cssi/SciSciGPT-SciSciNet huggingface dataset:
A Realistic Model for a Spin Glass

We develop exact integral equations satisfied by the spin-spin correlation functions of a realistic spin glass model. This is done by considering the magnetic particles in a spin glass to be bound states of hard sphere ‘atoms’ and classical ‘spins’, the former of which are quenched in position, while the latter are allowed to equilibrate. We develop the replica Ornstein-Zernike (ROZ) equations, which are satisfied by the correlation functions of such a partly quenched mixture. We prove that two widely used OZ closures, the Percus-Yevick approximation and mean-spherical approximation are indifferent to quenched disorder, i.e., they give tihe same results for quenched and for fully annealed systems. We extend the ROZ equations to apply to the spin glass by using the proper interaction-site formalism. Preliminary numerical results are discussed.
Mediation of the Mitogenic Action of Growth Hormone by Adenosine 3′5′-Monophosphate (Cyclic AMP)

SummaryBovine growth hormone stimulates the progression of rat thymocytes (maintained in vitro) into mitosis. The myogenic capacity of growth hormone is considerably increased by caffeine which suggests that the hormonal action is mediated by adenosine 3′5′-monophosphate. In support of this suggestion, it is shown that cyclic AMP has the necessary ability to strongly stimulate mitotic activity in thymocyte populations.
Analysis and forecast of rat density in Three Gorges reservoir area in Yichang,Hubei by Grey Model(1997-2012)

Objective To explorer the rat density variation in Three Gorges reservoir area in Yichang,Hubei.Methods By establishing GM(1,1)model of rat density in Three Gorges reservoir area in Yichang city from 1997to 2012,to forecast the indoor and outdoor rat density from 2013to 2014.Results The predicted values of rat density showed slight downward trend from 2013to 2014in Three Gorges reservoir area in Yichang city.The fitted models are significant statistically.The indoor rat densities will be 1.55%and 1.45%,1.30%and 1.29%for outdoor from 2013to 2014.Conclusion With the environment changes in Yichang Three Gorges reservoir,the rat density and constitute were changed correspondingly.It is suggested that rat density surveillance should be strengthened for vector-borne diseases control and prevention.
Molecular epidemiological characterization of enterovirus 71 in Lu′an city of Anhui province in 2010

Objective:To analyze the genetic characteristics and prevalence trends of Enterovirus 71(EV71) in patients with hand,foot and mouth disease(HFMD)in Lu′an City,Anhui Province,and provide scientific basis for further prevention and control of HFMD in this area.Methods: Throat swab specimens from HFMD patients from Lu′an city were collected for enterovirus nucleic acid detection in Lu′an CDC,and eight EV71 positive samples were randomly selected to conduct sequence determination of VP1 full length.The nucleotide sequences were aligned with EV71 reference strains around the world and the various types of EV71 strains in Mainland China by Bioedit and DNASTAR software.Phylogenetic tree was constructed by clustal W method.Results: The complete VP1 genes from all eight specimens were 891 nt in length,encoding 297 amino acids.Sequence analysis showed that the homogeneity of these 8 strains shared 96.7%to 99.4% in nucleotide acid identity,and 97.0%to 100% in amino acid identity to the representative strains of C4a genotype isolated in China.But when compared to the reference strain of genotype A and B,there were only 82.6%~83.2%,83.1%~85.0% in nucleotide acid identity and 96.6%~97.0%,96.0%~97.7% in amino acid identity among them.These results suggested that these 8 virus strains belonged to the EV71 C4a subgenotype.Conclusion: The strains isolated from Lu′an city in 2010 are closely related to those isolated from other provinces in China and all of them belong to C4a subgenotype.It indicated that the C4a genotype probably widely distributes and spreads in mainland of China.The present research is important for the basic research of enterovirus and prevention and control of the EV71 outbreak in China.
The importance of early cyclosporine levels in pediatric kidney transplantation.

