cssi/SciSciGPT-SciSciNet huggingface dataset:
Deregulation of CRTCs in Aging and Age-Related Disease Risk

Advances in public health in the past century have seen a sharp increase in human life expectancy. With these changes have come an increased prevalence of age-related pathologies and health burdens in the elderly. Patient age is the biggest risk factor for multiple chronic conditions that often occur simultaneously within a single individual. An alternative to disease-centric therapeutic approaches is that of 'geroscience', which aims to define molecular mechanisms that link age to overall disease risk. One such mechanism is deregulation of CREB-regulated transcriptional coactivators (CRTCs). Initially identified for their role in modulating CREB transcription, the past 5 years has seen an expansion in knowledge of new cellular regulators and roles of CRTCs beyond CREB. CRTCs have been shown to modulate organismal aging in Caenorhabditis elegans and to impact on age-related diseases in humans. We discuss CRTC deregulation as a new driver of aging that integrates the link between age and disease risk.
Blackcurrant anthocyanins stimulated cholesterol transport via post-transcriptional induction of LDL receptor in Caco-2 cells

We previously showed that polyphenol-rich blackcurrant extract (BCE) showed a hypocholesterolemic effect in mice fed a high fat diet. As direct cholesterol removal from the body via the intestine has been recently appreciated, we investigated the effect of BCE on the modulation of genes involved in intestinal cholesterol transport using Caco-2 cells as an in vitro model. Caco-2 cells were treated with BCE to determine its effects on mRNA and protein expression of genes important for intestinal cholesterol transport, low-density lipoprotein (LDL) uptake, cellular cholesterol content, and cholesterol transport from basolateral to apical membrane of Caco-2 cell monolayers. Cells were also treated with anthocyanin-rich or -poor fraction of BCE to determine the role of anthocyanin on BCE effects. BCE significantly increased protein levels of LDL receptor (LDLR) without altering its mRNA, which consequently increased LDL uptake into Caco-2 cells. This post-transcriptional induction of LDLR by BCE was markedly attenuated in the presence of rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1). In addition, BCE altered genes involved in cholesterol transport in the enterocytes, including apical and basolateral cholesterol transporters, in such a way that could enhance cholesterol flux from the basolateral to apical side of the enterocytes. Indeed, BCE significantly increased the flux of LDL-derived cholesterol from the basolateral to the apical chamber of Caco-2 monolayer. LDLR protein levels were markedly increased by anthocyanin-rich fraction, but not by anthocyanin-free fraction. mTORC1-dependent post-transcriptional induction of LDLR by BCE anthocyanins drove the transport of LDL-derived cholesterol to the apical side of the enterocytes. This may represent a potential mechanism for the hypocholesterolemic effect of BCE.
CYP2D6 genotype is not associated with survival in breast cancer patients treated with tamoxifen: results from a population-based study

A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy. Tumor-derived DNA was genotyped for common, functionally consequential CYP2D6 polymorphisms (*2, *3, *4, *6, *10, *41, and copy number variants) and assigned a CYP2D6 activity score (AS) ranging from none (0) to full (2). Patients with poor metabolizer (AS = 0) phenotype were compared to patients with AS > 0 and in secondary analyses AS was analyzed quantitatively. Clinical outcome of interest was recurrence free survival (RFS) and analyses using long-rank test were adjusted for relevant clinical covariates (nodal status, tumor size, etc.). CYP2D6 AS was not associated with RFS in tamoxifen treated patients in univariate analyses (p > 0.2). In adjusted analyses, increasing AS was associated with inferior RFS (Hazard ratio 1.43, 95% confidence interval 1.00–2.04, p = 0.05). In patients that did not receive tamoxifen treatment, increasing CYP2D6 AS, and AS > 0, were associated with superior RFS (each p = 0.0015). This population-based study does not support the hypothesis that patients with diminished CYP2D6 activity achieve inferior tamoxifen benefit. These contradictory findings suggest that the association between CYP2D6 genotype and tamoxifen treatment efficacy is null or near null, and unlikely to be useful in clinical practice.
Shock and lethality with anthrax edema toxin in rats are associated with reduced arterial responsiveness to phenylephrine and are reversed with adefovir.

The most important aspects of the present study are the findings that 1) in vivo challenge with anthrax edema but not lethal toxin depresses arterial contractile function measured both ex vivo and ...
What Causes Nystagmus

Background and Purpose: Nystagmus is a commonly encountered clinical finding both in children and adults. Despite its complexities, a fundamental understanding of the basic etiology and underlying pathophysiology of nystagmus is critical to manage these patients appropriately.Patients and Method: The subset of ocular motility disorders that constitutes true nystagmus is identified and delineated from saccadic intrusions. Once defined, we explore the causes of commonly encountered forms of nystagmus and their clinical features.Results: Three separate mechanisms work to integrate sensory input and calibrate ocular movements: the afferent visual pathway, the neural integrator, and the vestibular system. Specific neuroanatomical pathways and corresponding pathologic changes are reviewed.Conclusion: A basic understanding of the underlying pathophysiology of nystagmus is essential to clinical practice. Three main mechanisms utilize multifactorial sensory input to produce a normally functioning ocular mo...
Defining a role for Sonic hedgehog pathway activation in desmoplastic medulloblastoma by identifying GLI1 target genes

