October 2024. On a consolidated basis, revenue for October 2024 was approximately NT$314.24 […] The post TSMC Releases October 2024 Revenue Report appeared first on HPCwire. Full Article
rep Repairs to Tampa Bay Rays' Tropicana Field from Hurricane Milton put at $55.7 million By www.upi.com Published On :: Tue, 12 Nov 2024 17:27:58 -0500 It will cost $55.7 million to repair Tropicana Field, home to the MLB Tampa Bay Rays, in time for the 2026 home opener, St. Petersburg., Fla., city officials said Tuesday. Full Article
rep Blood tests for colon cancer screening not ready to replace colonoscopy, study indicates By www.upi.com Published On :: Mon, 28 Oct 2024 17:29:27 -0400 New blood tests screen for colorectal cancer in a much less invasive way than colonoscopy, but deaths will increase if many people choose this alternative, a new study indicates. Full Article
rep Report from HALO Details Issues Facing HPC-AI Industry By www.hpcwire.com Published On :: Mon, 28 Oct 2024 23:45:38 +0000 Intersect360 Research has released a comprehensive new report concerning the challenges facing the combined fields of high-performance computing (HPC) and artificial intelligence (AI). Titled “Issues Facing the HPC-AI Industry: Insights […] The post Report from HALO Details Issues Facing HPC-AI Industry appeared first on HPCwire. Full Article Features China cpu EU FPGA GPU HALO HPC/AI NPU
rep AI Has a Data Problem, Appen Report Says By www.hpcwire.com Published On :: Wed, 30 Oct 2024 18:26:30 +0000 AI may be a priority at American companies, but the difficulty in managing data and obtaining high quality data to train AI models is becoming a bigger hurdle to achieving […] The post AI Has a Data Problem, Appen Report Says appeared first on HPCwire. Full Article Features AI data availability data bottleneck data challenge data management data pipeline data quality GenAI Ryan Kolln Si Chen State of AI 2024 State of AI report
rep Report: SpaceX signs battery deal with South Korea-based LG Energy Solution to power Starship By www.upi.com Published On :: Mon, 11 Nov 2024 17:29:20 -0500 SpaceX has reportedly struck a deal with LG Energy Solution Ltd. to supply cylindrical lithium-ion batteries for Elon Musk's Starship rocket, expected to launch early next year, according to industry sources. Full Article
rep Trump selects former GOP Rep. Lee Zeldin to lead EPA By www.upi.com Published On :: Mon, 11 Nov 2024 19:15:53 -0500 President-elect Donald Trump has chosen former Republican Rep. Lee Zeldin of New York to run the Environmental Protection Agency. Full Article
rep Rep. Ruben Gallego claims victory over Kari Lake in Arizona Senate race By www.upi.com Published On :: Tue, 12 Nov 2024 02:08:43 -0500 Democratic Rep. Ruben Gallego was poised Monday night to defeat election denier and President-elect Donald Trump ally Kari Lake in a closely watched Senate race in Arizona. Full Article
rep Could we replace data centers with … plant DNA? | Cliff Kapono and Keolu Fox By www.ted.com Published On :: Mon, 21 Oct 2024 14:51:23 +0000 Is it possible to meet the world's seemingly infinite demand for data storage while also caring for the natural environment? Biomedical researcher Keolu Fox and professional surfer and scientist Cliff Kapono believe that Indigenous knowledge combined with the science of genetics may offer such a solution: using the DNA of plant cells (like those found in sugar cane) as mini data warehouses. Learn more about the incredible potential of this technology — and how it could help foster ecosystem resilience in a high-tech world. Full Article Higher Education
rep How 4 Communities Are Struggling to Prepare Kids for an Uncertain Future By www.edweek.org Published On :: Tue, 04 Feb 2020 00:00:00 +0000 Schools are slowly figuring out how to balance thinking globally with acting locally, and recognizing that some key skills are valuable no matter where students end up living. Full Article Wyoming
rep As coronavirus spikes, NYC prepares to close schools again By www.teachermagazine.org Published On :: 2020-11-13T15:59:52-05:00 Full Article Education
rep How Schools Are Preparing for the Perfect Storm of Holiday Travel and COVID-19 By www.teachermagazine.org Published On :: 2020-11-16T17:13:00-05:00 Schools are putting in place or considering measures such as extending holiday breaks or shifting back to full-time remote learning. Full Article Education
rep Here's What One State Is Doing to Prepare Students for the Jobs of the Future By blogs.edweek.org Published On :: Thu, 06 Jun 2019 00:00:00 +0000 Maryland may be a model for how states should approach educating students for the workforce of the future, according to a new policy brief. Full Article Maryland
rep Maryland Ranks Fourth on Quality Counts Annual Report Card By www.edweek.org Published On :: Tue, 03 Sep 2019 00:00:00 +0000 The state, which earned a B, saw its educational strength buoyed by strong performance in areas that measure socioeconomic factors that can affect the educational environment. Full Article Maryland
rep Helping Prepare Teachers in Massachusetts for Day One By blogs.edweek.org Published On :: Mon, 15 Oct 2018 00:00:00 +0000 Massachusetts' new performance assessment for teacher candidates helps boost readiness. Full Article Massachusetts
rep Massachusetts Ranks Second on Quality Counts Annual Report Card By www.edweek.org Published On :: Tue, 03 Sep 2019 00:00:00 +0000 The state, which earned a B-plus, led the nation in K-12 achievement rankings and outperformed other states in several key academic indicators, but fell short on funding equity. Full Article Massachusetts
rep Kentucky Teen Once Subject of Viral Video Warns Republicans of 'Outrage Mob' By blogs.edweek.org Published On :: Tue, 25 Aug 2020 00:00:00 +0000 A Kentucky teen who became the subject of a viral video after a class field trip warned viewers of the Republican National Convention of an "outrage mob" that threatens to silence conservative viewpoints. Full Article Kentucky
rep Do America's Public Schools Owe Black People Reparations? By www.edweek.org Published On :: Wed, 23 Sep 2020 00:00:00 +0000 School districts must make amends for their racist history, writes Daarel Burnette II. What should that look like? Full Article Virginia
rep Nevada Ranks 50th on Quality Counts Annual Report Card By www.edweek.org Published On :: Tue, 03 Sep 2019 00:00:00 +0000 The state, which earned a D-plus, was weak on socioeconomic factors that can affect the educational environment, and also in the school finance area. Full Article Nevada
rep Oklahoma Ranks 49th on Quality Counts Annual Report Card By www.edweek.org Published On :: Tue, 03 Sep 2019 00:00:00 +0000 The state, which earned a D-plus, has struggled with school finance issues and endured teacher strikes and battles over pay, but also earned B-plus for funding equity. Full Article Oklahoma
rep Supreme Court Won't Hear Challenge to Union Exclusive Representation By blogs.edweek.org Published On :: Mon, 05 Oct 2020 00:00:00 +0000 The justices declined to take up a major challenge to exclusive-bargaining arrangements for teachers' unions and other public employee labor organizations. Full Article Maine
rep N.Y. Private Schools Didn't Have to Report Abuse to Police. A New Law Changes That. By blogs.edweek.org Published On :: Thu, 27 Dec 2018 00:00:00 +0000 Private schools in New York soon will be required to report suspected sexual abuse of students in their schools to law enforcement, bringing the independent schools under the same rules as public schools. Full Article New_York
rep Report finds Loudoun school's admission policy discriminates By www.edweek.org Published On :: 2020-11-24T08:36:09-05:00 Full Article Education