Shoham Letzter
Trans. Amer. Math. Soc. 377 (), 5583-5615.
Abstract, references and article information

Frederic Heihoff
Proc. Amer. Math. Soc. 152 (), 5229-5247.
Abstract, references and article information

A. Della Corte, M. Farotti and S. Rodríguez Martín
Proc. Amer. Math. Soc. 152 (), 5163-5173.
Abstract, references and article information

Yong Suk Moon
Proc. Amer. Math. Soc. 152 (), 5095-5103.
Abstract, references and article information

Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.

TNF is a highly pro-inflammatory cytokine that contributes not only to the regulation of immune responses but also to the development of severe inflammatory diseases. TNF is synthesized as a transmembrane protein, which is further matured via proteolytic cleavage by metalloproteases such as ADAM17, a process known as shedding. At present, TNF is mainly detected by measuring the precursor or the mature cytokine of bulk cell populations by techniques such as ELISA or immunoblotting. However, these methods do not provide information on the exact timing and extent of TNF cleavage at single-cell resolution and they do not allow the live visualization of shedding events. Here, we generated C-tag TNF as a genetically encoded reporter to study TNF shedding at the single-cell level. The functionality of the C-tag TNF reporter is based on the exposure of a cryptic epitope on the C terminus of the transmembrane portion of pro-TNF on cleavage. In both denatured and nondenatured samples, this epitope can be detected by a nanobody in a highly sensitive and specific manner only upon TNF shedding. As such, C-tag TNF can successfully be used for the detection of TNF cleavage in flow cytometry and live-cell imaging applications. We furthermore demonstrate its applicability in a forward genetic screen geared toward the identification of genetic regulators of TNF maturation. In summary, the C-tag TNF reporter can be employed to gain novel insights into the complex regulation of ADAM-dependent TNF shedding.

Distinct cell types emerge from embryonic stem cells through a precise and coordinated execution of gene expression programs during lineage commitment. This is established by the action of lineage specific transcription factors along with chromatin complexes. Numerous studies have focused on epigenetic factors that affect embryonic stem cells (ESC) self-renewal and pluripotency. However, the contribution of chromatin to lineage decisions at the exit from pluripotency has not been as extensively studied. Using a pooled epigenetic shRNA screen strategy, we identified chromatin-related factors critical for differentiation toward mesodermal and endodermal lineages. Here we reveal a critical role for the chromatin protein, ARID4B. Arid4b-deficient mESCs are similar to WT mESCs in the expression of pluripotency factors and their self-renewal. However, ARID4B loss results in defects in up-regulation of the meso/endodermal gene expression program. It was previously shown that Arid4b resides in a complex with SIN3A and HDACS 1 and 2. We identified a physical and functional interaction of ARID4B with HDAC1 rather than HDAC2, suggesting functionally distinct Sin3a subcomplexes might regulate cell fate decisions Finally, we observed that ARID4B deficiency leads to increased H3K27me3 and a reduced H3K27Ac level in key developmental gene loci, whereas a subset of genomic regions gain H3K27Ac marks. Our results demonstrate that epigenetic control through ARID4B plays a key role in the execution of lineage-specific gene expression programs at pluripotency exit.

Visual Abstract

Julia Knöckel
Dec 22, 2020; 0:RA120.002432v1-mcp.RA120.002432
Research

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (Cltc), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of Cltc, similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking Cltc display higher Young's modulus, indicative of greater cellular stiffness, compared with WT mESCs. The increase in stiffness was accompanied by the presence of actin stress fibers and accumulation of the inactive, phosphorylated, actin-binding protein cofilin. Treatment of Cltc knockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young's modulus to values similar to those obtained with WT mESCs. However, a rescue in the expression profile of pluripotency factors was not obtained. Additionally, whereas WT mouse embryonic fibroblasts could be reprogrammed to a state of pluripotency, this was inhibited in the absence of Cltc. This indicates that the presence of active CME is essential for the pluripotency of embryonic stem cells. Additionally, whereas physical properties may serve as a simple readout of the cellular state, they may not always faithfully recapitulate the underlying molecular fate.

