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The complex non-centrosymmetric and chiral nature of helical structures endow materials that possess such motifs with unusual properties. However, despite their ubiquity in biological and organic systems, there is a severe lack of inorganic crystals that display helicity in extended lattices, where these unusual properties are expected to be most pronounced. Here, we report a new inorganic helical structure, gallium sulfur iodide (GaSI), within the exfoliable class of III-VI-VII (1:1:1) one-dimensional (1D) van der Waals (vdW) crystals. Through detailed structural analyses, including single-crystal X-ray diffraction, electron microscopy, and density functional theory (DFT), we elucidate the apparent noncrystallographic screw axis and the first example of an atomic scale helical structure bearing a squircular cross-section in GaSI. Crystallizing in the non-centrosymmetric P4̅ space group, we found that GaSI crystals exhibit pronounced second-harmonic generation. From diffuse reflectance spectroscopy, GaSI displays a sizeable bandgap of 3.69 eV, owing tostrong covalent interactions arising from the smaller sulfur atoms within the helix core. These results position GaSI as a promising exfoliable nonlinear optical material across a broad optical window.

In many high-stakes testing situations, test-takers are not allowed to draw on external writing resources while writing, a practice observed more frequently in classroom settings. This may pose problems with the representativeness of test tasks and score interpretations. This study investigates the domain definition of one particular test known as the English Placement Writing Test within an argument-based validation framework. Focusing on the domain definition inference, the following rebuttal was evaluated: Certain essential contextual factors in the academic writing domain are not modeled in the test tasks. To do so, lower- and intermediate-level ESL students (n=92) who previously took the test were surveyed and interviewed regarding their uses of computer-based and face-to-face human-assisted writing tools. Results showed that students at both levels were statistically similar in their attitudes toward and uptakes of such tools while writing. The difference in availability of external writing tools between the target and test domain may point to issues with task authenticity of the test.

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.

By the end of October 2022, the US HL-LHC Accelerator Upgrade Project (AUP) had completed fabrication of ten MQXFA magnets and tested eight of them. The MQXFA magnets are the low-beta quadrupole magnets to be used in the Q1 and Q3 Inner Triplet elements of the High Luminosity LHC. This AUP effort is shared by BNL, Fermilab, and LBNL, with strand verification tests at NHMFL. An important step of the AUP QA plan is the testing of MQXFA magnets in a vertical cryostat at BNL. The acceptance criteria that could be tested at BNL were all met by the first four production magnets (MQXFA03-MQXFA06). Subsequently, two magnets (MQXFA07 and MQXFA08) did not meet some of the criteria and were disassembled. Lessons learned during the disassembly of MQXFA07 caused a revision to the assembly specifications that were used for MQXFA10 and subsequent magnets. In this article, we present a summary of: 1) the fabrication and test data for all the MQXFA magnets; 2) the analysis of MQXFA07/A08 test results with characterization of the limiting mechanism; 3) the outcome of the investigation, including the lessons learned during MQXFA07 disassembly; and 4) the finite element analysis correlating observations with test performance.

This document provides recommendations regarding the role of imaging in the staging and follow-up of esophageal cancer. For initial clinical staging, locoregional extent and nodal disease are typically assessed with esophagogastroduodenoscopy and esophageal ultrasound. FDG-PET/CT or CT of the chest and abdomen is usually appropriate for use in initial clinical staging as they provide additional information regarding distant nodal and metastatic disease. The detection of metastatic disease is critical in the initial evaluation of patients with esophageal cancer because it will direct patients to a treatment pathway centered on palliative radiation rather than surgery. For imaging during treatment, particularly neoadjuvant chemotherapy, FDG-PET/CT is usually appropriate, because some studies have found that it can provide information regarding primary lesion response, but more importantly it can be used to detect metastases that have developed since the induction of treatment. For patients who have completed treatment, FDG-PET/CT or CT of the chest and abdomen is usually appropriate for evaluating the presence and extent of metastases in patients with no suspected or known recurrence and in those with a suspected or known recurrence. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the regulatory landscape in heart disease is unclear. Here, we use RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from up to 26 healthy controls, 18 individuals with idiopathic dilated cardiomyopathy (DCM), and five fetal hearts. Healthy individuals have a highly reproducible epigenomic landscape, consisting of more than 33,000 predicted heart enhancers. In contrast, we observe reproducible disease-associated changes in activity at 6,850 predicted heart enhancers. Combined analysis of adult and fetal samples reveals that the heart disease epigenome and transcriptome both acquire fetal-like characteristics, with 3,400 individual enhancers sharing fetal regulatory properties. We also provide a comprehensive data resource (http://heart.lbl.gov) for the mechanistic exploration of DCM etiology.

