Microscopic parameters of the van der Waals CrSBr antiferromagnet from microwave absorption experiments

Microwave absorption experiments employing a phase-sensitive external resistive detection are performed for a topical van der Waals antiferromagnet CrSBr. The field dependence of two resonance modes is measured in an applied field parallel to the three principal crystallographic directions, revealing anisotropies and magnetic transitions in this material. To account for the observed results, we formulate a microscopic spin model with a bi-axial single-ion anisotropy and inter-plane exchange. Theoretical calculations give an excellent description of full magnon spectra enabling us to precisely determine microscopic interaction parameters for CrSBr.Comment: includes a supplementary information documen

Gene expression profiling of Spodoptera frugiperda hemocytes and fat body using cDNA microarray reveals polydnavirus-associated variations in lepidopteran host genes transcript levels

BACKGROUND: Genomic approaches provide unique opportunities to study interactions of insects with their pathogens. We developed a cDNA microarray to analyze the gene transcription profile of the lepidopteran pest Spodoptera frugiperda in response to injection of the polydnavirus HdIV associated with the ichneumonid wasp Hyposoter didymator. Polydnaviruses are associated with parasitic ichneumonoid wasps and are required for their development within the lepidopteran host, in which they act as potent immunosuppressive pathogens. In this study, we analyzed transcriptional variations in the two main effectors of the insect immune response, the hemocytes and the fat body, after injection of filter-purified HdIV. RESULTS: Results show that 24 hours post-injection, about 4% of the 1750 arrayed host genes display changes in their transcript levels with a large proportion (76%) showing a decrease. As a comparison, in S. frugiperda fat body, after injection of the pathogenic JcDNV densovirus, 8 genes display significant changes in their transcript level. They differ from the 7 affected by HdIV and, as opposed to HdIV injection, are all up-regulated. Interestingly, several of the genes that are modulated by HdIV injection have been shown to be involved in lepidopteran innate immunity. Levels of transcripts related to calreticulin, prophenoloxidase-activating enzyme, immulectin-2 and a novel lepidopteran scavenger receptor are decreased in hemocytes of HdIV-injected caterpillars. This was confirmed by quantitative RT-PCR analysis but not observed after injection of heat-inactivated HdIV. Conversely, an increased level of transcripts was found for a galactose-binding lectin and, surprisingly, for the prophenoloxidase subunits. The results obtained suggest that HdIV injection affects transcript levels of genes encoding different components of the host immune response (non-self recognition, humoral and cellular responses). CONCLUSION: This analysis of the host-polydnavirus interactions by a microarray approach indicates that the presence of HdIV induces, directly or indirectly, variations in transcript levels of specific host genes, changes that could be responsible in part for the alterations observed in the parasitized host physiology. Development of such global approaches will allow a better understanding of the strategies employed by parasites to manipulate their host physiology, and will permit the identification of potential targets of the immunosuppressive polydnaviruses

Heat-Up Colloidal Synthesis of Shape-Controlled Cu-Se-S Nanostructures—Role of Precursor and Surfactant Reactivity and Performance in N2 Electroreduction

Copper selenide-sulfide nanostructures were synthesized using metal-organic chemical routes in the presence of Cu- and Se-precursors as well as S-containing compounds. Our goal was first to examine if the initial Cu/Se 1:1 molar proportion in the starting reagents would always lead to equiatomic composition in the final product, depending on other synthesis parameters which affect the reagents reactivity. Such reaction conditions were the types of precursors, surfactants and other reagents, as well as the synthesis temperature. The use of ‘hot-injection’ processes was avoided, focusing on ‘non-injection’ ones; that is, only heat-up protocols were employed, which have the advantage of simple operation and scalability. All reagents were mixed at room temperature followed by further heating to a selected high temperature. It was found that for samples with particles of bigger size and anisotropic shape the CuSe composition was favored, whereas particles with smaller size and spherical shape possessed a Cu2−xSe phase, especially when no sulfur was present. Apart from elemental Se, Al2Se3 was used as an efficient selenium source for the first time for the acquisition of copper selenide nanostructures. The use of dodecanethiol in the presence of trioctylphosphine and elemental Se promoted the incorporation of sulfur in the materials crystal lattice, leading to Cu-Se-S compositions. A variety of techniques were used to characterize the formed nanomaterials such as XRD, TEM, HRTEM, STEM-EDX, AFM and UV-Vis-NIR. Promising results, especially for thin anisotropic nanoplates for use as electrocatalysts in nitrogen reduction reaction (NRR), were obtained

Relationship between margin distance and local recurrence among patients undergoing wedge resection for small (≤2 cm) non–small cell lung cancer

