cssi/SciSciGPT-SciSciNet huggingface dataset:
Transcriptomic Segregation of Human Autoantigens Useful for the Diagnosis of Autoimmune Diseases

The measurement of autoantibodies in the clinical care of autoimmune patients allows for diagnosis, monitoring, and even disease prediction. Despite their clinical utility, the functional significance of autoantibody target proteins in many autoimmune diseases remains unclear. Here we present a comprehensive review of 52 autoantigens commonly employed for the serological diagnosis of 24 autoimmune diseases. We discuss their function, whether they have extracellular-exposed epitopes, and whether antibodies to these proteins are known to be pathogenic. Transcriptomics (RNA-Seq) datasets were mined to display messenger RNA (mRNA) expression of the autoantigens across 32 tissues and organs. This analysis revealed that autoantigens cluster into one of three groups: expression in the tissue most strongly affected in the disease (Group I), ubiquitous expression with enrichment in immune tissues (Group II), or expression in other tissues not typically associated with the clinical presentation (Group III). Clustering demonstrated that the autoantigens within Group I were often proteins containing extracellular epitopes, many of which are targets of pathogenic autoantibodies. Group II autoantigens were targets for several rheumatological diseases, including Sjogren syndrome, systemic lupus erythematosus, myositis, and systemic sclerosis, and were ubiquitously expressed with enrichment in immune-rich tissues. This raises the possibility that immune cells in Group II disorders may be the source of autoimmunization and/or targets of immune cell responses. Since tissues showing enriched autoantigen gene expression may contribute to the development of autoantibodies and subsequent autoimmunity, the emergent patterns arising from the autoantigen transcriptomic profiles may provide a new heuristic framework to deconvolute these complex disorders.
Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes

Among immunocompromised individuals, members of the human Herpesviridae family are frequently encountered pathogens. Cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus, Epstein-Barr virus, and human herpesvirus-6, -7, and -8 all establish latency after infection and can reactivate during periods of immunosuppression, leading to both direct and indirect adverse effects on the host including severe organ dysfunction as well as allograft rejection and loss after transplantation. While not all herpesviruses are primary respiratory pathogens, many of their manifestations include involvement of the respiratory tract. This article discusses the individual viruses, their epidemiology, and clinical manifestations as well as recommended treatment and preventive strategies.
Overview of an Emerging Standard on Architecture Processes – ISO/IEC 42020

A new, emerging standard on architecture practices is under development as ISO/IEC 42020. This paper provides an overview of the key concepts in this standard and the rationale for these ideas. The standard defines six architecture-related processes: governance, management, conceptualization, evaluation, elaboration, and enablement. These are comprised of 37 activities, having five to eight tasks specified for each activity. It is expected that these processes will be incorporated into the next version of INCOSE's Systems Engineering Handbook and in the Guide to the Systems Engineering Body of Knowledge. This standard can be used as a foundation for organizational training and guidebooks on architecture management and development.
A Photon Counting Microspectrophotometer for the Study of Single Vertebrate Photoreceptor Cells

In order to have a satisfactory description of how the visual system works, particularly a description on which one can base adequate quantitative as well as qualitative theories of visual function, including both normal and abnormal color perception, it’s obviously necessary to understand how photoreceptor cells transduce light signals. This paper concerns two techniques that may be useful in improving our knowledge in this area. The first is an improved microspectrophotometer for studying the pigments in single receptors. The second is a microchemical technique for the measurement of light induced reactions in single receptor outer segments. To begin with I would like to go briefly into some of the history of single receptor microspectrophotometry. Until reasonably accurate measurements on single cones in the goldfish were reported by MARKS and myself (1), MARKS (2, 3), and confirmed by LIEBMAN and ENTINE (4), and in human and rhesus monkey receptors by MARKS, DOBELLE and MACNICHOL, (5), and by BROWN and WALD (6), there was no direct evidence that there are three kinds of cones each having a different pigment in organisms known to have trichromatic vision, although much indirect evidence has accumulated over the course of many years from psychophysical and behavioral measurements, the study of defective color perception, and more recently, retinal densitometry. However, for a variety of reasons, the promising work on primate cones of the early 1960’s was soon dropped in the two laboratories in which it was done. Although LIEBMAN has reported confirmatory work, neither he nor anyone else to my knowledge has published any more data on single primate cones since then.
CYTOKERATIN 6 EXPRESSION IN PROSTATE STEM CELLS

