756 research outputs found

    Excitatory and inhibitory projections in parallel pathways from the inferior colliculus to the auditory thalamus

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    Individual subdivisions of the medial geniculate body (MG) receive a majority of their ascending inputs from 1 or 2 subdivisions of the inferior colliculus (IC). This establishes parallel pathways that provide a model for understanding auditory projections from the IC through the MG and on to auditory cortex. A striking discovery about the tectothalamic circuit was identification of a substantial GABAergic component. Whether GABAergic projections match the parallel pathway organization has not been examined. We asked whether the parallel pathway concept is reflected in guinea pig tectothalamic pathways and to what degree GABAergic cells contribute to each pathway. We deposited retrograde tracers into individual MG subdivisions (ventral, MGv; medial, MGm; dorsal, MGd; suprageniculate, MGsg) to label tectothalamic cells and used immunochemistry to identify GABAergic cells. The MGv receives most of its IC input (~75%) from the IC central nucleus (ICc); MGd and MGsg receive most of their input (~70%) from IC dorsal cortex (ICd); and MGm receives substantial input from both ICc (~40%) and IC lateral cortex (~40%). Each MG subdivision receives additional input (up to 32%) from non-dominant IC subdivisions, suggesting cross-talk between the pathways. The proportion of GABAergic cells in each pathway depended on the MG subdivision. GABAergic cells formed ~20% of IC inputs to MGv or MGm, ~11% of inputs to MGd, and 4% of inputs to MGsg. Thus, non-GABAergic (i.e., glutamatergic) cells are most numerous in each pathway with GABAergic cells contributing to different extents. Despite smaller numbers of GABAergic cells, their distributions across IC subdivisions mimicked the parallel pathways. Projections outside the dominant pathways suggest opportunities for excitatory and inhibitory crosstalk. The results demonstrate parallel tectothalamic pathways in guinea pigs and suggest numerous opportunities for excitatory and inhibitory interactions within and between pathways

    Design of experiments to generate a fuel cell electro-thermal performance map and optimise transitional pathways

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    The influence of the air cooling flow rate and current density on the temperature, voltage and power density is a challenging issue for air-cooled, open cathode fuel cells. Electro-thermal maps have been generated using large datasets (530 experimental points) to characterise these correlations, which reveal that the amount of cooling, alongside with the load, directly affect the cell temperature. This work uses the design of experiment (DoE) approach to tackle two challenges. Firstly, an S-optimal design plan is used to reduce the number of experiments from 530 to 555 to determine the peak power density in an electro-thermal map. Secondly, the design of experiment approach is used to determine the fastest way to reach the highest power density, yet limiting acute temperature gradients, via three intermediate steps of current density and air cooling rate

    Solid state NMR and X-ray diffraction studies of α-d-galacturonic acid monohydrate

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    Crystalline a-d-galacturonic acid monohydrate has been studied by 13C CPMAS NMR and X-ray crystallography. The molecular dynamics were investigated by evaluating 13C spin-lattice relaxation in the rotating frame (T1?) and chemical-shift-anisotropy properties of each carbon. Only limited molecular motions can be detected in the low frequency

    A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics

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    The heterogeneity of cellular microenvironments in tumors severely limits the efficacy of most cancer therapies. We have designed a microfluidic device that mimics the microenvironment gradients present in tumors that will enable the development of more effective cancer therapies. Tumor cell masses were formed within micron-scale chambers exposed to medium perfusion on one side to create linear nutrient gradients. The optical accessibility of the PDMS and glass device enables quantitative transmitted and fluorescence microscopy of all regions of the cell masses. Time-lapse microscopy was used to measure the growth rate and show that the device can be used for long-term efficacy studies. Fluorescence microscopy was used to demonstrate that the cell mass contained viable, apoptotic, and acidic regions similar to in vivo tumors. The diffusion coefficient of doxorubicin was accurately measured, and the accumulation of therapeutic bacteria was quantified. The device is simple to construct, and it can easily be reproduced to create an array of in vitro tumors. Because microenvironment gradients and penetration play critical roles controlling drug efficacy, we believe that this microfluidic device will be vital for understanding the behavior of common cancer drugs in solid tumors and designing novel intratumorally targeted therapeutics

    Behavioral Economic Measurement of Cigarette Demand: A Descriptive Review of Published Approaches to the Cigarette Purchase Task

