1,832 research outputs found

    Matrix Degradation in Human Immunodeficiency Virus Type 1-Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study.

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    Background: Extensive immunopathology occurs in human immunodeficiency virus (HIV)/tuberculosis (TB) coinfection, but the underlying molecular mechanisms are not well-defined. Excessive matrix metalloproteinase (MMP) activity is emerging as a key process but has not been systematically studied in HIV-associated TB. Methods: We performed a cross-sectional study of matrix turnover in HIV type 1 (HIV-1)-infected and -uninfected TB patients and controls, and a prospective cohort study of HIV-1-infected TB patients at risk of TB immune reconstitution inflammatory syndrome (TB-IRIS), in Cape Town, South Africa. Sputum and plasma MMP concentrations were quantified by Luminex, plasma procollagen III N-terminal propeptide (PIIINP) by enzyme-linked immunosorbent assay, and urinary lipoarabinomannan (LAM) by Alere Determine TB LAM assay. Peripheral blood mononuclear cells from healthy donors were cultured with Mycobacterium tuberculosis and extracellular matrix in a 3D model of TB granuloma formation. Results: MMP activity differed between HIV-1-infected and -uninfected TB patients and corresponded with specific TB clinical phenotypes. HIV-1-infected TB patients had reduced pulmonary MMP concentrations, associated with reduced cavitation, but increased plasma PIIINP, compared to HIV-1-uninfected TB patients. Elevated extrapulmonary extracellular matrix turnover was associated with TB-IRIS, both before and during TB-IRIS onset. The predominant collagenase was MMP-8, which was likely neutrophil derived and M. tuberculosis-antigen driven. Mycobacterium tuberculosis-induced matrix degradation was suppressed by the MMP inhibitor doxycycline in vitro. Conclusions: MMP activity in TB differs by HIV-1 status and compartment, and releases matrix degradation products. Matrix turnover in HIV-1-infected patients is increased before and during TB-IRIS, informing novel diagnostic strategies. MMP inhibition is a potential host-directed therapy strategy for prevention and treatment of TB-IRIS

    Textural variations in Neogene pelagic carbonate ooze at DSDP Site 593, southern Tasman Sea, and their paleoceanographic implications

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    Changes in Neogene sediment texture in pelagic carbonate-rich oozes on the Challenger Plateau, southern Tasman Sea, are used to infer changes in depositional paleocurrent velocities. The most obvious record of textural change is in the mud:sand ratio. Increases in the sand content are inferred to indicate a general up-core trend towards increasing winnowing of sediments resulting from increasing flow velocity of Southern Component Intermediate Water (SCIW), the forerunner of Antarctic Intermediate Water. In particular, the intervals c. 19-14.5 Ma, c. 9.5-8 Ma, and after 5 Ma are suggested to be times of increased SCIW velocity and strong sediment winnowing. Within the mud fraction, the fine silt to coarse clay sizes from 15.6 to 2 µm make the greatest contribution to the sediments and are composed of nannofossil plates. During extreme winnowing events it is the fine silt to very coarse clay material (13-3 µm) within this range that is preferentially removed, suggesting the 10 µm cohesive silt boundary reported for siliciclastic sediments does not apply to calcitic skeletal grains. The winnowed sediment comprises coccolithophore placoliths and spheres, represented by a mode at 4-7 µm. Further support for seafloor winnowing is gained from the presence in Hole 593 of a condensed sedimentary section from c. 18 to 14 Ma where the sand content increases to c. 20% of the bulk sample. Associated with the condensed section is a 6 m thick orange unit representing sediments subjected to particularly oxygen-rich, late early to early middle Miocene SCIW. Together these are inferred to indicate increased SCIW velocity resulting in winnowed sediment associated with faster arrival of oxygen-rich surface water subducted to form SCIW. Glacial development of Antarctica has been recorded from many deep-sea sites, with extreme glacials providing the mechanism to increase watermass flow. Miocene glacial zones Mi1b-Mi6 are identified in an associated oxygen isotope record from Hole 593, and correspond with times of particularly invigorated paleocirculation, bottom winnowing, and sediment textural changes

    Sustainability performance measurement : a preliminary classification framework of models and indicators

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    In this position paper we focus on the diversity of sustainability measurements. Based on existing research on performance measurement, we propose a preliminary classification framework summarizing sustainability models and indicators. By describing illustrative examples, we claim that several models and indicators can be distinguished with their own peculiarities. Having such a framework is interesting for both academia and business to structure the range of models and indicators and to ultimately select the appropriate sustainability measurement approach. The proposed framework should be validated by further research

    EMIC Waves in the Earth\u27s Inner Magnetosphere as a Function of Solar Wind Structures During Solar Maximum

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    Here we analyze the statistics of electromagnetic ion cyclotron (EMIC) waves observed in the Earth\u27s inner magnetosphere during coronal mass ejection (CME), high-speed stream (HSS), and quiet solar wind (QSW) conditions in the upstream solar wind (SW). For our analysis we use the EMIC wave observations by the two Van Allen Probes during their first magnetic local time (MLT) revolution. The major results of our analysis are as follows: (1) Criteria to identify the HSS, CME, and QSW conditions in the SW are formulated. (2) 54%, 36%, and 10% of EMIC wave events are observed during CME, HSS, and QSW, respectively. (3) 12% of events are closely associated with the fast growth of magnetospheric compression, among which 76%, 24%, and 0% are observed during CME, HSS, and QSW, respectively. (4) A majority of the QSW, HSS-driven, and CME-driven events is observed in the 9–12, 12–24, and 8–24 hr MLT sectors, respectively. (5) CME-driven events are distributed along all L shells, whereas the majority of the HSS-driven and QSW events are confined to L \u3e 3.5. (6) The fractions of events during CME and HSS have a maximum in the near-equatorial region, whereas the fractions of the QSW events have a minimum there. (7) Independent of the SW driver, no strong events are observed below the local O+ gyrofrequency, whereas 65–70% and 30–35% of events are observed between the O+ and He+ gyrofrequencies and above the He+ gyrofrequency, respectively

    Partner selection for reverse logistics centres in green supply chains: a fuzzy artificial immune optimisation approach

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    The design of reverse logistics networks has now emerged as a major issue for manufacturers, not only in developed countries where legislation and societal pressures are strong, but also in developing countries where the adoption of reverse logistics practices may offer a competitive advantage. This paper presents a new model for partner selection for reverse logistic centres in green supply chains. The model offers three advantages. Firstly, it enables economic, environment, and social factors to be considered simultaneously. Secondly, by integrating fuzzy set theory and artificial immune optimization technology, it enables both quantitative and qualitative criteria to be considered simultaneously throughout the whole decision-making process. Thirdly, it extends the flat criteria structure for partner selection evaluation for reverse logistics centres to the more suitable hierarchy structure. The applicability of the model is demonstrated by means of an empirical application based on data from a Chinese electronic equipment and instruments manufacturing company

    Science Goals and Overview of the Radiation Belt Storm Probes (RBSP) Energetic Particle, Composition, and Thermal Plasma (ECT) Suite on NASA’s Van Allen Probes Mission

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    The Radiation Belt Storm Probes (RBSP)-Energetic Particle, Composition, and Thermal Plasma (ECT) suite contains an innovative complement of particle instruments to ensure the highest quality measurements ever made in the inner magnetosphere and radiation belts. The coordinated RBSP-ECT particle measurements, analyzed in combination with fields and waves observations and state-of-the-art theory and modeling, are necessary for understanding the acceleration, global distribution, and variability of radiation belt electrons and ions, key science objectives of NASA’s Living With a Star program and the Van Allen Probes mission. The RBSP-ECT suite consists of three highly-coordinated instruments: the Magnetic Electron Ion Spectrometer (MagEIS), the Helium Oxygen Proton Electron (HOPE) sensor, and the Relativistic Electron Proton Telescope (REPT). Collectively they cover, continuously, the full electron and ion spectra from one eV to 10’s of MeV with sufficient energy resolution, pitch angle coverage and resolution, and with composition measurements in the critical energy range up to 50 keV and also from a few to 50 MeV/nucleon. All three instruments are based on measurement techniques proven in the radiation belts. The instruments use those proven techniques along with innovative new designs, optimized for operation in the most extreme conditions in order to provide unambiguous separation of ions and electrons and clean energy responses even in the presence of extreme penetrating background environments. The design, fabrication and operation of ECT spaceflight instrumentation in the harsh radiation belt environment ensure that particle measurements have the fidelity needed for closure in answering key mission science questions. ECT instrument details are provided in companion papers in this same issue. In this paper, we describe the science objectives of the RBSP-ECT instrument suite on the Van Allen Probe spacecraft within the context of the overall mission objectives, indicate how the characteristics of the instruments satisfy the requirements to achieve these objectives, provide information about science data collection and dissemination, and conclude with a description of some early mission results

    Partner selection in green supply chains using PSO – a practical approach

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    Partner selection is crucial to green supply chain management as the focal firm is responsible for the environmental performance of the whole supply chain. The construction of appropriate selection criteria is an essential, but often neglected pre-requisite in the partner selection process. This paper proposes a three-stage model that combines Dempster-Shafer belief acceptability theory and particle swarm optimization technique for the first time in this application. This enables optimization of both effectiveness, in its consideration of the inter-dependence of a broad range of quantitative and qualitative selection criteria, and efficiency in its use of scarce resources during the criteria construction process to be achieved simultaneously. This also enables both operational and strategic attributes can be selected at different levels of hierarchy criteria in different decision-making environments. The practical efficacy of the model is demonstrated by an application in Company ABC, a large Chinese electronic equipment and instrument manufacturer

    Use of caffeinated substances and risk of crashes in long distance drivers of commercial vehicles: case-control study

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    Objective: To determine whether there is an association between use of substances that contain caffeine and the risk of crash in long distance commercial vehicle drivers.Design: Case-control studySetting: New South Wales (NSW) and Western Australia (WA), Australia.Participants: 530 long distance drivers of commercial vehicles who were recently involved in a crash attended by police (cases) and 517 control drivers who had not had a crash while driving a commercial vehicle in the past 12 months.Main outcome measure: The likelihood of a crash associated with the use of substances containing caffeine after adjustment for factors including age, health disorders, sleep patterns, and symptoms of sleep disorders as well as exposures such as kilometres driven, hours slept, breaks taken, and night driving schedules.Results: Forty three percent of drivers reported consuming substances containing caffeine, such as tea, coffee, caffeine tablets, or energy drinks for the express purpose of staying awake. Only 3% reported using illegal stimulants such as amphetamine (“speed”); 3,4 methylenedioxymethamphetamine (ecstasy); and cocaine. After adjustment for potential confounders, drivers who consumed caffeinated substances for this purpose had a 63% reduced likelihood of crashing (odds ratio 0.37, 95% confidence interval 0.27 to 0.50) compared with drivers who did not take caffeinated substances.Conclusions: Caffeinated substances are associated with a reduced risk of crashing for long distance commercial motor vehicle drivers. While comprehensive mandated strategies for fatigue management remain a priority, the use of caffeinated substances could be a useful adjunct strategy in the maintenance of alertness while driving
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