With the dramatic advances made in Microsystems industry, System-on-a-Package (SOP) technology holds promise in terms of reduction in size, cost, and improved performance. To be able to achieve such ...benefits in an integrated system, it is necessary not to compromise the overall reliability of the system. Therefore, the SOP technology will require up-front system-level design-for-reliability approaches and appropriate reliability assessment methodologies to ensure the reliability of digital, optical, and RF functions as well as their interfaces. Design-for-reliability requires (i) Mechanics-based reliability prediction models for various failure mechanisms associated with Digital, Optical, and RF Functions, and their interfaces in the system (ii) Design optimization models for the selection of suitable materials and processing conditions, for reliability as well as functionality and (iii) System-level reliability models understanding the component and functional interaction. This presentation will focus on the reliability assessment of digital, optical, and RF functions in SOP-based microsystems 1. Upfront physics-based design-for-reliability models for various functional failure mechanisms are presented to evaluate various design options and material selection even before the prototypes are made. Advanced modeling methodologies and algorithms to accommodate material length scale effects, due to enhanced system integration and miniaturization are presented. System-level mixed-signal reliability is discussed thorough system-level reliability metrics relating component level failure mechanisms to system-level signal integrity as well as statistical aspects.
Structural variants (SVs) are an important source of human genetic diversity, but their contribution to traits, disease and gene regulation remains unclear. We mapped cis expression quantitative ...trait loci (eQTLs) in 13 tissues via joint analysis of SVs, single-nucleotide variants (SNVs) and short insertion/deletion (indel) variants from deep whole-genome sequencing (WGS). We estimated that SVs are causal at 3.5-6.8% of eQTLs-a substantially higher fraction than prior estimates-and that expression-altering SVs have larger effect sizes than do SNVs and indels. We identified 789 putative causal SVs predicted to directly alter gene expression: most (88.3%) were noncoding variants enriched at enhancers and other regulatory elements, and 52 were linked to genome-wide association study loci. We observed a notable abundance of rare high-impact SVs associated with aberrant expression of nearby genes. These results suggest that comprehensive WGS-based SV analyses will increase the power of common- and rare-variant association studies.
Reaction optimization is fundamental to synthetic chemistry, from optimizing the yield of industrial processes to selecting conditions for the preparation of medicinal candidates
. Likewise, ...parameter optimization is omnipresent in artificial intelligence, from tuning virtual personal assistants to training social media and product recommendation systems
. Owing to the high cost associated with carrying out experiments, scientists in both areas set numerous (hyper)parameter values by evaluating only a small subset of the possible configurations. Bayesian optimization, an iterative response surface-based global optimization algorithm, has demonstrated exceptional performance in the tuning of machine learning models
. Bayesian optimization has also been recently applied in chemistry
; however, its application and assessment for reaction optimization in synthetic chemistry has not been investigated. Here we report the development of a framework for Bayesian reaction optimization and an open-source software tool that allows chemists to easily integrate state-of-the-art optimization algorithms into their everyday laboratory practices. We collect a large benchmark dataset for a palladium-catalysed direct arylation reaction, perform a systematic study of Bayesian optimization compared to human decision-making in reaction optimization, and apply Bayesian optimization to two real-world optimization efforts (Mitsunobu and deoxyfluorination reactions). Benchmarking is accomplished via an online game that links the decisions made by expert chemists and engineers to real experiments run in the laboratory. Our findings demonstrate that Bayesian optimization outperforms human decisionmaking in both average optimization efficiency (number of experiments) and consistency (variance of outcome against initially available data). Overall, our studies suggest that adopting Bayesian optimization methods into everyday laboratory practices could facilitate more efficient synthesis of functional chemicals by enabling better-informed, data-driven decisions about which experiments to run.
Summary
Microglia, the primary resident immune cells of the central nervous system (CNS), exhibit dynamic behavior involving rapid process motility and cellular migration that is thought to underlie ...key functions of immune surveillance and tissue repair. Although age‐related changes in microglial activation have been implicated in the pathogenesis of neurodegenerative diseases of aging, how dynamic behavior in microglia is influenced by aging is not fully understood. In this study, we employed live imaging of retinal microglia in situ to compare microglial morphology and behavioral dynamics in young and aged animals. We found that aged microglia in the resting state have significantly smaller and less branched dendritic arbors, and also slower process motilities, which probably compromise their ability to survey and interact with their environment continuously. We also found that dynamic microglial responses to injury were age‐dependent. While young microglia responded to extracellular ATP, an injury‐associated signal, by increasing their motility and becoming more ramified, aged microglia exhibited a contrary response, becoming less dynamic and ramified. In response to laser‐induced focal tissue injury, aged microglia demonstrated slower acute responses with lower rates of process motility and cellular migration compared with young microglia. Interestingly, the longer term response of disaggregation from the injury site was retarded in aged microglia, indicating that senescent microglial responses, while slower to initiate, are more sustained. Together, these altered features of microglial behavior at rest and following injury reveal an age‐dependent dysregulation of immune response in the CNS that may illuminate microglial contributions to age‐related neuroinflammatory degeneration.
Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stressors, predisposing to major adverse clinical outcomes, including ...hospitalization, institutionalization, disability, and death in the general population of older adults. As the proportion of older adults living with HIV increases in the era of antiretroviral therapy, frailty is increasingly recognized to be of significant clinical and public health relevance to the HIV-infected population. This article reviews current knowledge on the epidemiology and biology of frailty and its potential role as a target for reducing disparities in outcomes in HIV; conceptual frameworks and current approaches to frailty measurement; existing data on frailty interventions; and important areas for future research focus necessary to develop and advance effective strategies to prevent or ameliorate frailty and its marked adverse consequences among people living with HIV.
Abstract
More than half of astronauts returning from long-duration missions on the International Space Station present with neuro-ocular structural and/or functional changes, including optic disc ...edema, optic nerve sheath distension, globe flattening, choroidal folds, or hyperopic shifts. This spaceflight-associated neuro-ocular syndrome (SANS) represents a major risk to future exploration class human spaceflight missions, including Mars missions. Although the exact pathophysiology of SANS is unknown, evidence thus far suggests that an increase in intracranial pressure (ICP) relative to the upright position on Earth, which is due to the loss of hydrostatic pressure gradients in space, may play a leading role. This review focuses on brain physiology in the spaceflight environment, specifically on how spaceflight may affect ICP and related indicators of cranial compliance, potential factors related to the development of SANS, and findings from spaceflight as well as ground-based spaceflight analog research studies.
We evaluated the prospective association of mitochondrial DNA copy number (mtDNA CN) with markers of kidney function among a cohort of persons who inject drugs (PWID). This is a Prospective cohort ...study nested in the AIDS linked to the intravenous experience cohort (community-based cohort of PWID in Baltimore, MD). mtDNA CN was measured at two time-points 5 years apart using a real-time polymerase chain reaction. Kidney function (estimated glomerular filtration rate eGFR, serum creatinine, urine protein) was measured annually. We used linear mixed effects models to evaluate kidney function trajectories (N = 946) and Cox regression models to assess hazard of incident CKD (eGFR < 60 at two consecutive visits, N = 739) and proteinuria (urine protein:creatinine ratio > 200, N = 573) by level of mtDNA CN (Low lowest quartile, vs high other three quartiles. Models were adjusted for demographic and behavioral characteristics, HIV and/or HCV infection, and comorbidity burden. Low mtDNA CN was independently associated with higher hazard of incident CKD (aHR: 2.33, 95% CI 1.42, 3.80) and proteinuria (aHR: 1.42, 95% CI 1.04, 1.96). Participants with low mtDNA CN had greater declines in eGFR and greater increases in serum creatinine over time. Low mtDNA CN is associated with more rapid kidney function decline and risk of incident CKD and proteinuria.
Elephantiasic Pretibial Myxedema Damani, Zaheed; Haber, Richard M.
Journal of cutaneous medicine and surgery,
05/2022, Letnik:
26, Številka:
3
Journal Article
Purpose of Review
While the characteristics associated with frailty in people with HIV (PWH) have been well described, little is known regarding interventions to slow or reverse frailty. Here we ...review interventions to prevent or treat frailty in the general population and in people with HIV (PWH).
Recent Findings
Frailty interventions have primarily relied on nonpharmacologic interventions (e.g., exercise and nutrition). Although few have addressed frailty, many of these therapies have shown benefit on components of frailty including gait speed, strength, and low activity among PWH. When nonpharmacologic interventions are insufficient, pharmacologic interventions may be necessary. Many interventions have been tested in preclinical models, but few have been tested or shown benefit among older adults with or without HIV.
Summary
Ultimately, pharmacologic and nonpharmacologic interventions have the potential to improve vulnerability that underlies frailty in PWH, though clinical data is currently sparse.
Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to ...health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline.
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