Ensuring that test-score use brings about socially positive consequences for test-takers is an important aspect of test validation. While many studies use an inductive approach to evaluate test consequences, few studies have implemented Appraisal analysis. To that end, this case study investigated the test consequences of an English reading placement test that was administered at a large American university. In this study, English as a second language (ESL) students (n=8) who took the placement test and an ESL reading course were interviewed; an Appraisal analysis was conducted to identify the students' positive and/or negative perceptions toward the placement test and the ESL reading course. Using an argument-based approach to validity framework, the findings were treated as evidence to evaluate the test consequences of the placement test. The results showed that, while taking the ESL course helped students gain some valuable academic reading skills, students felt that test anxiety, fatigue, and verbally demanding questions hindered their test performances. Understanding what students experienced while taking the test can help test-developers devise solutions that will improve the test-taking situation for future test-takers. This study also illustrates how an Appraisal analysis of test-takers' discourses can provide a systematic and fine-grained approach to evaluating positive and/or negative test consequences.

Children use language structures as a basis for learning how to read. Therefore, literacy learning for young children must incorporate the child's personal use of oral language. It is their personal oral language that supports them as they attempt new concepts and become better readers. Because of the important role that oral language plays in a young child's literacy development, it is of the utmost importance that adults who work with young children support the growth of the child's spoken language beginning in infancy. This article discusses activities that will support oral language development in young children so that they will have a strong linguistic foundation upon which to build literacy skills. Through interactions with the young child that include quality conversations and play, the child's language development will be strengthened, resulting in a greater foundation for literacy learning.

SignificanceThe mature capsids of HIV-1 are transiently stable complexes that self-assemble around the viral genome during maturation, and uncoat to release preintegration complexes that archive a double-stranded DNA copy of the virus in the host cell genome. However, a detailed view of how HIV cores rupture remains lacking. Here, we elucidate the physical properties involved in capsid rupture using a combination of large-scale all-atom molecular dynamics simulations and cryo-electron tomography. We find that intrinsic strain on the capsid forms highly correlated patterns along the capsid surface, along which cracks propagate. Capsid rigidity also increases with high strain. Our findings provide fundamental insight into viral capsid uncoating.

Transcriptional enhancers are a predominant class of noncoding regulatory elements that activate cell type-specific gene expression. Tissue-specific enhancer-associated chromatin signatures have proven useful to identify candidate enhancer elements at a genome-wide scale, but their sensitivity for the comprehensive detection of all enhancers active in a given tissue in vivo remains unclear. Here we show that a substantial proportion of in vivo enhancers are hidden from discovery by conventional chromatin profiling methods. In an initial comparison of over 1,200 in vivo validated tissue-specific enhancers with tissue-matched mouse developmental epigenome data, 14% (n=286) of active enhancers did not show canonical enhancer-associated chromatin signatures in the tissue in which they are active. To assess the prevalence of enhancers not detectable by conventional chromatin profiling approaches in more detail, we used a high throughput transgenic enhancer reporter assay to systematically screen over 1.3 Mb of mouse genomic sequence at two critical developmental loci, assessing a total of 281 consecutive 5kb regions for in vivo enhancer activity in mouse embryos. We observed reproducible enhancer-reporter activity in 88 tissue-specific elements, 26% of which did not show canonical enhancer-associated chromatin signatures in the corresponding tissues. Overall, we find these hidden enhancers are indistinguishable from marked enhancers based on levels of evolutionary conservation, enrichment of transcription factor families, and genomic positioning relative to putative target genes. In combination, our retrospective and prospective studies assessed only 0.1% of the mouse genome and identified 309 tissue-specific enhancers that are hidden from current chromatin-based enhancer identification approaches. Our findings suggest the existence of tens of thousands of active enhancers throughout the genome that remain undetected by current chromatin profiling approaches and are an unappreciated source of additional genome function of import in interpreting growing whole human genome sequencing data.

To date, American research has provided the foundation for what is known about the educational experiences of students living in military families. Given contextual differences that exist between the United States and Canada, it is unclear how representative the American findings are of the Canadian experience. Using semi-structured interviews, this phenomenological study collected data from six educators to better understand how the needs of military-connected students are addressed within Canadian secondary schools. Participants generally had a good understanding of the military lifestyle and its associated challenges for students. However, many participants were unaware of any formal mechanisms used to identify military-connected students, any professional development opportunities for educators, or any collaborations that exist between schools and the military to support such students. Given the current lack of Canadian research, this study will help contribute to the building of knowledge and capacity in the Canadian context.

A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-03089-4.

A large bore 'High-Temperature Superconductor Cable Test Facility Magnet' for testing advanced cables and inserts in high transverse field is in its design phase. This magnet will be the core component of a facility for developing conductors and accelerator magnets operating above 15 T, an enabling technology for next-generation fusion devices using magnetic confinement of plasma and for future energy frontier colliders. The procurement of Nb3Sn conductor, fabrication of cables, winding of coils, and assembly of the dipole magnet will be done at Lawrence Berkeley National Laboratory (LBNL) and the test pit and cryostat will be constructed at Fermi National Accelerator Laboratory. This article will present the conductor element of the LBNL project, specifically cable design parameters (based on the Bruker OST RRP^{\bigcirc \!\!\!\! {\hbox{R}}} Nb3Sn superconducting wire) and the development phase cable fabrication experience. Challenges of the cable fabrication will be discussed. The wire and cable planned for this magnet are similar to those under study for the Future Circular Collider and other large facility magnets. The successful fabrication of the development cable has positive implications for these other projects.

Spin defects in wide-bandgap semiconductors provide a promising platform to create qubits for quantum technologies. Their synthesis, however, presents considerable challenges, and the mechanisms responsible for their generation or annihilation are poorly understood. Here, we elucidate spin defect formation processes in a binary crystal for a key qubit candidate-the divacancy complex (VV) in silicon carbide (SiC). Using atomistic models, enhanced sampling simulations, and density functional theory calculations, we find that VV formation is a thermally activated process that competes with the conversion of silicon (VSi) to carbon monovacancies (VC), and that VV reorientation can occur without dissociation. We also find that increasing the concentration of VSi relative to VC favors the formation of divacancies. Moreover, we identify pathways to create spin defects consisting of antisite-double vacancy complexes and determine their electronic properties. The detailed view of the mechanisms that underpin the formation and dynamics of spin defects presented here may facilitate the realization of qubits in an industrially relevant material.

BackgroundA nonpedigreed male cat presented with epistaxis, severe bladder hemorrhage, and secondary urethral obstruction after cystocentesis.ObjectivesTo characterize the phenotype of a cat with bleeding diathesis and use a precision medicine approach to identify the molecular genetic defect by whole genome sequencing.MethodsAdenosine diphosphate (ADP) and arachidonic acid (AA)-induced whole blood platelet aggregometry was performed in the affected cat and a healthy cat. Platelet activation, measured by P-selectin expression, and surface integrin subunit β3 expression were evaluated by flow cytometry in the affected cat and healthy control. Total integrin subunit αIIb expression was assessed by western blot. Whole genome sequencing at 30× coverage was used to identify genetic variants that segregated in the affected cat compared to 194 cats from the 99 Lives Sequencing Consortium.ResultsPlatelet aggregometry identified significant impairment in platelet aggregation in response to ADP and AA compared to the control cat. Targeted protein expression analyses by flow cytometry and immunoblot analysis determined that the surface expression and total expression of the integrin, αIIbβ3, was absent. Whole genome sequencing identified a homozygous c.1986delC frameshift variant in the integrin subunit αIIb (ITGA2B) gene that was not detected in the control population. The p.Pro662fs (ITGA2B P662X) variant terminates translation of the protein at the extracellular domain of the integrin prematurely, which is predicted to affect expression of the β3 unit.Conclusions and clinical importanceThis novel ITGA2B variant and the associated phenotype closely resemble Glanzmann's thrombasthenia, which has never been reported in cats.