ObjectiveSuccessful pulmonary wedge resection for early-stage non–small cell lung cancer requires a pathologically confirmed negative margin. To date, however, no clear evidence is available regarding whether an optimal margin distance, defined as the distance from the primary tumor to the closest resection margin, exists. Toward addressing this gap, we investigated the relationship between the margin distance and local recurrence risk.MethodsWe reviewed all adult patients who had undergone wedge resection for small (≤2 cm) non–small cell lung cancer from January 2001 to August 2011, with follow-up through to December 31, 2011. The exclusion criteria included other active noncutaneous malignancies, bronchoalveolar carcinomas, lymph node or distant metastases at diagnosis, large cell cancer, adenosquamous cancer, multiple, multifocal, and/or metastatic disease, and previous chemotherapy or radiotherapy. Using Cox regression analysis, we examined the relationship between the margin distance and interval to local recurrence, adjusting for chronic obstructive pulmonary disease, forced expiratory volume in 1 second, smoking, diabetes, tumor size, tumor location, surgeon, open versus video-assisted thoracoscopic surgery, and whether the lymph nodes were sampled.ResultsOf 557 consecutive adult patients, 479 met our inclusion criteria. The overall, unadjusted 1- and 2-year local recurrences rate was 5.7% and 11.0%, respectively. From the adjusted analyses, an increased margin distance was significantly associated with a lower risk of local recurrence (P = .033). Patients with a 10-mm margin distance had a 45% lower local recurrence risk than those with a 5-mm distance (hazard ratio, 0.55; 95% confidence interval, 0.35-0.86). Beyond 15 mm, no evidence of additional benefit was associated with an increased margin distance.ConclusionsIn wedge resection for small non–small cell lung cancer, increasing the margin distance ≤15 mm significantly decreased the local recurrence risk, with no evidence of additional benefit beyond 15 mm

A Powerful Statistical Framework for Generalization Testing in GWAS, with Application to the HCHS/SOL

In GWAS, “generalization” is the replication of genotype-phenotype association in a population with different ancestry than the population in which it was first identified. The standard for reporting findings from a GWAS requires a two-stage design, in which discovered associations are replicated in an independent follow-up study. Current practices for declaring generalizations rely on testing associations while controlling the Family Wise Error Rate (FWER) in the discovery study, then separately controlling error measures in the follow-up study. While this approach limits false generalizations, we show that it does not guarantee control over the FWER or False Discovery Rate (FDR) of the generalization null hypotheses. In addition, it fails to leverage the two-stage design to increase power for detecting generalized associations. We develop a formal statistical framework for quantifying the evidence of generalization that accounts for the (in)consistency between the directions of associations in the discovery and follow-up studies. We develop the directional generalization FWER (FWERg) and FDR (FDRg) controlling r-values, which are used to declare associations as generalized. This framework extends to generalization testing when applied to a published list of SNP-trait associations. We show that our framework accommodates various SNP selection rules for generalization testing based on p-values in the discovery study, and still control FWERg or FDRg. A key finding is that it is often beneficial to use a more lenient p-value threshold then the genome-wide significance threshold. For instance, in a GWAS of Total Cholesterol (TC) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), when testing all SNPs with p-values\u3c 5 × 10−8 (15 genomic regions) for generalization in a large GWAS of whites, we generalized SNPs from 15 regions. But when testing all SNPs with p-values\u3c 6.6×10−5 (89 regions), we generalized SNPs from 27 regions

Functionalized metallic 2D transition metal dichalcogenide-based solid-state electrolyte for flexible all-solid-state supercapacitors

Highly efficient and durable flexible solid-state supercapacitors (FSSSCs) are emerging as low-cost devices for portable and wearable electronics due to the elimination of leakage of toxic/corrosive liquid electrolytes and their capability to withstand elevated mechanical stresses. Nevertheless, the spread of FSSSCs requires the development of durable and highly conductive solid-state electrolytes, whose electrochemical characteristics must be competitive with those of traditional liquid electrolytes. Here, we propose an innovative composite solid-state electrolyte prepared by incorporating metallic two-dimensional group-5 transition metal dichalcogenides, namely, liquid-phase exfoliated functionalized niobium disulfide (f-NbS2) nanoflakes, into a sulfonated poly(ether ether ketone) (SPEEK) polymeric matrix. The terminal sulfonate groups in f-NbS2 nanoflakes interact with the sulfonic acid groups of SPEEK by forming a robust hydrogen bonding network. Consequently, the composite solid-state electrolyte is mechanically/dimensionally stable even at a degree of sulfonation of SPEEK as high as 70.2%. At this degree of sulfonation, the mechanical strength is 38.3 MPa, and thanks to an efficient proton transport through the Grotthuss mechanism, the proton conductivity is as high as 94.4 mS cm–1 at room temperature. To elucidate the importance of the interaction between the electrode materials (including active materials and binders) and the solid-state electrolyte, solid-state supercapacitors were produced using SPEEK and poly(vinylidene fluoride) as proton conducting and nonconducting binders, respectively. The use of our solid-state electrolyte in combination with proton-conducting SPEEK binder and carbonaceous electrode materials (mixture of activated carbon, single/few-layer graphene, and carbon black) results in a solid-state supercapacitor with a specific capacitance of 116 F g–1 at 0.02 A g–1, optimal rate capability (76 F g–1 at 10 A g–1), and electrochemical stability during galvanostatic charge/discharge cycling and folding/bending stresses

Statin Efficacy and Safety for Lipid Modification in Apparently Healthy Male Military Aircrew

Introduction: Military aircrew men represent an elite group of relatively young, fit, and healthy people. The effectiveness of statin treatment in reducing low-density lipoprotein cholesterol (LDL-C) according to the current National Cholesterol Education Program (NCEP) guidelines, its safety, and compliance in this group of people has not yet been determined. Methods: We prospectively evaluated 84 military aircrew men (mean age 43 Ϯ 7 yr) with LDL-C above the current NCEP guidelines. The patients were divided into two groups according to their coronary risk factors: Group 1, LDL-C goal Ͻ 160 mg ⅐ dL Ϫ1 ; Group 2, LDL-C goal Ͻ 130 mg ⅐ dL Ϫ1 . All patients received statins in addition to therapeutic lifestyle changes and were followed for a mean of 3 Ϯ 1 yr according to a simple flow chart. Lipoprotein levels, liver function tests, creatinine phosphokinase, and subjective adverse reactions were checked periodically. Results: LDL-C significantly declined by 32% (p Ͻ 0.0001) within the first month of treatment and 99% of subjects achieved their LDL-C goal within 114 Ϯ 35 d from statin therapy initiation. The Framingham estimated 10-yr coronary risk showed a reduction at an average of 12 mo after statin therapy initiation from a baseline value of 6.54% to 3.95% (p ϭ 0.003). No subjects were grounded or disqualified from duty, there were no cardiovascular events during follow-up, and compliance to therapy was high [82/84 (98%)]. Discussion: Statin treatment in this highly select, relatively young group of aircrew men significantly and safely lowered LDL-C cholesterol levels

Leveraging Pleiotropy to Discover and interpret Gwas Results For Sleep-Associated Traits

Genetic association studies of many heritable traits resulting from physiological testing often have modest sample sizes due to the cost and burden of the required phenotyping. This reduces statistical power and limits discovery of multiple genetic associations. We present a strategy to leverage pleiotropy between traits to both discover new loci and to provide mechanistic hypotheses of the underlying pathophysiology. Specifically, we combine a colocalization test with a locus-level test of pleiotropy. In simulations, we show that this approach is highly selective for identifying true pleiotropy driven by the same causative variant, thereby improves the chance to replicate the associations in underpowered validation cohorts and leads to higher interpretability. Here, as an exemplar, we use Obstructive Sleep Apnea (OSA), a common disorder diagnosed using overnight multi-channel physiological testing. We leverage pleiotropy with relevant cellular and cardio-metabolic phenotypes and gene expression traits to map new risk loci in an underpowered OSA GWAS. We identify several pleiotropic loci harboring suggestive associations to OSA and genome-wide significant associations to other traits, and show that their OSA association replicates in independent cohorts of diverse ancestries. By investigating pleiotropic loci, our strategy allows proposing new hypotheses about OSA pathobiology across many physiological layers. For example, we identify and replicate the pleiotropy across the plateletcrit, OSA and an eQTL of DNA primase subunit 1 (PRIM1) in immune cells. We find suggestive links between OSA, a measure of lung function (FEV1/FVC), and an eQTL of matrix metallopeptidase 15 (MMP15) in lung tissue. We also link a previously known genome-wide significant peak for OSA in the hexokinase 1 (HK1) locus to hematocrit and other red blood cell related traits. Thus, the analysis of pleiotropic associations has the potential to assemble diverse phenotypes into a chain of mechanistic hypotheses that provide insight into the pathogenesis of complex human diseases

'What is the risk to me from COVID-19?': Public involvement in providing mortality risk information for people with 'high-risk' conditions for COVID-19 (OurRisk.CoV)

Patients and public have sought mortality risk information throughout the pandemic, but their needs may not be served by current risk prediction tools. Our mixed methods study involved: (1) systematic review of published risk tools for prognosis, (2) provision and patient testing of new mortality risk estimates for people with high-risk conditions and (3) iterative patient and public involvement and engagement with qualitative analysis. Only one of 53 (2%) previously published risk tools involved patients or the public, while 11/53 (21%) had publicly accessible portals, but all for use by clinicians and researchers.Among people with a wide range of underlying conditions, there has been sustained interest and engagement in accessible and tailored, pre- and postpandemic mortality information. Informed by patient feedback, we provide such information in 'five clicks' (https://covid19-phenomics.org/OurRiskCoV.html), as context for decision making and discussions with health professionals and family members. Further development requires curation and regular updating of NHS data and wider patient and public engagement