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The microstructural origins of premature fatigue failures were investigated on a variety of forged components manufactured from AZ80 and ZK60 magnesium, both at the test specimen level and the full-scale component level. Both stress and strain-controlled approaches were used to characterize the macroscopically defect-free forged material behaviour as well as with varying levels of defect intensities. The effect of thermomechanical processing defects due to forging of an industrially relevant full-scale component were characterized and quantified using a variety of techniques. The fracture initiation and early crack growth behaviour was deterministically traced back to a combination of various effects having both geometric and microstructural origins, including poor fusion during forging, entrainment of contaminants sub-surface, as well as other inhomogeneities in the thermomechanical processing history. At the test specimen level, the fracture behaviour under both stress and strain-controlled uniaxial loading was characterized for forged AZ80 Mg and a structure-property relationship was developed. The fracture surface morphology was quantitatively assessed revealing key features which characterize the presence and severity of intrinsic forging defects. A significant degradation in fatigue performance was observed as a result of forging defects accelerating fracture initiation and early crack growth, up to 6 times reduction in life (relative to the defect free material) under constant amplitude fully reversed fatigue loading. At the full-scale component level, the fatigue and fracture behaviour under combined structural loading was also characterized for a number of ZK60 forged components with varying levels of intrinsic thermomechanical processing defects. A novel in-situ non-contact approach (utilizing Digital-Image Correlation) was used as a screening test to establish the presence of these intrinsic defects and reliably predict their effect on the final fracture behaviour in an accelerated manner compared to conventional methods. [ABSTRACT FROM AUTHOR]

A combination of high resolution electron microscopy (HREM), electron energy loss spectroscopy (EELS), energy dispersive x-ray analysis (EDXA), and scanning transmission electron microscopy (STEM) techniques has been employed to characterize the structure and composition of vapor-deposited thin films of semi-insulating polycrystalline silicon (SIPOS) and their interfaces with Si. SIPOS layers containing ∼30 at. % of oxygen are amorphous when deposited at Si substrate temperature of 625 °C. Upon annealing at 900 °C in N2 for 30 min, Si crystallites up to ∼100 Å in size appear throughout the SIPOS layer, the microstructure of which appears to be a dispersion of Si crystallites in an amorphous matrix. The plasmon-loss spectra show a characteristic energy for each material: 16.7 eV for Si, 17.6 eV for SIPOS, and 23.2 eV for SiO2, which correlate empirically with increasing oxygen content in these materials. A combination of HREM and STEM revealed the existence of a 25–30-Å native oxide layer between the SIPOS and Si substrate. This native oxide yields a plasmon loss at 22 eV using a 10-Å probe in the STEM. [ABSTRACT FROM AUTHOR]

