COMPARISON OF SPRINT INTERVAL TRAINING AND MODERATE INTENSITY CONTINUOUS TRAINING TO MAXIMIZE NEUROMUSCULAR ADAPTATIONS

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Effects of High Functional Resistance Training on Parameters of Arterial Stiffness- Pilot Study

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Improving Utility of GPU in Accelerating Industrial Applications with User-centred Automatic Code Translation

SMEs (Small and medium-sized enterprises), particularly those whose business is focused on developing innovative produces, are limited by a major bottleneck on the speed of computation in many applications. The recent developments in GPUs have been the marked increase in their versatility in many computational areas. But due to the lack of specialist GPU (Graphics processing units) programming skills, the explosion of GPU power has not been fully utilized in general SME applications by inexperienced users. Also, existing automatic CPU-to-GPU code translators are mainly designed for research purposes with poor user interface design and hard-to-use. Little attentions have been paid to the applicability, usability and learnability of these tools for normal users. In this paper, we present an online automated CPU-to-GPU source translation system, (GPSME) for inexperienced users to utilize GPU capability in accelerating general SME applications. This system designs and implements a directive programming model with new kernel generation scheme and memory management hierarchy to optimize its performance. A web-service based interface is designed for inexperienced users to easily and flexibly invoke the automatic resource translator. Our experiments with non-expert GPU users in 4 SMEs reflect that GPSME system can efficiently accelerate real-world applications with at least 4x and have a better applicability, usability and learnability than existing automatic CPU-to-GPU source translators

On-Site Detection of Carcinoembryonic Antigen in Human Serum

Real-time connectivity and employment of sustainable materials empowers point-of-care diagnostics with the capability to send clinically relevant data to health care providers even in low-resource settings. In this study, we developed an advantageous kit for the on-site detection of carcinoembryonic antigen (CEA) in human serum. CEA sensing was performed using cellulose-based lateral flow strips, and colorimetric signals were read, processed, and measured using a smartphone-based system. The corresponding immunoreaction was reported by polydopamine-modified gold nanoparticles in order to boost the signal intensity and improve the surface blocking and signal-to-noise relationship, thereby enhancing detection sensitivity when compared with bare gold nanoparticles (up to 20-fold in terms of visual limit of detection). Such lateral flow strips showed a linear range from 0.05 to 50 ng/mL, with a visual limit of detection of 0.05 ng/mL and an assay time of 15 min. Twenty-six clinical samples were also tested using the proposed kit and compared with the gold standard of immunoassays (enzyme linked immunosorbent assay), demonstrating an excellent correlation (R = 0.99). This approach can potentially be utilized for the monitoring of cancer treatment, particularly at locations far from centralized laboratory facilities.</jats:p

NASA's Earth Venture-1 (EV-1) Airborne Science Investigations

In 2010, NASA announced the first Earth Venture (EV-1) selections in response to a recommendation made by the National Research Council for low-cost investigations fostering innovation in Earth science. The five EV-1 investigations span the Earth science focus areas of atmosphere, weather, climate, water and energy and, carbon and represent earth science researchers from NASA as well as other government agencies, academia and industry from around the world. The EV-1 missions are: 1) Airborne Microwave Observatory of Subcanopy and Subsurface (AirMOSS), 2) Airborne Tropical Tropopause Experiment (ATTREX), 3) Carbon in Arctic Reservoirs Vulnerability Experiment (CARVE), 4) Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER-AQ), and 5) Hurricane And Severe Storm Sentinel (HS3). The Earth Venture missions are managed out of the Earth System Science Pathfinder (ESSP) Program Office (Allen, et. al. 2010b

Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc −, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives: Our goal was to determine whether increased system xc − activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc −, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system xc − inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc − activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc − activity. Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc −. Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system xc − independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine

On the Use of Multiple Probe Insertions at the Same Site for Repeated Intracerebral Microdialysis Experiments in the Nigrostriatal Dopamine System of Rats

The effects of implantation of a dialysis probe into the striatum of awake rats on indices of dopamine (DA) and serotonin neurotransmission were assessed, first over 24 h following initial insertion of a probe, and then again following reinsertion of a probe at the same site 1 week later. It was found that the basal concentration of DA in dialysate stabilized within 20–40 min after probe implantation, although DA showed a modest decline 24 h later. There was, however, no significant difference in basal DA between two test sessions separated by 1 week. On the other hand, the basal concentrations of the DA metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, progressively increased for 2–3 h after probe implantation and decreased markedly by 24 h later. Furthermore, in contrast to DA, the DA metabolites decreased even further after the second probe insertion. Amphetamine-stimulated DA release was also greatly attenuated following the second probe insertion, relative to the first probe insertion. Two probe insertions had only modest effects on the concentration of 5-hydroxyindoleacetic acid in dialysate, relative to the DA metabolites. It is suggested the effects of two probe insertions on DA metabolism and amphetamine-stimulated DA release described here are indicative of probe-induced damage to the nigrostriatal DA system. If this is the case, multiple probe insertions may not provide a feasible strategy for within-subjects design dialysis experiments over extended periods of time, at least in the DA system of small animals. It is suggested further that a stable basal concentration of DA in dialysate may be an especially poor indicator of the integrity of the dopaminergic input to the striatum.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65235/1/j.1471-4159.1992.tb10044.x.pd

