Simulated X-ray Cluster Temperature Maps

Temperature maps are presented of the 9 largest clusters in the mock catalogues of Muanwong et al. for both the Preheating and Radiative models. The maps show that clusters are not smooth, featureless systems, but contain a variety of substructure which should be observable. The surface brightness contours are generally elliptical and features that are seen include cold clumps, hot spiral features, and cold fronts. Profiles of emission-weighted temperature, surface brightness and emission-weighted pressure across the surface brightness discontinuities seen in one of the bimodal clusters are consistent with the cold front in Abell 2142 observed by Markevitch et al.Comment: Submitted to Monthly Notices Royal Astronomical Societ

The JCSG high-throughput structural biology pipeline

The Joint Center for Structural Genomics high-throughput structural biology pipeline has delivered more than 1000 structures to the community over the past ten years and has made a significant contribution to the overall goal of the NIH Protein Structure Initiative (PSI) of expanding structural coverage of the protein universe

Identification of Unknown Protein Function Using Metabolite Cocktail Screening

SummaryProteins of unknown function comprise a significant fraction of sequenced genomes. Defining the roles of these proteins is vital to understanding cellular processes. Here, we describe a method to determine a protein function based on the identification of its natural ligand(s) by the crystallographic screening of the binding of a metabolite library, followed by a focused search in the metabolic space. The method was applied to two protein families with unknown function, PF01256 and YjeF_N. The PF01256 proteins, represented by YxkO from Bacillus subtilis and the C-terminal domain of Tm0922 from Thermotoga maritima, were shown to catalyze ADP/ATP-dependent NAD(P)H-hydrate dehydratation, a previously described orphan activity. The YjeF_N proteins, represented by mouse apolipoprotein A-I binding protein and the N-terminal domain of Tm0922, were found to interact with an adenosine diphosphoribose-related substrate and likely serve as ADP-ribosyltransferases. Crystallographic screening of metabolites serves as an efficient tool in functional analyses of uncharacterized proteins

Hidden Markov models identify major movement modes in accelerometer and magnetometer data from four albatross species

Funding was provided by an NSF CAREER award to L. Thorne under award number 79804, and by a Minghua Zhang Early Career Faculty Innovation award to L Thorne.Background : Inertial measurement units (IMUs) with high-resolution sensors such as accelerometers are now used extensively to study fine-scale behavior in a wide range of marine and terrestrial animals. Robust and practical methods are required for the computationally-demanding analysis of the resulting large datasets, particularly for automating classification routines that construct behavioral time series and time-activity budgets. Magnetometers are used increasingly to study behavior, but it is not clear how these sensors contribute to the accuracy of behavioral classification methods. Development of effective classification methodology is key to understanding energetic and life-history implications of foraging and other behaviors.  Methods : We deployed accelerometers and magnetometers on four species of free-ranging albatrosses and evaluated the ability of unsupervised hidden Markov models (HMMs) to identify three major modalities in their behavior: ‘flapping flight’, ‘soaring flight’, and ‘on-water’. The relative contribution of each sensor to classification accuracy was measured by comparing HMM-inferred states with expert classifications identified from stereotypic patterns observed in sensor data.  Results : HMMs provided a flexible and easily interpretable means of classifying behavior from sensor data. Model accuracy was high overall (92%), but varied across behavioral states (87.6, 93.1 and 91.7% for ‘flapping flight’, ‘soaring flight’ and ‘on-water’, respectively). Models built on accelerometer data alone were as accurate as those that also included magnetometer data; however, the latter were useful for investigating slow and periodic behaviors such as dynamic soaring at a fine scale.  Conclusions : The use of IMUs in behavioral studies produces large data sets, necessitating the development of computationally-efficient methods to automate behavioral classification in order to synthesize and interpret underlying patterns. HMMs provide an accessible and robust framework for analyzing complex IMU datasets and comparing behavioral variation among taxa across habitats, time and space.Publisher PDFPeer reviewe

The Role of Tailored Public Health Messaging to Young Adults during COVID-19: “There’s a lot of ambiguity around what it means to be safe”

The COVID-19 global incidence rate among young adults (age 19–40) drastically increased since summer 2020, and young adults were often portrayed by popular media as the "main spreader" of the pandemic. However, young adults faced unique challenges during the pandemic due to working in high-risk, low-paying essential service occupations, as well as having higher levels of financial insecurity and mental burden. This qualitative study aims to examine the attitudes and perceptions of health orders of young adults to better inform public health messaging to reach this demographic and increase compliance to public health orders. A total of 50 young adults residing in British Columbia, Canada, were recruited to participate in focus group in groups of four to six. Focus group discussions were conducted via teleconferencing. Thematic analysis revealed four major themes: 1) risks of contracting the disease, 2) the perceived impact of COVID-19, 3) responsibility of institutions, 4) and effective public health messaging. Contrary to existing literature, our findings suggest young adults feel highly responsible for protecting themselves and others. They face a higher risk of depression and anxiety compared to other age groups, especially when they take on multiple social roles such as caregivers and parents. Our findings suggest young adults face confusion due to inconsistent messaging and are not reached due to the ineffectiveness of existing strategies. We recommend using evidence-based strategies proven to promote behaviour change to address the barriers identified by young adults through tailoring public health messages, specifically by using positive messaging, messaging that considers the context of the intended audiences, and utilizing digital platforms to facilitate two-way communication

Public Health and the Built Environment: Historical, Empirical, and Theoretical Foundations for an Expanded Role

In 2000, the Center for Disease Control and Prevention\u27s National Center for Environmental Health issued a report that explored some of the ways in which sprawl impacts public health. The report has generated great interest, and state health officials are beginning to discuss the relationship between land use and public health. The CDC report has also produced a backlash. For example, the Southern California Building Industry Association labeled the report a ludicrous sham and argued that the CDC should stick to fighting physical diseases, not defending political ones. In this environment, it is understandable if the CDC looks to such critiques as simply the latest partisan recruit to a political debate. But critics of the CDC\u27s efforts in this area may substantially overstate their case in the other direction. There is now and has long been a demonstrated connection between health, including physical disease, and the built environment. Moreover, government has intervened in the past in response to this connection and it continues to do so. While neither past practice nor current evidence make government intervention inevitable, this paper argues that such intervention is appropriate and supported by theory as well as history and empirical evidence

A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia

BACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/ kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks

A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions

Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition, and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ∼380 previously unreported PPIs. We validated a subset using surface plasmon resonance and cell binding assays. Observed PPIs reveal a large and complex network of interactions both within and across biological systems. We identified new PPIs for receptors with well-characterized ligands and binding partners for “orphan” receptors. New PPIs include proteins expressed on multiple cell types and involved in diverse processes including immune and nervous system development and function, differentiation/proliferation, metabolism, vascularization, and reproduction. These PPIs provide a resource for further biological investigation into their functional relevance and may offer new therapeutic drug targets