We studied the impact of early cyclosporine (CSA) levels on the incidence of rejection in pediatric transplant recipients. Between 1 January 1984 and 31 December 1994, a total of 234 pediatric patients underwent kidney transplants and received CSA immunosuppression. We analyzed the impact of CSA levels (at 1 wk, 2 wk, 1 month, 2 months, and 3 months) on the incidence of rejection in the first 3 and the first 6 months post-transplant. We found that CSA levels at all timepoints correlated, i.e. recipients with low levels in the early post-transplant period tended to have low levels throughout the first 12 months. Multivariate analysis for risk factors by biopsy-proven rejection in the first 3 months revealed that the CSA trough level was the critical factor (p 100 ng/ml. Similarly, the CSA trough level at 1 month was the critical risk factor for biopsy-proven rejection within the first 6 months (p < 0.05). The major risk factor for graft loss within the first 12 months was a biopsy-proven rejection episode. We conclude that in pediatric kidney transplant recipients, early CSA trough levels < 100 ng/ml are associated with a significantly increased incidence of rejection in the first 6 months post-transplant.
Quadrupedal running with a flexible torso: control and speed transitions with sums-of-squares verification

This paper studies quadrupedal bounding in the presence of flexible torso and compliant legs with non-trivial inertia, and it proposes a method for speed transitions by sequentially composing locally stable bounding motions corresponding to different speeds. First, periodic bounding motions are generated simply by positioning the legs during flight via suitable (virtual) holonomic constraints imposed on the leg angles; at this stage, no control effort is developed on the support legs, producing efficient, nearly passive, bounding gaits. The resulting motions are then stabilized by a hybrid control law which coordinates the movement of the torso and legs in continuous time, and updates the leg touchdown angles in an event-based fashion. Finally, through sums-of-squares programming, formally verified estimates of the domain of attraction of stable fixed points are employed to realize stable speed transitions by switching among different bounding gaits in a sequential fashion.
Abstract WP8: Minor Stroke With Large Vessel Occlusion

Background and Rationale: Minor stroke symptoms (NIHSS Methods: We retrospectively reviewed patients who presented with minor stroke symptoms and LVO between the years of 2002 and 2015. In our primary analysis, we divided patients who underwent IAT based on 90 day modified Rankin Scale (mRS) into favorable (mRS 0-2) vs unfavorable outcome (mRS >2). Using unpaired t-test, we compared demographics, comorbidities, NIHSS at presentation, use of IV tPA, stent retrievers, IAT within 8 hours from last known well and location of LVO. In our secondary analysis, we compared the two cohorts with matched patients who received tPA only without IAT. Results: Risk of complication of patients undergoing IAT was low (4%). The overall good outcome in patients undergoing IAT was 62.5%. Patients with favorable outcome tended to have anterior circulation occlusion (70% vs 41.6%, p = 0.03) and tandem occlusions (32.5% vs 8.3%, p = 0.03) with higher rates of TICI 2b/3 recanalization (90% vs 62.5%, p = 0.008). There was no difference in favorable outcome between patients who received IV tPA only vs IAT +/- IV tPA (68.5% vs 62.5%, p = 0.5). However, the medical therapy group had higher rates of distal occlusions (46% vs 17.2%, p = 0.001) and the IAT group had higher rates of vertebrobasilar occlusion (20.4% vs 40.6%, p = 0.02). Conclusion: This study highlights good safety profile in patients undergoing IAT for strokes with minor symptoms. Favorable outcomes were observed in patients with successful recanalization, anterior circulation occlusions and tandem lesions. A randomized clinical trial is warranted to investigate the benefit of IAT in patients with low NIHSS over medical therapy alone and our findings can assist in patient selection.
An exhaustive algorithm for detecting copy number aberrations and large structural variants in whole-genome, mate-pair sequencing data.

e22171 Background: Structural variants (SV) including large copy number aberrations (CNV), translocations, inversions, and large insertions and deletions (INDEL) play a critical role in tumorigenes...
Temperature and Precipitation Variance in CMIP5 Simulations and Paleoclimate Records of the Last Millennium

National Science Foundation EaSM2 Grant [AGS-1243125]; Directorate for Geosciences [3008610]; Graduate Research Fellowship [DGE-1143953]; Kartchner Caverns scholarship fund; Department of Geosciences at the University of Arizona
Jungian Archetypes and the Personality of Jesus in the Synoptics

The Jungian archetypes anima and animus are used as a tool for studying the personality of Jesus. To carry out this analysis, the synoptic Gospels were examined and passages about Jesus were rated ...
Introduction to Statistical Quality Control

(1997). Introduction to Statistical Quality Control. Journal of Quality Technology: Vol. 29, No. 3, pp. 357-359.
Diffuse large B-cell lymphoma with strong aberrant expression of CD31.