The simplified epithelium of the human prostate gland is representative of a slowly growing but morphologically dynamic tissue. The normal prostate gland contains, in part, the persistent basal cell population and the putative stem cells. It has been postulated by others that the transformation of normal glandular structures into cancer glands and subsequent tumor progression may involve aberrant regulation of the stem cell population. In this chapter, the induction of cytokeratin 6 expression is postulated to participate in the transition of a stem cell from its specialized niche within the basal cell population into a differentiated state. The basic morphological features of the normal prostate gland are reviewed and the molecular features of the prostate stem cells are discussed. Data is presented to illustrate the defining features of a new epithelial phenotype in the prostate gland, containing both cytokeratin 6 expression and the capability to differentiate and reach from the basal cell layer to the luminal surface of the gland. These results underscore the plasticity of the epithelial cell layers and the potential for cytokeratin 6 to serve as an efficient marker for an important subset of the basal cell population. Further investigation will be required in animal models to determine the essential nature of the cytokeratin 6 expression for the normal development of the prostate gland.
Application of a Risk Score to Identify Older Adults with Community-Onset Pneumonia Most Likely to Benefit From Empiric Pseudomonas Therapy.

tudy Objective To assess the impact of empiric Pseudomonas pharmacotherapy on 30-day mortality in hospitalized patients with community-onset pneumonia stratified according to their risk (low, medium, or high) of drug-resistant pathogens. Design Retrospective cohort study. Data Source Veterans Health Administration database. Patients A total of 50,119 patients who were at least 65 years of age, hospitalized with pneumonia, and received antibiotics within 48 hours of admission between fiscal years 2002 and 2007; patients were stratified into empiric Pseudomonas therapy (31,027 patients) and no Pseudomonas therapy (19,092 patients) groups based on antibiotics received during their first 48 hours of admission. Measurements and Main Results: Results A recently developed clinical prediction scoring system that stratifies patients with community-onset pneumonia according to their risk of drug-resistant pathogens was used to identify patients who were likely to benefit from empiric Pseudomonas therapy as well as those in whom antipseudomonal therapy could be spared; patients were classified into low-risk (68%), medium-risk (21%), and high-risk (11%) groups. Of the 50,119 patients, 62% received Pseudomonas therapy. All-cause 30-day mortality was the primary outcome. Empiric Pseudomonas therapy (adjusted odds ratio 0.72, 95% confidence interval 0.62-0.84) was associated with lower 30-day mortality in the high-risk group but not the low- or medium-risk groups. Conclusion Application of a risk score for patients with drug-resistant pathogens can identify patients likely to benefit from empiric Pseudomonas therapy. Widespread use of this score could reduce overuse of anti-Pseudomonas antibiotics in low- to medium-risk patients and improve survival in high-risk patients. This article is protected by copyright. All rights reserved.
Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells

Apigenin (4',5,7,-trihydroxyflavone) is a flavonoid found in certain herbs, fruits, and vegetables. Apigenin can attenuate inflammation, which is associated with many chronic diseases of aging. Senescent cells-stressed cells that accumulate with age in mammals-display a pro-inflammatory senescence-associated secretory phenotype (SASP) that can drive or exacerbate several age-related pathologies, including cancer. Flavonoids, including apigenin, were recently shown to reduce the SASP of a human fibroblast strain induced to senesce by bleomycin. Here, we confirm that apigenin suppresses the SASP in three human fibroblast strains induced to senesce by ionizing radiation, constitutive MAPK (mitogen-activated protein kinase) signaling, oncogenic RAS, or replicative exhaustion. Apigenin suppressed the SASP in part by suppressing IL-1α signaling through IRAK1 and IRAK4, p38-MAPK, and NF-κB. Apigenin was particularly potent at suppressing the expression and secretion of CXCL10 (IP10), a newly identified SASP factor. Further, apigenin-mediated suppression of the SASP substantially reduced the aggressive phenotype of human breast cancer cells, as determined by cell proliferation, extracellular matrix invasion, and epithelial-mesenchymal transition. Our results support the idea that apigenin is a promising natural product for reducing the impact of senescent cells on age-related diseases such as cancer.
Speaking Stones: Material Agency and Interaction in Christian Enzensberger’s Geschichte der Natur

This chapter investigates the agentic dimensions of pebbles in Christian Enzensberger’s Nicht Eins und Doch: Geschichte der Natur. While stone is a material usually scorned for its inanimateness and has been infamously denounced as “worldless” by Martin Heidegger, Enzensberger lends stone a voice, thus defying a longstanding hierarchy that since the Middle Ages has placed lithic matter at the very bottom of worldly existence. Yet Enzensberger’s novel can be read as a continuation and expansion of Heidegger’s essay “Der Feldweg.” In an experimental, multilingual, and imaginative narrative about sensual encounters with the nonhuman world, Enzensberger’s text elucidates a greater range of human experience that emerges when humans give up their claim to exclusive agency to explore, in reversed manner, their entanglement with the earth.
Bag of works retrieval: TF*IDF weighting of works co-cited with a seed

