Superconductor based, tomographic, neutron diagnostics for fusion power monitoring.

We propose a scalable system of compact, superconducting neutron monitors, which can be embedded in any existing cryogenic infrastructure of a fusion system. The pixel-based nature of the detectors allows them to be placed at intervals following the circumference of a cooled zone, e.g.

Complete combinatorial mutational enumeration of a protein functional site enables sequence-landscape mapping and identifies highly-mutated variants that retain activity.

Understanding how proteins evolve under selective pressure is a longstanding challenge. The immensity of the search space has limited efforts to systematically evaluate the impact of multiple simultaneous mutations, so mutations have typically been assessed individually. However, epistasis, or the way in which mutations interact, prevents accurate prediction of combinatorial mutations based on measurements of individual mutations.

Growing Glycans in Rosetta: Accurate de novo glycan modeling, density fitting, and rational sequon design.

Carbohydrates and glycoproteins modulate key biological functions. However, experimental structure determination of sugar polymers is notoriously difficult. Computational approaches can aid in carbohydrate structure prediction, structure determination, and design.

Simultaneous enhancement of multiple functional properties using evolution-informed protein design.

A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Altering several properties likely necessitates numerous primary sequence changes, and novel methods are needed to accurately predict combinations of mutations that maintain or enhance function. Models of sequence co-variation (e.

Molecular basis for the transcriptional regulation of an epoxide-based virulence circuit in .

The opportunistic pathogen infects cystic fibrosis (CF) patient airways and produces a virulence factor Cif that is associated with worse outcomes. Cif is an epoxide hydrolase that reduces cell-surface abundance of the cystic fibrosis transmembrane conductance regulator (CFTR) and sabotages pro-resolving signals. Its expression is regulated by a divergently transcribed TetR family transcriptional repressor.

Simultaneous enhancement of multiple functional properties using evolution-informed protein design.

Designing optimized proteins is important for a range of practical applications. Protein design is a rapidly developing field that would benefit from approaches that enable many changes in the amino acid primary sequence, rather than a small number of mutations, while maintaining structure and enhancing function. Homologous protein sequences contain extensive information about various protein properties and activities that have emerged over billions of years of evolution.

Complete Combinatorial Mutational Enumeration of a protein functional site enables sequence-landscape mapping and identifies highly-mutated variants that retain activity.

Understanding how proteins evolve under selective pressure is a longstanding challenge. The immensity of the search space has limited efforts to systematically evaluate the impact of multiple simultaneous mutations, so mutations have typically been assessed individually. However, epistasis, or the way in which mutations interact, prevents accurate prediction of combinatorial mutations based on measurements of individual mutations.

IgG targeting distinct seasonal coronavirus- conserved SARS-CoV-2 spike subdomains correlates with differential COVID-19 disease outcomes.

Despite SARS-CoV-2 being a "novel" virus, early detection of anti-spike IgG in severe COVID-19 patients may be caused by the amplification of humoral memory responses against seasonal coronaviruses. Here, we examine this phenomenon by characterizing anti-spike IgG responses in non-hospitalized convalescent individuals across a spectrum of COVID-19 severity. We observe that disease severity positively correlates with anti-spike IgG levels, IgG cross-reactivity against other betacoronaviruses (β-CoVs), and FcγR activation.

A conical passive magnetic bearing with constant stiffness.

A nested conical passive magnetic bearing is presented. The bearing consists of a nested conical rotor inside a conical stator, i.e.

Analyses of the complex formation of staphylococcal enterotoxin A and the human gp130 cytokine receptor.

Superantigens (SAgs) are bacterial enterotoxins produced by Staphylococcus aureus. Staphylococcal enterotoxin type A (SEA), a staphylococcal superantigen, has been shown to bind to the cytokine signalling receptor glycoprotein 130 (gp130). The structural details, as well as the exact physiological role of this interaction, remain unclear.

Ensuring scientific reproducibility in bio-macromolecular modeling via extensive, automated benchmarks.

Each year vast international resources are wasted on irreproducible research. The scientific community has been slow to adopt standard software engineering practices, despite the increases in high-dimensional data, complexities of workflows, and computational environments. Here we show how scientific software applications can be created in a reproducible manner when simple design goals for reproducibility are met.

Plasma Electrolytic Polishing of Nitinol: Investigation of Functional Properties.

A novel, environmentally friendly, fast, and flexible polishing process for Nitinol parts is presented in this study. Nitinol samples with both superelastic and shape memory properties at room temperature were investigated. The chemical contamination and surface roughness of superelastic Nitinol plates were examined before and after plasma electrolytic polishing.

A Novel SCA3 Knock-in Mouse Model Mimics the Human SCA3 Disease Phenotype Including Neuropathological, Behavioral, and Transcriptional Abnormalities Especially in Oligodendrocytes.

Spinocerebellar ataxia type 3 is the most common autosomal dominant inherited ataxia worldwide, caused by a CAG repeat expansion in the Ataxin-3 gene resulting in a polyglutamine (polyQ)-expansion in the corresponding protein. The disease is characterized by neuropathological, phenotypical, and specific transcriptional changes in affected brain regions. So far, there is no mouse model available representing all the different aspects of the disease, yet highly needed for a better understanding of the disease pathomechanisms.

Biochemical and structural characterization of two cif-like epoxide hydrolases from .

Epoxide hydrolases catalyze the conversion of epoxides to vicinal diols in a range of cellular processes such as signaling, detoxification, and virulence. These enzymes typically utilize a pair of tyrosine residues to orient the substrate epoxide ring in the active site and stabilize the hydrolysis intermediate. A new subclass of epoxide hydrolases that utilize a histidine in place of one of the tyrosines was established with the discovery of the CFTR Inhibitory Factor (Cif) from .

Giant electrocaloric materials energy efficiency in highly ordered lead scandium tantalate.

Electrocaloric materials are promising working bodies for caloric-based technologies, suggested as an efficient alternative to the vapor compression systems. However, their materials efficiency defined as the ratio of the exchangeable electrocaloric heat to the work needed to trigger this heat remains unknown. Here, we show by direct measurements of heat and electrical work that a highly ordered bulk lead scandium tantalate can exchange more than a hundred times more electrocaloric heat than the work needed to trigger it.

Breakthroughs in computational design methods open up new frontiers for de novo protein engineering.

Proteins catalyze the majority of chemical reactions in organisms, and harnessing this power has long been the focus of the protein engineering field. Computational protein design aims to create new proteins and functions in silico, and in doing so, accelerate the process, reduce costs and enable more sophisticated engineering goals to be accomplished. Challenges that very recently seemed impossible are now within reach thanks to several landmark advances in computational protein design methods.

Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome.

To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53.

Toward complete rational control over protein structure and function through computational design.

The grand challenge of protein design is a general method for producing a polypeptide with arbitrary functionality, conformation, and biochemical properties. To that end, a wide variety of methods have been developed for the improvement of native proteins, the design of ideal proteins de novo, and the redesign of suboptimal proteins with better-performing substructures. These methods employ informatic comparisons of function-structure-sequence relationships as well as knowledge-based evaluation of protein properties to narrow the immense protein sequence search space down to an enumerable and often manually evaluable set of structures that meet specified criteria.

Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis.

Identification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular-like "rosette" state.

Individualized Chemotherapy Benefit Prediction by EndoPredict in Patients With Early Breast Cancer in an Indian Cohort.

Purpose: There are new advancements in the modulation of the treatment of patients with early-stage breast cancer, including the use of several molecular profiling tests to identify or select those patients who require additional adjuvant chemotherapy together with hormonal therapy on the basis of a recurrence score. One such tool is EndoPredict (Myriad Genetics; Salt Lake City, UT), which provides support in clinical decision making. The objective of this analysis was to study the landscape of absolute chemotherapy benefit and the likelihood of recurrence within 5 to 15 years in Indian patients with breast cancer who are undergoing EndoPredict testing.

Integration of the Rosetta suite with the python software stack via reproducible packaging and core programming interfaces for distributed simulation.

The Rosetta software suite for macromolecular modeling is a powerful computational toolbox for protein design, structure prediction, and protein structure analysis. The development of novel Rosetta-based scientific tools requires two orthogonal skill sets: deep domain-specific expertise in protein biochemistry and technical expertise in development, deployment, and analysis of molecular simulations. Furthermore, the computational demands of molecular simulation necessitate large scale cluster-based or distributed solutions for nearly all scientifically relevant tasks.

Genetic Variants in the Wingless Antagonist Genes (, , and ) Predict the Overall Survival and Prognosis of North Indian Lung Cancer Patients Treated with Platinum-Based Doublet Chemotherapy.

To investigate the prognostic implication of genetic variants within the wingless (Wnt) antagonist genes (, , and ) in North Indian lung cancer patients. A total of 212 subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism technique for 18 polymorphic sites in , , , , , and . Overall survival (OS) was estimated using the Kaplan-Meier survival analysis, and adjusted hazard ratio (HR) was obtained using the Cox regression method.

Cytosolic expression, solution structures, and molecular dynamics simulation of genetically encodable disulfide-rich de novo designed peptides.

Disulfide-rich peptides represent an important protein family with broad pharmacological potential. Recent advances in computational methods have made it possible to design new peptides which adopt a stable conformation de novo. Here, we describe a system to produce disulfide-rich de novo peptides using Escherichia coli as the expression host.