Adult progenitor cell populations typically exist in a quiescent state within a controlled niche environment. However, various stresses or forms of damage can disrupt this state, which often leads to dysfunction and aging. We built a glucocorticoid (GC)-induced liver damage model of mice, found that GC stress induced liver damage, leading to consequences for progenitor cells expansion. However, the mechanisms by which niche factors cause progenitor cells proliferation are largely unknown. We demonstrate that, within the liver progenitor cells niche, Galectin-3 (Gal-3) is responsible for driving a subset of progenitor cells to break quiescence. We show that GC stress causes aging of the niche, which induces the up-regulation of Gal-3. The increased Gal-3 population increasingly interacts with the progenitor cell marker CD133, which triggers focal adhesion kinase (FAK)/AMP-activated kinase (AMPK) signaling. This results in the loss of quiescence and leads to the eventual stemness exhaustion of progenitor cells. Conversely, blocking Gal-3 with the inhibitor TD139 prevents the loss of stemness and improves liver function. These experiments identify a stress-dependent change in progenitor cell niche that directly influence liver progenitor cell quiescence and function.

Large regions in tumor tissues, particularly pancreatic cancer, are hypoxic and nutrient-deprived because of unregulated cell growth and insufficient vascular supply. Certain cancer cells, such as those inside a tumor, can tolerate these severe conditions and survive for prolonged periods. We hypothesized that small molecular agents, which can preferentially reduce cancer cell survival under nutrient-deprived conditions, could function as anticancer drugs. In this study, we constructed a high-throughput screening system to identify such small molecules and screened chemical libraries and microbial culture extracts. We were able to determine that some small molecular compounds, such as penicillic acid, papyracillic acid, and auranofin, exhibit preferential cytotoxicity to human pancreatic cancer cells under nutrient-deprived compared with nutrient-sufficient conditions. Further analysis revealed that these compounds target to redox systems such as GSH and thioredoxin and induce accumulation of reactive oxygen species in nutrient-deprived cancer cells, potentially contributing to apoptosis under nutrient-deprived conditions. Nutrient-deficient cancer cells are often deficient in GSH; thus, they are susceptible to redox system inhibitors. Targeting redox systems might be an attractive therapeutic strategy under nutrient-deprived conditions of the tumor microenvironment.

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression.

Postoperative recurrence from microscopic residual disease must be prevented to cure intractable cancers, including pancreatic cancer. Key to this goal is the elimination of cancer stem cells (CSCs) endowed with tumor-initiating capacity and drug resistance. However, current therapeutic strategies capable of accomplishing this are insufficient. Using in vitro models of CSCs and in vivo models of tumor initiation in which CSCs give rise to xenograft tumors, we show that dexamethasone induces expression of MKP-1, a MAPK phosphatase, via glucocorticoid receptor activation, thereby inactivating JNK, which is required for self-renewal and tumor initiation by pancreatic CSCs as well as for their expression of survivin, an anti-apoptotic protein implicated in multidrug resistance. We also demonstrate that systemic administration of clinically relevant doses of dexamethasone together with gemcitabine prevents tumor formation by CSCs in a pancreatic cancer xenograft model. Our study thus provides preclinical evidence for the efficacy of dexamethasone as an adjuvant therapy to prevent postoperative recurrence in patients with pancreatic cancer.

Montgomery Blencowe
Dec 23, 2020; 0:jlr.RA120000713v1-jlr.RA120000713
Research Articles

When you log on to the SAS Risk Governance Framework and choose a solution, the web application might fail to load the solution content. When the problem occurs, you continue to see "Loading..." on the screen, an

Genome-wide association studies (GWAS) have implicated ~380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in ‘interferon signaling’, ‘autoimmune/immune activation’, ‘visual transduction’, and ‘protein catabolism’ were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

Communication between individuals via molecules, termed chemosignaling, is widespread among animal and plant species. However, we lack knowledge on the specific functions of the substances involved for most systems. The femoral gland is an organ that secretes a waxy substance involved in chemical communication in lizards. Although the lipids and volatile substances secreted by the femoral glands have been investigated in several biochemical studies, the protein composition and functions of secretions remain completely unknown. Applying a proteomic approach, we provide the first attempt to comprehensively characterize the protein composition of femoral gland secretions from the Galápagos marine iguana. Using samples from several organs, the marine iguana proteome was assembled by next-generation sequencing and MS, resulting in 7513 proteins. Of these, 4305 proteins were present in the femoral gland, including keratins, small serum proteins, and fatty acid-binding proteins. Surprisingly, no proteins with discernible roles in partner recognition or inter-species communication could be identified. However, we did find several proteins with direct associations to the innate immune system, including lysozyme C, antileukoproteinase (ALP), pulmonary surfactant protein (SFTPD), and galectin (LGALS1) suggesting that the femoral glands function as an important barrier to infection. Furthermore, we report several novel anti-microbial peptides from the femoral glands that show similar action against Escherichia coli and Bacillus subtilis such as oncocin, a peptide known for its effectiveness against Gram-negative pathogens. This proteomics data set is a valuable resource for future functional protein analysis and demonstrates that femoral gland secretions also perform functions of the innate immune system.

Recent efforts in gut microbiome studies have highlighted the importance of explicitly describing the ecological processes beyond correlative analysis. However, we are still at the early stage of understanding the organizational principles of the gut ecosystem, partially because of the limited information provided by currently used analytical tools in ecological modeling practices. Proteomics and metaproteomics can provide a number of insights for ecological studies, including biomass, matter and energy flow, and functional diversity. In this Mini Review, we discuss proteomics and metaproteomics-based experimental strategies that can contribute to studying the ecology, in particular at the mucosal-luminal interface (MLI) where the direct host-microbiome interaction happens. These strategies include isolation protocols for different MLI components, enrichment methods to obtain designated array of proteins, probing for specific pathways, and isotopic labeling for tracking nutrient flow. Integration of these technologies can generate spatiotemporal and site-specific biological information that supports mathematical modeling of the ecosystem at the MLI.

Esophageal squamous cell cancer (ESCC) is an aggressive malignancy with poor therapeutic outcomes. However, the alterations in proteins and post-translational modifications (PTMs) leading to the pathogenesis of ESCC remains unclear. Here, we provide the comprehensive characterization of the proteome, phosphorylome, lysine acetylome and succinylome for ESCC and matched control cells using quantitative proteomic approach. We identify abnormal protein and post-translational modification (PTM) pathways, including significantly downregulated lysine succinylation sites in cancer cells. Focusing on hyposuccinylation, we reveal that this altered PTM was enriched on enzymes of metabolic pathways inextricably linked with cancer metabolism. Importantly, ESCC malignant behaviors such as cell migration are inhibited once the level of succinylation was restored in vitro or in vivo. This effect was further verified by mutations to disrupt succinylation sites in candidate proteins. Meanwhile, we found that succinylation has a negative regulatory effect on histone methylation to promote cancer migration. Finally, hyposuccinylation is confirmed in primary ESCC specimens. Our findings together demonstrate that lysine succinylation may alter ESCC metabolism and migration, providing new insights into the functional significance of PTM in cancer biology.

Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol (GPI)-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology.

Delivering Sustainable Food and Land Use Systems: The Role of International Trade Research paper sysadmin 20 September 2019

This paper explores a set of core trade-related issues affecting the food and land use system, and proposes constructive ways forward in reconfiguring the global trading system towards delivering a more sustainable and healthy diet for all.