Although not presently possible in any system, the style of retrieval described here combines familiar components—co-citation linkages of documents and TF*IDF weighting of terms—in a way that could be implemented in future databases. Rather than entering keywords, the user enters a string identifying a work—a seed—to retrieve the strings identifying other works that are co-cited with it. Each of the latter is part of a “bag of works,” and it presumably has both a co-citation count with the seed and an overall citation count in the database. These two counts can be plugged into a standard formula for TF*IDF weighting such that all the co-cited items can be ranked for relevance to the seed, given that the entire retrieval is relevant to it by evidence from multiple co-citing authors. The result is analogous to, but different from, traditional “bag of words” retrieval, which it supplements. Some properties of the ranking are illustrated by works co-cited with three seeds: an article on search behavior, an information retrieval textbook, and an article on centrality in networks. While these are case studies, their properties apply to bag of works retrievals in general and have implications for users (e.g., humanities scholars, domain analysts) that go beyond any one example.
Benchmark Free Energies and Entropies for Saturated and Compressed Water

We use molecular simulation to compute the thermodynamic properties of 7 rigid models for water (SPC/E, TIP3P, TIP4P, TIP4P/2005, TIP4P/Ew, TIP5P, OPC) over a wide range of temperature and pressure. Carrying out expanded Wang–Landau simulations, we obtain a high accuracy estimate for the grand-canonical partition function which, in turn, provides access to all properties, including the free energy and entropy, both at the vapor–liquid coexistence and for compressed water. The results at coexistence highlight the close connection between the behavior of the statistical functions and the thermodynamic properties. They show that the subgroup {SPC/E,TIP4P/2005,TIP4P/Ew} provides the most accurate account of the vapor–liquid equilibrium properties. For compressed water, the comparison of the simulation results to the experimental data establishes that the TIP4P/Ew model performs best among the 7 models considered here, and captures the experimental trends for the dependence of entropy and molar Gibbs free ener...
MMICs for next generation radar

The rapid progress towards 5G wireless systems is accelerating the development of mm-wave semiconductor processes, broadband circuits, and system technologies. Similarly, next-generation radar is being expanded and redefined. Legacy radar systems are nearing the end of their life cycle and systems developers are aiming to upgrade their capability while reducing cost, size, and weight. Radar systems have requirements that result in technical circuit design challenges including high power, broadband, and low distortion. This paper focuses on MMIC design challenges specific to the design of next-generation radars that will operate in a crowded wireless environment, allow spectrum sharing, and dynamic frequency selection. Simulated and measured data are presented.
Warm Temperature of Birds and Mammals

Velocities of reactions in tissues and the rates of application of power to the operation of vital machinery are in general increased by warmth and depressed by cold. So the cold-blooded organisms act only as rapidly as their temperature permits, at levels imposed by their surroundings. Some poikilotherms can adapt their essential metabolism to some extent to the climate in their geographical range, and some adjustments for optimal activity can suit them for operation in the changing temperatures of the seasons. These adjustments are limited, slow and inflexible in relation to the daily and seasonal fluctuations that are so marked in arctic climates. Freezing arrests productive metabolism in all organisms.
The Contribution of the Built Environment to Physical Activity Among Young Women

Physical activity (PA) tends to decline with age, but changes are influenced by individual and contextual factors. Identifying the relative contributions of each may be useful in addressing inactiv...
Activity monitoring in men’s college soccer: a single season longitudinal study

ABSTRACTPerformance in soccer has been characterized previously using time-motion analyses; however, it is unclear if men’s college soccer shares performance characteristics with women’s college or men’s professional soccer. The purpose of this study was to compare proportions of matches spent walking, jogging, running, and sprinting in men’s college soccer. Twenty-two male college soccer players wore global positioning system units during matches. Proportions of walking, jogging, running, high-speed running, and sprinting were calculated for each player based on time period (first half, second half, extra time) and outcome (win, loss, tie). Multivariate analyses of variance were run for each time period to compare positions. Means, 95% confidence intervals, and effect sizes were calculated for each position based on time period and match outcome. There were differences in low-speed and high-speed activities based on position, with forwards and midfielders demonstrating increased high-speed activities. Po...
Entamoeba Moshkoviskii as a causative agent of diarrhea in children

