142 research outputs found

    Maintaining Information Dominance in Complex Environments

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    There are many risks to the U.S. Army’s command and control (C2) operations and to its intelligence and information warfare (IW) capabilities. The challenges include: significant uncertainty; sudden unexpected events; high noise and clutter levels in intelligence pictures; basic and complex deceptions exercised through a variety of channels; the actions of hidden malign actors; and novel forms of attack on U.S. and allied command, control, communications, computers, information/intelligence, surveillance, targeting acquisition, and reconnaissance (C4ISTAR) systems. If the U.S. Army is to secure and maintain information dominance in all environments, it must exploit complexity and uncertainty in the battlespace and not simply seek to overcome it. Innovation requires that new ideas are considered, and that old ideas should be robustly challenged. To achieve and maintain information dominance, the U.S. Army will also require a significant injection of innovation, a robust and resilient C2 and intelligence capability, novel technologies and an accelerated information operations capability development program that is broad, deep, sustained and well-coordinated. Furthermore, once information dominance is achieved, maintaining it will demand continuous change and development.https://press.armywarcollege.edu/monographs/1390/thumbnail.jp

    Pharmacotherapy for Chronic Insomnia: A Brief Survey of PCP Attitudes and Preferences

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    Purpose: To examine primary care professionals (PCP) attitudes and prescribing preferences toward hypnotic medications to treat chronic insomnia. Methods: An online survey was sent to members of the Dartmouth CO-OP, a practice-based primary care research network in Maine, Vermont, and New Hampshire. The survey begins with a case vignette of a 64-year old woman suffering from chronic insomnia. Clinicians were then presented with eight questions about management of the patient and their attitudes toward prescribing medications, focusing on benzodiazepines/benzodiazepine receptor agonists (BDZ/BZRAs). Results: 103 of 198 clinicians (52%) responded. Regarding choice of medication for the case vignette, 80% of respondents preferred the off-label use of hypnotics such as trazodone or melatonin; 11% stated they would choose BDZs and 21% would choose BZRAs. Strong majorities expressed that negative consequences would occur with use of BDZ/BZRAs, including tolerance (77%), dependence (68%), other side effects (53%), and addiction (51%). PCP preference for off- label prescribing was correlated to levels of concern about harms (addiction, dependence, tolerance, side effects) of BDZ/BZRAs as measured on a global medication risk score in this survey. In addition, 14% of respondents felt that pharmacotherapy was not an appropriate therapeutic option for chronic insomnia in the case vignette. Conclusion: Most of the clinicians surveyed acknowledged a legitimate role for hypnotic medications in chronic insomnia but expressed reservations toward BDZ/BZRAs despite their FDA approval and proven efficacy. There appears to be a gap between published guidelines for selection of sedative-hypnotic medications and PCP preferences

    Estimation of State-of-Charge and Capacity of Used Lithium-Ion Cells

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    We describe an approach to estimate state-of-charge and faded capacity of cobalt-based lithium-ion cell based on timedomain analysis of a short-term transient. This approach requires a relatively short-duration test and is suitable for repurposing cells for less demanding applications. The successful estimation requires previous characterization of the cells for the given family because lithium ion chemistries differ significantly. Two algorithms were considered for estimation of unknown state-of-charge and capacity: Bayesian inference and boosted regression trees. The achieved accuracy was 95 % of capacity estimations; estimations were within 2 % of the nominal cell capacity from the true value

    Cell bank characterization and fermentation optimization for production of recombinant heavy chain C-terminal fragment of botulinum neurotoxin serotype E (rBoNTE(H\u3csub\u3ec\u3c/sub\u3e): Antigen E) by \u3ci\u3ePichia pastoris\u3c/i\u3e

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    A process was developed for production of a candidate vaccine antigen, recombinant C-terminal heavy chain fragment of the botulinum neurotoxin serotype E, rBoNTE(Hc)in Pichia pastoris. P. pastoris strain GS115 was transformed with the rBoNTE(Hc) gene inserted into pHILD4 Escherichia coli—P. pastoris shuttle plasmid. The clone was characterized for genetic stability, copy number, and BoNTE(Hc) sequence. Expression of rBoNTE(Hc) from the Mut+ HIS4 clone was confirmed in the shake-flask, prior to developing a fed-batch fermentation process at 5 and 19 L scale. The fermentation process consists of a glycerol growth phase in batch and fed-batch mode using a defined medium followed by a glycerol/methanol transition phase for adaptation to growth on methanol and a methanol induction phase resulting in the production of rBoNTE(Hc). Specific growth rate, ratio of growth to induction phase, and time of induction were critical for optimal rBoNTE(Hc) production and minimal proteolytic degradation. A computer-controlled exponential growth model was used for process automation and off-gas analysis was used for process monitoring. The optimized process had an induction time of 9 h on methanol and produced up to 3 mg of rBoNTE(Hc) per gram wet cell mass as determined by HPLC and Western blot analysis

    The properties of the 2175AA extinction feature discovered in GRB afterglows

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    The unequivocal, spectroscopic detection of the 2175 bump in extinction curves outside the Local Group is rare. To date, the properties of the bump have been examined in only two GRB afterglows (GRB 070802 and GRB 080607). In this work we analyse in detail the detections of the 2175 extinction bump in the optical spectra of the two further GRB afterglows: GRB 080605 and 080805. We gather all available optical/NIR photometric, spectroscopic and X-ray data to construct multi-epoch SEDs for both GRB afterglows. We fit the SEDs with the Fitzpatrick & Massa (1990) model with a single or broken PL. We also fit a sample of 38 GRB afterglows, known to prefer a SMC-type extinction curve, with the same model. We find that the SEDs of GRB 080605 and GRB 080805 at two epochs are fit well with a single PL with a derived extinction of A_V = 0.52(+0.13 -0.16) and 0.50 (+0.13 -0.10), and 2.1(+0.7-0.6) and 1.5+/-0.2 respectively. While the slope of the extinction curve of GRB 080805 is not well-constrained, the extinction curve of GRB 080605 has an unusual very steep far-UV rise together with the 2175 bump. Such an extinction curve has previously been found in only a small handful of sightlines in the MW. One possible explanation of such an extinction curve may be dust arising from two different regions with two separate grain populations, however we cannot distinguish the origin of the curve. We finally compare the four 2175 bump sightlines to the larger GRB afterglow sample and to Local Group sightlines. We find that while the width and central positions of the bumps are consistent with what is observed in the Local Group, the relative strength of the detected bump (A_bump) for GRB afterglows is weaker for a given A_V than for almost any Local Group sightline. Such dilution of the bump strength may offer tentative support to a dual dust-population scenario.Comment: 9 pages, 8 figures, 3 tables, accepted to Ap

    Cell bank characterization and fermentation optimization for production of recombinant heavy chain C-terminal fragment of botulinum neurotoxin serotype E (rBoNTE(H\u3csub\u3ec\u3c/sub\u3e): Antigen E) by \u3ci\u3ePichia pastoris\u3c/i\u3e

    Get PDF
    A process was developed for production of a candidate vaccine antigen, recombinant C-terminal heavy chain fragment of the botulinum neurotoxin serotype E, rBoNTE(Hc)in Pichia pastoris. P. pastoris strain GS115 was transformed with the rBoNTE(Hc) gene inserted into pHILD4 Escherichia coli—P. pastoris shuttle plasmid. The clone was characterized for genetic stability, copy number, and BoNTE(Hc) sequence. Expression of rBoNTE(Hc) from the Mut+ HIS4 clone was confirmed in the shake-flask, prior to developing a fed-batch fermentation process at 5 and 19 L scale. The fermentation process consists of a glycerol growth phase in batch and fed-batch mode using a defined medium followed by a glycerol/methanol transition phase for adaptation to growth on methanol and a methanol induction phase resulting in the production of rBoNTE(Hc). Specific growth rate, ratio of growth to induction phase, and time of induction were critical for optimal rBoNTE(Hc) production and minimal proteolytic degradation. A computer-controlled exponential growth model was used for process automation and off-gas analysis was used for process monitoring. The optimized process had an induction time of 9 h on methanol and produced up to 3 mg of rBoNTE(Hc) per gram wet cell mass as determined by HPLC and Western blot analysis

    Effects of Acute Tryptophan Depletion on Brain Serotonin Function and Concentrations of Dopamine and Norepinephrine in C57BL/6J and BALB/cJ Mice

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    Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT). Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. Moreover, side effects such as vomiting and nausea after intake of amino acids (AA) still limit its use. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols. It has been used in preliminary clinical studies but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. We tested ATD Moja-De (TRP−) in two strains of mice: C57BL/6J, and BALB/cJ, which are reported to have impaired 5-HT synthesis and a more anxious phenotype relative to other strains of mice. ATD Moja-De lowered brain TRP, significantly decreased 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5-HIAA in both strains of mice, however more so in C57BL/6J than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A balanced (TRP+) control mixture did not raise 5-HT or 5-HIAA. The present findings suggest that ATD Moja-De effectively and specifically suppresses central serotonergic function. These results also demonstrate a strain- specific effect of ATD Moja-De on anxiety-like behavior

    LSST Science Book, Version 2.0

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    A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo
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