519 research outputs found

    Optogenetic Technology and Its In Vivo Applications

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    Optogenetics is a novel technology with the widely acknowledged potential to revolutionize cell biology and neuroscience. Essentially, optogenetic methods integrate optical and genetic tools to control the activity of whole cells or subcellular events. In recent years, optogenetics has been used to activate and to inhibit genetically defined neuronal populations within neural circuits. As such, it has been used to show the sufficiency or the necessity of specific neuronal cell types in generating behaviors across a number of animal species. When employed in rodent models of human neurological and psychiatric disorders, optogenetics has provided clinically relevant insights into the function of pathologic neural circuits. Recent progress in the in vivo applications of this methodology is reviewed in this article, with particular focus on behavioral applications in nematodes, fish, rodents, and nonhuman primates

    Agile software development in an earned value world: a survival guide

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    Agile methodologies are current best practice in software development. They are favored for, among other reasons, preventing premature optimization by taking a somewhat short-term focus, and allowing frequent replans/reprioritizations of upcoming development work based on recent results and current backlog. At the same time, funding agencies prescribe earned value management accounting for large projects which, these days, inevitably include substantial software components. Earned Value approaches emphasize a more comprehensive and typically longer-range plan, and tend to characterize frequent replans and reprioritizations as indicative of problems. Here we describe the planning, execution and reporting framework used by the LSST Data Management team, that navigates these opposite tensions

    Function of arteries and veins in conditions of simulated cardiac arrest

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    Introduction: The study examined the behavior of vasculature in conditions of eliminated cardiac function using mathematical modeling. In addition, we addressed the question of whether the stretch-recoil capability of veins, at least in part accounts for the slower response to simulated cardiac arrest. Methods: In the first set of computational experiments, blood flow and pressure patterns in veins and arteries during the first few seconds after cardiac arrest were assessed via a validated multi-scale mathematical model of the whole cardiovascular system, comprising cardiac dynamics, arterial and venous blood flow dynamics, and microcirculation. In the second set of experiments, the effects of stretch-recoil zones of venous vessels with different diameters and velocities on blood velocity and dynamic pressure analyzed using computational fluid dynamics (CFD) modeling. Results: In the first set of experiments, measurement of changes in velocity, dynamic pressure, and fluid flow revealed that the venous system responded to cardiac arrest more slowly compared to the arteries. This disparity might be due to the intrinsic characteristics of the venous system, including stretch-recoil and elastic fiber composition. In the second set of experiments, we attempted to determine the role of the stretch-recoil capability of veins in the slower response to cardiac arrest. During the second set of experiments, we found that this recoil behavior increased dynamic pressure, velocity, and blood flow. The enhancement in dynamic pressure through combining the results from both experiments yielded a 15-40% increase in maximum dynamic pressure due to stretch-recoil, depending on vein diameter under normal conditions. Conclusion: In the situation of cardiac arrest, the vein geometry changes continue, promoting smooth responses of the venous system. Moreover, the importance of such vein behavior in blood displacement may grow as the pressure on the venous side gradually decreases with time. Our experiments suggest that the driving force for venous return is the pressure difference that remains within the venous system after the energy coming from every ventricular systole spent to overcome the resistance created by arterial and capillary systems

    Exploring Author Gender in Book Rating and Recommendation

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    Collaborative filtering algorithms find useful patterns in rating and consumption data and exploit these patterns to guide users to good items. Many of the patterns in rating datasets reflect important real-world differences between the various users and items in the data; other patterns may be irrelevant or possibly undesirable for social or ethical reasons, particularly if they reflect undesired discrimination, such as gender or ethnic discrimination in publishing. In this work, we examine the response of collaborative filtering recommender algorithms to the distribution of their input data with respect to a dimension of social concern, namely content creator gender. Using publicly-available book ratings data, we measure the distribution of the genders of the authors of books in user rating profiles and recommendation lists produced from this data. We find that common collaborative filtering algorithms differ in the gender distribution of their recommendation lists, and in the relationship of that output distribution to user profile distribution

    Infinite factorization of multiple non-parametric views

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    Combined analysis of multiple data sources has increasing application interest, in particular for distinguishing shared and source-specific aspects. We extend this rationale of classical canonical correlation analysis into a flexible, generative and non-parametric clustering setting, by introducing a novel non-parametric hierarchical mixture model. The lower level of the model describes each source with a flexible non-parametric mixture, and the top level combines these to describe commonalities of the sources. The lower-level clusters arise from hierarchical Dirichlet Processes, inducing an infinite-dimensional contingency table between the views. The commonalities between the sources are modeled by an infinite block model of the contingency table, interpretable as non-negative factorization of infinite matrices, or as a prior for infinite contingency tables. With Gaussian mixture components plugged in for continuous measurements, the model is applied to two views of genes, mRNA expression and abundance of the produced proteins, to expose groups of genes that are co-regulated in either or both of the views. Cluster analysis of co-expression is a standard simple way of screening for co-regulation, and the two-view analysis extends the approach to distinguishing between pre- and post-translational regulation

    The age-redshift relation for Luminous Red Galaxies in the Sloan Digital Sky Survey

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    We present a detailed analysis of 17,852 quiescent, Luminous Red Galaxies (LRGs) selected from Sloan Digital Sky Survey (SDSS) Data Release Seven (DR7) spanning a redshift range of 0.0 < z < 0.4. These galaxies are co-added into four equal bins of velocity dispersion and luminosity to produce high signal-to-noise spectra (>100A^{-1}), thus facilitating accurate measurements of the standard Lick absorption-line indices. In particular, we have carefully corrected and calibrated these indices onto the commonly used Lick/IDS system, thus allowing us to compare these data with other measurements in the literature, and derive realistic ages, metallicities ([Z/H]) and alpha-element abundance ratios ([alpha/Fe]) for these galaxies using Simple Stellar Population (SSP) models. We use these data to study the relationship of these galaxy parameters with redshift, and find little evidence for evolution in metallicity or alpha-elements (especially for our intermediate mass samples). This demonstrates that our subsamples are consistent with pure passive evolving (i.e. no chemical evolution) and represent a homogeneous population over this redshift range. We also present the age-redshift relation for these LRGs and clearly see a decrease in their age with redshift (5 Gyrs over the redshift range studied here) which is fully consistent with the cosmological lookback times in a concordance Lambda CDM universe. We also see that our most massive sample of LRGs is the youngest compared to the lower mass galaxies. We provide these data now to help future cosmological and galaxy evolution studies of LRGs, and provide in the appendices of this paper the required methodology and information to calibrate SDSS spectra onto the Lick/IDS system.Comment: 26 pages, with several appendices containing data. Accepted for publication in MNRA

    Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production

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    Optic atrophy 1 (OPA1) is a mitochondrial inner membrane protein that has an important role in mitochondrial fusion and structural integrity. Dysfunctional OPA1 mutations cause atrophy of the optic nerve leading to blindness. Here, we show that OPA1 has an important role in the innate immune system. Using conditional knockout mice lacking Opa1 in neutrophils (Opa1(N Delta)), we report that lack of OPA1 reduces the activity of mitochondrial electron transport complex I in neutrophils. This then causes a decline in adenosine-triphosphate (ATP) production through glycolysis due to lowered NAD(+) availability. Additionally, we show that OPA1-dependent ATP production in these cells is required for microtubule network assembly and for the formation of neutrophil extracellular traps. Finally, we show that Opa1(N Delta) mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa.Peer reviewe

    Statistical properties of the dark matter haloes of dwarf galaxies and correlations with the environment

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    According to the now strongly supported concordance Λ\LambdaCDM model, galaxies may be grossly described as a luminous component embedded in a dark matter halo. The density profile of these mass dominating haloes may be determined by N - body simulations which mimic the evolution of the tiny initial density perturbations during the process leading to the structures we observe today. Unfortunately, when the effect of baryons is taken into account, the situation gets much more complicated due to the difficulties in simulating their physics. As a consequence, a definitive prediction of how dark matter haloes should presently look like is still missing. We revisit here this issue from an observational point of view devoting our attention to dwarf galaxies. Being likely dark matter dominated, these systems are ideal candidates to investigate the present day halo density profiles and check whether dark matter related quantities correlate with the stellar ones or the environment. By fitting a large sample of well measured rotation curves, we infer constraints on both halo structural parameters (such as the logarithmic slope of the density profile and its concentration) and derived quantities (e.g., the mass fraction and the Newtonian acceleration) which could then be used to constrain galaxy formation scenarios. Moreover, we investigate whether the halo properties correlates with the environment the galaxy lives in thus offering a new tool to deepen our understanding of galaxy formation.Comment: 14 pages, 8 tables, 5 figures, accepted for publication on MNRA

    The velocity distribution of nearby stars from Hipparcos data I. The significance of the moving groups

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    We present a three-dimensional reconstruction of the velocity distribution of nearby stars (<~ 100 pc) using a maximum likelihood density estimation technique applied to the two-dimensional tangential velocities of stars. The underlying distribution is modeled as a mixture of Gaussian components. The algorithm reconstructs the error-deconvolved distribution function, even when the individual stars have unique error and missing-data properties. We apply this technique to the tangential velocity measurements from a kinematically unbiased sample of 11,865 main sequence stars observed by the Hipparcos satellite. We explore various methods for validating the complexity of the resulting velocity distribution function, including criteria based on Bayesian model selection and how accurately our reconstruction predicts the radial velocities of a sample of stars from the Geneva-Copenhagen survey (GCS). Using this very conservative external validation test based on the GCS, we find that there is little evidence for structure in the distribution function beyond the moving groups established prior to the Hipparcos mission. This is in sharp contrast with internal tests performed here and in previous analyses, which point consistently to maximal structure in the velocity distribution. We quantify the information content of the radial velocity measurements and find that the mean amount of new information gained from a radial velocity measurement of a single star is significant. This argues for complementary radial velocity surveys to upcoming astrometric surveys
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