Comparison of post-Newtonian templates for extreme mass ratio inspirals

Extreme mass ratio inspirals (EMRIs), the inspirals of compact objects into supermassive black holes, are important gravitational wave sources for the Laser Interferometer Space Antenna (LISA). We study the performance of various post-Newtonian (PN) template families relative to the high precision numerical waveforms in the context of EMRI parameter estimation with LISA. Expressions for the time domain waveforms TaylorT1, TaylorT2, TaylorT3, TaylorT4 and TaylorEt are derived up to 22PN order, i.e $\mathcal{O}(v^{44})$ ($v$ is the characteristic velocity of the binary) beyond the Newtonian term, for a test particle in a circular orbit around a Schwarzschild black hole. The phase difference between the above 22PN waveform families and numerical waveforms are evaluated during two-year inspirals for two prototypical EMRI systems with mass ratios $10^{-4}$ and $10^{-5}$. We find that the dephases (in radians) for TaylorT1 and TaylorT2, respectively, are about $10^{-9}$ ($10^{-2}$) and $10^{-9}$ ($10^{-3}$) for mass ratio $10^{-4}$ ($10^{-5}$). This suggests that using 22PN TaylorT1 or TaylorT2 waveforms for parameter estimation of EMRIs will result in accuracies comparable to numerical waveform accuracy for most of the LISA parameter space. On the other hand, from the dephase results, we find that TaylorT3, TaylorT4 and TaylorEt fare relatively poorly as one approaches the last stable orbit. This implies that, as for comparable mass binaries using the 3.5PN phase of waveforms, the 22PN TaylorT3 and TaylorEt approximants do not perform well enough for the EMRIs. The reason underlying the poor performance of TaylorT3, TaylorT4 and TaylorEt relative to TaylorT1 and TaylorT2 is finally examined.Comment: 10 page

Daily physical activity patterns during the early stage of Alzheimer’s disease

Background - Alzheimer’s disease (AD) is a neurodegenerative disease that results in severe disability. Very few studies have explored changes in daily physical activity patterns during early stages of AD when components of physical function and mobility may be preserved. Methods - Patients with mild AD and controls (n=92) recruited from the University of Kansas Alzheimer’s Disease Center Registry, wore the Actigraph GT3X+ for seven days, and provided objective physical function (VO2 max) and mobility data. Using multivariate linear regression, we explored whether individuals with mild AD had different daily average and diurnal physical activity patterns compared to controls independent of non-cognitive factors that may affect physical activity, including physical function and mobility. Results - We found that mild AD was associated with less moderate-intensity physical activity (p<0.05), lower peak activity (p<0.01), and lower physical activity complexity (p<0.05) particularly during the morning. Mild AD was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for non-cognitive covariates. Conclusions - These findings suggest that factors independent of physical capacity and mobility may drive declines in moderate-intensity physical activity, and not lower-intensity or sedentary activity, during the early stage of AD. This underscores the importance of a better mechanistic understanding of how cognitive decline and AD pathology impact physical activity. Findings emphasize the potential value of designing and testing time-of-day specific physical activity interventions targeting individuals in the early stages of AD, prior to significant declines in mobility and physical function

The association between physical activity and cognition: the Baltimore Experience Corps Trial

Abstract Background Because of population aging, the number of people with AD is expected to triple (11-16 million) by 2050. Over the past decade pharmaceutical interventions focused on AD have had minimal success in targeting the underlying pathology of the disease and modifying disease course. Because of these difficulties, research focus has recently expanded from disease modifying pharmaceutical therapies to lifestyle interventions. Physical activity in particular may have beneficial effects on cognition and brain health, however older adults – especially those with socio-demographic risk factors – are becoming increasingly inactive and have difficulty initiating and adhering to exercise programs. Understanding and evaluating the nature of the benefits of low-intensity activity, the characteristics of dose required to achieve health benefits, and the mechanisms of change particularly within low socio-economic status (SES) populations is essential to designing sustainable lifestyle interventions that can be easily and effectively integrated into communities. The aims of this dissertation are to 1) better characterize and understand the relationship between objectively measured low-intensity physical activity and cognition; 2) inform the feasibility of a civic-engagement volunteer service program to increase physical activity in a socio-demographically at risk population; and 3) explore the potential of objective physical activity devices to be used as biometric signals of disability. Methods The study sample is from the Baltimore Experience Corps Trial (BECT), an intention-to-treat, randomized, controlled effectiveness trial, and the Brian Health Study (BHS), a substudy within the BECT. Physical activity was measured using both objective and self-report measures. Cognitive measures included domain specific psychometric measures and neuroimaging measures obtained from structural brain imaging. Physical function measures included both performance-based and self-report measures. Results Objective measures of physical activity within the low-intensity range were associated in cross-section with physical function and both behavioral and structural measures of brain structure. These objective measures, which are important in order to characterize physical activity and change particularly within the low-intensity range, captured increases in total and low-intensity walking activity associated with the intervention in women within the BECT, and a decrease in moderate- to vigorous-intensity walking activity in men. Self-report measures of physical activity did not sensitively capture low-intensity physical activity or the relationship between physical activity and cognition; however, as expected, sensitively captured moderate- to vigorous physical activity and its association with physical function. Self-report measures additionally indicated declines across both intervention arms in women within the BECT and marginal negative intervention effects particularly in moderate- to vigorous-intensity physical activity, and captured declines in the control group for men, and positive intervention effects at 24 months. Objective measures are extremely useful in order to sensitively capture physical activity, and can be used in order to better measure and understand the relationship between physical function/ activity and cognition

Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study.

BACKGROUND: There is growing evidence that Alzheimer disease (AD) is a pervasive metabolic disorder with dysregulation in multiple biochemical pathways underlying its pathogenesis. Understanding how perturbations in metabolism are related to AD is critical to identifying novel targets for disease-modifying therapies. In this study, we test whether AD pathogenesis is associated with dysregulation in brain transmethylation and polyamine pathways. METHODS AND FINDINGS: We first performed targeted and quantitative metabolomics assays using capillary electrophoresis-mass spectrometry (CE-MS) on brain samples from three groups in the Baltimore Longitudinal Study of Aging (BLSA) (AD: n = 17; Asymptomatic AD [ASY]: n = 13; Control [CN]: n = 13) (overall 37.2% female; mean age at death 86.118 ± 9.842 years) in regions both vulnerable and resistant to AD pathology. Using linear mixed-effects models within two primary brain regions (inferior temporal gyrus [ITG] and middle frontal gyrus [MFG]), we tested associations between brain tissue concentrations of 26 metabolites and the following primary outcomes: group differences, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (neuritic plaque burden), and Braak (neurofibrillary pathology) scores. We found significant alterations in concentrations of metabolites in AD relative to CN samples, as well as associations with severity of both CERAD and Braak, mainly in the ITG. These metabolites represented biochemical reactions in the (1) methionine cycle (choline: lower in AD, p = 0.003; S-adenosyl methionine: higher in AD, p = 0.005); (2) transsulfuration and glutathione synthesis (cysteine: higher in AD, p < 0.001; reduced glutathione [GSH]: higher in AD, p < 0.001); (3) polyamine synthesis/catabolism (spermidine: higher in AD, p = 0.004); (4) urea cycle (N-acetyl glutamate: lower in AD, p < 0.001); (5) glutamate-aspartate metabolism (N-acetyl aspartate: lower in AD, p = 0.002); and (6) neurotransmitter metabolism (gamma-amino-butyric acid: lower in AD, p < 0.001). Utilizing three Gene Expression Omnibus (GEO) datasets, we then examined mRNA expression levels of 71 genes encoding enzymes regulating key reactions within these pathways in the entorhinal cortex (ERC; AD: n = 25; CN: n = 52) and hippocampus (AD: n = 29; CN: n = 56). Complementing our metabolomics results, our transcriptomics analyses also revealed significant alterations in gene expression levels of key enzymatic regulators of biochemical reactions linked to transmethylation and polyamine metabolism. Our study has limitations: our metabolomics assays measured only a small proportion of all metabolites participating in the pathways we examined. Our study is also cross-sectional, limiting our ability to directly test how AD progression may impact changes in metabolite concentrations or differential-gene expression. Additionally, the relatively small number of brain tissue samples may have limited our power to detect alterations in all pathway-specific metabolites and their genetic regulators. CONCLUSIONS: In this study, we observed broad dysregulation of transmethylation and polyamine synthesis/catabolism, including abnormalities in neurotransmitter signaling, urea cycle, aspartate-glutamate metabolism, and glutathione synthesis. Our results implicate alterations in cellular methylation potential and increased flux in the transmethylation pathways, increased demand on antioxidant defense mechanisms, perturbations in intermediate metabolism in the urea cycle and aspartate-glutamate pathways disrupting mitochondrial bioenergetics, increased polyamine biosynthesis and breakdown, as well as abnormalities in neurotransmitter metabolism that are related to AD

Detection of Toxigenic and Atoxigenic Strains of Aspergillus flavus in Telangana and Andhra Pradesh

In groundnut Aspergillus flavus causes aflatoxin contamination which is a qualitative problem occurring at both pre-and post-harvest stages. These aflatoxins have carcinogenic, hepatotoxic, teratogenic and immuno-suppressive effects. The A. flavus strains which produces aflatoxins are called as toxigenic and which do not produce toxins are called as atoxigenic starins. To detect the toxigenic and atoxigenic starins of A. flavus from Telangana and Andhra Pradesh (AP), pod samples were collected from eight selected oil mills/traders’ in Mahaboobnagar, Rangareddy, Nizamabad, Karimnagar (Telangana); and Anantapur (AP) districts. A total of 24 A. flavus cultures were isolated from the collected pod samples. These isolates were identified as toxigenic/atoxigenic using cultural detection methods on Yeast extract sucrose (YES) media and coconut agar medium (CAM). Based on cultural methods, it was confirmed that there were18 toxigenic, five atoxigenic and one false positive/negative strain out of the 24 A. flavus isolates obtained from surveyed oil mills. Atoxigenic strains were obtained from Karimnagar and Nizamabad districts of Telangana

Human resource management in the age of generative artificial intelligence::Perspectives and research directions on ChatGPT

ChatGPT and its variants that use generative artificial intelligence (AI) models have rapidly become a focal point in academic and media discussions about their potential benefits and drawbacks across various sectors of the economy, democracy, society, and environment. It remains unclear whether these technologies result in job displacement or creation, or if they merely shift human labour by generating new, potentially trivial or practically irrelevant, information and decisions. According to the CEO of ChatGPT, the potential impact of this new family of AI technology could be as big as “the printing press”, with significant implications for employment, stakeholder relationships, business models, and academic research, and its full consequences are largely undiscovered and uncertain. The introduction of more advanced and potent generative AI tools in the AI market, following the launch of ChatGPT, has ramped up the “AI arms race”, creating continuing uncertainty for workers, expanding their business applications, while heightening risks related to well‐being, bias, misinformation, context insensitivity, privacy issues, ethical dilemmas, and security. Given these developments, this perspectives editorial offers a collection of perspectives and research pathways to extend HRM scholarship in the realm of generative AI. In doing so, the discussion synthesizes the literature on AI and generative AI, connecting it to various aspects of HRM processes, practices, relationships, and outcomes, thereby contributing to shaping the future of HRM research

HemaMax™, a Recombinant Human Interleukin-12, Is a Potent Mitigator of Acute Radiation Injury in Mice and Non-Human Primates

HemaMax, a recombinant human interleukin-12 (IL-12), is under development to address an unmet medical need for effective treatments against acute radiation syndrome due to radiological terrorism or accident when administered at least 24 hours after radiation exposure. This study investigated pharmacokinetics, pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12), and HemaMax to increase survival after total body irradiation (TBI) in mice and rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an optimal 20 ng/mouse dose significantly increased percent survival and survival time when administered 24 hours after TBI between 8–9 Gy (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by increases in plasma interferon-γ (IFN-γ) and erythropoietin levels, recovery of femoral bone hematopoiesis characterized with the presence of IL-12 receptor β2 subunit–expressing myeloid progenitors, megakaryocytes, and osteoblasts. Mitigation of jejunal radiation damage was also examined. At allometrically equivalent doses, HemaMax showed similar pharmacokinetics in rhesus monkeys compared to m-HemaMax in mice, but more robustly increased plasma IFN-γ levels. HemaMax also increased plasma erythropoietin, IL-15, IL-18, and neopterin levels. At non-human primate doses pharmacologically equivalent to murine doses, HemaMax (100 ng/Kg and 250 ng/Kg) administered at 24 hours after TBI (6.7 Gy/LD50/30) significantly increased percent survival of HemaMax groups compared to vehicle (p<0.05 Pearson's chi-square test). This survival benefit was accompanied by a significantly higher leukocyte (neutrophils and lymphocytes), thrombocyte, and reticulocyte counts during nadir (days 12–14) and significantly less weight loss at day 12 compared to vehicle. These findings indicate successful interspecies dose conversion and provide proof of concept that HemaMax increases survival in irradiated rhesus monkeys by promoting hematopoiesis and recovery of immune functions and possibly gastrointestinal functions, likely through a network of interactions involving dendritic cells, osteoblasts, and soluble factors such as IL-12, IFN-γ, and cytoprotectant erythropoietin