The present investigational study was intentionally aimed to detect of E.moshkoviskii in stool as the first study and new record in Iraq by using polymerase chain reaction technique. Additionally understand the prevalence of these three parasites (E.moshkoviskii, E.dispar, and E.histolytica) in the human population. Stool sampling of 190 specimens was performed from clinically recognized patients suffering diarrhea with an inflammatory feature from Al-Diwaniya Teaching Hospital, Maternity and Children Hospital, Afak general Hospital and some Hospitals in the province of Iraq. All samples undergo full history was distributed according to name, age, gender, address, bloody diarrhea and clinical symptoms. General stool examination was done to samples within 30 minutes. The samples were divided into two sterile containers the first one grown in media and the second two were kept frozen at -20 Ċ (deep freezing) for DNA extraction used for PCR. From extracted DNA was added 5µl in PCR tube (master mix) with 1.5 µl forward primer and 1.5µl reverse primer, then 12µl from nuclease-free water, all volume was completed to 20 µl. One hundred ninety stool samples were collected and examined by general stool examination positive for Entamoeba spp The present study showed the high prevalence of amoebiasis in rural area more than urban area, the result revealed that the infected patients in rural area 119 (62.6%) while in urban area 71 (37.3%) The present study revealed the high percentage (25.2%) of infection with gastrointestinal symptoms under the age of 14 years old and above the age of 45 years. In the present study was showed the PCR product was detected in 182 (96 %) samples, and 8 (4 %) were detected as negative utilizing PCR test. The present study concluded that presence of three-identical species of Entamoeba utilizing PCR to target stool-based DNA of patients expressing gastrointestinal symptoms (E.moshkoviskii, E. dispar, and E.histolytica) could be grown in modified Lock's – egg slant medium . The single round PCR described in this study is a specific and sensitive method for distinguishing between those species. Keywords: E.moshkoviskii; Polymerase chain reaction technique; Diarrhea.
Ecotoxicological effects of carbon nanotubes: test methods and current research

Abstract: Carbon nanotubes are an important class of nanomaterials with a broad range of potential commercial applications. One limitation to the commercialization of these products is the lack of a thorough understanding of the potential risks they may pose in the environment after their inadvertent or intentional release into ecosystems. The focus of this chapter is on the potential ecotoxicological risks of carbon nanotubes. Topics discussed in this chapter include quantification of carbon nanotubes in environmentally relevant media, methodological issues for ecotoxicity testing, important trends in the results obtained to date, and potential topics for future research.
Articulate Images: Bringing the Pictures of Science and Natural History into the Art Curriculum

What images should we study? Which have value? Which are significant? These questions lie at the heart of one of the most critical issues in art education today in the debate over whether the field should maintain a narrow focus on fine an or expand its scope to include all of visual culture. In this article, I argue for the inclusion of informational images in the content of art education. As examples of informational images, I focus on the pictures of science and natural history, which are visual forms not only integral to visual culture, but can be seen as opportunities for broadening and deepening our understanding of visual images, aesthetics, textuality and visuality.
Humans Before Settlements

In the first of three chapters about the origins of human settlements in deep history, Bowen and Gleeson use their general systems theory (GST) model of decision-making to synthesize information about how prehistoric people lived for at least 290,000 years before the first permanent settlements were created just 10,000 years ago. The GST approach allows readers to appreciate how prehistoric people adapted their hunter-gatherer cultures throughout the world, and how they thrived by evolving early agricultural behaviors to cultivate wild plants and animals in order to sustain their nomadic way of life. Today’s humans are much like their prehistoric ancestors.
Association of Hospitalization, Critical Illness, and Infection with Brain Structure in Older Adults

Objectives To examine the association between hospitalization, critical illness, and infection occurring during middle‐ and late‐life and structural brain abnormalities in older adults. Design Prospective cohort study. Setting Atherosclerosis Risk in Communities (ARIC) Study. Participants A community sample of adults who were 44 to 66 years of age at study baseline. Measurements Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision, codes) on all participants over a 24‐year surveillance period. Subsequently, a subset of participants underwent 3‐Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)). Results Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate‐adjusted regression, hospitalization was associated with 0.12–standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00–0.24) and poorer white matter microstructural integrity (0.17‐SD lower FA, 95% CI=–0.27 to –0.06; 0.16‐SD greater MD, 95% CI=0.07–0.25) than no hospitalization. There was a dose‐dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity (p‐trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (–1.64 cm3, 95% CI=–3.16 to –0.12); major infection was associated with smaller AD signature region (–1.28 cm3, 95% CI=–2.21 to –0.35) and larger ventricular volume (3.79 cm3, 95% CI= 0.81–6.77). Conclusions Whereas all‐cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD.
CS-19 Heart failure hospitalizations among SLE and diabetes mellitus patients compared to the general U.S. medicaid population