4568 The oncogenic transcription factor GLI1 mediates Sonic hedgehog (Shh) signaling and transforms cells in culture. As expected, GLI1 is expressed in the subset of medulloblastomas, usually of desmoplastic histology, that contains Patched-1 mutations and demonstrates up-regulation of the downstream genes in the Shh signal transduction pathway. Desmoplastic histology has recently been found to be associated with a favorable prognosis. To identify roles that Shh pathway activation may play in this subset of medulloblastomas, we identified GLI1 target genes in transformed rat kidney epithelial cells (RK3E) and then compared these targets genes with the previously published gene expression profile that defines the subset of medulloblastomas defined by up-regulation of Shh pathway genes (Thompson et al., J Clin Oncol, 24, 1924-31, 2006) in order to identify a subset of GLI1 targets specifically expressed in medulloblastomas. Since studies of RK3E cells have the advantage over studies of human tumor tissue of allowing identification of specific direct GLI1 target genes following experimental manipulation of GLI1 expression, we used oligonucleotide microarrays, containing over 31,000 DNA sequences to provide a set of downstream target genes in RK3E cells transformed by GLI1 (RK3E + GLI1). We identified 1823 genes whose expression was altered more than 2 fold in 2 independent RK3E + GLI1 cell lines; 572 genes were up-regulated and 1251 down-regulated. Of these, we identified 30 whose expression was similarly and uniquely altered in medulloblastomas showing up-regulation of Shh pathway genes. Of interest, up-regulation of p53 was observed in the RK3E + GLI1 cells and the medulloblastomas showing up-regulation of Shh pathway genes. We identified potential GLI1 binding elements in either the promoter region or regulatory introns in 13 of these genes, suggesting that these may represent immediate targets (Bcl2, PRPSAP1, MGMT, GLI1, CSCC4, MYCL1, SLC19A1, NTRK2, PRKCH, PLTP, PRNP, SLIT2, and CCPG1). Using gel mobility shifts we confirmed that GLI1 binds the regulatory regions of Bcl2 and PRPSAP1, and using cotransfection assays showed that it activates transcription through the PRPSAP1 promoter. Roles previously defined for some of the 30 targets include regulation of cell growth and proliferation, cell-cell interactions, signal transduction, cell metabolism, and apoptosis. Collectively, review of the literature reveals that the targets may affect cell behavior by converging on the MYC and JUN oncogenic pathways and on the Bcl2 and p53 cell survival pathways.
Challenges of using RNA-seq in the clinical setting

RNA-seq is a mature and well-established method for studying the complexity of the transcriptome in the research setting. As this method moves from the research realm to the clinical context, new opportunities for the development of bioinformatics methods arise. During this talk I will present some of the challenges we have found during our work to release a clinical test for tumor samples using RNA-seq. During the first part of the talk I will focus on fusion detection, how it is affected by the degradation of the sample and how to quantify such effect using Fusion Sense [1]. I will also comment on the opportunities and challenges of annotating and predicting the clinical importance of fusions. During the second part of the talk I will comment on variant calling in RNA-seq and how to account for the effects of library preparation by using RVboost [2]. I will then show some preliminary work of leveraging this method in the context of estimating tumor mutational burden in Formalin-Fixed Paraffin-Embedded (FFPE) samples.
Social Influences on Children's Cognition: State of the Art and Future Directions

Publisher Summary This chapter reviews research on the relationship between social interaction and cognitive development. It proposes a framework that allows to explain a wide range of findings and to hypothesize about the nature of changes in social influence across development. Although it argues that social interaction may facilitate cognitive development, it also point to some limitations of this facilitation. The chapter acknowledges important individual differences in participation and in the effects of social influence and suggests that some tasks are more amenable to collaborative learning than others. The goal is to incorporate the available data into a developmental framework for studying and evaluating social influences on cognition. A theoretical overview of approaches to the study of social influences on children's cognition is presented. The chapter offers a preliminary framework for conceptualizing social influences across development and discusses some additional issues that need to be considered when studying social influences on cognition.
Research on Reading Disabilities in the Colorado Learning Disabilities Research Center

The Stavanger conference on dyslexia (November, 1997) highlighted the strong contributions from Norway and other Nordic countries to our understanding of this important problem. The Center for Reading Research, founded by Torleiv Hoien, has played a major role in supporting strong basic research on dyslexia and has hosted several excellent international conferences. The Center for Reading Research has fostered a high level of collaboration among different researchers with different perspectives on dyslexia. This collaboration has substantially increased our understanding of the etiology and remediation of reading disabilities. In this chapter, I present an overview of the history, methods, and some major results of a similarly collaborative research program at the University of Colorado in Boulder.
The History of Plasma Processing

Publisher Summary This chapter presents the history of plasma processing. Plasma technology or dry etching technology is one of the newer requirements in semiconductor wafer manufacturing that has seen significant implementation. The ashing of photoresists was the initial process that was implemented in various manufacturing lines. Thin-film plasma deposition was recognized very early, before plasma etching needs, as a new source of low-temperature dielectric materials for passivation of integrated circuit surfaces. Plasma processing, and particularly plasma etching, was beginning to be recognized because of the emergence of n -channel silicon gate MOS (NMOS) technology; NMOS was the primary technology that produced dynamic random access memories and logic circuits such as microprocessors. Plasma processing was originally introduced without requirements for stringent dimensional control on the patterning of silicon nitride and polycrystalline silicon. It was considered as a direct replacement for wet etching.
Is it Time to Test the Effect of Weight Loss on Testosterone

Testosterone is a sex-steroid hormone, synthesized in the testes, with biologic effects on numerous tissues. Low circulating concentrations, seen with testicular or hypothalamic–pituitary defects, are often associated with decreased sexual function, muscle mass, and poor quality of life, along with a risk of osteoporosis. Primary testicular failure can be due to testicular trauma, chemotherapy, radiation therapy, or chromosomal abnormalities, although secondary causes, also termed centrally mediated hypogonadism, are associated with pituitary tumors or hypothalamic disease. In addition to these well-known etiologies, there is an increasing appreciation that hypogonadism can be the result of aging, medications, and chronic diseases. A physiological decrease in testosterone concentrations has been well documented after the fourth or fifth decade of life and has been postulated to result from a decline in both testicular and hypothalamic–pituitary function. In scenarios in which the patient has a clear pathophysiologic mechanism for the hypogonadism, treatment with testosterone is nearly always recommended to alleviate symptoms of hypogonadism and maintain secondary sexual characteristics (1). Men on replacement therapy should be monitored for polycythemia, falls in serum high-density lipoprotein, worsening of sleep apnea, and increase in prostate-specific antigen concentrations (2, 3). Because long-term evidence of safety with supplementation is yet to be established, testosterone therapy is not routinely recommended in older men or in men with an unclear underlying etiology for their low testosterone concentrations. Because low serum testosterone is commonly observed in chronic illness, there may be less invasive ways to naturally increase serum concentrations. This circumstance creates an opportunity to explore other intervention options that could favorably increase the endogenous testosterone production in the absence of potential side effects. The interpretation of laboratory tests can be confusing in men as they age and become more obese because both factors modulate sex by hormone-binding globulin (SHBG)3 concentrations. Obese …
Mesoscale multi-physics simulation of rapid solidification of Ti-6Al-4V alloy

Abstract Powder bed fusion is a recently developed additive manufacturing (AM) technique for alloys, which builds parts by selectively melting metallic powders with a high-energy laser or electron beam. Nevertheless, there is still a lack of fundamental understanding of the rapid solidification process for better quality control. To simulate the microstructure evolution of alloys during the rapid solidification, in this research, a mesoscale multi-physics model is developed to simultaneously consider solute transport, phase transition, heat transfer, latent heat, and melt flow. In this model, the phase-field method simulates the dendrite growth of alloys, whereas the thermal lattice Boltzmann method models heat transfer and fluid flow. The phase-field method and the thermal lattice Boltzmann method are tightly coupled. The simulation results of Ti-6Al-4V show that the consideration of latent heat is necessary because it reveals the details of the formation of secondary arms and provides more realistic kinetics of dendrite growth. The proposed multi-physics simulation model provides new insights into the complex solidification process in AM.
Sjögren's Syndrome: More Than Just Dry Eye.

Purpose:Sjogren's syndrome (SS) is a common autoimmune disease affecting about four million Americans. Although approximately 1 in 10 patients with clinically-significant aqueous deficient dry eye has underlying SS, widespread underappreciation of SS leads to significant underdiagnosis, delays in di
Alternative Adjoint Boltzmann Transport Operators in Alternative Hilbert Spaces in Spherical Geometry: Theory and Paradigm Applications

AbstractThe solution of the customary adjoint Boltzmann equation for linear transport of particles and radiation, referred to as the “adjoint flux,” plays a prominent role in reactor physics, shiel...
The resonant brain: How attentive conscious seeing regulates action sequences that interact with attentive cognitive learning, recognition, and prediction