• Meeting future global food security requirements is not just about quantity; it is also about meeting growing needs in a way that safeguards human as well as planetary health. But national priorities and policies often remain out of sync with aspirations for more sustainable and healthy food systems.
• International trade and trade policies play an ambiguous role in the current food system. With 80 per cent of the world’s population depending on imports to meet at least part of their food and nutritional requirements, trade has a unique function in offsetting imbalances between supply and demand. However, in the absence of effective regulatory frameworks or pricing frameworks that internalize environmental, social or health costs, trade can exacerbate and globalize challenges associated with food production and land use trends such as deforestation, land degradation, greenhouse gas emissions, biodiversity loss and the shift to unhealthy diets.
• Over the last two decades, trade in agricultural products (excluding intra-EU flows) has more than tripled in value, to reach $1.33 trillion. The geography of global food trade flows has also shifted, primarily towards South–South trade, which now accounts for roughly a quarter of total agricultural trade flows. The nature of global trade has changed drastically, with traditional exports such as wheat and coffee growing slowly at around 2 per cent per year, while products such as palm oil, fruit juice, soft drinks and other processed products have grown at 8 per cent or more annually.
• This overall increase in trade in agricultural products raises questions about the growing utilization of resources, such as water or soil nutrients, that are embedded in those products through production and processing. Trade itself also causes negative environmental impacts, starting with greenhouse gas emissions associated with transport and storage. If the environmental cost associated with production and trade is not reflected in the final price of goods, trade may accelerate the depletion of resources or their unsustainable use.
• It is critical to ensure that trade policy options pursued by producing and consuming countries alike will support a transition to more sustainable and healthier food and land use systems. The first step in addressing trade-related food systems challenges must involve rebuilding trust among policy actors. There is a need for new spaces for informal dialogue among actors, and ‘soft’ governance mechanisms that can help rebuild consensus on the best ways forward. Meeting these challenges also requires an appreciation of the complex interactions between sectoral policies (e.g. on water, land, food, etc.) and their multiple interfaces with trade policies.
• Conditioning the use of subsidies on their sustainability and/or health impacts encourages the delivery of essential public goods in ways that are consistent with sustainability and health goals. A first step therefore is the removal of perverse incentives (e.g. subsidies encouraging the overuse of fertilizers or pesticides or the overproduction of certain commodities, as well as certain biofuels subsidies) and replacing them with market-correcting subsidies.
• Trade facilitation measures for fruits and vegetables that are aimed at easing transit at the border, by cutting unnecessary bureaucracy and reducing waiting times, can improve their availability, reduce costs and improve food quality and safety for consumers. Similarly, measures aimed at improving sustainable cold storage and upgrading value chains can support better diets and consumption by increasing the availability of fresh produce on markets, especially in developing countries.
• A global food stamps programme developed through the G20 and facilitated by the UN’s food agencies could address purchasing power imbalances and tackle malnutrition in developing countries. If carefully designed, such ‘safety net’ schemes can not only contribute to improving calorific intakes but also help deliver more balanced and healthier diets. Careful attention must be given to how such a scheme would work in practice, building on experience to date with similar initiatives.
• Integrating the notion of sustainable food and inputs trade in the post-2020 global biodiversity framework can help to deliver more sustainable and healthier food and land use systems. This could be achieved by likeminded countries introducing a set of goals or targets aimed at mitigating the role of trade in placing indirect pressure on biodiversity, and to encourage trade in biodiversity-based products including natural ingredients produced ethically and following sustainability principles and criteria.
• An SDG-oriented agenda for agricultural trade is needed. It could be formed by countries seeking to remove perverse incentives, guaranteeing a safe harbour for market-correcting measures, clarifying existing rules and establishing plurilateral negotiations among subsets of the WTO membership, or sectoral approaches, to address specific challenges.
• Greenhouse gas emissions resulting from trade need to be addressed. Governments could seek to achieve this through ensuring the carbon neutrality of existing and new trade deals, either by connecting carbon markets among contracting parties or by developing joint initiatives to tax international maritime and air transport emissions.

This study evaluates the diagnostic utility of PET/MRI for primary, locoregional, and nodal head and neck squamous cell carcinoma (HNSCC) through systematic review and metaanalysis. Methods: A systematic search was conducted using PubMed and Scopus to identify studies on the diagnostic accuracy of PET/MRI for HNSCC. The search included specific terms and excluded nonhybrid PET/MRI studies, and those with a sample size of fewer than 10 patients were excluded. Results: In total, 15 studies encompassing 638 patients were found addressing the diagnostic test accuracy for PET/MRI within the chosen subject domain. Squamous cell carcinoma of the nasopharynx was the most observed HNSCC subtype (n = 198). The metaanalysis included 12 studies, with pooled sensitivity and specificity values of 93% and 95% per patient for primary disease evaluation, 93% and 96% for locoregional evaluation, and 89% and 98% per lesion for nodal disease detection, respectively. An examination of a subset of studies comparing PET/MRI against PET/CT or MRI alone for evaluating nodal and locoregional HNSCC found that PET/MRI may offer slightly higher accuracy than other modalities. However, this difference was not statistically significant. Conclusion: PET/MRI has excellent potential for identifying primary, locoregional, and nodal HNSCC.

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/

LONDON and TORONTO, Sept. 30, 2024 — Alphawave Semi, a global leader in high-speed connectivity and compute silicon for the world’s technology infrastructure, has unveiled the availability of the industry’s […]

The post Alphawave Semi and TSMC Collaborate on 3nm UCIe Die-to-Die Subsystem for AI and HPC appeared first on HPCwire.

Bahraini leaders committed Thursday to partnering with a new U.S. Navy task force to ramp up new unmanned system efforts.

Nov. 6, 2024 — CoolIT Systems, a world leader in liquid cooling systems for artificial intelligence (AI) and high-performance computing (HPC), will showcase its latest AI cooling products at the Supercomputing […]

The post CoolIT Systems Showcases AI and HPC Liquid Cooling Solutions at SC24 appeared first on HPCwire.

A former Jeopardy! winner led a new study that probes how linked memory systems may give trivia buffs an edge in their game

COLOGNE, Germany, Nov. 1, 2024 — DeepL has announced it will be among the first to commercially deploy the Nvidia DGX SuperPOD with DGX GB200 systems. The Nvidia DGX SuperPOD, […]

The post DeepL to Debut Nvidia DGX SuperPOD with DGX GB200 Systems in Europe appeared first on HPCwire.

One of the most difficult problems with quantum computing relates to increasing the size of the quantum computer. Researchers globally are seeking to solve this “challenge of scale.” To bring […]

The post Recipe for Scaling: ARQUIN Framework for Simulating a Distributed Quantum Computing System appeared first on HPCwire.

Quantum computing pioneer D-Wave today announced it had completed calibration and benchmarking the latest latest version of its Advantage2 quantum processor, a 4,400-plus-qubit device. D-Wave said that compared with the […]

The post D-Wave Readies 4,400-plus-qubit Advantage2 System for Use appeared first on HPCwire.

Here's a wild stat: nearly one-third of the world's food production goes to waste each year, a major contributor to the climate crisis. Farmer and UN climate champion Gonzalo Muñoz sheds light on the international negotiations aimed at turning the food system into a climate solution, rather than part of the problem — and shows the progress already underway.

Small groups of Portland youngsters gathered in gardens, played with plant-based dyes, and cooked up vegan meals as part of Camp ELSO's mission to foster STEM learning for students of color.

Teacher-evaluation reforms in places like New Mexico, Tennessee, Denver, and the District of Columbia have paid off, says the National Council on Teacher Quality.

Tennessee improved its teacher evaluation and training systems by integrating data and teacher voice, according to a new report. But value-added measures that evaluate teachers based on student test scores remain controversial.

Along with winter vegetables, STEM is blooming in Imperial County. Dennis and Daniel Gibbs are growing young scientists by transplanting the scientific method to the second grade.

Utah is one of four states where state laws conflict with components of the federal Every Student Succeeds Act meaning districts may have to answer to two separate accountability systems this fall.

Instead of creating change through compliance and extrinsic motivators, the new era of education and education policy will require ecosystems of policy, regulation, investment, and operating structure that enable, rather than dictate. Under New Hampshire's PACE accountability system districts and sc