Background Both SLE and diabetes mellitus (DM) patients have elevated risks of atherosclerotic cardiovascular disease. Risk of heart failure (HF), an end-stage of cardiovascular disease and a leading cause of hospitalization in the U.S., is also elevated among DM patients, but has not been well studied in SLE. We investigated rates and risks of HF hospitalization among SLE patients compared to age- and sex-matched DM and general Medicaid patients. Methods We used Medicaid Analytic eXtract (MAX) data, containing billing claims for Medicaid patients from the 29 most populated US states 2007–2010. We identified SLE and DM patients, ages 18–65, using ≥3 ICD-9 codes for SLE or DM, each separated by ≥30 days. Index date was 3rd diagnosis code. We matched each SLE patient at index date to 2 DM patients and 4 general Medicaid patients without SLE or DM, by age at index date and sex. Baseline period was 6 months of continuous Medicaid enrollment prior to index date for all patients. Subjects were followed until death, disenrollment or end of follow-up. We used ICD-9 codes to identify HF hospital discharge diagnosis and calculated rates of first HF hospitalization event per 1000 person-years for each cohort. Cox proportional hazard models, accounting for competing risk of death, estimated hazard ratios (HR) for first HF hospitalization events. In a secondary analysis, we excluded those with baseline HF. Results 40,212 SLE patients were matched to 80,424 DM and 1 60 848 general patients. In all cohorts, 92% were female, and mean age was 40.3 (±12.1) years. Mean follow-up was 1.8 (±1.1) years for SLE, 1.8 (±1.1) years for DM, and 1.6 (±1.2) years for general patients. Baseline CVD was present in 18% of SLE, 13% of DM and 1% of non-SLE, non-DM cohorts, and baseline HF in 6% of SLE, 5% of DM and Conclusion SLE and DM patients had significantly higher rates of HF hospitalization than age- and sex-matched general Medicaid patients. The risk of HF hospitalization was >2 x higher among both SLE and DM patients, with important implications for improving care for SLE. Acknowledgements This study was funded by NIH K24 AR066109 and R01 AR057327.
Recent intensification of the seasonal rainfall cycle in equatorial Africa revealed by farmer perceptions, satellite-based estimates, and ground-based station measurements

Smallholder farmers and livestock keepers in sub-Saharan Africa are on the frontlines of climate variability and change. Yet, in many regions, a paucity of weather and climate data has prevented rigorous assessment of recent climate trends and their causes, thereby limiting the effectiveness of forecasts and other services for climate adaptation. In rainfed systems, farmer perceptions of changing rainfall and weather patterns are important precursors for annual cropping decisions. Here, we propose that combining such farmer perceptions of trends in seasonal rainfall with satellite-based rainfall estimates and climate station data can reduce uncertainties regarding regional climatic trends. In western Uganda, a rural and climatically complex transition zone between eastern and central equatorial Africa, data from 980 smallholder households suggest distinct changes in seasonal bimodal rainfall over recent decades, specifically wetter rainy seasons and drier dry seasons. Data from three satellite-based rainfall products beginning in 1983 largely corroborate respondent perceptions over the last 10–20 years, particularly in the southernmost sites near Queen Elizabeth National Park. In addition, combining all three information sources suggests an increasing trend in annual rainfall, most prominently in the north near Murchison Falls National Park over the past two decades; this runs counter to recent research asserting the presence of a drying trend in the region. Our study is unique in evaluating and cross-validating these multiple data sources to identify climatic change affecting people in a poorly understood region, while providing insights into regional-scale climate controls.
Proceedings of the 17th International Workshop on Mobile Computing Systems and Applications

It is our great pleasure to welcome you to the Seventeenth Workshop on Mobile Computing Systems and Applications -- HotMobile'16. This year's workshop continues the series of highly selective, interactive workshops focused on mobile applications, systems, and environments, as well as their underlying state-of-the-art technologies. HotMobile's small workshop format makes it ideal for processing and discussing new directions or controversial approaches. The call for papers attracted submissions from Asia, Europe, and the United States. The program committee reviewed and accepted 18 papers out of 55 submissions (acceptance rate 32%). We also encourage attendees to attend the keynote and invited talk presentations. These valuable and insightful talks can and will guide us to a better understanding of the future: Keynote: Hot or Not? Moving forward from Weiser's vision of ubiquitous computing -- Speaker: Gregory D. Abowd (School of Interactive Computing, Georgia Tech)
The Hardware Security Behind Azure Sphere

Traditional MCUs are price sensitive devices ill-prepared for the security challenges of internet connectivity. Azure Sphere MCUs are a new cross-over class of MCU with built-in Microsoft security technology, connectivity, and headroom to support dynamic new experiences. The MediaTek MT3620 combines ARM Cortex-A processor performance with real-time guarantees of an ARM Cortex-M class processor. It incorporates the Microsoft Pluton Security Subsystem to create a hardware root of trust, store private keys, and execute complex cryptographic operations. The MCU has built-in network connectivity to provide secure access to the cloud and the Azure Sphere Security Service. Azure Sphere OS is a secured OS that creates a trustworthy platform. It incorporates a custom Linux kernel, secured application containers, and security monitoring. The combination of the Pluton security hardware, Azure Sphere OS, and Azure Sphere Security Service provide certificate-based communications authentication, device and software authentication, device and application operation visibility, and secure updates.
Higher urate in LRRK2 mutation carriers resistant to Parkinson disease

OBJECTIVE LRRK2 mutations, the most common genetic cause of Parkinson disease (PD), display incomplete penetrance, indicating the importance of other genetic and environmental influences on disease pathogenesis in LRRK2 mutation carriers. The present study investigates whether urate, an antioxidant, Nrf2 activator, and inverse risk factor for idiopathic PD, is one such candidate biomarker of PD risk modulation in pathogenic LRRK2 mutation carriers. METHODS Banked plasma samples or urate levels were obtained for 3 cohorts of age- and sex-matched subjects with and without a known LRRK2 mutation in PD and unaffected controls to conduct a pilot study of 192 subjects from the LRRK2 Cohort Consortium (LCC) and 2 validation studies of 380 additional subjects from the LCC and 922 subjects from the Parkinson's Progression Markers Initiative. Urate levels were compared by multiple regression between subjects with and without a PD diagnosis conditional on LRRK2 status, controlling for age and sex. RESULTS Nonmanifesting LRRK2 mutation carriers had significantly higher levels of urate than those who developed PD in each of the 3 independent cohorts. A meta-analysis demonstrated an adjusted mean difference of 0.62 mg/dL (p < 0.001), with similar results for separate assessments of women (p < 0.02) and men (p < 0.001). A 2 mg/dL increment in urate concentration decreased the odds of having PD by approximately 50% (odds ratio = 0.48, p = 0.004). INTERPRETATION These findings identify and substantiate urate as a biomarker of resistance to PD among LRRK2 mutation carriers. Ann Neurol 2019;85:593-599.
Evaluation of the effects of biochar on diet digestibility and methane production from growing and finishing steers

The objectives of these studies were to evaluate the effects of biochar (0%, 0.8%, or 3% of diet dry matter) on diet digestibility and methane and carbon dioxide production from cattle on growing and finishing diets. The growing diet consisted of 21% brome hay, 20% wheat straw, 30% corn silage, 22% wet distillers grains plus solubles, and 7% supplement. The finishing diet consisted of 53% dry-rolled corn, 15% corn silage, 25% wet distillers grains plus solubles, and 7% supplement. In both trials biochar replaced fine ground corn in the supplement. Six crossbred steers (initial body weight [BW] 529 kg; SD = 16 kg) were used in both the growing and finishing trial. The growing diets were evaluated over 6 periods followed by the finishing trial with 3 periods. Digestibility measures were taken over 4 d after at least 8 d of adaptation to diets followed by 2 d of gas emission measurements using headbox calorimeters. Dry matter intake (DMI) was not affected (P ≥ 0.43; 7.91 kg/d) by biochar inclusion in the growing study and increased quadratically (P = 0.07) in the finishing study with 0.8% biochar inclusion having the greatest DMI (12.9 kg/d). Organic matter (OM) and neutral detergent fiber (NDF) digestibility increased quadratically (P = 0.10) in the growing study whereas OM digestibility tended to linearly decrease (P = 0.13) and NDF digestibility was not affected (P ≥ 0.39) by biochar inclusion in the finishing diet. Digestible energy intake (Mcal/d) was not affected (P ≥ 0.25) by biochar inclusion in the growing or finishing study. Methane production (g/d) tended to decrease quadratically (P = 0.14) in the growing study and was decreased 10.7% for the 0.8% biochar treatment relative to the control. There were no statistical differences in methane production (g/d) in the finishing study (P ≥ 0.32) but cattle on the 0.8% biochar treatment produced numerically less (9.6%) methane than the control. Methane production as g/kg DMI of the 0.8% biochar treatment relative to the control was numerically reduced 9.5% and 18.4% in the growing and finishing studies, respectively (P ≥ 0.13). Carbon dioxide production (g/d and g/kg of intake) quadratically decreased (P ≤ 0.06) in the growing study but was not affected by treatment in the finishing study (P ≥ 0.34). Although biochar is not a U.S. Food and Drug Administration -approved feed for cattle, the initial research shows potential as a methane mitigation strategy in both growing and finishing diets.
Simultaneous spatial and temporal coarse-graining: from atomistic models to continuum elastodynamics