This article describes mechanistic links that exist in advanced brains between processes that regulate conscious attention, seeing, and knowing, and those that regulate looking and reaching. These mechanistic links arise from basic properties of brain design principles such as complementary computing, hierarchical resolution of uncertainty, and adaptive resonance. These principles require conscious states to mark perceptual and cognitive representations that are complete, context sensitive, and stable enough to control effective actions. Surface-shroud resonances support conscious seeing and action, whereas feature-category resonances support learning, recognition, and prediction of invariant object categories. Feedback interactions between cortical areas such as peristriate visual cortical areas V2, V3A, and V4, and the lateral intraparietal area (LIP) and inferior parietal sulcus (IPS) of the posterior parietal cortex (PPC) control sequences of saccadic eye movements that foveate salient features of attended objects and thereby drive invariant object category learning. Learned categories can, in turn, prime the objects and features that are attended and searched. These interactions coordinate processes of spatial and object attention, figure-ground separation, predictive remapping, invariant object category learning, and visual search. They create a foundation for learning to control motor-equivalent arm movement sequences, and for storing these sequences in cognitive working memories that can trigger the learning of cognitive plans with which to read out skilled movement sequences. Cognitive-emotional interactions that are regulated by reinforcement learning can then help to select the plans that control actions most likely to acquire valued goal objects in different situations. Many interdisciplinary psychological and neurobiological data about conscious and unconscious behaviors in normal individuals and clinical patients have been explained in terms of these concepts and mechanisms.
Evaluation and Management of Movement Disorders in Children

Sleep-related movement disorders (SRMD) are a group of conditions that involve simple, non-purposeful, and stereotyped movements that occur during sleep or sleep-wake transitions. In pediatric patients, these events may be concerning to parents and may be brought up during the screening for sleep disorders of the allergic child. Fortunately, the majority of these disorders are benign, require no treatment, and resolve spontaneously. Some sleep-related movement disorders, like restless legs syndrome and rhythmic movement disorder, are seen at sleep onset, while others, such as periodic limb movement disorder and benign sleep myoclonus of infancy, occur in the sleeping child. In some cases, like with bruxism, a condition may occur in either during sleep or while the child is awake. Normal variants, including hypnic jerks, hypnogogic foot tremor, and catathrenia, which may be confused with more concerning conditions, are also discussed. For each condition, diagnostic criteria and pediatric literature regarding the evaluation and treatment are reviewed.
Cryptocurrencies and Securities Fraud: In Need of Legal Guidance

The specificity of statutes is important when the statute provides for criminal penalties. This Essay examines a cryptocurrency fraud prosecution, looking at the issue of whether cryptocurrency is included in securities fraud statutes. It also looks at proposed legislation that would omit cryptocurrency as a security, but then calls for enhanced regulation and tax relief. Additional clarification is needed to ascertain whether cryptocurrency fraud can be prosecuted under current securities fraud statutes. This Essay questions such prosecutions when the location of key definitions rest within agency regulations. Although specificity may not be needed to account for every imaginable type of fraud, when it comes to cryptocurrencies, Congress needs to provide more direction.
47,XYY,dup(13q12.11),t(4;9)(q21.1;q22.3),r(21)(p12q22.3) with azoospermia and low intelligence

A 27-year-old patient with azoospermia and low intelligence was reported having a rare karyotype 47,XYY,dup(13q12.11),t(4;9)(q21.1;q22.3),r(21)(p12q22.3). Clinical genetic tests, including next-generation sequencing (NGS), karyotyping, fluorescence in situ hybridization (FISH), and azoospermia factor (AZF) microdeletions, were conducted. The results showed that (1) one copy of chromosome 21 lost a short arm and appeared as a marker, but subsequent detection confirmed that it was a ring 21; (2) there was a reciprocal translocation between chromosome 4 and chromosome 9; (3) NGS revealed a duplication of 0.3 Mb on 13q12.11 and two Y chromosomes; (4) the Y chromosome showed no AZF microdeletions; and (5) FISH confirmed the two Y chromosomes. To our knowledge, this is the first reported case with rare karyotype, combined with four abnormal chromosomal changes simultaneously. Because no Online Mendelian Inheritance in Man genes were found in duplication fragment on 13q12.11, this duplication is not associated with low intelligence.
Assessment of Publication Trends of Systematic Reviews and Randomized Clinical Trials, 1995 to 2017.

This cross-sectional study assesses the growth in the number of systematic reviews and meta-analyses vs randomized clinical trials from 1995 to 2017.
Does rhythmic auditory stimulation compared to no rhythmic auditory stimulation improve patient’s static and dynamic standing balance post stroke?

AbstractBackground: Rhythmic auditory stimulation (RAS) uses music or a metronome to stimulate the audio-motor pathway in the brain. This type of stimulation uses external auditory cueing to try to...
Clarifying Conundrums: How Goal Hierarchies Resolve Seeming Contradictions in Motivated Responding

In October 2016, Naval Petty Officer Jeffrey Thomas, under deployment to fight in the global war on terror, found himself amidst a barrage of enemy fire from the Islamic State of Iraq and Syria, kn...
Does adoption of an evidence-based practice lead to job turnover? Results from a randomized trial.

It is important to understand the impact of implementation of evidence-based practices (EBPs) on the workforce. EBP implementation can increase job demands, stress, and burnout, and may thereby exacerbate turnover. This study examined the effects of implementation of an EBP on turnover among staff at nine child welfare agencies. A total of 102 providers were randomized to either adopt an EBP, SafeCare© , or continue providing services as usual. Participants completed a baseline survey assessing demographics, attitudes toward EBPs, and organizational functioning, and provider turnover was recorded for up to 18 months following implementation. The overall turnover rate was 35%, but did not differ by EBP assignment (odds ratio [OR] = 1.27; 95% confidence interval [0.66, 2.45]). Variables associated with turnover included age (OR = 0.92), years since degree completion (OR = 0.94), prior exposure to EBP (OR = 3.91), believing that adopting an EBP was burdensome (OR = 0.52), and motivation for change (OR = 0.89). EBP assignment moderated two aspects of negative attitudes toward EBP (divergence and monitoring) to predict turnover; those attitudes were only positively related to turnover for individuals assigned to the EBP (OR = 1.46, 1.16). Implications of the findings for implementation are discussed.
Experimental Renovascular Disease Induces Endothelial Cell Mitochondrial Damage and Impairs Endothelium-Dependent Relaxation of Renal Artery Segments.

Background Mitochondria modulate endothelial cell (EC) function, but may be damaged during renal disease. We hypothesized that the ischemic and metabolic constituents of swine renovascular disease (RVD) induce mitochondrial damage and impair the function of renal artery ECs. Methods Pigs were studied after 16 weeks of metabolic syndrome (MetS), renal artery stenosis (RAS), or MetS + RAS, and Lean pigs served as control (n = 6 each). Mitochondrial morphology, homeostasis, and function were measured in isolated primary stenotic-kidney artery ECs. EC functions were assessed in vitro, whereas vasoreactivity of renal artery segments was characterized in organ baths. Results Lean + RAS and MetS + RAS ECs showed increased mitochondrial area and decreased matrix density. Mitochondrial biogenesis was impaired in MetS and MetS + RAS compared with their respective controls. Mitochondrial membrane potential similarly decreased in MetS, Lean + RAS, and MetS + RAS groups, whereas production of reactive oxygen species increased in MetS vs. Lean, but further increased in both RAS groups. EC tube formation was impaired in MetS, RAS, and MetS + RAS vs. Lean, but EC proliferation and endothelial-dependent relaxation of renal artery segments were blunted in MetS vs. Lean, but further attenuated in Lean + RAS and MetS + RAS. Conclusions MetS and RAS damage mitochondria in pig renal artery ECs, which may impair EC function. Coexisting MetS and RAS did not aggravate EC mitochondrial damage in the short time of our in vivo studies, suggesting that mitochondrial injury is associated with impaired renal artery EC function.
Spectra and structure of silicon containing compounds. XXI: Infrared and raman spectra, conformational stability, ab initio calculations and vibrational assignments for chlorodimethylmethoxysilane

The Raman (50 to 3200 cm−1) and infrared (50 to 3500 cm−1) spectra of chlorodimethylmethoxysilane, Cl(CH3)2SiOCH3, in the vapor and solid phases have been recorded. Raman spectra of the liquid including depolarization ratios have also been recorded. Optimized geometries and conformational stabilities have been obtained from ab initio calculations utilizing the RHF/3–21G* and RHF/6–31G* basis sets. The calculations from both of these basis sets indicated the gauche conformer to be significantly more stable than the trans conformer. Since the gauche has twice the multiplicity of the trans form it is unlikely that the trans conformer will be detected in the fluid phases at room temperature. This is supported by the fact that no infrared or Raman bands were found to vanish in the spectra of the crystalline solid. The vibrational frequencies have been calculated using appropriate scaling factors, and the vibrational spectra are interpreted in detail. The results have been compared with those obtained for some related molecules.
High-resolution PET detector with 100 ps coincidence time resolution using side-by-side phoswich design

We propose a new high-resolution TOF PET detector, a "side-by-side phoswich detector", where two crystals with fast and slow decay time are side-coupled to a row of photosensors. Monte Carlo simulation was conducted to find the optimal conditions for a side-by-side phoswich design. Then a proof-of-concept PET detector was built comprising two 1.9×1.9×10 mm3 LSO crystals (τ_d=34.39 and 43.07 ns) sidecoupled with three 4×4 mm2 SensL SiPMs. A CTR of 107.07 ps was achieved at 32V bias voltage with a 2 mV leading edge threshold for the side-by-side phoswich configuration. The side-by-side phoswich detector showed good energy resolution of 10.35% at 511 keV and good crystal separation in two 1.9×1.9×10 mm3 crystals with different decay time when we applied the time-over-threshold technique. These results indicate we can achieve high resolution, 10% energy resolution and 100-ps coincidence timing resolution (CTR) all at once.
Analysis of surveillance results of schistosomiasis in Hexi reservoir area from 2012 to 2015

