465 research outputs found

    Weld analysis and control system

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    The invention is a Weld Analysis and Control System developed for active weld system control through real time weld data acquisition. Closed-loop control is based on analysis of weld system parameters and weld geometry. The system is adapted for use with automated welding apparatus having a weld controller which is capable of active electronic control of all aspects of a welding operation. Enhanced graphics and data displays are provided for post-weld analysis. The system provides parameter acquisition, including seam location which is acquired for active torch cross-seam positioning. Torch stand-off is also monitored for control. Weld bead and parent surface geometrical parameters are acquired as an indication of weld quality. These parameters include mismatch, peaking, undercut, underfill, crown height, weld width, puddle diameter, and other measurable information about the weld puddle regions, such as puddle symmetry, etc. These parameters provide a basis for active control as well as post-weld quality analysis and verification. Weld system parameters, such as voltage, current and wire feed rate, are also monitored and archived for correlation with quality parameters

    The \u3ci\u3eExxon Valdez\u3c/i\u3e Reopener: Natural Resources Damage Settlements and Roads Not Taken

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    The 1989 Exxon Valdez oil spill caused extensive natural resource damage to the Prince William Sound. Lawsuits addressing this natural resource damage resulted in a settlement that required Exxon to pay 900millionovertimetotrusteeschargedwithspendingthismoneytorestorethedamagedenvironmentoftheSoundandnearbyareas.ThesettlementincludedaReopenerClause,whichpledgesExxontospendanadditional900 million over time to trustees charged with spending this money to restore the damaged environment of the Sound and nearby areas. The settlement included a “Reopener Clause,” which pledges Exxon to spend an additional 100 million to fund restoration or rehabilitation of resources whose injuries were not foreseeable in 1989. This Article urges the State of Alaska and the United States to seek enforcement of the Reopener Clause, to restore natural resources and Native subsistence uses that were not addressed in the initial settlement and have not recovered from the Exxon Valdez oil spill. Alternatively, this Article urges Native entities to intervene in the case and seek enforcement of the Reopener Clause. To date, neither Alaska nor the federal government have requested any of the $100 million Exxon may be required to pay to compensate for additional damages resulting from the oil spill. We offer extended comment on this most famous of all natural resource damage cases. Special attention will be paid to legal roads not taken

    Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis

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    Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites <i>Trypanosoma brucei</i> (<i>T.b.</i>) <i>gambiense</i> or <i>T.b.rhodesiense</i> and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage <i>T.b.rhodesiense</i> infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-͎-cyclodextrin and melarsoprol randomly-methylated-β-cyclodextrin. We found that these compounds retain trypanocidal properties <i>in vitro</i> and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy

    Coarse-grained simulation of transmembrane peptides in the gel phase

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    We use Dissipative Particle Dynamics simulations, combined with parallel tempering and umbrella sampling, to investigate the potential of mean force between model transmembrane peptides in the various phases of a lipid bilayer, including the low-temperature gel phase. The observed oscillations in the effective interaction between peptides are consistent with the different structures of the surrounding lipid phases

    Nesiritide: Harmful or Harmless?

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90328/1/phco.26.10.1465.pd

    Genome resequencing reveals multiscale geographic structure and extensive linkage disequilibrium in the forest tree Populus trichocarpa

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    This is the publisher’s final pdf. The article is copyrighted by the New Phytologist Trust and published by John Wiley & Sons, Inc. It can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291469-8137. To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work.•Plant population genomics informs evolutionary biology, breeding, conservation and bioenergy feedstock development. For example, the detection of reliable phenotype–genotype associations and molecular signatures of selection requires a detailed knowledge about genome-wide patterns of allele frequency variation, linkage disequilibrium and recombination.\ud •We resequenced 16 genomes of the model tree Populus trichocarpa and genotyped 120 trees from 10 subpopulations using 29 213 single-nucleotide polymorphisms.\ud •Significant geographic differentiation was present at multiple spatial scales, and range-wide latitudinal allele frequency gradients were strikingly common across the genome. The decay of linkage disequilibrium with physical distance was slower than expected from previous studies in Populus, with r² dropping below 0.2 within 3–6 kb. Consistent with this, estimates of recent effective population size from linkage disequilibrium (N[subscript e] ≈ 4000–6000) were remarkably low relative to the large census sizes of P. trichocarpa stands. Fine-scale rates of recombination varied widely across the genome, but were largely predictable on the basis of DNA sequence and methylation features.\ud •Our results suggest that genetic drift has played a significant role in the recent evolutionary history of P. trichocarpa. Most importantly, the extensive linkage disequilibrium detected suggests that genome-wide association studies and genomic selection in undomesticated populations may be more feasible in Populus than previously assumed