Abstract This paper aims at providing a new angle to the classical thermodynamic description of the elastodynamics of solids at finite temperature via the simultaneous spatio-temporal coarse-graining of the atomistic Hamiltonian equations of motion. First, we show by means of various numerical examples, that the spectral kinetic energy density of atomistic trajectories as projected in the normal modes of the system, reveals the anticipated coupling between the spatial and temporal scales, as well as the separation between the elastic and thermal material behavior. The ratio between these two scales provides a single parameter ϵ, whose limit to zero, denotes the upscaling to the continuum scale in the limit of infinite length/time scale separation. The coarse-graining procedure for the identified slow (elastic) variables is then performed by combining mathematical results of Bornemann (2006) based on notions of weak convergence, and statistical mechanics results of Berdichevsky (1997). The resulting continuum description and relations, obtained in generalized coordinates, are all in complete agreement with well-known results in the thermodynamics of solids. Yet, the upscaling exercise delivers simple mathematical insight into some of these classical continuum expressions. Specifically, the potential structure of the reversible elastodynamic equations of motion, with the mechanical forces given by the derivatives of free energy at constant temperature, becomes quite apparent. In addition, the non-commutativity of weak limits and nonlinear functions provides a simple mathematical explanation for the temperature dependence of the mechanical properties of materials, or the fact that thermal energy is finite, while thermal vibrations are negligibly small at the continuum scale. The limit ϵ → 0 is also explored numerically for two examples of a beam undergoing elastic vibrations at various temperatures. The first example is an illustrative mass-spring system, where the atoms’ mass, interatomic distance and potentials are suitably scaled with ϵ, while the length of the beam remains constant; and the second example explores an iron beam of increasing length and fixed atomistic description. In both cases, the scaling of all quantities is analyzed in detail, and the coarse-grained description is compared to the behavior obtained via full atomistic simulations.
Laser speckle micro-rheology for investigating the biomechanics of breast cancer progression

The extra-cellular matrix (ECM) of the tissue significantly remodels during both development and disease. This is often perceived by the apparent changes to the bulk stiffness of the tissue. Nevertheless, the ECM micromechanical alterations and their implications to normal development and pathogenies remain poorly understood, largely due to the absence of high-resolution imaging tool for mapping the ECM stiffness at length scales sensed by cells. We have developed a novel optical imaging technology, termed laser speckle micro-rheology (LSM) that offers the unique capability to map the micro-mechanical properties of ECM, within the tissue. In LSM, the specimen is illuminated by a coherent laser beam and back-scattered speckle patterns are acquired by a high-speed camera. Spatio-temporal analysis of speckle frames yields the map of viscoelastic modulus, G. Here we demonstrate the capability of LSM for micro-mechanical mapping of the tissue through imaging a micro-structured phantoms and a normal human breast tissue specimens. These results open new avenues for investigating the mechano-biological mediators of disease and development in the future.
New strategies for conformal, superconformal, and ultrasmooth films by low temperature chemical vapor deposition

In the following review, the authors describe how the kinetics of film growth can be controlled in innovative ways to achieve the deposition of conformal, superconformal, area-selective, and ultrasmooth films by low-temperature CVD. Illustrative experimental data and kinetic models are given for the growth of a variety of materials, including transition metals, metal oxides, and metal diborides. Key results are as follows: (i) For precursors that exhibit site blocking on the growth surface, CVD can afford a high degree of conformal coverage on very high aspect ratio features. (ii) The problem of conformal coverage has been solved analytically and presented as a conformal zone diagram. (iii) “Nonconformal” precursor molecules can be made to afford highly conformal films by adding a suitable neutral molecule to enhance surface site blocking. (iv) An inhibitor that adsorbs strongly to the growth material, but not to the substrate surface, can be used to moderate the size distribution of nuclei such that the film is ultrasmooth at coalescence. (v) An inhibitor that binds preferentially to hydroxyl sites on an oxide surface can be used to completely suppress film nucleation and afford area-selective growth. (vi) Superconformal growth, which affords a V-shaped coating and complete fill of a deep trench, can be achieved using one of three approaches, depending on the precursor chemistry. (vii) The science and technology of CVD can further be expanded by the chemical design of new precursors that have a favorable combination of high partial pressure, suitable reactivity at low substrate temperature, and ligand groups that desorb cleanly.
Mercury (II) sensing via cyclization of a dithioamide into a benzimidazole derivative: A structural and spectroscopic study

Abstract An o-phenylenediamine-derived dithioamide L was found to sense Hg(II) in the UV–visible via Hg(II)-mediated cyclization leading to a new benzimidazole derivative (L′). Both L and L′ have been characterized by single-crystal X-ray crystallography. The structure of L reveals relatively strong intramolecular H-bonding interactions of N H...S type. The extended structure is consolidated by several classical hydrogen bonding interactions. For L′, analysis of the packing pattern reveals few non-classical H-bonding contacts. Spectroscopic studies by FT-IR, UV–Visible, 1H-and 13C NMR support the single-crystal X-ray crystallography results and confirm the formation of the new benzimidazole derivative. UV–Vis titrations suggest and NMR confirms that the cyclization reaction occurs via an initial formation of a Hg(II) complex, which is too transient to be fully characterized. As this reaction is Hg(II)-mediated, dithioamide L acts as a selective Hg(II) sensor as shown by UV–Visible titrations and a selectivity study against Pb(II), Cd(II), Ca(II), Zn(II), Ag(I), and Cr(III): For Hg(II), but not for other metals, a distinct color change from yellow to pink is observed with corresponding UV–Vis spectroscopic changes and an isosbestic point at 270 nm.
Site-specific resolution of anionic residues in proteins using solid-state NMR spectroscopy