![Figure][1] A 49-year-old man presented with an 8.8 × 6.5 cm, left infraclavicular subpectoral mass. A biopsy showed predominantly spindle-ish cells (panels A-B, hematoxylin and eosin stain; original magnifications shown on pictures) and was therefore worked up for soft tissue tumors
The Nature of Feedback Given to Elementary Student Teachers from University Supervisors after Observations of Mathematics Lessons

This research explores the frequency and nature of mathematics-specific feedback given to elementary student teachers by university supervisors across a collection of post-lesson observation forms. Approximately one-third of the forms (n=250) analysed from five large universities had no comments related to mathematics. Forms that did have mathematics-specific feedback varied in terms of the number of summary, strength, and suggestion (i.e., type) comments and in the pedagogical focus (e.g., tasks, discourse) of those comments. Chi-square tests of independence indicated the frequency of forms with mathematics-specific feedback differed significantly by university. Results of additional Chi-square tests showed significant interactions between the type of comments and university and between the pedagogical foci of the comments and comment type. Contributing factors and implications, including connectedness of the university supervisors to the programs, professional development provided to university supervisors, and the organization of the forms, are discussed.
Determination of Yield and Flow Surfaces for Inconel 718 Under Axial-Torsional Loading at Temperatures Up to 649 C

An experimental program to determine flow surfaces has been established and implemented for solution annealed and aged IN718. The procedure involved subjecting tubular specimens to various ratios of axial-torsional stress at temperatures between 23 and 649 C and measuring strain with a biaxial extensometer. Each stress probe corresponds to a different direction in stress space, and unloading occurs when a 30 microstrain (1 micro eplison = 10(exp -6) mm/mm) offset is detected. This technique was used to map out yield loci in axial-torsional stress space. Flow surfaces were determined by post-processing the experimental data to determine the inelastic strain rate components. Surfaces of constant inelastic strain rate (SCISRS) and surfaces of constant inelastic power (SCIPS) were mapped out in the axial-shear stress plane. The von Mises yield criterion appeared to closely fit the initial loci for solutioned IN718 at 23 C. However, the initial loci for solutioned IN718 at 371 and 454 C, and all of the initial loci for aged IN718 were offset in the compression direction. Subsequent loci showed translation, distortion, and for the case of solutioned IN718, a slight cross effect. Aged IN718 showed significantly more hardening behavior than solutioned IN718.
Crystal structure of a class 3 aldehyde dehydrogenase at 2.6 A resolution.

Class 3 ALDHs prefer NAD as coenzyme, but can use NADP effectively in vitro. They function as dimers of identical ~50kDa monomers, and share about 30% sequence identity with either of the tetrameric class 1 or 2 enzymes. Interest in the Class 3 ALDH (ALDH-3) has focused on its diversity of expression (Lindahl, 1992). No ALDH-3 activity is detectable in normal mammalian liver, but high levels are obtained after exposure to certain xenobiotics. Many neoplasms possess elevated ALDH-3 activities, while many normal tissues, such as cornea and stomach constitutively express ALDH-3. ALDH-3 enzymes prefer aromatic aldehydes and medium chain-length (C-6 to C-10) aliphatic aldehydes as substrate. Known substrates include benzaldehyde and hexenal as well as 4-hydroxynonenal derived from membrane lipid peroxidation (Lindahl and Peterson, 1991). The microsomal ALDH-3 has also received clinical attention from the recent demonstration that Sjogren-Larsson Syndrome is the result of mutations inactivating this “fatty aldehyde dehydrogenase” (DeLaurenzi, et al, 1996).
A collaborative, academic approach to optimizing the national clinical research infrastructure: The first year of the Trial Innovation Network

Inefficiencies in the national clinical research infrastructure have been apparent for decades. The National Center for Advancing Translational Science—sponsored Clinical and Translational Science Award (CTSA) program is able to address such inefficiencies. The Trial Innovation Network (TIN) is a collaborative initiative with the CTSA program and other National Institutes of Health (NIH) Institutes and Centers that addresses critical roadblocks to accelerate the translation of novel interventions to clinical practice. The TIN’s mission is to execute high-quality trials in a quick, cost-efficient manner. The TIN awardees are composed of 3 Trial Innovation Centers, the Recruitment Innovation Center, and the individual CTSA institutions that have identified TIN Liaison units. The TIN has launched a national scale single (central) Institutional Review Board system, master contracting agreements, quality-by-design approaches, novel recruitment support methods, and applies evidence-based strategies to recruitment and patient engagement. The TIN has received 113 submissions from 39 different CTSA institutions and 8 non-CTSA Institutions, with projects associated with 12 different NIH Institutes and Centers across a wide range of clinical/disease areas. Already more than 150 unique health systems/organizations are involved as sites in TIN-related multisite studies. The TIN will begin to capture data and metrics that quantify increased efficiency and quality improvement during operations.
The political economy of public education

Abstract I study the relationship between income inequality and public spending in education in a voting model. Voters collectively choose the uniform quality level of public education, the amount of a public good, and the tax rate on labor income. Parents can decide to opt-out of the public education system by purchasing private education at the desired quality level, and children’s expected income is assumed to be increasing in the quality of education. I show that higher income inequality is associated with higher governmental spending in education if and only if the expected marginal returns to education are larger for the children of relatively low income parents. In turn, better public education tends to reduce future inequality. These results are consistent with most findings in the empirical literature about public investment in education. Lastly, I show that for other kind of publicly provided goods, such as health care, the relationship with income inequality exhibits an ambiguous or opposite sign.
‘Architectures of happiness’: Designing the Malltiplex in India

ABSTRACTThis paper looks at the gendered architecture and industrial design of the most predominant fused space of urban entertainment in contemporary India: the mallitplex. Drawing upon fieldwork ...
The digestive system in Zygentoma as an insect model for high cellulase activity

The digestive system of selected phytophagous insects has been examined as a potential prospecting resource for identification of novel cellulolytic enzymes with potential industrial applications. In contrast to other model species, however, limited detailed information is available that characterizes cellulolytic activity and systems in basal hexapod groups. As part of a screening effort to identify insects with highly active cellulolytic systems, we have for the first time, identified species of Zygentoma that displayed the highest relative cellulase activity levels when compared to all other tested insect groups under the experimental conditions, including model species for cellulolytic systems such as termite and cockroach species in Rhinotermitidae (formerly Isoptera) and Cryptocercidae (formerly Blattodea). The goal of the present study was to provide a morphohistological characterization of cellulose digestion and to identify highly active cellulase enzymes present in digestive fluids of Zygentoma species. Morphohistological characterization supported no relevant differences in the digestive system of firebrat (Thermobia domestica) and the gray silverfish (Ctenolepisma longicaudata). Quantitative and qualitative cellulase assays identified the foregut as the region with the highest levels of cellulase activity in both T. domestica and C. longicaudata. However, T. domestica was found to have higher endoglucanase, xylanase and pectinase activities compared to C. longicaudata. Using nano liquid chromatography coupled to tandem mass spectrometry (nanoLC/MS/MS) and a custom gut transcriptome we identified cellulolytic enzymes from digestive fluids of T. domestica. Among the identified enzymes we report putative endoglucanases matching to insect or arthropod enzymes and glucan endo-1,6-β-glucosidases matching bacterial enzymes. These findings support combined activities of endogenous and symbiont-derived plant cell wall degrading enzymes in lignocellulose digestion in Zygentoma and advance our understanding of cellulose digestion in a primitive insect group.
GAN-SRAF: Sub-Resolution Assist Feature Generation Using Conditional Generative Adversarial Networks

