Long-Period Building Response to Earthquakes in the San Francisco Bay Area

This article reports a study of modeled, long-period building responses to ground-motion simulations of earthquakes in the San Francisco Bay Area. The earthquakes include the 1989 magnitude 6.9 Loma Prieta earthquake, a magnitude 7.8 simulation of the 1906 San Francisco earthquake, and two hypothetical magnitude 7.8 northern San Andreas fault earthquakes with hypocenters north and south of San Francisco. We use the simulated ground motions to excite nonlinear models of 20-story, steel, welded moment-resisting frame (MRF) buildings. We consider MRF buildings designed with two different strengths and modeled with either ductile or brittle welds. Using peak interstory drift ratio (IDR) as a performance measure, the stiffer, higher strength building models outperform the equivalent more flexible, lower strength designs. The hypothetical magnitude 7.8 earthquake with hypocenter north of San Francisco produces the most severe ground motions. In this simulation, the responses of the more flexible, lower strength building model with brittle welds exceed an IDR of 2.5% (that is, threaten life safety) on 54% of the urban area, compared to 4.6% of the urban area for the stiffer, higher strength building with ductile welds. We also use the simulated ground motions to predict the maximum isolator displacement of base-isolated buildings with linear, single-degree-of-freedom (SDOF) models. For two existing 3-sec isolator systems near San Francisco, the design maximum displacement is 0.5 m, and our simulations predict isolator displacements for this type of system in excess of 0.5 m in many urban areas. This article demonstrates that a large, 1906-like earthquake could cause significant damage to long-period buildings in the San Francisco Bay Area

Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis

It is well known that angiogenesis is linked to fibrotic processes in fibroproliferative diseases, but insights into pathophysiological processes are limited, due to lack of understanding of molecular mechanisms controlling endothelial and fibroblastic homeostasis. We demonstrate here that the matrix receptor anthrax toxin receptor 1 (ANTXR1), also known as tumor endothelial marker 8 (TEM8), is an essential component of these mechanisms. Loss of TEM8 function in mice causes reduced synthesis of endothelial basement membrane components and hyperproliferative and leaky blood vessels in skin. In addition, endothelial cell alterations in mutants are almost identical to those of endothelial cells in infantile hemangioma lesions, including activated VEGF receptor signaling in endothelial cells, increased expression of the downstream targets VEGF and CXCL12, and increased numbers of macrophages and mast cells. In contrast, loss of TEM8 in fibroblasts leads to increased rates of synthesis of fiber-forming collagens, resulting in progressive fibrosis in skin and other organs. Compromised interactions between TEM8-deficient endothelial and fibroblastic cells cause dramatic reduction in the activity of the matrix-degrading enzyme MMP2. In addition to insights into mechanisms of connective tissue homeostasis, our data provide molecular explanations for vascular and connective tissue abnormalities in GAPO syndrome, caused by loss-of-function mutations in ANTXR1. Furthermore, the loss of MMP2 activity suggests that fibrotic skin abnormalities in GAPO syndrome are, in part, the consequence of pathophysiological mechanisms underlying syndromes (NAO, Torg and Winchester) with multicentric skin nodulosis and osteolysis caused by homozygous loss-of-function mutations in MMP2

Piano Recital - Studio of Dr. Mayumi Matzen

Piano recital at the studio of Dr. Mayumi Matzen.https://digitalcommons.usu.edu/music_programs/1069/thumbnail.jp

Prioritization of knowledge-needs to achieve best practices for bottom trawling in relation to seabed habitats

Management and technical approaches that achieve a sustainable level of fish production while at the same time minimizing or limiting the wider ecological effects caused through fishing gear contact with the seabed might be considered to be ‘best practice’. To identify future knowledge-needs that would help to support a transition towards the adoption of best practices for trawling, a prioritization exercise was undertaken with a group of 39 practitioners from the seafood industry and management, and 13 research scientists who have an active research interest in bottom-trawl and dredge fisheries. A list of 108 knowledge-needs related to trawl and dredge fisheries was developed in conjunction with an ‘expert task force’. The long list was further refined through a three stage process of voting and scoring, including discussions of each knowledge-need. The top 25 knowledge-needs are presented, as scored separately by practitioners and scientists. There was considerable consistency in the priorities identified by these two groups. The top priority knowledge-need to improve current understanding on the distribution and extent of different habitat types also reinforced the concomitant need for the provision and access to data on the spatial and temporal distribution of all forms of towed bottom-fishing activities. Many of the other top 25 knowledge-needs concerned the evaluation of different management approaches or implementation of different fishing practices, particularly those that explore trade-offs between effects of bottom trawling on biodiversity and ecosystem services and the benefits of fish production as food.Fil: Kaiser, Michel J.. Bangor University; Reino UnidoFil: Hilborn, Ray. University of Washington; Estados UnidosFil: Jennings, Simon. Fisheries and Aquaculture Science; Reino UnidoFil: Amaroso, Ricky. University of Washington; Estados UnidosFil: Andersen, Michael. Danish Fishermen; DinamarcaFil: Balliet, Kris. Sustainable Fisheries Partnership; Estados UnidosFil: Barratt, Eric. Sanford Limited; Nueva ZelandaFil: Bergstad, Odd A. Institute of Marine Research; NoruegaFil: Bishop, Stephen. Independent Fisheries Ltd; Nueva ZelandaFil: Bostrom, Jodi L. Marine Stewardship Council; Reino UnidoFil: Boyd, Catherine. Clearwater Seafoods; CanadáFil: Bruce, Eduardo A. Friosur S.A.; ChileFil: Burden, Merrick. Marine Conservation Alliance; Estados UnidosFil: Carey, Chris. Independent Fisheries Ltd.; Estados UnidosFil: Clermont, Jason. New England Aquarium; Estados UnidosFil: Collie, Jeremy S. University of Rhode Island,; Estados UnidosFil: Delahunty, Antony. National Federation of Fishermen; Reino UnidoFil: Dixon, Jacqui. Pacific Andes International Holdings Limited; ChinaFil: Eayrs, Steve. Gulf of Maine Research Institute; Estados UnidosFil: Edwards, Nigel. Seachill Ltd.; Reino UnidoFil: Fujita, Rod. Environmental Defense Fund; Reino UnidoFil: Gauvin, John. Alaska Seafood Cooperative; Estados UnidosFil: Gleason, Mary. The Nature Conservancy; Estados UnidosFil: Harris, Brad. Alaska Pacific University; Estados UnidosFil: He, Pingguo. University of Massachusetts Dartmouth; Estados UnidosFil: Hiddink, Jan G. Bangor University; Reino UnidoFil: Hughes, Kathryn M. Bangor University; Reino UnidoFil: Inostroza, Mario. EMDEPES; ChileFil: Kenny, Andrew. Fisheries and Aquaculture Science; Reino UnidoFil: Kritzer, Jake. Environmental Defense Fund; Estados UnidosFil: Kuntzsch, Volker. Sanford Limited; Estados UnidosFil: Lasta, Mario. Diag. Montegrande N° 7078. Mar del Plata; ArgentinaFil: Lopez, Ivan. Confederacion Española de Pesca; EspañaFil: Loveridge, Craig. South Pacific Regional Fisheries Management Organisation; Nueva ZelandaFil: Lynch, Don. Gorton; Estados UnidosFil: Masters, Jim. Marine Conservation Society; Reino UnidoFil: Mazor, Tessa. CSIRO Marine and Atmospheric Research; AustraliaFil: McConnaughey, Robert A. US National Marine Fisheries Service; Estados UnidosFil: Moenne, Marcel. Pacificblu; ChileFil: Francis. Marine Scotland Science; Reino UnidoFil: Nimick, Aileen M. Alaska Pacific University; Estados UnidosFil: Olsen, Alex. A. Espersen; DinamarcaFil: Parker, David. Young; Reino UnidoFil: Parma, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Penney, Christine. Clearwater Seafoods; CanadáFil: Pierce, David. Massachusetts Division of Marine Fisheries; Estados UnidosFil: Pitcher, Roland. CSIRO Marine and Atmospheric Research; AustraliaFil: Pol, Michael. Massachusetts Division of Marine Fisheries; Estados UnidosFil: Richardson, Ed. Pollock Conservation Cooperative; Estados UnidosFil: Rijnsdorp, Adriaan D. Wageningen IMARES; Países BajosFil: Rilatt, Simon. A. Espersen; DinamarcaFil: Rodmell, Dale P. National Federation of Fishermen's Organisations; Reino UnidoFil: Rose, Craig. FishNext Research; Estados UnidosFil: Sethi, Suresh A. Alaska Pacific University; Estados UnidosFil: Short, Katherine. F.L.O.W. Collaborative; Nueva ZelandaFil: Suuronen, Petri. Fisheries and Aquaculture Department; ItaliaFil: Taylor, Erin. New England Aquarium; Estados UnidosFil: Wallace, Scott. The David Suzuki Foundation; CanadáFil: Webb, Lisa. Gorton's Inc.; Estados UnidosFil: Wickham, Eric. Unit four –1957 McNicoll Avenue; CanadáFil: Wilding, Sam R. Monterey Bay Aquarium; Estados UnidosFil: Wilson, Ashley. Department for Environment; Reino UnidoFil: Winger, Paul. Memorial University Of Newfoundland; CanadáFil: Sutherland, William J. University of Cambridge; Reino Unid

An Evolutionarily Conserved Enhancer Regulates Bmp4 Expression in Developing Incisor and Limb Bud

To elucidate the transcriptional regulation of Bmp4 expression during organogenesis, we used phylogenetic footprinting and transgenic reporter analyses to identify Bmp4 cis-regulatory modules (CRMs). These analyses identified a regulatory region located ∼46 kb upstream of the mouse Bmp4 transcription start site that had previously been shown to direct expression in lateral plate mesoderm. We refined this regulatory region to a 396-bp minimal enhancer, and show that it recapitulates features of endogenous Bmp4 expression in developing mandibular arch ectoderm and incisor epithelium during the initiation-stage of tooth development. In addition, this enhancer directs expression in the apical ectodermal ridge (AER) of the developing limb and in anterior and posterior limb mesenchyme. Transcript profiling of E11.5 mouse incisor dental lamina, together with protein binding microarray (PBM) analyses, allowed identification of a conserved DNA binding motif in the Bmp4 enhancer for Pitx homeoproteins, which are also expressed in the developing mandibular and incisor epithelium. In vitro electrophoretic mobility shift assays (EMSA) and in vivo transgenic reporter mutational analyses revealed that this site supports Pitx binding and that the site is necessary to recapitulate aspects of endogenous Bmp4 expression in developing craniofacial and limb tissues. Finally, Pitx2 chromatin immunoprecipitation (ChIP) demonstrated direct binding of Pitx2 to this Bmp4 enhancer site in a dental epithelial cell line. These results establish a direct molecular regulatory link between Pitx family members and Bmp4 gene expression in developing incisor epithelium

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc