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Sterol regulatory element-binding protein Sre1 regulates carotenogenesis in the red yeast Xanthophyllomyces dendrorhous [Research Articles]

Xanthophyllomyces dendrorhous is a basidiomycete yeast that produces carotenoids, mainly astaxanthin. Astaxanthin is an organic pigment of commercial interest due to its antioxidant and coloring properties. X. dendrorhous has a functional SREBP pathway, and the Sre1 protein is the SREBP homolog in this yeast. However, how sterol regulatory element (Sre)1 promotes the biosynthesis of sterols and carotenoids in X. dendrorhous is unknown. In this work, comparative RNA-sequencing analysis between modified X. dendrorhous strains that have an active Sre1 protein and the WT was performed to identify Sre1-dependent genes. In addition, Sre1 direct target genes were identified through ChIP combined with lambda exonuclease digestion (ChIP-exo) assays. SRE motifs were detected in the promoter regions of several Sre1 direct target genes and were consistent with the SREs described in other yeast species. Sre1 directly regulates genes related to ergosterol biosynthesis as well as genes related to the mevalonate (MVA) pathway, which synthesizes the building blocks of isoprenoids, including carotenoids. Two carotenogenic genes, crtE and crtR, were also identified as Sre1 direct target genes. Thus, carotenogenesis in X. dendrorhous is regulated by Sre1 through the regulation of the MVA pathway and the regulation of the crtE and crtR genes. As the crtR gene encodes a cytochrome P450 reductase, Sre1 regulates pathways that include cytochrome P450 enzymes, such as the biosynthesis of carotenoids and sterols. These results demonstrate that Sre1 is a sterol master regulator that is conserved in X. dendrorhous.




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Membrane-bound sn-1,2-diacylglycerols explain the dissociation of hepatic insulin resistance from hepatic steatosis in MTTP knockout mice [Research Articles]

Microsomal triglyceride transfer protein (MTTP) deficiency results in a syndrome of hypolipidemia and accelerated NAFLD. Animal models of decreased hepatic MTTP activity have revealed an unexplained dissociation between hepatic steatosis and hepatic insulin resistance. Here, we performed comprehensive metabolic phenotyping of liver-specific MTTP knockout (L-Mttp–/–) mice and age-weight matched wild-type control mice. Young (10–12-week-old) L-Mttp–/– mice exhibited hepatic steatosis and increased DAG content; however, the increase in hepatic DAG content was partitioned to the lipid droplet and was not increased in the plasma membrane. Young L-Mttp–/– mice also manifested normal hepatic insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamps, no PKC activation, and normal hepatic insulin signaling from the insulin receptor through AKT Ser/Thr kinase. In contrast, aged (10-month-old) L-Mttp–/– mice exhibited glucose intolerance and hepatic insulin resistance along with an increase in hepatic plasma membrane sn-1,2-DAG content and PKC activation. Treatment with a functionally liver-targeted mitochondrial uncoupler protected the aged L-Mttp–/– mice against the development of hepatic steatosis, increased plasma membrane sn-1,2-DAG content, PKC activation, and hepatic insulin resistance. Furthermore, increased hepatic insulin sensitivity in the aged controlled-release mitochondrial protonophore-treated L-Mttp–/– mice was not associated with any reductions in hepatic ceramide content. Taken together, these data demonstrate that differences in the intracellular compartmentation of sn-1,2-DAGs in the lipid droplet versus plasma membrane explains the dissociation of NAFLD/lipid-induced hepatic insulin resistance in young L-Mttp–/– mice as well as the development of lipid-induced hepatic insulin resistance in aged L-Mttp–/– mice.




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Kir2.1 Interactome Mapping Uncovers PKP4 as a Modulator of the Kir2.1-Regulated Inward Rectifier Potassium Currents [Research]

Kir2.1, a strong inward rectifier potassium channel encoded by the KCNJ2 gene, is a key regulator of the resting membrane potential of the cardiomyocyte and plays an important role in controlling ventricular excitation and action potential duration in the human heart. Mutations in KCNJ2 result in inheritable cardiac diseases in humans, e.g. the type-1 Andersen-Tawil syndrome (ATS1). Understanding the molecular mechanisms that govern the regulation of inward rectifier potassium currents by Kir2.1 in both normal and disease contexts should help uncover novel targets for therapeutic intervention in ATS1 and other Kir2.1-associated channelopathies. The information available to date on protein-protein interactions involving Kir2.1 channels remains limited. Additional efforts are necessary to provide a comprehensive map of the Kir2.1 interactome. Here we describe the generation of a comprehensive map of the Kir2.1 interactome using the proximity-labeling approach BioID. Most of the 218 high-confidence Kir2.1 channel interactions we identified are novel and encompass various molecular mechanisms of Kir2.1 function, ranging from intracellular trafficking to cross-talk with the insulin-like growth factor receptor signaling pathway, as well as lysosomal degradation. Our map also explores the variations in the interactome profiles of Kir2.1WT versus Kir2.1314-315, a trafficking deficient ATS1 mutant, thus uncovering molecular mechanisms whose malfunctions may underlie ATS1 disease. Finally, using patch-clamp analysis, we validate the functional relevance of PKP4, one of our top BioID interactors, to the modulation of Kir2.1-controlled inward rectifier potassium currents. Our results validate the power of our BioID approach in identifying functionally relevant Kir2.1 interactors and underline the value of our Kir2.1 interactome as a repository for numerous novel biological hypotheses on Kir2.1 and Kir2.1-associated diseases.




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Molecular Profiling of Innate Immune Response Mechanisms in Ventilator-associated Pneumonia [Research]

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection, leading to high morbidity and mortality. Currently, bronchoalveolar lavage (BAL) is used in hospitals for VAP diagnosis and guiding treatment options. Although BAL collection procedures are invasive, alternatives such as endotracheal aspirates (ETA) may be of diagnostic value, however, their use has not been thoroughly explored. Longitudinal ETA and BAL were collected from 16 intubated patients up to 15 days, of which 11 developed VAP. We conducted a comprehensive LC–MS/MS based proteome and metabolome characterization of longitudinal ETA and BAL to detect host and pathogen responses to VAP infection. We discovered a diverse ETA proteome of the upper airways reflective of a rich and dynamic host-microbe interface. Prior to VAP diagnosis by microbial cultures from BAL, patient ETA presented characteristic signatures of reactive oxygen species and neutrophil degranulation, indicative of neutrophil mediated pathogen processing as a key host response to the VAP infection. Along with an increase in amino acids, this is suggestive of extracellular membrane degradation resulting from proteolytic activity of neutrophil proteases. The metaproteome approach successfully allowed simultaneous detection of pathogen peptides in patients' ETA, which may have potential use in diagnosis. Our findings suggest that ETA may facilitate early mechanistic insights into host-pathogen interactions associated with VAP infection and therefore provide its diagnosis and treatment.




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Slight Deuterium Enrichment in Water Acts as an Antioxidant: Is Deuterium a Cell Growth Regulator? [Research]

Small admixtures in water, e.g. of metal ions, often act as cell growth regulators. Here we report that enrichment of deuterium content in water, normally found at 8 mm concentration, two-three folds increases cell proliferation and lowers the oxidative stress level as well. Acting as an anti-oxidant, deuterium-enriched water prevents the toxic effect of such oxidative agents as hydrogen peroxide and auranofin. This action is opposite to that of deuterium depletion that is known to suppress cell growth and induce oxidative stress in mitochondria. We thus hypothesize that deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. Because growth acceleration is reduced approximately by half by addition to water a minute amount (0.15%) of 18O isotope, at least part of the deuterium effect on cell growth can be explained by the isotopic resonance phenomenon. A slight (2-fold) enrichment of deuterium in water accelerates human cell growth. Quantitative MS based proteomics determined changes in protein abundances and redox states and found that deuterium-enriched water acts mainly through decreasing ROS production in mitochondria. This action is opposite to that of deuterium depletion that suppresses cell growth by inducing oxidative stress. Thus deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. The role of isotopic resonance in this effect was validated by further experiments on bacteria.




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Identification of Microorganisms by Liquid Chromatography-Mass Spectrometry (LC-MS1) and in Silico Peptide Mass Libraries [Technological Innovation and Resources]

Over the past decade, modern methods of MS (MS) have emerged that allow reliable, fast and cost-effective identification of pathogenic microorganisms. Although MALDI-TOF MS has already revolutionized the way microorganisms are identified, recent years have witnessed also substantial progress in the development of liquid chromatography (LC)-MS based proteomics for microbiological applications. For example, LC-tandem MS (LC-MS2) has been proposed for microbial characterization by means of multiple discriminative peptides that enable identification at the species, or sometimes at the strain level. However, such investigations can be laborious and time-consuming, especially if the experimental LC-MS2 data are tested against sequence databases covering a broad panel of different microbiological taxa. In this proof of concept study, we present an alternative bottom-up proteomics method for microbial identification. The proposed approach involves efficient extraction of proteins from cultivated microbial cells, digestion by trypsin and LC–MS measurements. Peptide masses are then extracted from MS1 data and systematically tested against an in silico library of all possible peptide mass data compiled in-house. The library has been computed from the UniProt Knowledgebase covering Swiss-Prot and TrEMBL databases and comprises more than 12,000 strain-specific in silico profiles, each containing tens of thousands of peptide mass entries. Identification analysis involves computation of score values derived from correlation coefficients between experimental and strain-specific in silico peptide mass profiles and compilation of score ranking lists. The taxonomic positions of the microbial samples are then determined by using the best-matching database entries. The suggested method is computationally efficient – less than 2 mins per sample - and has been successfully tested by a test set of 39 LC-MS1 peak lists obtained from 19 different microbial pathogens. The proposed method is rapid, simple and automatable and we foresee wide application potential for future microbiological applications.




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Novel Proteomic Profiling of Epididymal Extracellular Vesicles in the Domestic Cat Reveals Proteins Related to Sequential Sperm Maturation with Differences Observed between Normospermic and Teratospermic Individuals [Research]

Extracellular vesicles (EVs) secreted by the epididymal epithelium transfer to spermatozoa key proteins that are essential in promoting motility and subsequent fertilization success. Using the domestic cat model, the objectives were to (1) characterize and compare protein content of EVs between segments of the epididymis, and (2) compare EV protein compositions between normo- and teratospermic individuals (producing >60% of abnormal spermatozoa). Epididymal EVs from adult cats were isolated and assessed via liquid chromatography tandem MS. Both male types shared 3008 proteins in total, with 98 and 20 EV proteins unique to normospermic and teratospermic males, respectively. Expression levels of several proteins changed between epididymal segments in both male types. Several proteins in both groups were related to sperm motility (e.g. hexokinase 1, adenylate kinase isoenzyme) and zona pellucida or oolemma binding (e.g. disintegrin and metalloproteinase domain proteins, zona binding proteins 1 and 2). Interestingly, seven cauda-derived EV proteins trended downward in teratospermic compared with normospermic males, which may relate to poor sperm quality. Collective results revealed, for the first time, EV proteins related to sequential sperm maturation with differences observed between normospermic and teratospermic individuals.




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Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays [11. Microarrays/Combinatorics/Display Technology]

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.




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Isolation of acetylated and unmodified protein N-terminal peptides by strong cation exchange chromatographic separation of TrypN-digested peptides [Technological Innovation and Resources]

We developed a simple and rapid method to enrich protein N-terminal peptides, in which the protease TrypN is first employed to generate protein N-terminal peptides without Lys or Arg and internal peptides with two positive charges at their N-termini, and then the N-terminal peptides with or without N-acetylation are separated from the internal peptides by strong cation exchange chromatography according to a retention model based on the charge/orientation of peptides. This approach was applied to 20 μg of human HEK293T cell lysate proteins to profile the N-terminal proteome. On average, 1,550 acetylated and 200 unmodified protein N-terminal peptides were successfully identified in a single LC/MS/MS run with less than 3% contamination with internal peptides, even when we accepted only canonical protein N-termini registered in the Swiss-Prot database. Since this method involves only two steps, protein digestion and chromatographic separation, without the need for tedious chemical reactions, it should be useful for comprehensive profiling of protein N-termini, including proteoforms with neo-N-termini.




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Proteogenomic characterization of the pathogenic fungus Aspergillus flavus reveals novel genes involved in aflatoxin production [Research]

Aspergillus flavus (A. flavus), a pathogenic fungus, can produce carcinogenic and toxic aflatoxins that are a serious agricultural and medical threat worldwide. Attempts to decipher the aflatoxin biosynthetic pathway have been hampered by the lack of a high-quality genome annotation for A. flavus. To address this gap, we performed a comprehensive proteogenomic analysis using high-accuracy mass spectrometry data for this pathogen. The resulting high-quality dataset confirmed the translation of 8,724 previously-predicted genes, and identified 732 novel proteins, 269 splice variants, 447 single amino acid variants, 188 revised genes. A subset of novel proteins was experimentally validated by RT-PCR and synthetic peptides. Further functional annotation suggested that a number of the identified novel proteins may play roles in aflatoxin biosynthesis and stress responses in A. flavus. This comprehensive strategy also identified a wide range of post-translational modifications (PTMs), including 3,461 modification sites from 1,765 proteins. Functional analysis suggested the involvement of these modified proteins in the regulation of cellular metabolic and aflatoxin biosynthetic pathways. Together, we provided a high quality annotation of A. flavus genome and revealed novel insights into the mechanisms of aflatoxin production and pathogenicity in this pathogen.




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Prediction and validation of mouse meiosis-essential genes based on spermatogenesis proteome dynamics [Research]

The molecular mechanism associated with mammalian meiosis has yet to be fully explored, and one of the main reasons for this lack of exploration is that some meiosis-essential genes are still unknown. The profiling of gene expression during spermatogenesis has been performed in previous studies, yet few studies have aimed to find new functional genes. Since there is a huge gap between the number of genes that are able to be quantified and the number of genes that can be characterized by phenotype screening in one assay, an efficient method to rank quantified genes according to phenotypic relevance is of great importance. We proposed to rank genes by the probability of their function in mammalian meiosis based on global protein abundance using machine learning. Here, nine types of germ cells focusing on continual substages of meiosis prophase I were isolated, and the corresponding proteomes were quantified by high-resolution mass spectrometry. By combining meiotic labels annotated from the MGI mouse knockout database and the spermatogenesis proteomics dataset, a supervised machine learning package, FuncProFinder, was developed to rank meiosis-essential candidates. Of the candidates whose functions were unannotated, four of ten genes with the top prediction scores, Zcwpw1, Tesmin, 1700102P08Rik and Kctd19, were validated as meiosis-essential genes by knockout mouse models. Therefore,  mammalian meiosis-essential genes could be efficiently predicted based on the protein abundance dataset, which provides a paradigm for other functional gene mining from a related abundance dataset.




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The Chatham House Sustainable Laboratories Initiative: Prior Assessment Tool

The Chatham House Sustainable Laboratories Initiative: Prior Assessment Tool Other resource sysadmin 14 June 2019

Laboratories are critical for supporting effective infectious disease surveillance and outbreak response. This tool is meant to help structure a conversation between funding partners and recipient countries on how to most effectively establish or repurpose laboratories in low-resource environments.

Copyright: Getty Images/ER Productions Limited

Introduction

Laboratories are critical for supporting effective infectious disease surveillance and outbreak response, and lack of adequate laboratory capacity is a global challenge. As part of global health security initiatives, cooperative threat reduction efforts and international development programmes, sophisticated laboratories have been provided to mitigate biological threats and bolster a country’s capacity for detection, diagnosis and storage of high-consequence pathogens. Very often, these use the assumptions, standards and templates applied in high-income countries. However, it can be difficult or even impossible to sustain these facilities in low-resource environments. There can sometimes be limited local technical capacity and capability, which can result in a high reliance on imported expertise, skills, equipment and other resources. Sustainability can therefore be hard to achieve. In addition, when a funding partner withdraws, the laboratories can become disused, foundering without the trained personnel and financial resources to sustain them.

To help address this situation, a proposal gaining increasing support internationally is to adopt an approach based on a local risk assessment, whereby laboratories are appropriately and optimally tailored to the local risks and to the resources available, both in the short and longer term, without compromising biosafety and biosecurity.

A Chatham House workshop was convened in Abuja, Nigeria, in 2018 to explore what West African countries would find most appropriate in terms of building laboratory capacity, what the main challenges have been so far, and what needs to be done to improve the sustainability of laboratories in the region. It emerged that there was a need for a more structured conversation between the funding partner and recipient country early in the process – prior to embarking on the detailed planning phase for the establishment or repurposing of a laboratory. This should involve careful consideration and an assessment of existing and planned capacity, needs and contextual issues, together with proposals for how to address the issues revealed, so that any ensuing laboratory demonstrably supports the national strategy and therefore flourishes.

The purpose of this tool

This tool aims to provide a structure for such a conversation. Developed in close collaboration with international experts and West African stakeholders, it seeks to increase local ownership and help partners ensure they have given due attention to all the relevant aspects, including risks and benefits, that need to be considered at an early stage. It should provide clarity on what is needed and improve the sustainability of any laboratory project that might result from the discussions. The tool can be applied when a new laboratory is being considered, or when an existing laboratory is to be repurposed or strengthened. It is also appropriate for use with public health, veterinary and environmental laboratories. Although the tool was developed in the context of high-consequence pathogens in Africa, it is anticipated that it will find global application.

It should support recipient countries to take stock of their capacities and capabilities, identify gaps, conduct an analysis of their needs and to develop the business case that can assist in seeking the necessary political and financial support for the laboratory. Meanwhile, it should facilitate the process of due diligence for the funding partner and provide a better understanding of what the recipient country perspective and realities are, and what the scale and nature of any investment might be.




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The Justice Laboratory: International Law in Africa

The Justice Laboratory: International Law in Africa Book dora.popova 30 March 2022

The Justice Laboratory is the first major study of the institutions created to enforce international criminal justice standards in Sub-Saharan Africa, including the UN tribunal for the Rwandan genocide.

Since the Second World War, the United Nations and other international actors have created laws, treaties, and institutions to punish perpetrators of genocide, war crimes, and crimes against humanity. But international criminal justice now seems to be a declining force — its energy sapped by long delays in prosecutions, lagging public attention, and a globally rising authoritarianism that disregards legal niceties.

The Justice Laboratory reviews five examples of international criminal justice as they have been applied across Africa, where brutal civil conflicts in recent decades resulted in varying degrees of global attention and action.

Written in an accessible style, the book explores the connections between politics and the doctrine of international criminal law. Highlighting little-known institutional examples and under-discussed political situations, the book contributes to a broader international understanding of African politics and international criminal justice, and the lessons African experiences can offer to other countries.

This book is part of the Insights series.

 

Praise for The Justice Laboratory

Integrating legal and political analysis, Kerstin Bree Carlson provides a highly accessible and provocative examination of the promises and pitfalls of seeking accountability in a range of contemporary international criminal justice interventions in Africa.

Victor Peskin, School of Politics and Global Studies, Arizona State University

About the author

Kerstin Bree Carlson is associate professor of international law at the Department of Social Science and Business, Roskilde University, where she teaches topics in law and society, global studies, international politics, and Nordic migration.

Purchase




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Hernandez healthy, ready to run atop lineup

Cesar Hernandez scored 91 runs last season, the Phillies' highest mark since Rollins scored 102 in 2012. Now the luster is no longer there for players who score 100 runs or post 100 RBIs, but Hernandez should score at least 100 runs this season, if he stays healthy and if the Phillies' offense improves as expected.




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Correction: Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer. [Additions and Corrections]

VOLUME 279 (2004) PAGES 33438–33446For Fig. 1B, the second, third, and fifth panels were mistakenly duplicated during article preparation as no yeast colonies were observed in these conditions. The corrected images are presented in the revised Fig. 1B. This correction does not affect the results or conclusions of the work. The authors apologize for the error.jbc;295/50/17382/F1F1F1Figure 1B.




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GLP-1 receptor agonists: European drug regulator asks makers for evidence of self-harm




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Reshaping NATO for an uncertain future

Reshaping NATO for an uncertain future The World Today mhiggins.drupal 25 May 2022

A Chatham House expert panel outlines the challenges for delegates at the Madrid summit where the roadmap for the transatlantic alliance will be created

This year had already been earmarked as pivotal for the shape and direction of European security even before Russia, a nuclear superpower, rolled its tanks into Ukraine.

On the agenda at the NATO summit in Madrid in June is the Strategic Concept, which sets out the alliance’s direction and priorities for the next decade. There is much to discuss. From shared values to the state of the security environment, the Strategic Concept will have a direct impact on the global security landscape.

Ten years ago, the world was a very different place. The United States had just withdrawn from its bloody war in Iraq and was still embroiled in Afghanistan fighting the Taliban. In China, Xi Jinping was poised to become the next president, while refugees escaping the vicious civil war in Syria were heading towards Europe. In Africa, Islamist activity in Mali was about to spread throughout the Sahel.

Now, Russia’s illegal war in Ukraine rages on NATO’s doorstep, spurring the once neutral countries of Sweden and Finland to seek membership. How will Russia’s aggression towards Ukraine affect the western security agenda and what will be the shape of the new NATO that emerges from these talks?  To help answer these questions, The World Today convened a panel of Chatham House experts to consider what the next 10 years holds for NATO.

Here is what they said.

Alice Billon-Galland
We shouldn’t expect a revolution, but more an adaptation of reforms that have taken place at NATO for quite a long time, especially since the Wales summit in 2014. NATO allies will have to decide on the Russian threat perception and decide how they want to reinforce their deterrence and defence posture in the East, and how this affects their ability to maintain a 360-degree approach and to carry out the ambitious NATO 2030 agenda.

Patricia Lewis
We need to understand how deterrence works far better and we should have better metrics by now. Russia and NATO do not wish to engage in conventional warfare with each other, which suggests that Nato’s conventional deterrence is working. That said, Putin’s nuclear threats have not been within the framework of deterrence. But nuclear deterrence has not worked in the way strategists imagined since the end of the Cold War, and we need a much clearer hard look at these weapons once this is all over.

Had we followed through on disarmament in the 1990s, Putin would have held very little sway today. Nuclear weapons and despots are not a good mix and with these weapons there are no small mistakes. We would be foolish to imagine that rationality will hold when it comes to nuclear decision-making.

It is time to put arms control back on the agenda and strengthen our efforts to prevent nuclear proliferation. We need to put the elimination of these weapons back on the UN Security Council agenda.

Andrew Dorman
Finland and Sweden coming into NATO completely transforms the Baltic. It makes the deployment of reinforcements to the Baltic states an awful lot easier. From the Kremlin’s point of view, the last thing they want is another border with NATO. Russia is already overly committed and hasn’t got enough forces to deal with Ukraine. Its border with Finland is enormous. And NATO would be gaining two very robust, well-organized military forces. You are seeing a lot more NATO assets starting to look at the high north.

Hans Kundnani
I am actually slightly less worried about the Russian threat to NATO countries than I was before February 24. The war has demonstrated how weak the Russian military is, and so the idea that it might present a threat to Finland and Sweden seems less plausible than before. It is not even clear to me that Russia could do very much in other south-eastern European countries. It already seems pretty overstretched. This should make us more relaxed, rather than more worried, about threats to other countries and in particular to NATO countries or to Finland and Sweden.

Leslie Vinjamuri
Sweden and Finland moving forward with their requests for membership is a sign of success for the West, but it also raises important questions for the future of European security. The possibility that we lock in a division that might suit Europe and the United States now does not bode well for a Russia maybe 10 years out or with a different leader.

Alice Billon-Galland
We need to avoid mission creep, but we also need to avoid going back to a position where NATO only focuses on Russia and then set an agenda for 10 years based on that threat assessment alone. We will risk missing out on the next big challenge if we go back on something too specific. We risk being reactive, whereas the Strategic Concept is an exercise that should be proactive and provide a space for transatlantic partners to share broader common security concerns.

Patricia Lewis
NATO is open to all countries in the transatlantic area, and it is even possible that Russia could join in the future should they wish to apply. But it is important to remember that NATO is a political-military alliance, and its politics are fundamental to its cohesion, far more than that of any weapon system or a specific enemy. It will continue to address a wider range of threats as it has in, for example, Afghanistan and many of those will be directly related to the impacts of climate change.

One thing to note, in light of Russia’s nuclear threats, is that NATO’s characterization of itself as a ‘nuclear alliance’ should be revised. NATO needs to be resilient to ebbs and flows of weapon systems and not become over-reliant on one system which has recently demonstrated severe negative impacts.

Hans Kundnani
During the Cold War, what held the alliance together was a shared perception of a threat from the Soviet Union – not a set of shared values. After all, there were authoritarian states in NATO. After the end of the Cold War that overwhelming sense of a shared threat from the Soviet Union disappeared and NATO tried to reinvent itself as a community alliance of democracies with shared values.

But we now once again have authoritarian states in NATO. So it was really in danger of being pulled apart. The war in Ukraine has refocused NATO on its original, historic mission: collective security in relation to Russia. In that sense it has given NATO a lifeline.

Creon Butler
Shared values are still an awful lot stronger as an element of what ties NATO together now than they were in the past. I think you now have the threat perception coming back full force. But I still think you have that very strong element of values, indeed the extra countries that are coming in are very strong democratic countries.

The interesting question is the out-of-area stuff – the Afghanistan-related stuff and counterterrorism more generally, and how important those threats remain. I guess there is an element to that which is a global kind of threat, counterterrorism, but there is also the out-of-area activity which obviously has been transformed following the withdrawal from Afghanistan.

Alice Billon-Galland
The crisis management mandate needs to be looked at again with some of the lessons learnt after Afghanistan and Libya, especially given what happened in Kabul, and all the discussion around cooperative security. The question is not only how do we work with partners and countries in the region, but how do we want to engage with China, for instance? How do we want to work on new technologies? How do we want to work with the European Union, with the United Nations?

The alliance must decide what it wants to do versus  what it wants to set aside and have other organizations do, while it refocuses on its core historic tasks.

Andrew Dorman
One of the sensitive, ongoing debates within NATO is whether it has a global role or whether it has a more transatlantic role. There are divisions within NATO about which is its focus. I think the answer, to a degree, is both. One of the real challenges for policymakers, particularly the Biden administration, is that they are going to be pushing for NATO to act as a global player.

This is one of the dilemmas that NATO faces. It could spend all its time focused purely on the short term – that is Russia –  and ignore China, and then suddenly need to think, ‘Oh heck’. What happens if , as a result of this, Russia is essentially dropped into the China camp and Putin becomes Xi Jinping’s poodle? That is a real dilemma, and why I think the US is going to focus on a global NATO.

Leslie Vinjamuri
NATO may have a role to play in Washington’s China strategy. But it won’t be the most important institution. The Biden administration is relying on multiple frameworks for engaging in the Indo-Pacific. For example, the Quad – a partnership between the US, Japan, India and Australia – is designed to secure India’s participation. Pulling India into the region where it has economic power, influence, military and security capabilities and can move the needle. It is both an intelligent and pragmatic strategy to have a number of groupings, a patchwork of overlapping partnerships, including existing alliances. That seems right to me.