NMR spectroscopy is commonly used to infer site-specific acid dissociation constants (pKa) since the chemical shift is sensitive to the protonation state. Methods that probe atoms nearest to the functional groups involved in acid/base chemistry are the most sensitive for determining the protonation state. In this work, we describe a magic-angle-spinning (MAS) solid-state NMR approach to measure chemical shifts on the side chain of the anionic residues aspartate and glutamate. This method involves a combination of double quantum spectroscopy in the indirect dimension and REDOR dephasing to provide a sensitive and resolved view of these amino acid residues that are commonly involved in enzyme catalysis and membrane protein transport. To demonstrate the applicability of the approach, we carried out measurements using a microcrystalline soluble protein (ubiquitin) and a membrane protein embedded in lipid bilayers (EmrE). Overall, the resolution available from the double quantum dimension and confidence in identification of aspartate and glutamate residues from the REDOR filter make this method the most convenient for characterizing protonation states and deriving pKa values using MAS solid-state NMR.
Achieving Uniform Lithium Electrodeposition in Cross-Linked Poly(ethylene oxide) Networks: “Soft” Polymers Prevent Metal Dendrite Proliferation

The propensity of lithium to form nonplanar, mossy, or dendritic electrodeposits at current densities below the diffusion limit is a well-known, fundamental barrier to commercialization of energy-d...
Victimization profiles in girls involved in the juvenile justice system: A latent class analysis.

Abstract Background Previous research has demonstrated that youth involved in the juvenile justice system endorse diverse patterns of victimization. However, previous research investigating victimization profiles among youth involved in the juvenile justice system has primarily consisted of boys. Objective This study investigated victimization profiles and correlates of victimization exposure, including posttraumatic stress symptoms and risk behaviors, in a sample of girls involved in the juvenile justice system. Participants and Setting Participants were 245 girls involved in the juvenile justice system (Mage = 15.57, SD = 1.13) participating in a dating violence prevention program. The sample was racially diverse, and 48 % self-identified as Hispanic/Latina. Method Prior to participating in the intervention, participants completed self-report measures of adversity and victimization exposure, posttraumatic stress symptoms, and risk behaviors. Results Results of latent class analysis identified three distinct victimization profiles. The first class (n = 106) was characterized by low levels of victimization. The second class (n = 98) experienced predominantly emotional victimization (i.e., emotional dominant). The third class (n = 41) was characterized by exposure to polyvictimization (i.e., polyvictimization predominant). Girls categorized into the polyvictimization dominant class evidenced the greatest levels of posttraumatic stress symptoms, substance use, suicidal behaviors, and sexual risk behaviors. Conclusions Girls involved in the juvenile justice system report distinct patterns of victimization, which are differentially associated with posttraumatic stress symptoms and risk behaviors. The present study underscores the importance of implementing trauma-informed assessment and intervention practices within juvenile justice systems.
Bringing Ukraine Back into Focus: How to End the New Cold War and Provide Effective Political Assistance to Ukraine

There is insufficient recognition of the fact that we are actually dealing with two crises that must be addressed simultaneously. The first crisis is the longstanding conflict within Ukraine over whether post-Soviet Ukraine should be a monocultural or bicultural nation. The second crisis, which has been superimposed onto the first, is the crisis in Russian relations with the It also has deep historical and cultural roots.These two crises came together with explosive impact when President Yanukovych was ousted from office on Feb 22, 2014.
A Patient-based Computational Model that Predicts Pressure Drop in Supravalvar Aortic Stenosis in Patients with Williams Syndrome

Assessment of supravalvar aortic stenosis (SVAS) severity in Williams syndrome (WS) is often complicated by the discrepancy in pressure drops obtained via peak-instantaneous Doppler and peak-to-peak cardiac catheterization measurements. With SVAS, static pressure in the left ventricle is converted to kinetic energy, maximal at the vena contracta, some of which is recovered through pressure energy and some of which is lost through thermal energy and deformation. The phenomenon …
Rewriting French Geographies in Les Français peints par eux-mêmes

This article considers the Paris-province divide, which has meaningfully shaped the way one imagines the French territory, and which Les Francais peints par eux-memes problematizes during the first...