Objective: Interleukin (IL)-22 is a potential therapeutic protein for the treatment of metabolic diseases such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease due to its involvement in multiple cellular pathways and observed hepatoprotective effects. The short serum half-life of IL-22 has previously limited its use in clinical applications; however, the development of mRNA-lipid nanoparticle (LNP) technology offers a novel therapeutic approach that uses a host-generated IL-22 fusion protein. In the present study, the effects of administration of an mRNA-LNP encoding IL-22 on metabolic disease parameters was investigated in various mouse models., Methods: C57BL/6NCrl mice were used to confirm mouse serum albumin (MSA)-IL-22 protein expression prior to assessments in C57BL/6NTac and CETP/ApoB transgenic mouse models of metabolic disease. Mice were fed either regular chow or a modified amylin liver nonalcoholic steatohepatitis-inducing diet prior to receiving either LNP-encapsulated MSA-IL-22 or MSA mRNA via intravenous or intramuscular injection. Metabolic markers were monitored for the duration of the experiments, and postmortem histology assessment and analysis of metabolic gene expression pathways were performed., Results: MSA-IL-22 was detectable for ≥8 days following administration. Improvements in body weight, lipid metabolism, glucose metabolism, and lipogenic and fibrotic marker gene expression in the liver were observed in the MSA-IL-22-treated mice, and these effects were shown to be durable., Conclusions: These results support the application of mRNA-encoded IL-22 as a promising treatment strategy for metabolic syndrome and associated comorbidities in human populations., Competing Interests: Declaration of competing interest At the time of this analysis, all authors were employees of Moderna, Inc. and may hold stock/stock options in the company., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The Head Start program, including Head Start for children aged 3-5 years and Early Head Start for infants, toddlers, and pregnant women, promotes early learning and healthy development among children aged 0-5 years whose families meet the annually adjusted Federal Poverty Guidelines* throughout the United States. † These programs are funded by grants administered by the U.S. Department of Health and Human Services' Administration for Children and Families (ACF). In March 2020, Congress passed the Coronavirus Aid, Relief, and Economic Security (CARES) Act, § which appropriated $750 million for Head Start, equating to approximately $875 in CARES Act funds per enrolled child. In response to the coronavirus disease 2019 (COVID-19) pandemic, most states required all schools (K-12) to close or transition to virtual learning. The Office of Head Start gave its local programs that remained open the flexibility to use CARES Act funds to implement CDC-recommended guidance (1) and other ancillary measures to provide in-person services in the early phases of community transmission of SARS-CoV-2, the virus that causes COVID-19, in April and May 2020, when many similar programs remained closed. Guidance included information on masks, other personal protective equipment, physical setup, supplies necessary for maintaining healthy environments and operations, and the need for additional staff members to ensure small class sizes. Head Start programs successfully implemented CDC-recommended mitigation strategies and supported other practices that helped to prevent SARS-CoV-2 transmission among children and staff members. CDC conducted a mixed-methods analysis to document these approaches and inform implementation of mitigation strategies in other child care settings. Implementing and monitoring adherence to recommended mitigation strategies reduces risk for COVID-19 transmission in child care settings. These approaches could be applied to other early care and education settings that remain open for in-person learning and potentially reduce SARS-CoV-2 transmission., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Although tap dancing is a popular dance genre, little is known about the biomechanics and motor control of this complex motor skill. We conducted a detailed 3D kinematic analysis of movement timing, amplitude, and symmetry in three experienced female tap dancers. Kinematic analyzes of three basic tap dance steps (nerve beats, brush brush stamps, and heel ball walks) were undertaken. A 10-camera Vicon motion analysis system was used to collect the data. The results showed the feet and knees to play a major role in movement execution. Each step required at least 10° of ankle motion (range: 10° to 66.8°). Knee range of motion varied from 1.3° to 147.4°. For each of the dance steps the hips showed the smallest amplitude of movement, which was not greater than 21° in two out of the three dance steps. Analyzes of movement timing showed that each of the dance steps was fast, accurate, and well synchronized. The nerve beats took on average 0.50 seconds, the brush brush stamps 1.36 seconds, and the heel ball walks 4.03 seconds. A high degree of symmetry in total movement amplitude was evident at the ankles,knees, and hips for the nerve beats and heel ball walks. There was a mild degree of asymmetry at the hip for the brush brush stamp steps (symmetry index 90%). The results showed that experienced dancers had very high levels of proficiency in controlling movement amplitude, timing, and inter-limb coordination across the ankles, knees, and hips. This resulted in skilled, fast, and well executed dance steps.

Human walking can be viewed essentially as a continuum of anterior balance loss followed by a step that re-stabilizes balance. To secure balance an extended base of support can be assistive but healthy young adults tend to walk with relatively narrower steps compared to vulnerable populations (e.g. older adults and patients). It was, therefore, hypothesized that wide step walking may enhance dynamic balance at the cost of disturbed optimum coupling of muscle functions, leading to additional muscle work and associated reduction of gait economy. Young healthy adults may select relatively narrow steps for a more efficient gait. The current study focused on the effects of wide step walking on hip abductor and adductor muscles and spatio-temporal gait parameters. To this end, lower body kinematic data and ground reaction forces were obtained using an Optotrak motion capture system and AMTI force plates, respectively, while AnyBody software was employed for muscle force simulation. A single step of four healthy young male adults was captured during preferred walking and wide step walking. Based on preferred walking data, two parallel lines were drawn on the walkway to indicate 50% larger step width and participants targeted the lines with their heels as they walked. In addition to step width that defined walking conditions, other spatio-temporal gait parameters including step length, double support time and single support time were obtained. Average hip muscle forces during swing were modeled. Results showed that in wide step walking step length increased, Gluteus Minimus muscles were more active while Gracilis and Adductor Longus revealed considerably reduced forces. In conclusion, greater use of abductors and loss of adductor forces were found in wide step walking. Further validation is needed in future studies involving older adults and other pathological populations.

Background: In dogs with ischaemic stroke, a very common site of infarction is the cerebellum. The aim of this study was to characterise neurological signs in relation to infarct topography in dogs with suspected cerebellar ischaemic stroke and to report short-term outcome confined to the hospitalisation period. A retrospective multicentre study of dogs with suspected cerebellar ischaemic stroke examined from 2010-2015 at five veterinary referral hospitals was performed. Findings from clinical, neurological, and paraclinical investigations including magnetic resonance imaging were assessed., Results: Twenty-three dogs, 13 females and 10 males with a median age of 8 years and 8 months, were included in the study. The Cavalier King Charles Spaniel (n = 9) was a commonly represented breed. All ischaemic strokes were located to the vascular territory of the rostral cerebellar artery including four extensive and 19 limited occlusions. The most prominent neurological deficits were gait abnormalities (ataxia with hypermetria n = 11, ataxia without hypermetria n = 4, non-ambulatory n = 6), head tilt (n = 13), nystagmus (n = 8), decreased menace response (n = 7), postural reaction deficits (n = 7), and proprioceptive deficits (n = 5). Neurological signs appeared irrespective of the infarct being classified as extensive or limited. All dogs survived and were discharged within 1-10 days of hospitalisation., Conclusions: Dogs affected by rostral cerebellar ischaemic stroke typically present with a collection of neurological deficits characterised by ataxia, head tilt, and nystagmus irrespective of the specific cerebellar infarct topography. In dogs with peracute to acute onset of these neurological deficits, cerebellar ischaemic stroke should be considered an important differential diagnosis, and neuroimaging investigations are indicated. Although dogs are often severely compromised at presentation, short-term prognosis is excellent and rapid clinical improvement may be observed within the first week following the ischaemic stroke.

Shamanic belief systems represent the first form of religious practice visible within the global archaeological record. Here we report on the earliest known evidence of shamanic costume: modified red deer crania headdresses from the Early Holocene site of Star Carr (c. 11 kya). More than 90% of the examples from prehistoric Europe come from this one site, establishing it as a place of outstanding shamanistic/cosmological significance. Our work, involving a programme of experimental replication, analysis of macroscopic traces, organic residue analysis and 3D image acquisition, metrology and visualisation, represents the first attempt to understand the manufacturing processes used to create these artefacts. The results produced were unexpected--rather than being carefully crafted objects, elements of their production can only be described as expedient.

Objective: To compare radiographic elbow arthrosis with arthroscopic cartilage pathology in Labrador retrievers with elbow osteoarthritis secondary to medial coronoid process (MCP) disease., Study Design: Retrospective epidemiological study., Animals: Labrador retrievers (n = 317; 592 elbow joints)., Methods: Data were collected retrospectively (June 2007-June 2011) to identify Labrador retrievers with thoracic limb lameness and elbow pain, a complete set of elbow radiographs, and a comprehensive arthroscopic surgery report. Each radiograph was scored for osteophytosis on the anconeal process and ulnar subtrochlear sclerosis using a modification of the International Elbow Working Group (IEWG) scoring system. Elbows affected by traumatic MCP fracture, humeral condylar osteochondrosis, or ununited anconeal process were excluded. The arthroscopic report was used to generate a composite cartilage score (CCS; 0 = normal, 1 = mild, 2 = moderate, 3 = severe) for each elbow joint. Ordinal regression analysis was performed to test the relationship between radiographic arthrosis score and CCS., Results: There was a significant relationship between radiographic elbow arthrosis and CCS (P < .001). Elbows with a higher radiographic score were significantly more likely to have a higher CCS than elbows with a lower radiographic score. For every month increase in age, the odds of having a higher CCS increased by 0.016 (1.6%)., Conclusions: Radiographic arthrosis can be used to predict the severity of arthroscopic cartilage pathology in Labrador retrievers affected by MCP disease., (© Copyright 2014 by The American College of Veterinary Surgeons.)

Antibodies' protective, pathological, and therapeutic properties result from their considerable diversity. This diversity is almost limitless in potential, but actual diversity is still poorly understood. Here we use deep sequencing to characterize the diversity of the heavy-chain CDR3 region, the most important contributor to antibody binding specificity, and the constituent V, D, and J segments that comprise it. We find that, during the stepwise D-J and then V-DJ recombination events, the choice of D and J segments exert some bias on each other; however, we find the choice of the V segment is essentially independent of both. V, D, and J segments are utilized with different frequencies, resulting in a highly skewed representation of VDJ combinations in the repertoire. Nevertheless, the pattern of segment usage was almost identical between two different individuals. The pattern of V, D, and J segment usage and recombination was insufficient to explain overlap that was observed between the two individuals' CDR3 repertoires. Finally, we find that while there are a near-infinite number of heavy-chain CDR3s in principle, there are about 3-9 million in the blood of an adult human being.

Background: Bacterial viruses (phages) play a critical role in shaping microbial populations as they influence both host mortality and horizontal gene transfer. As such, they have a significant impact on local and global ecosystem function and human health. Despite their importance, little is known about the genomic diversity harbored in phages, as methods to capture complete phage genomes have been hampered by the lack of knowledge about the target genomes, and difficulties in generating sufficient quantities of genomic DNA for sequencing. Of the approximately 550 phage genomes currently available in the public domain, fewer than 5% are marine phage., Methodology/principal Findings: To advance the study of phage biology through comparative genomic approaches we used marine cyanophage as a model system. We compared DNA preparation methodologies (DNA extraction directly from either phage lysates or CsCl purified phage particles), and sequencing strategies that utilize either Sanger sequencing of a linker amplification shotgun library (LASL) or of a whole genome shotgun library (WGSL), or 454 pyrosequencing methods. We demonstrate that genomic DNA sample preparation directly from a phage lysate, combined with 454 pyrosequencing, is best suited for phage genome sequencing at scale, as this method is capable of capturing complete continuous genomes with high accuracy. In addition, we describe an automated annotation informatics pipeline that delivers high-quality annotation and yields few false positives and negatives in ORF calling., Conclusions/significance: These DNA preparation, sequencing and annotation strategies enable a high-throughput approach to the burgeoning field of phage genomics.

We present an automated, high throughput library construction process for 454 technology. Sample handling errors and cross-contamination are minimized via end-to-end barcoding of plasticware, along with molecular DNA barcoding of constructs. Automation-friendly magnetic bead-based size selection and cleanup steps have been devised, eliminating major bottlenecks and significant sources of error. Using this methodology, one technician can create 96 sequence-ready 454 libraries in 2 days, a dramatic improvement over the standard method.

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.

The Lyell McEwin Health Service (LMHS) is a major public hospital located in the northern suburbs of Adelaide, a region where the death rate from ischaemic heart disease (IHD) is higher than the expected death rate in the population. A retrospective case note study conducted at this hospital investigated the duration that patients with unstable angina pectoris (UA) or acute myocardial infarction (AMI) spent in the emergency department (ED) before admission to the critical care unit (CCU) and the factors that contributed to delays of greater than 70 minutes. All patients admitted to the LMHS over an 18 month period with a discharge diagnosis related group (DRG) for AMI and UA were included in the study. A total of 667 case notes were examined; 403 of these cases met the inclusion criteria for the study. The mean duration between arrival in the ED and subsequent admission to the CCU was found to be 161 minutes. DRG was a major factor in the length of time spent in the ED. The mean duration for patients with AMI was 124 minutes, whilst for UA the duration was 190 minutes (difference = 66 minutes, p<0.001). Other factors that were significant were gender (females = mean duration 29 minutes > males, p=0.015), and mode of transport to the ED (arrival by ambulance mean duration 30 minutes < private transport, Recommendations arising from this study included that a system be established to enable the rapid assessment of all patients suspected of suffering AMI and UA, inclusive of their expeditious transfer to the CCU. In addition, a staff development programme was proposed to ensure medical and nursing staff became aware of a bias in this hospital toward transferring male patients in a shorter timeframe than females with the same DRG.