IL6 Mediates Suppression of T- and NK-cell Function in EMT-associated TKI-resistant EGFR-mutant NSCLC

Purpose: Patients with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations are initially responsive to tyrosine kinase inhibitors (TKI). However, therapeutic resistance eventually emerges, often via secondary EGFR mutations or EGFR-independent mechanisms such as epithelial-to-mesenchymal transition. Treatment options after EGFR-TKI resistance are limited as anti-PD-1/PD-L1 inhibitors typically display minimal benefit. Given that IL6 is associated with worse outcomes in patients with NSCLC, we investigate whether IL6 in part contributes to this immunosuppressed phenotype. Experimental design: We utilized a syngeneic genetically engineered mouse model (GEMM) of EGFR-mutant NSCLC to investigate the effects of IL6 on the tumor microenvironment and the combined efficacy of IL6 inhibition and anti-PD-1 therapy. Corresponding in vitro studies used EGFR-mutant human cell lines and clinical specimens. Results: We identified that EGFR-mutant tumors which have oncogene-independent acquired resistance to EGFR-TKIs were more mesenchymal and had markedly enhanced IL6 secretion. In EGFR-mutant GEMMs, IL6 depletion enhanced activation of infiltrating natural killer (NK)- and T-cell subpopulations and decreased immunosuppressive regulatory T and Th17 cell populations. Inhibition of IL6 increased NK- and T cell-mediated killing of human osimertinib-resistant EGFR-mutant NSCLC tumor cells in cell culture. IL6 blockade sensitized EGFR-mutant GEMM tumors to PD-1 inhibitors through an increase in tumor-infiltrating IFNγ+ CD8+ T cells. Conclusions: These data indicate that IL6 is upregulated in EGFR-mutant NSCLC tumors with acquired EGFR-TKI resistance and suppressed T- and NK-cell function. IL6 blockade enhanced antitumor immunity and efficacy of anti-PD-1 therapy warranting future clinical combinatorial investigations

IL6 Mediates Suppression of T- and NK-cell Function in EMT-associated TKI-resistant EGFR-mutant NSCLC

PURPOSE: Patients with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations are initially responsive to tyrosine kinase inhibitors (TKI). However, therapeutic resistance eventually emerges, often via secondary EGFR mutations or EGFR-independent mechanisms such as epithelial-to-mesenchymal transition. Treatment options after EGFR-TKI resistance are limited as anti-PD-1/PD-L1 inhibitors typically display minimal benefit. Given that IL6 is associated with worse outcomes in patients with NSCLC, we investigate whether IL6 in part contributes to this immunosuppressed phenotype. EXPERIMENTAL DESIGN: We utilized a syngeneic genetically engineered mouse model (GEMM) of EGFR-mutant NSCLC to investigate the effects of IL6 on the tumor microenvironment and the combined efficacy of IL6 inhibition and anti-PD-1 therapy. Corresponding in vitro studies used EGFR-mutant human cell lines and clinical specimens. RESULTS: We identified that EGFR-mutant tumors which have oncogene-independent acquired resistance to EGFR-TKIs were more mesenchymal and had markedly enhanced IL6 secretion. In EGFR-mutant GEMMs, IL6 depletion enhanced activation of infiltrating natural killer (NK)- and T-cell subpopulations and decreased immunosuppressive regulatory T and Th17 cell populations. Inhibition of IL6 increased NK- and T cell-mediated killing of human osimertinib-resistant EGFR-mutant NSCLC tumor cells in cell culture. IL6 blockade sensitized EGFR-mutant GEMM tumors to PD-1 inhibitors through an increase in tumor-infiltrating IFNγ+ CD8+ T cells. CONCLUSIONS: These data indicate that IL6 is upregulated in EGFR-mutant NSCLC tumors with acquired EGFR-TKI resistance and suppressed T- and NK-cell function. IL6 blockade enhanced antitumor immunity and efficacy of anti-PD-1 therapy warranting future clinical combinatorial investigations

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure