Liquid Hydrogen Target Experience at SLAC

Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small "beer can" targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin-wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability.This paper surveys the evolution of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible

Pasteurella multocida Heddleston serovar 3 and 4 strains share a common lipopolysaccharide biosynthesis locus but display both inter- and intrastrain lipopolysaccharide heterogeneity

Pasteurella multocida is a Gram-negative multispecies pathogen and the causative agent of fowl cholera, a serious disease of poultry which can present in both acute and chronic forms. The major outer membrane component lipopolysaccharide (LPS) is both an important virulence factor and a major immunogen. Our previous studies determined the LPS structures expressed by different P. multocida strains and revealed that a number of strains belonging to different serovars contain the same LPS biosynthesis locus but express different LPS structures due to mutations within glycosyltransferase genes. In this study, we report the full LPS structure of the serovar 4 type strain, P1662, and reveal that it shares the same LPS outer core biosynthesis locus, L3, with the serovar 3 strains P1059 and Pm70. Using directed mutagenesis, the role of each glycosyltransferase gene in LPS outer core assembly was determined. LPS structural analysis of 23 Australian field isolates that contain the L3 locus revealed that at least six different LPS outer core structures can be produced as a result of mutations within the LPS glycosyltransferase genes. Moreover, some field isolates produce multiple but related LPS glycoforms simultaneously, and three LPS outer core structures are remarkably similar to the globo series of vertebrate glycosphingolipids. Our in-depth analysis showing the genetics and full range of P. multocida lipopolysaccharide structures will facilitate the improvement of typing systems and the prediction of the protective efficacy of vaccines

Precambrian Plate Tectonics in Northern Hudson Bay: Evidence From P and S Wave Seismic Tomography and Analysis of Source Side Effects in Relative Arrival-Time Data Sets

The geology of northern Hudson Bay, Canada, documents more than 2 billion years of history including the assembly of Precambrian and Archean terranes during several Paleoproterozoic orogenies, culminating in the Trans‐Hudson Orogen (THO) ∼1.8 Ga. The THO has been hypothesized to be similar in scale and nature to the ongoing Himalaya‐Karakoram‐Tibetan orogen, but the nature of lithospheric terrane boundaries, including potential plate‐scale underthrusting, is poorly understood. To address this problem, we present new P and S wave tomographic models of the mantle seismic structure using data from recent seismograph networks stretching from northern Ontario to Nunavut (60–100∘W and 50–80∘N). The large size of our network requires careful mitigation of the influence of source side structure that contaminates our relative arrival time residuals. Our tomographic models reveal a complicated internal structure in the Archean Churchill plate. However, no seismic wave speed distinction is observed across the Snowbird Tectonic Zone, which bisects the Churchill. The mantle lithosphere in the central region of Hudson Bay is distinct from the THO, indicating potential boundaries of microcontinents and lithospheric blocks between the principal colliders. Slow wave speeds underlie southern Baffin Island, the leading edge of the generally high wave speed Churchill plate. This is interpreted to be Paleoproterozoic material underthrust beneath Baffin Island in a modern‐style subduction zone setting

Salmonella Enteritidis Infections, United States, 1985–1999

Salmonella enterica serotype Enteritidis emerged as an important illness during the 1980s. Investigations showed that consumption of undercooked eggs was the major risk factor for disease, and a variety of prevention and control efforts were initiated during the 1990s. We describe sporadic infections and outbreaks of S. Enteritidis in the United States from 1985 through 1999 and discuss prevention and control efforts. After reaching a high of 3.9 per 100,000 population in 1995, S. Enteritidis infections declined to 1.98 per 100,000 in 1999. While the total number of outbreaks decreased by half, those in the western states tripled. Outbreaks of S. Enteritidis phage type 4 infections accounted for 49% of outbreaks in 1999. Outbreak-associated deaths in health facilities decreased from 14 in 1987 to 0 in 1999. Overall, rates of sporadic S. Enteritidis infection, outbreaks, and deaths have declined dramatically. For further reductions, control measures should continue to be applied along the entire farm-to-table continuum

Summer thermal structure and anticyclonic circulation of Lake Erie

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95057/1/grl29007.pd

Synergistic Apoptosis Induction in Leukemic Cells by the Phosphatase Inhibitor Salubrinal and Proteasome Inhibitors

Cells adapt to endoplasmic reticulum (ER)-stress by arresting global protein synthesis while simultaneously activating specific transcription factors and their downstream targets. These processes are mediated in part by the phosphorylation-dependent inactivation of the translation initiation factor eIF2alpha. Following restoration of homeostasis protein synthesis is resumed when the serine/threonine-protein phosphatase PP1 dephosphorylates and reactivates eIF2alpha. Proteasome inhibitors, used to treat multiple myeloma patients evoke ER-stress and apoptosis by blocking the ER-associated degradation of misfolded proteins (ERAD), however, the role of eIF2alpha phosphorylation in leukemic cells under conditions of proteasome inhibitor-mediated ER stress is currently unclear.Bcr-Abl-positive and negative leukemic cell lines were used to investigate the functional implications of PP1-related phosphatase activities on eIF2alpha phosphorylation in proteasome inhibitor-mediated ER stress and apoptosis. Rather unexpectedly, salubrinal, a recently identified PP1 inhibitor capable to protect against ER stress in various model systems, strongly synergized with proteasome inhibitors to augment apoptotic death of different leukemic cell lines. Salubrinal treatment did not affect the phosphorlyation status of eIF2alpha. Furthermore, the proapoptotic effect of salubrinal occurred independently from the chemical nature of the proteasome inhibitor, was recapitulated by a second unrelated phosphatase inhibitor and was unaffected by overexpression of a dominant negative eIF2alpha S51A variant that can not be phosphorylated. Salubrinal further aggravated ER-stress and proteotoxicity inflicted by the proteasome inhibitors on the leukemic cells since characteristic ER stress responses, such as ATF4 and CHOP synthesis, XBP1 splicing, activation of MAP kinases and eventually apoptosis were efficiently abrogated by the translational inhibitor cycloheximide.Although PP1 activity does not play a major role in regulating the ER stress response in leukemic cells, phosphatase signaling nevertheless significantly limits proteasome inhibitor-mediated ER-stress and apoptosis. Inclusion of specific phosphatase inhibitors might therefore represent an option to improve current proteasome inhibitor-based treatment modalities for hematological cancers

Public health interventions for Aedes control in the time of Zikavirus- A metareview on effectiveness of vector control strategies

Background: There is renewed interest in effective control measures to control Zika and dengue vectors. A synthesis of published systematic reviews with a focus on grading of intervention evidence is warranted to determine the reliability of evidence for control strategies. Methodology: We conducted a meta-review (a systematic review of systematic reviews) assessing the effectiveness of any Aedes control measure. We searched Scopus and Medline for relevant reviews through to 11 May 2016. Titles, abstracts and full texts were assessed independently for inclusion by two authors. Data extraction was performed independently in duplicate using a standardised form and validity of the evidence in each review was assessed using GRADE criteria. Findings: 13 eligible systematic reviews that investigated the effect of community interventions on entomological parameters (such as vector density) or disease incidence were included. Quality of evidence was mostly low to very low due to poor reporting of study design, observational methodologies, heterogeneity, and indirect outcomes, hindering an evidence-based recommendation. Biological controls seem to achieve better reduction of entomological indices than chemical controls, while educational campaigns can reduce breeding habitats and interrupt disease transmission cycle. Integrated control strategies may not add efficiency to educational campaigns. Conclusions: Despite decades of Aedes mosquito abatement programmes, mosquito populations are widely established and abundant, and associated with a significant disease burden. The efficiency of any control programme is dependent on local settings and resources. More good quality primary studies for the control of Aedes transmitted diseases are still required

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Rapid Environmental Change over the Past Decade Revealed by Isotopic Analysis of the California Mussel in the Northeast Pacific

The anthropogenic input of fossil fuel carbon into the atmosphere results in increased carbon dioxide (CO2) into the oceans, a process that lowers seawater pH, decreases alkalinity and can inhibit the production of shell material. Corrosive water has recently been documented in the northeast Pacific, along with a rapid decline in seawater pH over the past decade. A lack of instrumentation prior to the 1990s means that we have no indication whether these carbon cycle changes have precedence or are a response to recent anthropogenic CO2 inputs. We analyzed stable carbon and oxygen isotopes (δ13C, δ18O) of decade-old California mussel shells (Mytilus californianus) in the context of an instrumental seawater record of the same length. We further compared modern shells to shells from 1000 to 1340 years BP and from the 1960s to the present and show declines in the δ13C of modern shells that have no historical precedent. Our finding of decline in another shelled mollusk (limpet) and our extensive environmental data show that these δ13C declines are unexplained by changes to the coastal food web, upwelling regime, or local circulation. Our observed decline in shell δ13C parallels other signs of rapid changes to the nearshore carbon cycle in the Pacific, including a decline in pH that is an order of magnitude greater than predicted by an equilibrium response to rising atmospheric CO2, the presence of low pH water throughout the region, and a record of a similarly steep decline in δ13C in algae in the Gulf of Alaska. These unprecedented changes and the lack of a clear causal variable underscores the need for better quantifying carbon dynamics in nearshore environments

Triad pattern algorithm for predicting strong promoter candidates in bacterial genomes

Abstract Background Bacterial promoters, which increase the efficiency of gene expression, differ from other promoters by several characteristics. This difference, not yet widely exploited in bioinformatics, looks promising for the development of relevant computational tools to search for strong promoters in bacterial genomes. Results We describe a new triad pattern algorithm that predicts strong promoter candidates in annotated bacterial genomes by matching specific patterns for the group I σ70 factors of Escherichia coli RNA polymerase. It detects promoter-specific motifs by consecutively matching three patterns, consisting of an UP-element, required for interaction with the α subunit, and then optimally-separated patterns of -35 and -10 boxes, required for interaction with the σ70 subunit of RNA polymerase. Analysis of 43 bacterial genomes revealed that the frequency of candidate sequences depends on the A+T content of the DNA under examination. The accuracy of in silico prediction was experimentally validated for the genome of a hyperthermophilic bacterium, Thermotoga maritima, by applying a cell-free expression assay using the predicted strong promoters. In this organism, the strong promoters govern genes for translation, energy metabolism, transport, cell movement, and other as-yet unidentified functions. Conclusion The triad pattern algorithm developed for predicting strong bacterial promoters is well suited for analyzing bacterial genomes with an A+T content of less than 62%. This computational tool opens new prospects for investigating global gene expression, and individual strong promoters in bacteria of medical and/or economic significance.</p