A Cultured Learning Environment: Implementing a Problem- and Service-Based Microbiology Capstone Course to Assess Process- and Skill-Based Learning Objectives

In this study, a problem-based capstone course was designed to assess the University of Wyoming Microbiology Program’s skill-based and process-based student learning objectives. Students partnered with a local farm, a community garden, and a free downtown clinic in order to conceptualize, propose, perform, and present studies addressing problems experienced by these partners. Instructor assessments enabled understanding of student competencies, and according to external subject matter experts students demonstrated mastery of all learning objectives on the final research presentation. Community partners were completely satisfied with the students’ solutions, professionalism, and communication. Instructional diagnosis and student course evaluations showed satisfaction, engagement, and growth. Assessments enabled reflective practice by faculty and led to improvements of the capstone course and the microbiology program. Consequently, the course gained institutional support and an official course listing

Seismic Loss and Downtime Assessment of Existing Tall Steel-Framed Buildings and Strategies for Increased Resilience

In areas of high seismicity in the United States, the design of many existing tall buildings followed guidelines that do not provide an explicit understanding of performance during major earthquakes. This paper presents an assessment of the seismic performance of existing tall buildings and strategies for increased resilience for a case study city, San Francisco, where an archetype tall building is designed based on an inventory of the existing tall building stock. A 40-story moment-resisting frame system is selected as a representative tall building. The archetype building is rectangular in plan and represents the state of design and construction practice from the mid-1970s to the mid-1980s. Nonlinear response history analysis (NLRHA) are conducted with ground motions representative of the design earthquake hazard level defined in current building codes, with explicit consideration of near-fault directivity effects. Mean transient interstory drifts and story accelerations under the 10% in 50-year ground motion hazard range from 0.19 to 1.14% and 0.15 to 0.81 g, respectively. In order to influence decision making, performance is reported as the expected consequences in terms of direct economic losses and downtime. Furthermore, to achieve increased levels of resilience, a number of strategies are proposed including seismic improvements to structural and nonstructural systems as well as mitigation measures to minimize impeding factors. Expected direct economic losses for the archetype building are in the order of 34% of building cost and downtime estimates for functional recovery are 87 weeks. The strategies presented in this paper enable up to a 92% reduction in losses and minimize downtime for functional recovery to 1 day or less

Risk-based seismic performance assessment of existing tall steel-framed buildings in San Francisco

This study presents the results of a risk-based seismic performance assessment of an archetype tall building representative of the existing tall building stock in San Francisco, CA. The archetype tall building, selected based on an inventory of existing tall buildings, is a 40- storey Moment Resisting Frame (MRF) representative of design and construction practice from the 1970-s to the mid-1980s. A Multiple Stripe Analysis (MSA) was conducted at 8 different intensity levels ranging from frequent to very rare seismic events, i.e. from 85% to 1% probability of exceedance in 50 years. Non-Linear Response History Analyses (NLRHA) were conducted with ground motions representative of each intensity level considered. The results of the NLRHA results were used to assess the probability of earthquake losses, considering collapse potential and the probability of the building deemed irreparable due to permanent residual drifts in the structure. Based on the MSA results, the collapse fragility of the structure, assumed to follow a lognormal cumulative distribution expressed as a function of spectral acceleration at the fundamental period of the structure (T=5 seconds), has an estimated median of 0.15g and a dispersion of 0.30. A number of loss metrics were developed for the archetype building including: a loss function, which provides the annual frequency of exceeding a certain value of loss, e.g. the expected 500 year loss equals $53M or 39$0.6M or 0.46% of the building replacement cost; and loss exceedance rates, e.g. a loss of 10% building replacement cost or $13.5M has an exceedance rate of 95 years. The use of these results to benchmark the performance of the archetype tall building against the design intent in current building codes and to assess the impact of structural retrofit or other building enhancements is discussed

Seismic Loss and Downtime Estimates of Existing Tall Buildings and Strategies for Increased Resilience

Tall buildings play an important role in the socio-economic activity of major metropolitan areas. The resilience of these structures is critical to ensure a successful recovery after major disasters. Events such as the Canterbury earthquake in 2011 have highlighted the impact of poor performing buildings on the business continuity of downtown districts, where tall buildings are typically clustered together. Following the 2011 earthquake, Christchurch’s Central Business District (CBD) red zone covered a significant area of the city and more than 60% of the businesses were displaced (CERC 2012). Until the introduction of Performance Based Seismic Design (PBSD) in the 1990s, buildings were designed using conventional building codes, which follow a prescriptive force-based approach based on the first mode translational response of the structure (FEMA 2006). Researchers and engineers have raised concerns that the prescriptive approach of building codes is not suitable for tall building design due to the significant contribution of higher mode effects (PEER 2010a). As a result of these shortcomings, several jurisdictions in areas of high seismicity throughout the Unites States (e.g. Los Angeles and San Francisco) have adopted a PBSD approach for the design of new tall buildings. While new designs follow a more adequate approach, little is known about the seismic performance of older existing tall buildings that were designed prior to the adoption of PBSD (Almufti et al. 2012). This paper presents an assessment of the seismic performance of existing tall buildings in a case study city, San Francisco, where an archetype tall building is designed based on an inventory of the existing tall building stock. Non-Linear Response History Analysis (NLRHA) are conducted with ground motions representative of the design earthquake hazard level defined in current building codes, with explicit consideration of near-fault directivity effects. In order to influence decision making, performance is reported as the expected consequences in terms of direct economic losses and downtime. Once the performance of the archetype building is assessed, a range of structural and nonstructural enhancements are explored for enhanced performance as well as mitigation measures for increased resilience. Expected direct economic losses for the archetype building are in the order of 34% of building cost and downtime estimates for functional recovery are 87 weeks. The strategies presented in this paper enable up to a 92% reduction in losses and minimize downtime for functional recovery to 1 day

Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development

Fetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy. The reason why specific embryonic tissues are sensitive toward ethanol is not understood. We found that in neural crest-derived cell (NCC) cultures from the first branchial arch of E10 mouse embryos, incubation with ethanol increases the number of apoptotic cells by fivefold. Apoptotic cells stain intensely for ceramide, suggesting that ceramide-induced apoptosis mediates ethanol damage to NCCs. Apoptosis is reduced by incubation with CDP-choline (citicoline), a precursor for the conversion of ceramide to sphingomyelin. Consistent with NCC cultures, ethanol intubation of pregnant mice results in ceramide elevation and increased apoptosis of NCCs in vivo. Ethanol also increases the protein level of prostate apoptosis response 4 (PAR-4), a sensitizer to ceramide-induced apoptosis. Prenatal ethanol exposure is concurrent with malformation of parietal bones in 20% of embryos at day E18. Meninges, a tissue complex derived from NCCs, is disrupted and generates reduced levels of TGF-β1, a growth factor critical for bone and brain development. Ethanol-induced apoptosis of NCCs leading to defects in the meninges may explain the simultaneous presence of cranial bone malformation and cognitive retardation in FAS. In addition, our data suggest that treatment with CDP-choline may alleviate the tissue damage caused by alcohol

A history of high-power laser research and development in the United Kingdom

The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders