Properties of Multivesicular Release from Mouse Rod Photoreceptors Support Transmission of Single-Photon Responses

Vision under starlight requires rod photoreceptors to transduce and transmit single-photon responses to the visual system. Small single-photon voltage changes must therefore cause detectable reductions in glutamate release. We found that rods achieve this by employing mechanisms that enhance release regularity and its sensitivity to small voltage changes. At the resting membrane potential in darkness, mouse rods exhibit coordinated and regularly timed multivesicular release events, each consisting of ~17 vesicles and occurring two to three times more regularly than predicted by Poisson statistics. Hyperpolarizing rods to mimic the voltage change produced by a single photon abruptly reduced the probability of multivesicular release nearly to zero with a rebound increase at stimulus offset. Simulations of these release dynamics indicate that this regularly timed, multivesicular release promotes transmission of single-photon responses to post-synaptic rod-bipolar cells. Furthermore, the mechanism is efficient, requiring lower overall release rates than uniquantal release governed by Poisson statistics

Toward a Manifold Encoding Neural Responses

Understanding circuit properties from physiological data presents two challenges: (i) recordings do not reveal connectivity, and (ii) stimuli only exercise circuits to a limited extent. We address these challenges for the mouse visual system with a novel neural manifold obtained using unsupervised algorithms. Each point in our manifold is a neuron; nearby neurons respond similarly in time to similar parts of a stimulus ensemble. This ensemble includes drifting gratings and flows, i.e., patterns resembling what a mouse would “see” running through fields. Regarding (i), our manifold differs from the standard practice in computational neuroscience: embedding trials in neural coordinates. Topology matters: we infer that, if the circuit consists of separate components, the manifold is discontinuous (illustrated with retinal data). If there is significant overlap between circuits, the manifold is nearly-continuous (cortical data). Regarding (ii), most of the cortical manifold is not activated with conventional gratings, despite their prominence in laboratory settings. Our manifold suggests organizing cortical circuitry by a few specialized circuits for specific members of the stimulus ensemble, together with circuits involving ‘multi-stimuli’-responding neurons. To approach real circuits, local neighborhoods in the manifold are identified with actual circuit components. For retinal data, we show these components correspond to distinct ganglion cell types by their mosaic-like receptive field organization, while for cortical data, neighborhoods organize neurons by type (excitatory/inhibitory) and anatomical layer. In summary: the topology of neural organization reflects well the underlying anatomy and physiology of the retina and the visual cortex

Caffeine gum improves reaction time but reduces composure versus placebo during the extra-time period of simulated soccer match-play in male semi-professional players

This study aimed to determine whether caffeine gum influenced perceptual-cognitive and physical performance during the extra-time period of simulated soccer match-play. Semi-professional male soccer players (n=12, age: 22 ± 3 years, stature: 1.78 ± 0.06 m, mass: 75 ± 9 kg) performed 120-min soccer specific exercise on two occasions. In a triple blind, randomised, crossover design, players chewed caffeinated (200-mg; caffeine) or control (0-mg; placebo) gum for 5-min following 90-min of soccer specific exercise. Perceptual-cognitive skills (i.e., passing accuracy, reaction time, composure, adaptability) were assessed using a soccer specific virtual reality simulator, collected pre- and post-trial. Neuromuscular performance (reactive-strength index, vertical jump height, absolute and relative peak power output, and negative vertical displacement) and sprint performance (15- and 30-m) were measured at pre-trial, half-time, 90-min and post-trial. Caffeine gum attenuated declines in reaction time (pre: 90.8 ± 0.8 AU to post: 90.7 ± 0.8 AU) by a further 4.2% than placebo (pre: 92.1 ± 0.8 AU to post: 88.2 ± 0.8 AU; p <0.01). Caffeine gum reduced composure by 4.7% (pre: 69.1 ± 0.8 AU to post: 65.9 ± 0.8 AU) versus placebo (pre: 68.8 ± 0.8 AU to post: 68.3 ± 0.8 AU; p <0.01). Caffeine gum did not influence any other variables (p >0.05). Where caffeine gum is consumed by players prior to extra-time, reaction time increases but composure may be compromised, and neuromuscular and sprint performance remain unchanged. Future work should assess caffeine gum mixes with substances like L-theanine that promote a relaxed state under stressful conditions

Children’s participation in school grounds developments: creating a place for education that promotes children’s social inclusion

Abstract This paper advances the idea that ‘education for the social inclusion of children’ is similar but different to ‘inclusive education’ as it has come to be understood and used by some authors and UK government documents. ‘Inclusive education’ tends to carry an inward emphasis on the participation of children in the education system (with discussions on school culture, transitions, truancy, exclusion rates, underachievement, and school leaving age). In contrast, education for the promotion of children’s social inclusion requires an outward emphasis on children's participation in 'mainstream' society while they are still children. The latter emphasis is seen to be lacking in educational policy discourse in Scotland though a recent shift in policy towards education for active citizenship is noted. Examples are provided to show how many policy statements enact a limitation on the scope for education to promote children’s social inclusion by emphasising children’s deficits as social actors and focussing on the ‘condition’ of social exclusion. The paper draws on an empirical study of children’s participation in changing school grounds in Scotland. The analysis shows how the enclosure of learning in books, classrooms and normative curricula was challenged. Learning from school grounds developments was constructed relationally and spatially but the scope of what was to be learned was often delineated by adults. The paper closes with a discussion of how education that promotes the social inclusion of children will benefit from seeing both children and adults as current though partial citizens and utilising socio-spatial opportunities for the generation of uncertain curricula through their shared and/or differentiated participation

Assessment of natural resource conditions in and adjacent to Dry Tortugas National Park

This project characterized and assessed the condition of coastal water resources in the Dry Tortugas National Park (DRTO) located in the Florida Keys. The goal of the assessment was to: (1) identify the state of knowledge of natural resources that exist within the DRTO, (2) summarize the state of knowledge about natural and anthropogenic stressors and threats that affected these resources, and (3) describe strategies being implemented by DRTO managers to meet their resource management goals. The park, located in the Straits of Florida 113 km (70 miles) west of Key West, is relatively small (269 square kilometers) with seven small islands and extensive shallow water coral reefs. Significant natural resources within DRTO include coastal and oceanic waters, coral reefs, reef fisheries, seagrass beds, and sea turtle and bird nesting habitats. This report focuses on marine natural resources identified by DRTO resource managers and researchers as being vitally important to the Tortugas region and the wider South Florida ecosystem. Selected marine resources included physical resources (geology, oceanography, and water quality) and biological resources (coral reef and hardbottom benthic assemblages, seagrass and algal communities, reef fishes and macro invertebrates, and wildlife [sea turtles and sea-birds]). In the past few decades, some of these resources have deteriorated because of natural and anthropogenic factors that are local and global in scale. To meet mandated goals (Chapter 1), resource managers need information on: (1) the types and condition of natural and cultural resources that occur within the park and (2) the stressors and threats that can affect those resources. This report synthesizes and summarizes information on: (1) the status of marine natural resources occurring at DRTO; and (2) types of stressors and threats currently affecting those resources at the DRTO. Based on published information, the assessment suggests that marine resources at DRTO and its surrounding region are affected by several stressors, many of which act synergistically. Of the nine resource components assessed, one resource category – water quality – received an ecological condition ranking of "Good"; two components – the nonliving portion of coral reef and hardbottom and reef fishes – received a rating of "Caution"; and two components – the biotic components of coral reef and hardbottom substrates and sea turtles – received a rating of "Significant concern" (Table E-1). Seagrass and algal communities and seabirds were unrated for ecological condition because the available information was inadequate. The stressor category of tropical storms was the dominant and most prevalent stressor in the Tortugas region; it affected all of the resource components assessed in this report. Commercial and recreational fishing were also dominant stressors and affected 78% of the resource components assessed. The most stressed resource was the biotic component of coral reef and hardbottom resources, which was affected by 76% of the stressors. Water quality was the least affected; it was negatively affected by 12% of stressors. The systematic assessment of marine natural resources and stressors in the Tortugas region pointed to several gaps in the information. For example, of the nine marine resource components reviewed in this report, the living component of coral reefs and hardbottom resources had the best rated information with 25% of stressor categories rated "Good" for information richness. In contrast, the there was a paucity of information for seagrass and algal communities and sea birds resource components

High-sensitivity rod photoreceptor input to the blue-yellow color opponent pathway in macaque retina.

Small bistratified cells (SBCs) in the primate retina carry a major blue-yellow opponent signal to the brain. We found that SBCs also carry signals from rod photoreceptors, with the same sign as S cone input. SBCs exhibited robust responses under low scotopic conditions. Physiological and anatomical experiments indicated that this rod input arose from the AII amacrine cell-mediated rod pathway. Rod and cone signals were both present in SBCs at mesopic light levels. These findings have three implications. First, more retinal circuits may multiplex rod and cone signals than were previously thought to, efficiently exploiting the limited number of optic nerve fibers. Second, signals from AII amacrine cells may diverge to most or all of the approximately 20 retinal ganglion cell types in the peripheral primate retina. Third, rod input to SBCs may be the substrate for behavioral biases toward perception of blue at mesopic light levels

The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer

© The Author 2015.Background: The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. Patients and methods: The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse. Conclusion: The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good