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    The cigarette purchase task (CPT) is a behavioral economic method for assessing demand for cigarettes. Growing interest in behavioral correlates of tobacco use in clinical and general populations as well as empirical efforts to inform policy has seen an increase in published articles employing the CPT. Accordingly, an examination of the published methods and procedures for obtaining these behavioral economic metrics is timely. The purpose of this investigation was to provide a review of published approaches to using the CPT. We searched specific Boolean operators ([“behavioral economic” AND “purchase task”] OR [“demand” AND “cigarette”]) and identified 49 empirical articles published through the year 2018 that reported administering a CPT. Articles were coded for participant characteristics (e.g., sample size, population type, age), CPT task structure (e.g., price framing, number and sequence of prices; vignettes, contextual factors), and data analytic approach (e.g., method of generating indices of cigarette demand). Results of this review indicate no standard approach to administering the CPT and underscore the need for replicability of these behavioral economic measures for the purpose of guiding clinical and policy decisions

    Associations between the vaginal microbiome and Candida colonization in women of reproductive age

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    Background The composition of bacteria within the vaginal microbiome has garnered a lot of recent attention and has been associated with reproductive health and disease. Despite the common occurrence of yeast (primarily Candida) within the vaginal microbiome, there is still an incomplete picture of relationships between yeast and bacteria (especially lactobacilli), as well as how such associations are governed. Such relationships could be important to a more holistic understanding of the vaginal microbiome and its connection to reproductive health. Objective To perform molecular characterization of clinical specimens to define associations between vaginal bacteria (especially Lactobacillus species) and Candida colonization. In vitro studies were conducted to test the two most common dominant Lactobacillus species (Lactobacillus crispatus and Lactobacillus iners) in their ability to inhibit Candida growth and to examine the basis for such inhibition. Study Design A nested cross-sectional study of reproductive age women from the Contraceptive CHOICE Project was conducted. Vaginal swabs from 299 women were selected to balance race and BV status, resulting in similar representation of black and white women in each of the three Nugent score categories [normal (0-3), intermediate (4-6), and bacterial vaginosis (7-10)]. Sequencing of the 16S ribosomal gene (V4 region) was used to determine the dominant Lactobacillus species present (primarily L. iners and L. crispatus), defined as >50% of the community. Subjects without dominance by a single Lactobacillus species were classified as Diverse. A Candida-specific qPCR targeting the internally transcribed spacer 1 (ITS1) was validated using vaginal samples collected from a second cohort of women and used to assess Candida colonization. 255 nonpregnant women with sufficient bacterial biomass for analysis were included in the final analysis. Generalized linear models were employed to evaluate associations between Lactobacillus dominance, sociodemographic and risk characteristics and vaginal Candida colonization. In separate in vitro studies, the potential of cell-free supernatants from L. crispatus and L. iners cultures to inhibit Candida growth was evaluated. Results Forty-two women (16%) were vaginally colonized with Candida. Microbiomes characterized as Diverse (38%), L. iners-dominant (39%), and L. crispatus-dominant (20%) were the most common. The microbiome, race and Candida colonization co-varied with a higher prevalence of Candida among black women and L. iners-dominant communities compared to white women and L. crispatus-dominant communities. L. iners-dominant communities were more likely to harbor Candida than L. crispatus-dominant communities (OR = 2.85, 95% CI: 1.03 to 7.21; Fisher’s Exact, p = 0.048). In vitro, L. crispatus produced greater concentrations of lactic acid and exhibited significantly more pH-dependent growth inhibition of C. albicans, suggesting a potential mechanism for the clinical observations. Conclusion In nonpregnant women, L. iners-dominant communities were significantly more likely to harbor Candida than L. crispatus-dominant communities, suggesting that Lactobacillus species have different relationships with Candida. In vitro experiments indicate that L. crispatus may impede Candida colonization more effectively than L. iners through a greater production of lactic acid

    The DREEM, part 1: measurement of the educational environment in an osteopathy teaching program

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    Background Measurement of the educational environment has become more common in health professional education programs. Information gained from these investigations can be used to implement and measure changes to the curricula, educational delivery and the physical environment. A number of questionnaires exist to measure the educational environment, and the most commonly utilised of these is the Dundee Ready Educational Environment Measure (DREEM). Methods The DREEM was administered to students in all year levels of the osteopathy program at Victoria University (VU), Melbourne, Australia. Students also completed a demographic survey. Inferential and correlational statistics were employed to investigate the educational environment based on the scores obtained from the DREEM. Results A response rate of 90% was achieved. The mean total DREEM score was 135.37 (+/- 19.33) with the scores ranging from 72 to 179. Some subscales and items demonstrated differences for gender, clinical phase, age and whether the student was in receipt of a government allowance. Conclusions There are a number of areas in the program that are performing well, and some aspects that could be improved. Overall students rated the VU osteopathy program as more positive than negative. The information obtained in the present study has identified areas for improvement and will enable the program leaders to facilitate changes. It will also provide other educational institutions with data on which they can make comparisons with their own programs

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

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    A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN
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