Traumatic Brain Injury, Microglia, and Beta Amyloid

Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer's Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (Aβ). Data from both AD and TBI studies suggest that microglia play a central role in Aβ accumulation after TBI. This paper focuses on the current research on the role of microglia response to Aβ after TBI

Radiation Hydrodynamical Instabilities in Cosmological and Galactic Ionization Fronts

Ionization fronts, the sharp radiation fronts behind which H/He ionizing photons from massive stars and galaxies propagate through space, were ubiquitous in the universe from its earliest times. The cosmic dark ages ended with the formation of the first primeval stars and galaxies a few hundred Myr after the Big Bang. Numerical simulations suggest that stars in this era were very massive, 25 - 500 solar masses, with H II regions of up to 30,000 light-years in diameter. We present three-dimensional radiation hydrodynamical calculations that reveal that the I-fronts of the first stars and galaxies were prone to violent instabilities, enhancing the escape of UV photons into the early intergalactic medium (IGM) and forming clumpy media in which supernovae later exploded. The enrichment of such clumps with metals by the first supernovae may have led to the prompt formation of a second generation of low-mass stars, profoundly transforming the nature of the first protogalaxies. Cosmological radiation hydrodynamics is unique because ionizing photons coupled strongly to both gas flows and primordial chemistry at early epochs, introducing a hierarchy of disparate characteristic timescales whose relative magnitudes can vary greatly throughout a given calculation. We describe the adaptive multistep integration scheme we have developed for the self-consistent transport of both cosmological and galactic ionization fronts.Comment: 6 pages, 4 figures, accepted for proceedings of HEDLA2010, Caltech, March 15 - 18, 201

Radiation Hydrodynamical Evolution of Primordial H II Regions

We simulate the ionization environment of z ~ 20 luminous objects formed within the framework of the current CDM cosmology and compute their UV escape fraction. These objects are likely single very massive stars that are copious UV emitters. We present analytical estimates as well as one--dimensional radiation hydrodynamical calculations of the evolution of these first HII regions in the universe. The initially D--type ionization front evolves to become R--type within $\lesssim 10^5$ yrs at a distance $\sim1$ pc. This ionization front then completely overruns the halo, accelerating an expanding shell of gas outward to velocities in excess of 30 km s$^{-1}$, about ten times the escape velocity of the confining dark matter halo. We find that the evolution of the HII region depends only weakly on the assumed stellar ionizing luminosities. Consequently, most of the gas surrounding the first stars will leave the dark halo whether or not the stars produce supernovae. If they form the first massive seed black holes these are unlikely to accrete within a Hubble time after they formed until they are incorporated into larger dark matter halos that contain more gas. Because these I--fronts exit the halo on timescales much shorter than the stars' main sequence lifetimes their host halos have UV escape fractions of $\gtrsim 0.95$, fixing an important parameter for theoretical studies of cosmological hydrogen reionization.Comment: 10 pages, 8 figures, in emulateapj5 format, revised version submitted to Ap

Evaluating the baseline hemoglobin, albumin, lymphocyte, and platelet (HALP) score in the United States adult population and comorbidities: an analysis of the NHANES

Introduction: As a composite immunonutritional biomarker, the Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) score has shown promise in assessing a patient\u27s overall health status by integrating several routinely collected laboratory indicators. This biomarker has been examined in many different populations of patients and disease states (i.e., cancer), but an integrated, universal rubric using standardized thresholds has not thus far been developed. Pre-existing large population-based databases represent an ideal source to examine the distribution of HALP and the influence of diverse health statuses on this score. Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) between 2017–2020, evaluating 8,245 participants across numerous demographic, socioeconomic, and health-related variables. Univariate and multivariate linear regression analyses assessed the associations between HALP scores and these factors. Results: Our findings revealed significant associations between HALP scores and various demographic, socioeconomic, and health conditions. The median HALP score among the representative population was 49.0, with varying median scores across different groups and normal reference ranges for males and females. Multivariate regression analysis showed that anemia treatment, age over 65 years, weak/failing kidneys, and cancer were independent risk factors associated with lower HALP scores. Male participants demonstrated higher HALP scores than female participants, and age was inversely related to HALP. Moreover, HALP scores were negatively associated with the number of comorbidities. Conclusion/discussion: This study set out to explore the HALP score from a population-based perspective, uncovering notable associations that offer vital insights into the score\u27s clinical relevance and future applications. By determining a median HALP score of 49.0 and normal reference ranges within our diverse, representative sample, we establish a robust foundation for researchers to refine optimal HALP applications and thresholds. Considering the growing focus on personalized medicine, HALP holds promise as a prognostic tool, enabling clinicians to comprehend their patients\u27 immunonutritional status better and deliver customized care

A Flexible and Non-instrusive Approach for Computing Complex Structural Coverage Metrics

Software analysis tools and techniques often leverage structural code coverage information to reason about the dynamic behavior of software. Existing techniques instrument the code with the required structural obligations and then monitor the execution of the compiled code to report coverage. Instrumentation based approaches often incur considerable runtime overhead for complex structural coverage metrics such as Modified Condition/Decision (MC/DC). Code instrumentation, in general, has to be approached with great care to ensure it does not modify the behavior of the original code. Furthermore, instrumented code cannot be used in conjunction with other analyses that reason about the structure and semantics of the code under test. In this work, we introduce a non-intrusive preprocessing approach for computing structural coverage information. It uses a static partial evaluation of the decisions in the source code and a source-to-bytecode mapping to generate the information necessary to efficiently track structural coverage metrics during execution. Our technique is flexible; the results of the preprocessing can be used by a variety of coverage-driven software analysis tasks, including automated analyses that are not possible for instrumented code. Experimental results in the context of symbolic execution show the efficiency and flexibility of our nonintrusive approach for computing code coverage informatio

Unsatisfiability proofs for distributed clause-sharing SAT solvers

Distributed clause-sharing SAT solvers can solve problems up to one hundred times faster than sequential SAT solvers by sharing derived information among multiple sequential solvers working on the same problem. Unlike sequential solvers, however, distributed solvers have not been able to produce proofs of unsatisfiability in a scalable manner, which has limited their use in critical applications. In this paper, we present a method to produce unsatisfiability proofs for distributed SAT solvers by combining the partial proofs produced by each sequential solver into a single, linear proof. Our approach is more scalable and general than previous explorations for parallel clause-sharing solvers, allowing use on distributed solvers without shared memory. We propose a simple sequential algorithm as well as a fully distributed algorithm for proof composition. Our empirical evaluation shows that for large-scale distributed solvers (100 nodes of 16 cores each), our distributed approach allows reliable proof composition and checking with reasonable overhead. We analyze the overhead and discuss how and where future efforts may further improve performance

Necrostatin-1 Reduces Histopathology and Improves Functional Outcome after Controlled Cortical Impact in Mice

Necroptosis is a newly identified type of programmed necrosis initiated by the activation of tumor necrosis factor alpha (TNF?)/Fas. Necrostatin-1 is a specific inhibitor of necroptosis that reduces ischemic tissue damage in experimental stroke models. We previously reported decreased tissue damage and improved functional outcome after controlled cortical impact (CCI) in mice deficient in TNF? and Fas. Hence, we hypothesized that necrostatin-1 would reduce histopathology and improve functional outcome after CCI in mice. Compared with vehicle-/inactive analog-treated controls, mice administered necrostatin-1 before CCI had decreased propidium iodide-positive cells in the injured cortex and dentate gyrus (6 h), decreased brain tissue damage (days 14, 35), improved motor (days 1 to 7), and Morris water maze performance (days 8 to 14) after CCI. Improved spatial memory was observed even when drug was administered 15 mins after CCI. Necrostatin-1 treatment did not reduce caspase-3-positive cells in the dentate gyrus or cortex, consistent with a known caspase-independent mechanism of necrostatin-1. However, necrostatin-1 reduced brain neutrophil influx and microglial activation at 48 h, suggesting a novel anti-inflammatory effect in traumatic brain injury (TBI). The data suggest that necroptosis plays a significant role in the pathogenesis of cell death and functional outcome after TBI and that necrostatin-1 may have therapeutic potential for patients with TBI

Three-Dimensional Dynamical Instabilities in Galactic Ionization Fronts

Ionization front instabilities have long been of interest for their suspected role in a variety of phenomena in the galaxy, from the formation of bright rims and 'elephant trunks' in nebulae to triggered star formation in molecular clouds. Numerical treatments of these instabilities have historically been limited in both dimensionality and input physics, leaving important questions about their true evolution unanswered. We present the first three-dimensional radiation hydrodynamical calculations of both R-type and D-type ionization front instabilities in galactic environments (i.e., solar metallicity gas). Consistent with linear stability analyses of planar D-type fronts, our models exhibit many short-wavelength perturbations growing at early times that later evolve into fewer large-wavelength structures. The simulations demonstrate that both self-consistent radiative transfer and three-dimensional flow introduce significant morphological differences to unstable modes when compared to earlier two-dimensional approximate models. We find that the amplitude of the instabilities in the nonlinear regime is primarily determined by the efficiency of cooling within the shocked neutral shell. Strong radiative cooling leads to long, extended structures with pronounced clumping while weaker cooling leads to saturated modes that devolve into turbulent flows. These results suggest that expanding H II regions may either promote or provide turbulent support against the formation of later generations of stars, with potential consequences for star formation rates in the galaxy today.Comment: 16 pages, 9 figures, accepted to Ap

Interactions Between Transient and Sustained Neural Signals Support the Generation and Regulation of Anxious Emotion

Anxious emotion can manifest on brief (threat response) and/or persistent (chronic apprehension and arousal) timescales, and prior work has suggested that these signals are supported by separable neural circuitries. This fMRI study utilized a mixed block-event–related emotional provocation paradigm in 55 healthy participants to simultaneously measure brief and persistent anxious emotional responses, testing the specificity of, and interactions between, these potentially distinct systems. Results indicated that components of emotional processing networks were uniquely sensitive to transient and sustained anxious emotion. Whereas the amygdala and midbrain showed only transient responses, the ventral basal forebrain and anterior insula showed sustained activity during extended emotional contexts that tracked positively with task-evoked anxiety. States of lesser anxiety were associated with greater sustained activity in the ventromedial prefrontal cortex. Furthermore, ventromedial prefrontal recruitment was lower in individuals with higher scores on intolerance of uncertainty measures, and this hyporecruitment predicted greater transient amygdala responding to potential threat cues. This work demonstrates how brain circuitries interact across temporal scales to support brief and persistent anxious emotion and suggests potentially divergent mechanisms of dysregulation in clinical syndromes marked by brief versus persistent symptoms of anxiety.Psycholog