OBJECTIVE To understand the changes of schistosomiasis epidemic situation, so as to provide the evidence for formulating schistosomiasis control strategy in the Hexi reservoir area. METHODS From 2012 to 2015, Xinyuan Village, Meishan Town in the north entrance of Hexi reservoir was selected as a monitoring site. According to the requirements of the monitoring program of schistosomiasis surveillance in Zhejiang Province, the Schistosoma japonicum infection was investigated by using the serological screening (IHA), and the basic situation of the surveillance site was also investigated. RESULTS From 2012 to 2015, 167 environments (21.68 hm2) were surveyed, and 2 slices (0.1 hm2) were found with Oncomelania hupensis snails. The detection rate of frames with snails was 0.12%, and the living snail density was 0.0192 snails per 0.1 m2. Totally 374 snails were dissected and no schistosome infected snails were found. A total of 970 local residents and 8 748 mobile people were investigated with the serological tests, and no schistosome infected people were found. In addition, 3 085 cattle were investigated and no infected ones were found. CONCLUSIONS The schistosomiasis epidemic situation is stable in the Hexi reservoir area, but we still should strengthen the monitoring of imported source of infection and snail status, and increase the efforts of environmental transformation.
The Kindertransport: Contesting Memory

In The Kindertransport: Contesting Memory, Jennifer Craig-Norton contrasts the oral testimonies of individuals that were part of the Kindertransport during World War II, specifically focusing on th...
Is Tranexamic Acid Associated With Mortality or Multiple Organ Failure Following Severe Injury

BACKGROUND Tranexamic acid (TXA) administration is recommended in severely injured trauma patients. We examined TXA administration, admission fibrinolysis phenotypes, and clinical outcomes following traumatic injury and hypothesized that TXA was associated with increased multiple organ failure (MOF). METHODS Two-year, single-center, retrospective investigation. Inclusion criteria were age ≥ 18 years, Injury Severity Score (ISS) >16, admitted from scene of injury, thromboelastography within 30 min of arrival. Fibrinolysis was evaluated by lysis at 30 min (LY30) and fibrinolysis phenotypes were defined as: Shutdown: LY30 ≤ 0.8%, Physiologic: LY30 0.81-2.9%, Hyperfibrinolysis: LY30 ≥ 3.0%. Primary outcomes were 28-day mortality and MOF. The association of TXA with mortality and MOF was assessed among the entire study population and in each of the fibrinolysis phenotypes. RESULTS Four hundred twenty patients: 144/420 Shutdown (34.2%), 96/420 Physiologic (22.9%), and 180/410 Hyperfibrinolysis (42.9%). There was no difference in 28-day mortality by TXA administration among the entire study population (P = 0.52). However, there was a significant increase in MOF in patients who received TXA (11/46, 23.9% vs 16/374, 4.3%; P < 0.001). TXA was associated MOF (OR: 3.2, 95% CI 1.2-8.9), after adjusting for confounding variables. There was no difference in MOF in patients who received TXA in the Physiologic (1/5, 20.0% vs 7/91, 7.7%; P = 0.33) group. There was a significant increase in MOF among patients who received TXA in the Shutdown (3/11, 27.3% vs 5/133, 3.8%; P = 0.001) and Hyperfibrinolysis (7/30, 23.3% vs 5/150, 3.3%; P = 0.001) groups. CONCLUSIONS Administration of TXA following traumatic injury was associated with MOF in the fibrinolysis shutdown and hyperfibrinolysis phenotypes and warrants continued evaluation.
Dielectric Heating of Commercial Insulation Materials

Dielectric heating in commercial insulation materials is approximated using a simple method. Orders of magnitude differences in dielectric heating are predicted for cured VPI resins, polymer compositions used as wire coatings, and several composite insulation materials. The recommended materials characterization utilized Broadband Dielectric Thermal Analysis (DETA) on idealized laboratory samples. At increased power switching frequencies, dielectric heating may add to the total heat load in electric machinery. The concern is that the resulting increased local temperature could indicate the onset of thermal aging.
Multiracial Faculty Members’ Experiences with Biculturalism

Framed by the concept of biculturalism this study explores how 26 Multiracial faculty members form and use biculturalism to navigate an academy steeped in monoculturalism, or the belief that all pe...
Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development

Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac are effective for colorectal cancer prevention in humans and some animal models, but concerns over gastro-intestinal (GI) ulceration and bleeding limit their potential for chemopreventive use in broader populations. Recently, the combination of aspirin with a phospholipid, packaged as PL-ASA, was shown to reduce GI toxicity in a small clinical trial. However, these studies were done for relatively short periods of time. Since prolonged, regular use is needed for chemopreventive benefit, it is important to know whether GI safety is maintained over longer use periods and whether cancer prevention efficacy is preserved when an NSAID is combined with a phospholipid. As a first step to answering these questions, we treated seven to eight-week-old, male and female C57B/6 Apcmin/+ mice with the NSAID sulindac, with and without phosphatidylcholine (PC) for 3-weeks. At the end of the treatment period, we evaluated polyp burden, gastric toxicity, urinary prostaglandins (as a marker of sulindac target engagement), and blood chemistries. Both sulindac and sulindac-PC treatments resulted in significantly reduced polyp burden, and decreased urinary prostaglandins, but sulindac-PC treatment also resulted in the reduction of gastric lesions compared to sulindac alone. Together these data provide pre-clinical support for combining NSAIDs with a phospholipid, such as phosphatidylcholine to reduce GI toxicity while maintaining chemopreventive efficacy.
Exploration of Solar Cell Materials for Developing Novel PUFs in Cyber-Physical Systems

Internet of Things (IoT) devices can be considered a significant component within cyber-physical systems. They can provide network communication in addition to controlling the various sensors and actuators that exist within the larger cyber-physical system. IoT devices tend to be small and contain a limited battery supply. They typically have strict constraints placed on their power consumption and available hardware resources. It is for these reasons that energy-efficiency is a major consideration in the design of these resource-constrained devices. In addition, these devices are often deployed in unsecured locations which raises concerns about the security of the device. However, the limited amount of available resources presents an obstacle towards the implementation of security protocols for these cyber-physical systems. Physically Unclonable Functions (PUFs) show promise as a potential security option. PUFs can help provide protection from issues such as IC piracy, counterfeiting, etc. Furthermore, solar cells have been utilized as a power source in IoT devices. In this paper, we propose a novel solar cell-based PUF that leverages the intrinsic variations present in solar cells. As a proof of concept, we have constructed multiple copies our proposed solar cell-based PUF using amorphous silicon, monocrystalline silicon, and polycrystalline solar cells. The reliability and uniformity of the responses produced by the copies of the PUFs made from the different types of solar cells were evaluated against variations in temperature and light intensity. From our experiments, we found that with respect to temperature the range of average reliability values was 84.41–91.20% and the range of average uniformity values was 49.34–51.26%. With respect to light intensity, the range of average reliability values was 95.45–97.75% and the range of average uniformity values was 48.74–52.81%. In addition, Monte Carlo simulations performed on monocrystalline silicon resulted in a uniqueness value of 49.989%.
Fearing the worst yet to come: Derrida and health anxiety:

Building from the works of Jacques Derrida, this article explores health anxiety’s aporetic relationship with medicine through a deconstructive approach. I argue that attention to Derrida’s writing...
A molecular dynamics study of domain switching in BiFeO3 nanofilm under DC electric field

Abstract The performance of ferroelectric materials is deeply rooted in the domain switching process triggered by an applied electric field. To understand the effect of controlling factors on the domain switching characteristics, nanoscale studies are essential. In this work, an atomistic-scale computational framework is developed to study the domain switching process of bismuth ferrite (BiFeO3) nanofilms. Through a series of molecular dynamics simulations, the effects of duration and magnitude of an electric field, domain size and nanofilm thickness on the domain switching behavior are investigated. The evolution of domains under different magnitudes and durations of the applied electric field is studied, and the results of unswitched and switched cases are summarized in a switching map. Analysis of various nanofilms reveals that by increasing the film thickness, the switching time is increased. Furthermore, the nanofilms with different domain sizes and configurations are examined, and the minimum domain size for complete reversal switching is obtained. Our results are helpful to predict and tune the switching process in ferroelectric materials.
Dissecting melanocytes to predict melanoma.

With advanced high-throughput technologies, scientists can now use transcriptional signatures to study melanocytes as they become cancer. A new study identifies transcriptional programs at single-cell resolution across platforms and species, which enables prediction of melanoma prognosis and response to immune-checkpoint inhibitor therapy.
Internalizing Symptoms in Children Being Reared by Grandparents in Rural Appalachia: Risk and Protective Factors:

The present study investigates factors associated with anxiety, depression, and stress in children being reared by their grandparents in rural Appalachia. Grandparent-headed households, in which gr...
Racial disparities for COVID19 mortality in Georgia: Spatial analysis by age based on excess deaths.

Introduction This study uses multiple measures of excess deaths to analyze racial disparities in COVID-19 mortality across Georgia. Methods The Georgia Department of Public Health provided monthly mortality data for 2010-2020 stratified by race/ethnicity, age, county, and recorded cause of death. We first calculate crude mortality rates by health district during the time period for all groups for March through June for our historical period to identify significant time-series outliers in 2020 distinguishable from general trend variations. We then calculate the mean and standard deviation of mortality rates by age and racial subgroup to create historic confidence intervals that contextualize rates in 2020. Lastly, we use risk ratios to identify disparities in mortality between Black and White mortality rates both in the 2010-2019 period and in 2020. Results Time-series analysis identified three health districts with significant increases in mortality in 2020, located in metro Atlanta and Southwest Georgia. Mortality rates decreased sharply in 2020 for children in both racial categories in all sections of the state, but rose in a majority of districts for both categories in adult and older populations. Risk ratios also increased significantly in 2020 for children and older populations, showing rising disparities in mortality during the pandemic even as crude mortality rates declined for children classified as Black. Conclusions Increased mortality during the COVID-19 outbreak disproportionately affected African-Americans, possibly due, in part, to pre-existing disparities prior to the pandemic linked to social determinants of health. The pandemic deepened these disparities, perhaps due to unequal resources to effectively shelter-in-place or access medical care. Future research may identify local factors underlying geographically heterogenous differences in mortality rates to inform future policy interventions.
Practice burdens or responsibilities

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Modality from a Historical Perspective

‘Modality’ is defined as a semantic supercategory distinct from ‘modals’, which are structural expressions. Recent diachronic cross-linguistic work on both modality and modals is reviewed, with particular attention to the role of dynamic (‘ability’) modality in the rise of modal expressions. Since much research in the last decade has focused on non-verbal expressions of modality, the historical development of adjectives into modals, e.g. had better, Japanese –(r)eba ii ‘it is good if’, is highlighted, as is the development of modal adjectives, e.g. essential, and adverbs, e.g. surely. Modal expressions are shown to be subjectified over time, e.g. both deontic and epistemic must originated in relatively objective expressions, but are extended to meanings based in the speaker’s perspective, Japanese –be-si ‘appropriate, inevitable’ (future-oriented) came to be used subjectively to express speaker’s conjecture (present-oriented). Finally some hypothesized correlations between culture, cultural change and shifts in modal meanings and uses are discussed.
A Product Line Architecture for a Network Product

Given a set of related (and existing) network products, the goal of this architectural exercise was to define a generic architecture that was sufficient to encompass existing and future products in such a way as to satisfy the following two requirements: 1) represent the range of products from single board, centralized systems to multiple board, distributed systems; and 2) support dynamic reconfigurability.
A Review of: “Loose Space: Possibility and Diversity in Urban Life”

Drivers speeding toward profits on the global causeway seldom slow down to experience firsthand its seemingly dark and dirty underside; a collection of forgotten and eclectic spaces cast aside by t...
Characterization of the copper-thiolate cluster in yeast metallothionein and two truncated mutants.

Cu-metallothionein was purified from Saccharomyces cerevisiae harboring plasmids containing mutated CUP1 metallothionein genes resulting in deletions at the carboxy-terminal end of the polypeptide. The truncated polypeptides are recovered as polypeptides of 35 and 48 residues in length. The Cu-S cluster in the wild-type metallothionein and the two truncates were characterized. The truncated proteins, designated T35 and T48, contain 4 and 2 fewer cysteinyl residues, respectively, compared to the 12 cysteines in wild-type metallothionein; yet the mutant molecules bind Cu(I) ions in a stoichiometry comparable to the wild-type protein, i.e. 7-8 mol eq. The Cu(I) ions bound to T48 are as tenaciously bound as those bound to the wild-type molecule. The electronic transitions in the ultraviolet are similar for Cu-T48 and the wild-type protein. Both mutants and wild-type Cu-protein exhibit luminescence. The corrected emission maxima occurs at 609 nm with a corrected excitation peak near 277 nm. The luminescence quantum yield and lifetime of fluorescence decay of Cu-T48 and wild-type Cu-metallothionein are similar. The absolute quantum yield of the wild-type Cu-protein luminescence is 0.0058 and has a 440-ns lifetime. The similar fluorescence rate constant in the two molecules suggests they possess a similar chromophore. The Cu-T35 protein is more labile than Cu-T48 or the wild-type protein in the association of Cu(I) ions and the air sensitivity of the electronic transitions and luminescence. Although T48 lacks 2 of the 12 cysteines in the wild-type protein, we are unable to detect any differences in the properties of the native metal clusters in the two molecules; T35 lacking 4 cysteinyl residues forms a Cu(I) cluster with properties significantly different from the wild-type molecule. Properties of the Cu-thiolate cluster were also studied in Cu(I)-reconstituted samples. The cluster in wild-type metallothionein forms in all-or-nothing fashion. This conclusion is based on copper binding stoichiometry and luminescence studies. The relative quantum yield of samples with intermediate Cu(I) levels was constant, consistent with all-or-none cluster formation.
Identification of Homogeneous and Heterogeneous Variables in Pooled Cohort Studies

Pooled analyses integrate data from multiple studies and achieve a larger sample size for enhanced statistical power. When heterogeneity exists in variables' effects on the outcome across studies, the simple pooling strategy fails to present a fair and complete picture of the effects of heterogeneous variables. Thus, it is important to investigate the homogeneous and heterogeneous structure of variables in pooled studies. In this article, we consider the pooled cohort studies with time-to-event outcomes and propose a penalized Cox partial likelihood approach with adaptively weighted composite penalties on variables' homogeneous and heterogeneous effects. We show that our method can characterize the variables as having heterogeneous, homogeneous, or null effects, and estimate non-zero effects. The results are readily extended to high-dimensional applications where the number of parameters is larger than the sample size. The proposed selection and estimation procedure can be implemented using the iterative shooting algorithm. We conduct extensive numerical studies to evaluate the performance of our proposed method and demonstrate it using a pooled analysis of gene expression in patients with ovarian cancer.