Touch down in Vancouver and it was raining. Listening to friends from the Pacific Northwest talk, I always kind of suspected that they were lying when they complained about how grey it was and how much it rains. I’d been to the region four or five times, at across all time of the year and always […]

The article A Perfect Day in Vancouver (Finally!) originated at EverInTransit.com

HEY uses a branch deploy system that I’ve written about here on SvN and talked about frequently on Twitter. Plenty of other companies have implemented their own version of branch deploys (typically under a different name), but this was my own implementation, so I’m proud of it. First, a primer on how it works: Developer… keep reading

Shortly after President-elect Donald Trump appointed Tom Homan as “border czar,” the immigration hardliner’s hilarious 2019 smackdown of Democratic Rep. Alexandria Ocasio-Cortez of New York went viral on social media. […]

The post Flashback: Video of Tom Homan Taking Down AOC Resurfaces, Showing Why Trump Picked Him appeared first on The Western Journal.

Junyi Xie
J. Amer. Math. Soc. 38 (), 1-62.
Abstract, references and article information

Michael Dean
Jul 1, 2001; 42:1007-1017
Thematic Reviews

EJ Blanchette-Mackie
Jun 1, 1995; 36:1211-1226
Articles

Robert W. Mahley
Jan 1, 1999; 40:1-16
Reviews

Expert

N. R. Ikonomov and S. P. Suetin
Trans. Moscow Math. Soc. 83 (), 33-54.
Abstract, references and article information

Pierre Lairez, Eric Pichon-Pharabod and Pierre Vanhove
Math. Comp. 93 (), 2985-3025.
Abstract, references and article information

Sangsan Warakkagun
Conform. Geom. Dyn. 28 (), 115-130.
Abstract, references and article information

Jong In Han and Sijong Kwak
Trans. Amer. Math. Soc. 377 (), 5561-5581.
Abstract, references and article information

Víctor González-Aguilera, Alvaro Liendo, Pedro Montero and Roberto Villaflor Loyola
Trans. Amer. Math. Soc. 377 (), 5483-5511.
Abstract, references and article information

WendyHarris1955 posted a photo:

unbranded
plywood (basswood)
175 pieces
280 x 350 mm

TED: "I fink this lickle cat an' tiger pussle's cute. It's got pussycat wimsys an' it's shaped, so it's gonna be a keeper. The wobbly edj wuz a bit fiddly an' I 'ad to check the pikchur to make shure I 'ad it rite, but uvverwise it's a good'un.
That peece of cake I'm abowt to eat is Mum's 'ome-made froot cake spredd wiv butter - s'nice cuz she puts whisky in it. That's the cake, not the butter!"

Luiz Ricardo Abreu Melo
Proc. Amer. Math. Soc. 152 (), 5373-5380.
Abstract, references and article information

Neelarnab Raha
Proc. Amer. Math. Soc. 152 (), 5067-5081.
Abstract, references and article information

Chorismate mutase (CM), an essential enzyme at the branch-point of the shikimate pathway, is required for the biosynthesis of phenylalanine and tyrosine in bacteria, archaea, plants, and fungi. MtCM, the CM from Mycobacterium tuberculosis, has less than 1% of the catalytic efficiency of a typical natural CM and requires complex formation with 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase for high activity. To explore the full potential of MtCM for catalyzing its native reaction, we applied diverse iterative cycles of mutagenesis and selection, thereby raising kcat/Km 270-fold to 5 × 105 m−1s−1, which is even higher than for the complex. Moreover, the evolutionarily optimized autonomous MtCM, which had 11 of its 90 amino acids exchanged, was stabilized compared with its progenitor, as indicated by a 9 °C increase in melting temperature. The 1.5 Å crystal structure of the top-evolved MtCM variant reveals the molecular underpinnings of this activity boost. Some acquired residues (e.g. Pro52 and Asp55) are conserved in naturally efficient CMs, but most of them lie beyond the active site. Our evolutionary trajectories reached a plateau at the level of the best natural enzymes, suggesting that we have exhausted the potential of MtCM. Taken together, these findings show that the scaffold of MtCM, which naturally evolved for mediocrity to enable inter-enzyme allosteric regulation of the shikimate pathway, is inherently capable of high activity.

Visual Abstract

Qin Zhang
Nov 17, 2020; 0:RA120.002325v1-mcp.RA120.002325
Research

The subcellular localization of Arf family proteins is generally thought to be determined by their corresponding guanine nucleotide exchange factors. By promoting GTP binding, guanine nucleotide exchange factors induce conformational changes of Arf proteins exposing their N-terminal amphipathic helices, which then insert into the membranes to stabilize the membrane association process. Here, we found that the N-terminal amphipathic motifs of the Golgi-localized Arf family protein, Arfrp1, and the endosome- and plasma membrane–localized Arf family protein, Arl14, play critical roles in spatial determination. Exchanging the amphipathic helix motifs between these two Arf proteins causes the switch of their localizations. Moreover, the amphipathic helices of Arfrp1 and Arl14 are sufficient for cytosolic proteins to be localized into a specific cellular compartment. The spatial determination mediated by the Arfrp1 helix requires its binding partner Sys1. In addition, the residues that are required for the acetylation of the Arfrp1 helix and the myristoylation of the Arl14 helix are important for the specific subcellular localization. Interestingly, Arfrp1 and Arl14 are recruited to their specific cellular compartments independent of GTP binding. Our results demonstrate that the amphipathic motifs of Arfrp1 and Arl14 are sufficient for determining specific subcellular localizations in a GTP-independent manner, suggesting that the membrane association and activation of some Arf proteins are uncoupled.

SAS  Episode Analytics 3.1 requires the ability to capture user interactions with the user interface for auditing purposes. To support the required functionality a new table has been add

When you use SAS/ACCESS Interface to PostgreSQL to query a Yellowbrick database, the SAS OBS= option is not generating a limit clause on the query that is passed to the database. Click the

The SAS 9.4M4 (TS1M4) Hot Fix D7G004 for ODS Templates installs national language support (NLS) content regardless of whether the languages were installed during the initial deployment. Having sparse

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.

Hirschsprung disease (HSCR) is a heterogeneous group of neurocristopathy characterized by the absence of the enteric ganglia along a variable length of the intestine. Genetic defects play a major role in the pathogenesis of HSCR while family studies of pathogenic variants in all the known genes (loci) only demonstrate incomplete penetrance and variable expressivity for unknown reasons. Here, we applied large-scale, quantitative proteomics of human colon tissues from 21 patients using iTRAQ method followed by bioinformatics analysis. Selected findings were confirmed by parallel reaction monitoring (PRM) verification. At last the interesting differentially expressed proteins were confirmed by western blot. A total of 5341 proteins in human colon tissues were identified. Among them, 664 proteins with >1.2-fold difference were identified in 6 groups: groups A1 and A2 pooled protein from the ganglionic and aganglionic colon of male, long-segment HSCR patients (L-HSCR, n=7); groups B1 and B2 pooled protein from the ganglionic and aganglionic colon of male, short-segment HSCR patients (S-HSCR, n=7); and groups C1 and C2 pooled protein from the ganglionic and aganglionic colon of female, S-HSCR patients (n=7). Based on these analyses, 49 proteins from 5 pathways were selected for PRM verification, including ribosome, endocytosis, spliceosome, oxidative phosphorylation and cell adhesion. The downregulation of three neuron projection development genes ARF4, KIF5B and RAB8A in the aganglionic part of the colon were verified in 15 paired colon samples using WB. The findings of this study will shed new light on the pathogenesis of HSCR and facilitate the development of therapeutic targets.

In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

Timely repair of DNA double-strand breaks (DSBs) is essential to maintaining genomic integrity and preventing illnesses induced by genetic abnormalities. We previously demonstrated that the E3 ubiquitin ligase SMURF2 plays a critical tumor suppressing role via its interaction with RNF20 (ring finger protein 20) in shaping chromatin landscape and preserving genomic stability. However, the mechanism that mobilizes SMURF2 in response to DNA damage remains unclear. Using biochemical approaches and MS analysis, we show that upon the onset of the DNA-damage response, SMURF2 becomes phosphorylated at Ser384 by ataxia telangiectasia mutated (ATM) serine/threonine kinase, and this phosphorylation is required for its interaction with RNF20. We demonstrate that a SMURF2 mutant with an S384A substitution has reduced capacity to ubiquitinate RNF20 while promoting Smad3 ubiquitination unabatedly. More importantly, mouse embryonic fibroblasts expressing the SMURF2 S384A mutant show a weakened ability to sustain the DSB response compared with those expressing WT SMURF2 following etoposide treatment. These data indicate that SMURF2-mediated RNF20 ubiquitination and degradation controlled by ataxia telangiectasia mutated–induced phosphorylation at Ser384 constitutes a negative feedback loop that regulates DSB repair.

Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret ¹⁸F-FMISO hypoxia PET. Methods: We randomly selected 123 patients with human papillomavirus–positive oropharyngeal cancer enrolled in a phase II trial who underwent 123 ¹⁸F-FDG PET/CT and 134 ¹⁸F-FMISO PET/CT scans. Four independent nuclear medicine physicians with no ¹⁸F-FMISO experience read the scans. Interpretation by a fifth nuclear medicine physician with over 2 decades of ¹⁸F-FMISO experience was the reference standard. Performance was evaluated after initial instruction and subsequent dedicated training. Scans were considered positive for hypoxia by visual assessment if ¹⁸F-FMISO uptake was greater than floor-of-mouth uptake. Additionally, SUV_max was determined to evaluate whether quantitative assessment using tumor-to-background ratios could be helpful to define hypoxia positivity. Results: Visual assessment produced a mean sensitivity and specificity of 77.3% and 80.9%, with fair interreader agreement ( = 0.34), after initial instruction. After dedicated training, mean sensitivity and specificity improved to 97.6% and 86.9%, with almost perfect agreement ( = 0.86). Quantitative assessment with an estimated best SUV_max ratio threshold of more than 1.2 to define hypoxia positivity produced a mean sensitivity and specificity of 56.8% and 95.9%, respectively, with substantial interreader agreement ( = 0.66), after initial instruction. After dedicated training, mean sensitivity improved to 89.6% whereas mean specificity remained high at 95.3%, with near-perfect interreader agreement ( = 0.86). Conclusion: Nuclear medicine physicians without ¹⁸F-FMISO hypoxia PET reading experience demonstrate much improved interreader agreement with dedicated training using specific interpretation criteria.