    Multigenerational Independent Colony for Extraterrestrial Habitation, Autonomy, and Behavior Health (MICEHAB): An Investigation of a Long Duration, Partial Gravity, Autonomous Rodent Colony

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    The path from Earth to Mars requires exploration missions to be increasingly Earth-independent as the foundation is laid for a sustained human presence in the following decades. NASA pioneering of Mars will expand the boundaries of human exploration, as a sustainable presence on the surface requires humans to successfully reproduce in a partial gravity environment independent from Earth intervention. Before significant investment is made in capabilities leading to such pioneering efforts, the challenges of multigenerational mammalian reproduction in a partial gravity environment need be investigated. The Multi-generational Independent Colony for Extraterrestrial Habitation, Autonomy, and Behavior health is designed to study these challenges. The proposed concept is a conceptual, long duration, autonomous habitat designed to house rodents in a partial gravity environment with the goal of understanding the effects of partial gravity on mammalian reproduction over multiple generations and how to effectively design such a facility to operate autonomously while keeping the rodents healthy in order to achieve multiple generations. All systems are designed to feed forward directly to full-scale human missions to Mars. This paper presents the baseline design concept formulated after considering challenges in the mission and vehicle architectures such as: vehicle automation, automated crew health management/medical care, unique automated waste disposal and hygiene, handling of deceased crew members, reliable long-duration crew support systems, and radiation protection. This concept was selected from an architectural trade space considering the balance between mission science return and robotic and autonomy capabilities. The baseline design is described in detail including: transportation and facility operation constraints, artificial gravity system design, habitat design, and a full-scale mock-up demonstration of autonomous rodent care facilities. The proposed concept has the potential to integrate into existing mission architectures in order to achieve exploration objectives, and to demonstrate and mature common capabilities that enable a range of destinations and missions

    Genomic and transcriptomic variation defines the chromosome-scale assembly of Haemonchus contortus, a model gastrointestinal worm

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    International audienceHaemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Here, we report using PacBio long-read and OpGen and 10X Genomics long-molecule methods to generate a highly contiguous 283.4 Mbp chromosome-scale genome assembly including a resolved sex chromosome for the MHco3(ISE).N1 isolate. We show a remarkable pattern of conservation of chromosome content with Caenorhabditis elegans, but almost no conservation of gene order. Short and long-read transcriptome sequencing allowed us to define coordinated transcriptional regulation throughout the parasite’s life cycle and refine our understanding of cis- and trans-splicing. Finally, we provide a comprehensive picture of chromosome-wide genetic diversity both within a single isolate and globally. These data provide a high-quality comparison for understanding the evolution and genomics of Caenorhabditis and other nematodes and extend the experimental tractability of this model parasitic nematode in understanding helminth biology, drug discovery and vaccine development, as well as important adaptive traits such as drug resistance

    Limited-sampling strategies for anidulafungin in critically ill patients

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    Efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Determination of the anidulafungin AUC along with MIC values can therefore be useful. Since obtaining a full concentration-time curve to determine an AUC is not always feasible or appropriate, limited-sampling strategies may be useful in adequately estimating exposure. The objective of this study was to develop a model to predict the individual anidulafungin exposure in critically ill patients using limited-sampling strategies. Pharmacokinetic data were derived from 20 critically ill patients with invasive candidiasis treated with anidulafungin. These data were used to develop a two-compartment model in MW\Pharm using an iterative 2-stage Bayesian procedure. Limited- sampling strategies were subsequently investigated using two methods, a Bayesian analysis and a linear regression analysis. The best possible strategies for these two methods were evaluated by a Bland-Altman analysis for correlation of the predicted and observed AUC from 0 to 24 h (AUC(0-24)) values. Anidulafungin exposure can be adequately estimated with the concentration from a single sample drawn 12 h after the start of the infusion either by linear regression (R-2 = 0.99; bias, 0.05%; root mean square error [RMSE], 3%) or using a population pharmacokinetic model (R-2 = 0.89; bias, -0.1%; RMSE, 9%) in critically ill patients and also in less severely ill patients, as reflected by healthy volunteers. Limited sampling can be advantageous for future studies evaluating the pharmacokinetics and pharmacodynamics of anidulafungin and for therapeutic drug monitoring in selected patients
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