Patricia Lewis
It is unlikely that the US would want to create a global NATO. The US and its allies in other regions may wish to model future alliances on NATO, that have strong relationships with it in areas such as political coherence, interoperability, and joint training and exercises and such. But political decision-making would be better suited to sit within specific regional contexts.

Washington has formal alliances in the Indo-Pacific region that commit the US to, for example, the defence of Australia through the Anzus security treaty, as well as Japan. As Washington increases its focus on the Pacific, the existing political-military relationships in the region could become more coherent. We might see a version of a Pacific-Asia Treaty Organization emerge – a Pato. All this depends on how China uses its power and how perspectives in the region evolve.

Creon Butler
I am not sure it is a problem that NATO does not have a specific focus on dealing with the China threat. It potentially has a role in dealing with those things that are seen by the membership as common threats. Which clearly is Russia now but has added terrorism in the past and may well include other things. China is not a common threat in the way that Russia is perceived to be. Of course, something could happen, not least something with Taiwan, which would change that, but that is not where NATO is at present.

Alice Billon-Galland
I think we should really avoid a false dichotomy between ‘NATO should do only Russia’ and ‘NATO should do everything’ because there are lots of activities in the middle where the alliance can bring some added value – and that is exactly what we should be discussing. The issue around China and NATO is being completely overblown. We need to be very clear that the purpose of NATO is to defend the Euro-Atlantic space, but that may include keeping an eye on ‘when China comes to us’, as NATO Secretary-General Jens Stoltenberg often says.

Hans Kundnani
None of the regional partners in Asia that you need to deal with the China challenge are in NATO – and can’t be – so it is just the wrong vehicle to deal with the Indo-Pacific. But there is also a bit of a tension here between Indo-Pacific and Euro-Atlantic. People in Asia also look at the different threat perceptions in completely different ways than we do in Europe. There are a number of reasons why people in India do not support the war in the Ukraine, but one of them is that they see China, not Russia, as the real threat.

Andrew Dorman
I think so much of the debate we have had so far is about political NATO as supposed to military NATO. One of its key roles is how military forces operate, engage and conduct operations, plan operations through deterrents and so forth. NATO as the template of the West does work. That is why it is in the interest of the US to keep this going. It is one of the ways of making sure, for example, the US Pacific fleet remains compatible with the US Atlantic fleet by forcing them to operate the same system, which is the NATO system.

It is one of the things the American forces learnt out of Afghanistan and Iraq. There is a NATO way which is a global footprint. NATO’s role within the African Union is as a template for peacekeeping operations. You have got the likes of Australia and South Korea and Japan very much integrated into NATO. It doesn’t have to be a formal political NATO, but it does strike me to be in the interest of the West to have them reach forces capable of operating with one another.

Patricia Lewis
One of the most interesting developments in the past year has been the creation of Aukus, the security pact between Australia, Britain and the United States. That grew out of the Five Eyes intelligence partnership which led to the need to develop new, interoperable equipment such as nuclear-powered submarines. We will have to see how it develops, but maybe it could be the start of a PATO in the region.  

Creon Butler
In the current situation, we have a crucial partnership between NATO and the EU over Russia, in terms of the long-term future they hold out for Ukraine, but also with the G7 because that is the place to organize the financial support for Ukraine and the economic and financial sanctions against Russia. They are different memberships but the combination of the EU, G7 and NATO is an absolutely crucial alliance of different alliances, with different memberships serving different purposes but having an overall impact that can potentially be very effective.

Leslie Vinjamuri
We work with the institutions that we have, but not always with a clear recognition of their limitations. We are facing a dark moment for the UN Security Council, with one of its founder members blatantly violating the UN’s most important norm. Yet many people in the rest of the world say, ‘Yes, but in 2003, the United States violated Iraq’s sovereignty …’ Where the West sees moral clarity, and so condemns Russia’s invasion of Ukraine, there is an assumption by much of the rest of the world of moral equivalence between these two invasions.

Working through the UN Security Council is going to be difficult for some time. This means that states are probably going to find different strategies for working around, rather than through, the Security Council.




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NATO must now transform old missions into new strategy

NATO must now transform old missions into new strategy Expert comment NCapeling 21 June 2022

As the war in Ukraine becomes prolonged and unpredictable, risks for the transatlantic alliance will increase, as will the global shockwaves of the conflict.

As a revitalized NATO alliance deals with a crisis that has major economic and humanitarian as well as military dimensions, the need for it to develop both a European and a global containment strategy grows ever more urgent.

Bolstering NATO’s defences so as to provide the capability to repel any form of Russian attack on land, at sea, in the air, or through space and cyberspace is a key aspect of this strategy as, in recent weeks, more combat forces able to defend territory have taken the form of additional troops, ships, and aircraft reinforcing the Baltic states and the Black Sea coastlines of Poland and Romania.

Ten allies have so far contributed to this effort, placing 40,000 troops under direct NATO command. Those sceptical about the future of the transatlantic security relationship have been confounded by the major role the US has played in this effort, sending parts of the 82nd Airborne Division and 3rd Armoured Division to Poland, and redeploying US Stryker brigades from Germany and Italy to the Baltic states and Romania.

Although many other allies have sent useful assets – such as French and UK aircraft to Romania or German and Netherlands Patriot batteries to Slovakia – the US contribution still surpasses all European efforts put together. The US now has 100,000 troops in Europe, the most it has deployed there since the mid-1990s.

Transitioning from temporary to permanent deployment

NATO has also mobilized its high-readiness Reaction Force for the first time and aims to establish four new multinational battalions in the Black Sea region – with France offering to lead the one in Romania, Italy in Bulgaria, and the Czech Republic in Slovakia. Most of these deployments are on a temporary basis, but the receiving allies would understandably like them to stay longer and for NATO to commit to permanent stationed forces.

The decision of Germany to increase its defence spending to two per cent of GDP and to devote €100 billion to modernizing the Bundeswehr makes it technically possible for NATO to move to a Cold War-style forward, armoured defence

Although this would oblige the alliance to break formally from the pledge it made to Moscow in 1997 not to station substantial combat forces or nuclear weapons or build military infrastructure on the territory of its new member states in eastern Europe, this was a political undertaking linked to circumstances prevailing at the time.

Given Russia’s behaviour, there is no reason why NATO should not now abandon it. There is also a question over whether NATO could also repeal the NATO-Russia Founding Act and the NATO-Russia Council, or simply leave them in suspension for a future, more cooperative, and less bellicose Russian regime.

Beyond showing the flag along its eastern flank, NATO does face longer-term issues which need to be clarified in its new Strategic Concept. First is whether to abandon its current strategy of reinforcement and military mobility across Europe – known as the Enhanced Forward Presence in the NATO jargon – in favour of the deployment of heavy armoured brigades or even divisions in fixed positions close to borders.

This will be expensive in the long-run and deprive allies of the flexibility they have enjoyed since the end of the Cold War to use their forces as and where they wish – from deployments in the Sahel or Afghanistan to fighting forest fires or building emergency hospitals for COVID-19 patients at home. The only exception is when they have put forces on rotation into the NATO high readiness forces or the European Union (EU) Battle Groups.

Germany’s commitment gives NATO more options

The decision of Germany to increase its defence spending to two per cent of GDP and to devote €100 billion to modernizing the Bundeswehr makes it technically possible for NATO to move to a Cold War-style forward, armoured defence. But it is unclear how quickly Berlin could raise its new divisions given its problems with procurement and government/industry relations in the defence sector.

It may make more sense for Germany not to launch new acquisition programmes but to buy existing off-the-shelf capabilities – as it has recently done with its decision to buy 35 US F35 aircraft – which other European countries are also acquiring, offering economies of scale and cheaper operating and maintenance costs.

But if Germany abandons ambitious defence projects with France – which prefers a ‘buy European’ approach – such as the Future European Air Combat System, the relationship with France will become strained and French plans for EU self-reliance in the military field put at risk.

As a country averse to war fighting and narrow military approaches to security, it is uncertain how much of the conventional defence burden in NATO Germany would be willing to take on, so this could be the opportunity to create more integrated European units with France, the Benelux, Poland, and Italy, even with the post-Brexit UK.

In reinforcing the alliance’s eastern flank, allies have sent forces to wherever they like and largely under national command, but this would not work in a real war

The UK has doubled the size of its forces in Estonia and sent 1,000 troops to Poland, as well as devoting a substantial portion of its army, navy, and airforce to regular NATO exercises in the Baltic region. London was also the first ally to grant Sweden and Finland a temporary security guarantee pending full integration into the alliance.

NATO will likely settle on a compromise, increasing the size of its battalions on its eastern flank – turning them into battle groups – but giving each one a larger reserve force which will remain in Germany or other European allied countries.

A NATO strategic plan is now needed

The other issue for NATO is to develop a single theatre-wide strategic plan managed by the Supreme Allied Commander, Europe (SACEUR) and the NATO command structure. In reinforcing the alliance’s eastern flank, allies have sent forces to wherever they like and largely under national command, but this would not work in a real war.

One thing NATO has done well in this crisis is its political messaging. As Russia has become more threatening and reckless, it has been essential for NATO to be consistent and predictable

NATO must revise its exercises to prepare and train for the new threat level, ensuring its forward deployed forces are fully integrated with local forces and the police and border guards to anticipate and respond to any Russian hybrid war tactics. It also needs to step up its joint planning and interoperability with Sweden and Finland and bring their territories into its standing defence plans.

One thing NATO has done well in this crisis is its political messaging. As Russia has become more threatening and reckless, it has been essential for NATO to be consistent and predictable. Re-affirming its core defensive purpose, calmly rejecting Putin’s nuclear posturing, and refusing to put NATO forces in Ukraine may be frustrating for some but it is vital not to play into Putin’s playbook regarding an ‘aggressive NATO’ or give him the sense he is being pushed into a corner. However, NATO strategic ambiguity can be useful when considering how to respond to a Russian escalation in Ukraine itself, such as using chemical weapons.

The key questions for NATO are:

  • What should be the balance between permanently deployed and rotational forces in NATO’s new posture?
  • What should be the balance of US/Canadian and European forces in this posture?
  • How can the capability development programmes under EU Strategic Autonomy (such as PESCO and the European Defence Fund) be geared to support the European role and responsibility in the alliance? Air and missile defence would seem to be priorities given Russia’s reliance on long range strikes.
  • How can the EU’s Strategic Compass, NATO’s next Strategic Concept and the third NATO-EU Joint Declaration be harmonized to bring the two institutions more closely together in responding to Russian hybrid operations and influence campaigns, and in assisting both Ukraine and others such as Georgia and Moldova?
  • What should be the balance between forces for collective defence with heavy armour and directed artillery fire, and those for expeditionary missions beyond Europe such as counterterrorism, stabilization and peacekeeping?

NATO is revived and refocused

Although the Russian invasion of Ukraine is a catastrophe for Ukraine and Europe more generally, the multilateral system has discovered a new energy and sense of purpose as NATO has been revived and refocused on its core mission.

The EU and the US have pulled together with daily coordination of their policies and actions, and the EU is also facing up to its geo-political role, as recognizing the EU aspirations of Ukraine, Moldova, and Georgia as well as the countries of the western Balkans shows its responsibility for the security and economic integration of the whole of Europe.




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Independent Thinking: Sweden, Finland, and NATO

Independent Thinking: Sweden, Finland, and NATO Audio NCapeling 31 March 2023

Episode 21 of our weekly podcast examines the latest developments relating to Sweden and Finland’s proposed accession to NATO.

The Hungarian parliament has finally ratified Finland’s membership to the NATO alliance, two weeks after President Erdogan in Turkey gave his seal of approval following a meeting with the Finnish president.

Sweden however remains trapped in limbo, with both Turkey and Hungary delaying Stockholm’s membership and Erdogan in particular asking for more concessions.

The panel discusses why Turkey and Hungary took issue with Sweden and Finland, what the strategic situation in the Baltic looks like now with only Finland joining NATO, and the challenges facing Sweden amid its fraught ties with President Erdogan.

We also look ahead to Turkey’s presidential election in May as recent opinion polls point to a neck-and-neck race, with some polls even showing President Erdogan falling behind the opposition. The panel examines what the sentiment is like in Turkey ahead of the election, and how the world would respond if there was a change in power in Ankara for the first time in 20 years.

Joining Bronwen Maddox on the podcast this week is Henri Vanhanen, research fellow with the Finnish Institute of International Affairs, and Galip Dalay, associate fellow with our Middle East and North Africa programme.

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.




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[68Ga]Ga-PSMA-11 PET/CT-Positive Hepatic Inflammatory Pseudotumor: Possible PSMA-Avid Pitfall in Nuclear Imaging




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[68Ga]Ga-RAYZ-8009: A Glypican-3-Targeted Diagnostic Radiopharmaceutical for Hepatocellular Carcinoma Molecular Imaging--A First-in-Human Case Series

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [68Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [68Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with 68Ga from a 68Ge/68Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [68Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non–tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor–to–healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUVmax of these lesions was 19.6 (range, 2.7–95.3), and the mean SUVmean was 10.1 (range, 1.0–49.2) at approximately 60 min after administration. Uptake in non–tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUVmean, <1.6), with a continuous decline to 4 h after administration (mean SUVmean, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUVmax of 31.3) and decreased gradually afterward. Conclusion: [68Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [68Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.




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Dual Somatostatin Receptor/18F-FDG PET/CT Imaging in Patients with Well-Differentiated, Grade 2 and 3 Gastroenteropancreatic Neuroendocrine Tumors

Our purpose was to prospectively assess the distribution of NETPET scores in well-differentiated (WD) grade 2 and 3 gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and to determine the impact of the NETPET score on clinical management. Methods: This single-arm, institutional ethics review board–approved prospective study included 40 patients with histologically proven WD GEP NETs. 68Ga-DOTATATE PET and 18F-FDG PET were performed within 21 d of each other. NETPET scores were evaluated qualitatively by 2 reviewers, with up to 10 marker lesions selected for each patient. The quantitative parameters that were evaluated included marker lesion SUVmax for each tracer; 18F-FDG/68Ga-DOTATATE SUVmax ratios; functional tumor volume (FTV) and metabolic tumor volume (MTV) on 68Ga-DOTATATE and 18F-FDG PET, respectively; and FTV/MTV ratios. The treatment plan before and after 18F-FDG PET was recorded. Results: There were 22 men and 18 women (mean age, 60.8 y) with grade 2 (n = 24) or grade 3 (n = 16) tumors and a mean Ki-67 index of 16.1%. NETPET scores of P0, P1, P2A, P2B, P3B, P4B, and P5 were documented in 2 (5%), 5 (12.5%), 5 (12.5%) 20 (50%), 2 (5%), 4 (10%), and 2 (5%) patients, respectively. No association was found between the SUVmax of target lesions on 68Ga-DOTATATE and the SUVmax of target lesions on 18F-FDG PET (P = 0.505). 18F-FDG/68Ga-DOTATATE SUVmax ratios were significantly lower for patients with low (P1–P2) primary NETPET scores than for those with high (P3–P5) primary NETPET scores (mean ± SD, 0.20 ± 0.13 and 1.68 ± 1.44, respectively; P < 0.001). MTV on 18F-FDG PET was significantly lower for low primary NETPET scores than for high ones (mean ± SD, 464 ± 601 cm3 and 66 ± 114 cm3, respectively; P = 0.005). A change in the type of management was observed in 42.5% of patients after 18F-FDG PET, with the most common being a change from systemic therapy to peptide receptor radionuclide therapy and from debulking surgery to systemic therapy. Conclusion: There was a heterogeneous distribution of NETPET scores in patients with WD grade 2 and 3 GEP NETs, with more than 1 in 5 patients having a high NETPET score and a frequent change in management after 18F-FDG PET. Quantitative parameters including 18F-FDG/68Ga-DOTATATE SUVmax ratios in target lesions and FTV/MTV ratios can discriminate between patients with high and low NETPET scores.




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Medical supply company McKesson to pay more than $400K over discriminatory hiring

McKesson Medical-Surgical Inc. entered into an agreement with the Labor Department on Monday resolving employment discrimination issues involving nearly 900 Black, Hispanic, and White applicants at a distribution center




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Stellantis trimming 1,100 jobs at its Toledo Jeep Gladiator plant

About 1,100 workers will be laid off indefinitely in January from the Jeep Gladiator plant in Toledo, Ohio, Stellantis officials announced Wednesday.




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HPC System Administrator

HPC System Administrator University of California Los Angeles Budgeted Pay Scale: Full Salary Range: USD $76,200.00/Yr. - USD $158,800.00/Yr. Department Summary UCLAs Office of Advanced Research Computing (OARC) melds expert staff and technical infrastructure to amplify and accelerate the impact of UCLA research in the age of networked data and computation. OARC expertise and resources are available to all UCLA researchers, who are engaged in digital research and scholarship. We work with faculty, student, and postdoctoral researchers; instructors; and staff and administrators. OARC is a relationship-building organization. We enable digital scholarship through collaborations, partnerships, and networked communities to advance cutting-edge research capabilities at UCLA and beyond. OARC supports and enhances the university mission of education, research, and service through the development and execution of innovative and sustainable technology practices, programs, services, infrastructure, policies, and partnerships. Position Summary HPC System Administrator UCLAs Office of Advanced Research Computing (OARC) supports and enhances the university mission of education, research, and service through the development and execution of innovative and sustainable technology practices, programs, services, infrastructure, policies, and partnerships. The OARC High Performance Computing (HPC) Systems Research Technology Group (RTG) supports thousands of UCLA researchers and over 300 research groups through consultation and the operation of the Hoffman2 High Performance Research Cluster. More information on the Hoffman2 cluster may be found at Hoffman2 Cluster Documentation The Hoffman2 cluster environment consists of approximately 1000 compute nodes, GPU nodes, high speed networking, high-performance storage, backup equipment, and extensive hardware and software support infrastructure, spread across multiple data centers. The HPC System Administrator, as part of the HPC team, will serve as a technical expert supporting OARCs HPC environment in the areas of systems and application software development, HPC cluster system administration and management of the backup system environment. Requires the ability to work from UCLAs Westwood campus as operational demands dictate. FlexWork / hybrid schedules will be considered based on work demands and operational needs. Salary & Compensation *UCLA provides a full pay range. Actual salary offers consider factors, including budget, prior experience, skills, knowledge, abilities, education, licensure and certifications, and other business considerations. Salary offers at the top of the range are not common. Visit https://ucnet.universityofcalifornia.edu/compensation-and-benefits/index.html to discover benefits that start on day one, and https://ucnet.universityofcalifornia.edu/compensation-and-benefits/total-compensation-calculator.html to calculate the total compensation value with benefits. Qualifications • 3 years Experience with software and applications development, Linux system administration, and two or more modern programming languages (e.g. Python, C++, Java). (Required) • Expert knowledge of Python, SQL, bash, git, and associated build systems, libraries, and development tools. Demonstrated knowledge of common programming paradigms (e.g., asynchronous, concurrent, and object-oriented). Demonstrated ability to create high-quality system tools and software. (Required) • Ability to work independently or in a development team, and effectively estimate time and effort required to complete tasks. Ability to analyze, benchmark, debug, and test software in a technically sound manner and to generate clear, readable reports and summaries. (Required) • Demonstrated working knowledge of HPC cluster architectures and concepts (e.g., provisioning, benchmarking, scalability, and parallelizing code) and ability to stay current with industry best practices. (Required) • Detailed knowledge of Red Hat Enterprise Linux and related distributions. Solid system administration skills including scripting, pipelines, and UNIX operating system fundamentals. (Required) • Working knowledge of protocols, applications, and formats including, but not limited to, TCP/IP, HTTP, DHCP, SSH, NFS, JSON, XML, and HTML. (Required) • Demonstrated ability to troubleshoot and debug computing problems including, corrupted data, file management, application software, and operating system problems. Accurately, and independently respond to production problems in multiple complex operating systems and software components. (Required) • Knowledge of validation, verification, and disaster recovery capabilities for both hardware and software. (Required) • Demonstrated skill in writing well-organized, complete, and technically and grammatically correct documents and procedures to be used by technical and non-technical personnel of diverse backgrounds at various levels in the organization, including researchers, peers, and management. (Required) • Demonstrated oral communication and presentation skills sufficient to effectively obtain and impart technical information and explain concepts on a one-to-one basis as well as in meetings with or presentations to multiple clients. (Required) • Demonstrated problem-solving skills and the ability to break down and define complex problems, formulate solutions, identify cause and effect relationships, make appropriate decisions, and communicate concepts clearly and appropriately with researchers and peers. (Required) • Ability to prioritize tasks, prepare project plans, schedules, effectively manage projects in areas of responsibility, complete tasks, projects in a timely manner. Work effectively both independently and as part of a team, follow through follow through on assignments with minimal direction. (Required) • Demonstrated skill in establishing and maintaining cooperative working relationships with staff, students, and vendors. Ability to communicate and interact effectively with persons of diverse backgrounds. (Required) Education, Licenses, Certifications & Personal Affiliations • Bachelors Degree Bachelors degree in computer science, software engineering, or a related field. (Required) And • Masters Degree Masters degree in computer science, software engineering or a related field . (Preferred) Special Conditions for Employment • Background Check: Continued employment is contingent upon the completion of a satisfactory background investigation. • Live Scan Background Check: A Live Scan background check must be completed prior to the start of employment. • COVID and Flu Vaccinations: The position is subject to providing evidence of inoculation. Schedule 8:00 am to 5:00 pm Union/Policy Covered 99-Policy Covered To apply, please visit: https://apptrkr.com/5770145 Application Deadline: 8:50 p.m. on Copyright ©2024 Jobelephant.com Inc. All rights reserved. https://www.jobelephant.com/




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Capitals' Alex Ovechkin nets game winner vs. Predators, extends goal streak

Alex Ovechkin calmly slid into the right circle and sniped a snapshot past a blinded Juuse Saros to lead the Washington Capitals to a 3-2 triumph over the Nashville Predators.




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Chicago Bears fire offensive coordinator Shane Waldron, commit to QB Caleb Williams

Chicago Bears coach Matt Eberflus has fired offensive coordinator Shane Waldron, the team said Tuesday. The dismissal came less than a day after Eberflus committed to quarterback Caleb Williams, but promised "changes."




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Ultra Accelerator Link Consortium Launches with Industry Leaders, Opens Membership to Drive AI Connectivity Standards

BEAVERTON, Ore., Oct. 29, 2024 — Ultra Accelerator Link (UALink) Consortium, led by Board Members from AMD, Amazon Web Services (AWS), Astera Labs, Cisco, Google, Hewlett Packard Enterprise (HPE), Intel, Meta […]

The post Ultra Accelerator Link Consortium Launches with Industry Leaders, Opens Membership to Drive AI Connectivity Standards appeared first on HPCwire.




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GIGABYTE Joins AI Accelerator Skyscraper Congress to Highlight Sustainable Supercomputing Advances

Oct. 31, 2024 — Giga Computing, a subsidiary of GIGABYTE and a leader in generative AI servers and advanced cooling technologies, will participate in today’s AI Accelerator Skyscraper Congress, hosted […]

The post GIGABYTE Joins AI Accelerator Skyscraper Congress to Highlight Sustainable Supercomputing Advances appeared first on HPCwire.




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NSF Issues Next Solicitation and More Detail on National Quantum Virtual Laboratory

After percolating for roughly a year, NSF has issued the next solicitation for the National Quantum Virtual Lab program — this one focused on design and implementation phases of the […]

The post NSF Issues Next Solicitation and More Detail on National Quantum Virtual Laboratory appeared first on HPCwire.




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Ukraine-led Rapid Trident exercise to increase U.S., NATO interoperability

The Rapid Trident 21 exercise to enhance interoperability between Ukraine, U.S. and NATO partners started Monday, with an opening ceremony, and will run through Oct. 1.




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Aliro Quantum Debuts Aliro Simulator, Enhancing Quantum Network Simulation and Visualization

BOSTON, Dec. 12, 2023 — Aliro Quantum today announced the controlled availability of Aliro Simulator, a versatile, modular quantum network simulator equipped to model all portions of a quantum network from […]

The post Aliro Quantum Debuts Aliro Simulator, Enhancing Quantum Network Simulation and Visualization appeared first on HPCwire.




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Movie review: 'Gladiator II' entertains with epic violence, flamboyant acting

"Gladiator II" has even more crowd-pleasing combat events than the original and an operatic story showcasing flamboyant performances.




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This refrigerator is saving lives | Norah Magero

TED Fellow and renewable energy expert Norah Magero envisions an Africa that pioneers its own technological future, shifting the narrative from dependence and consumption to self-reliance and innovation. She shares how she developed VacciBox — a solar-powered refrigeration system made in Kenya to keep vaccines cold in off-grid areas — and highlights the power of homegrown solutions to transform health care.




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What's Behind the Gender Pay Gap Among Educators?

Female teachers, principals, and superintendents in Pennsylvania earn significantly less money than their male counterparts, a new study shows.




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How America's Leaders Have Failed Educators on COVID-19

Principals and superintendents are caught between politicians’ demands, an anxious public, and experts’ contrary advice about the path forward during the pandemic. The unspoken message: You’re on your own.




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Oregon Educator Named Superintendent of the Year

Matthew Utterback, the superintendent of the North Clackamas district in Oregon, was named last week as the 2017 National Superintendent of the Year.




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ECOT Looms Over Ohio Gubernatorial Candidates' Education Plans

Any discussion in politics of the future of education in Ohio inevitably turns to the Electronic Classroom of Tomorrow.




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How Will Schools Pay for Compensatory Services for Special Ed. Students?

States’ efforts so far suggest there won’t be enough money to go around for all the learning losses of students with disabilities from COVID-19 school shutdowns.




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Virginia educator sues school board over pay disparity




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Survey: Michigan educators feel unsafe returning to school




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Maryland Opens Door to Noneducators to Become Superintendents of Schools

Maryland's state school board will allow noneducators to be appointed as superintendents of school systems.




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Maryland Backs Away From Allowing Noneducators as Superintendents

A vote by a professional-standards board means Maryland will not permit noneducators to be appointed as schools superintendents, after all.




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How Layoffs Upend Life for Educators, Students, and Districts

Pandemic-inflicted budget cuts have cost thousands of educators their jobs. Here’s how that’s playing out in five districts around the country.




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How Will Schools Pay for Compensatory Services for Special Ed. Students?

States’ efforts so far suggest there won’t be enough money to go around for all the learning losses of students with disabilities from COVID-19 school shutdowns.




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Serving Special Needs Students During COVID-19: A Rural Educator's Story

Just because a rural school system has internet doesn’t mean everyone can afford it. That’s why James Barrett delivers paper work packets, along with meals, to his students during the COVID-19 crisis.




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Virginia educator sues school board over pay disparity




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State Legislators Revamp Funding in Texas, Nevada

Several states this year sought to replace their funding formulas, a monumental fiscal and political feat, but only a handful of legislatures have been able to get proposals to their governors' desks.




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Educators Who Ran for Office Share Their Lessons Learned (Video)

Watch a discussion between three educators who ran for their state legislatures about their experiences on the campaign trail.




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How America's Leaders Have Failed Educators on COVID-19

Principals and superintendents are caught between politicians’ demands, an anxious public, and experts’ contrary advice about the path forward during the pandemic. The unspoken message: You’re on your own.