CAMBRIDGE, England, Oct. 15, 2024 — Nu Quantum has announced a proof-of-principle prototype that advances the development of modular, distributed quantum computers by enabling connections across different qubit modalities and […]

The post Nu Quantum Unveils Qubit-Photon Interface to Enable Distributed Quantum Computing Networks appeared first on HPCwire.

CHANDLER, Ariz., Oct. 23, 2024 — The global edge computing market is expected to grow by more than 30 percent in the next five years, serving mission-critical applications in the […]

The post Microchip Expands 64-Bit Portfolio with High-Performance PIC64HX Microprocessors for Edge Computing appeared first on HPCwire.

American horse racing turned to turf during the weekend, and Kentucky's Lane's End Farm enjoyed a banner weekend in the top contests.

All-Pro left tackle Tristan Wirfs and tight ends Sam LaPorta and Dalton Kincaid were among key players injured in Week 10 of the NFL season.

Aug. 19, 2024 — SURF’s innovation department recently collaborated with Cornelis Networks to advance networking capabilities for high-performance computing (HPC) clusters. The collaboration marks a new step forward for SURF […]

The post Cornelis Networks Partners with SURF to Enhance HPC Cluster Networking Capabilities appeared first on HPCwire.

About This Webinar Oracle’s next generation HPC architecture with Intel compute instance based on 3rd Generation Intel® Xeon® Scalable processors, code named “Ice Lake”, changes the game for HPC in […]

The post Speed up Innovation with performance gains of up to 42% on the most powerful HPC Cloud appeared first on HPCwire.

MLCommons this week issued the results of its latest MLPerf Inference (v3.1) benchmark exercise. Nvidia was again the top performing accelerator, but Intel (Xeon CPU) and Habana (Gaudi1 and 2) […]

The post MLPerf Releases Latest Inference Results and New Storage Benchmark appeared first on HPCwire.

There are really two stories packaged in the most recent MLPerf  Training 4.0 results, released today. The first, of course, is the results. Nvidia (currently king of accelerated computing) wins […]

The post MLPerf Training 4.0 – Nvidia Still King; Power and LLM Fine Tuning Added appeared first on HPCwire.

When storage is mentioned in an AI or Big Data analytics context, it is assumed to be a high-performance system. In practice, it may not be, and the user eventually […]

The post High-Performance Storage for AI and Analytics Panel appeared first on HPCwire.

The surge in digital transformation across industries has led to exponential data growth, driving a heightened demand for computing power. However, this growth also intensifies concerns about energy consumption and […]

The post Renewable Power Unlock New Efficiencies for High-Performance Computing appeared first on HPCwire.

REDWOOD CITY, Calif., Nov. 4, 2024 — MinIO has announced compelling new optimizations and benchmarks for Arm-based chipsets powering on its object store. These optimizations underscore the relevance of low-power, […]

The post MinIO Optimizes Arm-Based Chipsets for High-Performance AI appeared first on HPCwire.

SAN JOSE, Calif., Nov. 12, 2024 — VDURA, a leader in data infrastructure for AI and HPC, today has announced a groundbreaking release of its VDURA Data Platform software, designed to […]

The post VDURA Unveils Next-Gen Data Platform with Enhanced AI and HPC Performance appeared first on HPCwire.

The Biden administration has sanctioned the West Darfur commander of the Rapid Support Forces on accusations that troops under his control have been responsible for violence targeting civilians.

Struggling to be kind to yourself? Learn how to direct compassion inwards with these simple techniques.

When monarch butterflies migrate, they produce one of the most iconic wildlife spectacles in the world — and provide us with an important indicator of ecological health, says photographer Jaime Rojo. Telling a story about our relationship to the natural world, he shares his experience photographing these mesmerizing insects deep in their remote mountain habitats in Mexico, diving into the latest research into the mysteries of their multi-thousand-mile journey and sharing how each of us can join the growing movement to protect them.

Are you a clinician looking to master CBT for Perfectionism? Or, learn more about the CBT model of perfectionism below. CBT Model of Perfectionism Perfectionism is not the same thing as conscientiousness. For example, in a recent study of older adults, perfectionism was both associated with increased risk of mortality whereas conscientiousness was associated with […]

The post Cognitive Behavioral Therapy Model of Perfectionism appeared first on Dr Alice Boyes.