The LANL hemorrhagic fever virus database, a new platform for analyzing biothreat viruses

Hemorrhagic fever viruses (HFVs) are a diverse set of over 80 viral species, found in 10 different genera comprising five different families: arena-, bunya-, flavi-, filo- and togaviridae. All these viruses are highly variable and evolve rapidly, making them elusive targets for the immune system and for vaccine and drug design. About 55 000 HFV sequences exist in the public domain today. A central website that provides annotated sequences and analysis tools will be helpful to HFV researchers worldwide. The HFV sequence database collects and stores sequence data and provides a user-friendly search interface and a large number of sequence analysis tools, following the model of the highly regarded and widely used Los Alamos HIV database [Kuiken, C., B. Korber, and R.W. Shafer, HIV sequence databases. AIDS Rev, 2003. 5: p. 52–61]. The database uses an algorithm that aligns each sequence to a species-wide reference sequence. The NCBI RefSeq database [Sayers et al. (2011) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res., 39, D38–D51.] is used for this; if a reference sequence is not available, a Blast search finds the best candidate. Using this method, sequences in each genus can be retrieved pre-aligned. The HFV website can be accessed via http://hfv.lanl.gov

Trends and Costs of External Electrical Bone Stimulators and Grafting Materials in Anterior Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective review. PURPOSE: To identify the trends in stimulator use, pair those trends with various grafting materials, and determine the influence of stimulators on the risk of revision surgery. OVERVIEW OF LITERATURE: A large number of studies has reported beneficial effects of electromagnetic energy in healing long bone fractures. However, there are few clinical studies regarding the use of electrical stimulators in spinal fusion. METHODS: We used insurance billing codes to identify patients with lumbar disc degeneration who underwent anterior lumbar interbody fusion (ALIF). Comparisons between patients who did and did not receive electrical stimulators following surgery were performed using logistic regression analysis, chi-square test, and odds ratio (OR) analysis. RESULTS: Approximately 19% of the patients (495/2,613) received external stimulators following ALIF surgery. There was a slight increase in stimulator use from 2008 to 2014 (multi-level R2=0.08, single-level R2=0.05). Patients who underwent multi-level procedures were more likely to receive stimulators than patients who underwent single-level procedures (p0.05), except those in the multilevel ALIF+PLF cohort, wherein the patients who underwent stimulation had higher rates of revision surgery. CONCLUSIONS: Concurrent PLF or multi-level procedures increased patients\u27 likelihood of receiving stimulators, however, the presence of comorbidities did not. Patients who received BMA plus autograft or allograft were more likely to receive stimulation. Patients with and without bone stimulators had similar rates of revision surgery

Interactive Use of Cloud Services: Amazon SQS and S3

Abstract-Interactive use of cloud services is of keen interest to science end users, including for storing and accessing shared data sets. This paper evaluates the viability of interactively using two important cloud services offered by Amazon: SQS (Simple Queue Service) and S3 (Simple Storage Service). Specifically, we first measure the send-to-receive message latencies of SQS and then determine and devise rate controls to obtain suitable latencies and latency variations. Second, for S3, when transferring data into the cloud, we determine that increased parallelism in TransferManager can significantly improve upload performance, achieving up to 4 times improvements with careful elimination of upload bottlenecks

Long-term Hydro-economic Analysis Tool for Evaluating Global Groundwater Cost and Supply: Superwell v1.0

Groundwater plays a key role in meeting water demands, supplying over 40 % of irrigation water globally, with this role likely to grow as water demands and surface water variability increase. A better understanding of the future role of groundwater in meeting sectoral demands requires an integrated hydro-economic evaluation of its cost and availability. Yet substantial gaps remain in our knowledge and modeling capabilities related to groundwater availability, feasible locations for extraction, extractable volumes, and associated extraction costs, which are essential for large-scale analyses of integrated human-water systems scenarios, particularly at the global scale. To address these needs, we developed Superwell, a physics-based groundwater extraction and cost accounting model that operates at 0.5° (≈50x50 km) gridded spatial resolution with global coverage. The model produces location-specific groundwater supply-cost curves that provide the levelized cost to access different quantities of available groundwater. The inputs to Superwell include recent high-resolution hydrogeologic datasets of permeability, porosity, aquifer thickness, depth to water table, and hydrogeological complexity zones. It also accounts for well capital and maintenance costs, and the energy costs required to lift water to the surface. The model employs a Theis-based scheme coupled with an amortization-based cost accounting formulation to simulate groundwater extraction and quantify the cost of groundwater pumping. The result is a spatiotemporally flexible, physically-realistic, economics-based model that produces groundwater supply-cost curves. We show examples of these supply-cost curves and the insights that can be derived from them across a set of scenarios designed to explore model outcomes. The supply-cost curves produced by the model show that most nonrenewable groundwater in storage globally is extractable at costs lower than 0.23 USD/m3, while half of the volume remains extractable at under 0.138 USD/m3. We also demonstrate and discuss examples of how these cost curves could be used by linking Superwell’s outputs with other models to explore coupled human-environmental systems challenges, such as water resources planning and management, or broader analyses of multi-sectoral feedbacks

The Molecular Anatomy of Spontaneous Germline Mutations in Human Testes

The frequency of the most common sporadic Apert syndrome mutation (C755G) in the human fibroblast growth factor receptor 2 gene (FGFR2) is 100–1,000 times higher than expected from average nucleotide substitution rates based on evolutionary studies and the incidence of human genetic diseases. To determine if this increased frequency was due to the nucleotide site having the properties of a mutation hot spot, or some other explanation, we developed a new experimental approach. We examined the spatial distribution of the frequency of the C755G mutation in the germline by dividing four testes from two normal individuals each into several hundred pieces, and, using a highly sensitive PCR assay, we measured the mutation frequency of each piece. We discovered that each testis was characterized by rare foci with mutation frequencies 103 to >104 times higher than the rest of the testis regions. Using a model based on what is known about human germline development forced us to reject (p < 10−6) the idea that the C755G mutation arises more frequently because this nucleotide simply has a higher than average mutation rate (hot spot model). This is true regardless of whether mutation is dependent or independent of cell division. An alternate model was examined where positive selection acts on adult self-renewing Ap spermatogonial cells (SrAp) carrying this mutation such that, instead of only replacing themselves, they occasionally produce two SrAp cells. This model could not be rejected given our observed data. Unlike the disease site, similar analysis of C-to-G mutations at a control nucleotide site in one testis pair failed to find any foci with high mutation frequencies. The rejection of the hot spot model and lack of rejection of a selection model for the C755G mutation, along with other data, provides strong support for the proposal that positive selection in the testis can act to increase the frequency of premeiotic germ cells carrying a mutation deleterious to an offspring, thereby unfavorably altering the mutational load in humans. Studying the anatomical distribution of germline mutations can provide new insights into genetic disease and evolutionary change

An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Alcohol industry corporate social responsibility initiatives and harmful drinking : a systematic review

Background: There is growing awareness of the detrimental effects of alcohol industry commercial activities, and concern about possible adverse impacts of its corporate social responsibility (CSR) initiatives, on public health. The aims of this systematic review were to summarize and examine what is known about CSR initiatives undertaken by alcohol industry actors in respect of harmful drinking globally. Methods: We searched for peer-reviewed studies published since 1980 of alcohol industry CSR initiatives in seven electronic databases. The basic search strategy was organized around the three constructs of 'alcohol', 'industry' and 'corporate social responsibility'. We performed the searches on 21 July 2017. Data from included studies were analyzed inductively, according to the extent to which they addressed specified research objectives. Results: A total of 21 studies were included. We identified five types of CSR initiatives relevant to the reduction of harmful drinking: alcohol information and education provision; drink driving prevention; research involvement; policy involvement and the creation of social aspects organizations. Individual companies appear to undertake different CSR initiatives than do industry-funded social aspects organizations. There is no robust evidence that alcohol industry CSR initiatives reduce harmful drinking. There is good evidence, however, that CSR initiatives are used to influence the framing of the nature of alcohol-related issues in line with industry interests. Conclusions: This research literature is at an early stage of development. Alcohol policy measures to reduce harmful drinking are needed, and the alcohol industry CSR initiatives studied so far do not contribute to the attainment of this goal

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

Growth and cellular differentiation: a physical-biochemical conundrum? The example of the hand

Currently, the predominant hypothesis explains cellular differentiation as an essentially genetic intracellular process. The goal of this paper is to suggest that cell growth and differentiation may be, simply, the result of physical and chemical constraints.Bone growth occurs at the level of cartilage conjunction (growth plate) in a zone of lesser constrain. It appears that this growth also induces muscle, tendon, nerve and skin elongation. This cartilage growth by itself seems to explain the elongation of the hand. Growth stops at puberty likely because of feed-back from an increasing muscle load. The ossification (that is differentiation of cartilage into bone) appears to result from the shear stress induced. The study of bone age, obtained by X-ray picture of the hand, shows that ossification of epiphyses is very precise both in time and space. Computer modelization suggests that this ossification occurs where shear stress is greatest. The cartilage which does not ossify (joint, nose, larynx, ear, bronchus, etc.) is not exposed to high shear.Shear stress induces the secretion of extracellular matrix and a change of the biochemical environment of the cell. Precipitation of calcium phosphate, as in ossification, seems related to the alkalosis induced by shear stress.To speak in more general terms, loss of cellular differentiation, as occurs with cancer, can result from a change in the physical–chemical environments