As the integrated circuits (IC) technology continues to scale, resolution enhancement techniques (RETs) are mandatory to obtain high manufacturing quality and yield. Among various RETs, sub-resolution assist feature (SRAF) generation is a key technique to improve the target pattern quality and lithographic process window. While model-based SRAF insertion techniques have demonstrated high accuracy, they usually suffer from high computational cost. Therefore, more efficient techniques that can achieve high accuracy while reducing runtime are in strong demand. In this work, we leverage the recent advancement in machine learning for image generation to tackle the SRAF insertion problem. In particular, we propose a new SRAF insertion framework, GAN-SRAF, which uses conditional generative adversarial networks (CGANs) to generate SRAFs directly for any given layout. Our proposed approach incorporates a novel layout to image encoding using multi-channel heatmaps to preserve the layout information and facilitate layout reconstruction. Our experimental results demonstrate $\sim 14. 6 \times $ reduction in runtime when compared to the previous best machine learning approach for SRAF generation, and $\sim 144 \times $ reduction compared to model-based approach, while achieving comparable quality of results.
Synthetic studies towards batrachotoxin 1. A furan-based intramolecular diels-alder route to construct the a-d ring system

Abstract A stereoselective intramolecular Diels-Alder reaction has been developed using annelated furans to produce functionalized steroidal nuclei, which can serve as advanced intermediates in the synthesis of batrachotoxin.
The Justificatory Force of Religious Experience

Under ordinary circumstances, perceptual experience provides good grounds for belief. Some argue that religious experiences are unlike ordinary perception, and so do not justify the corresponding beliefs. Applying Alston’s doxastic practice approach to epistemology, we can see that the question comes down to whether some defeater or other is operative that removes the experience’s justificatory force.
A Wireless fNIRS Patch with Short-Channel Regression to Improve Detection of Hemodynamic Response of Brain

The functional near-infrared spectroscopy (fNIRS) utilizes near-infrared (NIR) light sources and light detectors to non-invasively image hemodynamic responses of the brain. The unique advantages of fNIRS over the other existing brain imaging technologies led to widespread adoption of fNIRS in various brain research studies including neurology, neuroscience, clinical psychology, and psychiatry. The fNIRS systems are portable, inexpensive and provide higher temporal resolution for scanning a brain. In this paper, we present a wireless wearable fNIRS patch that has the capability of short channel regression to improve the detection of hemodynamic responses of the brain. The patch has two targeted fNIRS channels and a short-channel. The short-channel measures the background hemodynamic responses explicitly from the extracerebral region. Then it performs a regression process to eliminate background interferences from the targeted fNIRS channels to reduce the influence of the interferences. We have interfaced the patch with our laboratory-developed portable fNIRS controller. The patch and the controller are wearable. The controller is wirelessly connected to a host computer to receive commands from it and to wirelessly transmit measurement data to the host computer for the data processing and visualization. The graphical user interface (GUI) in the host computer helps the user to record and visualize fNIRS data. The experimental results of imaging prefrontal cortex of the brain using the fNIRS patch show that the patch has the potential to reduce unrelated hemodynamic activity from the targeted fNIRS channels.
What Makes a Good Pore Former: A Study of Synthetic Melittin Derivatives

Pore formation by membrane-active peptides, naturally encountered in innate immunity and infection, could have important medical and technological applications. Recently, the well-studied lytic peptide melittin has formed the basis for the development of combinatorial libraries from which potent pore-forming peptides have been derived, optimized to work under different conditions. We investigate three such peptides, macrolittin70, which is most active at neutral pH; pHD15, which is active only at low pH; and MelP5_Δ6, which was rationally designed to be active at low pH but formed only small pores. There are three, six, and six acidic residues in macrolittin70, pHD15, and MelP5_Δ6, respectively. We perform multi-microsecond simulations in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) of hexamers of these peptides starting from transmembrane orientations at neutral pH (all residues at standard protonation), low pH (acidic residues and His protonated), and highly acidic environments in which C-termini are also protonated. Previous simulations of the parent peptides melittin and MelP5 in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) are repeated in POPC. We find that the most potent pore-forming peptides exhibit strong interpeptide interactions, including salt bridges, H-bonds, and polar interactions. Protonation of the C-terminus promotes helicity and pore size. The proximity of the peptides allows fewer lipid headgroups to line the pores than in previous simulations, making the pores intermediate between barrel stave and toroidal. Based on these structures and geometrical arguments, we attempt to rationalize the factors that under different conditions can increase or decrease pore stability and propose mutations that could be tested experimentally.
Within- and between-person associations of neighborhood poverty with alcohol use and consequences: a monthly study of young adults

Abstract Background Studies have shown associations between neighborhood disadvantage and alcohol misuse among adults. Less is known about the role of neighborhood context in young adults (YAs), who engage in more disordered forms of alcohol use compared to other age groups. Using data collected monthly, this study examined whether YAs reported more alcohol use and consequences when they were living in neighborhoods with greater concentration of poverty. Method This study used data from 746 participants aged 18–23 years living in the Seattle, WA, region. Surveys were administered each month for 24 consecutive months. Measures included typical number of drinks per week and past month count of alcohol-related consequences. Residential addresses at each month were geocoded and linked to census-tract level percentage of households living at or below poverty threshold. Multilevel over-dispersed Poisson models were used to estimate associations between standardized monthly deviations in tract-level poverty from one’s average and alcohol outcomes. Results Across 14,247 monthly observations, the mean number of typical drinks per week was 4.8 (SD = 7.4) and the mean number of alcohol consequences was 2.1 (SD = 3.5). On months when they were living in neighborhoods with higher levels of poverty than their average, participants reported significantly higher levels of alcohol consequences (Count Ratio = 1.05; p = .045). Conclusion YAs may engage in more problematic forms of drinking when they reside in neighborhoods with higher levels of disadvantage. During a time of frequent residential changes, YAs moving to more disadvantaged neighborhoods may benefit from additional supports.
School Psychologists Involvement in and Knowledge of Secondary Transition: Results from a Statewide Survey

Secondary transition has traditionally been the domain of special education, but recent research has explored potential avenues for school psychologists to become involved in secondary transition. The purpose of this study was to explore school psychologists’ knowledge of and involvement in secondary transition. Using a survey methodology, 3.5% of school psychologists in the sample reported receiving training in secondary transition during their graduate program. Most trainings in this area occurred as a result of in-service professional development. School psychologists reported being involved most often in helping students to understand their disabilities. The implications of these findings and opportunities for further research as well as training opportunities for school psychologists are discussed in this article.
Machine Learning for Integrating Social Determinants in Cardiovascular Disease Prediction Models: A Systematic Review

Summary Background Cardiovascular disease (CVD) is the number one cause of death worldwide, and CVD burden is increasing in low-resource settings and for lower socioeconomic groups worldwide. Machine learning (ML) algorithms are rapidly being developed and incorporated into clinical practice for CVD prediction and treatment decisions. Significant opportunities for reducing death and disability from cardiovascular disease worldwide lie with addressing the social determinants of cardiovascular outcomes. We sought to review how social determinants of health (SDoH) and variables along their causal pathway are being included in ML algorithms in order to develop best practices for development of future machine learning algorithms that include social determinants. Methods We conducted a systematic review using five databases (PubMed, Embase, Web of Science, IEEE Xplore and ACM Digital Library). We identified English language articles published from inception to April 10, 2020, which reported on the use of machine learning for cardiovascular disease prediction, that incorporated SDoH and related variables. We included studies that used data from any source or study type. Studies were excluded if they did not include the use of any machine learning algorithm, were developed for non-humans, the outcomes were bio-markers, mediators, surgery or medication of CVD, rehabilitation or mental health outcomes after CVD or cost-effective analysis of CVD, the manuscript was non-English, or was a review or meta-analysis. We also excluded articles presented at conferences as abstracts and the full texts were not obtainable. The study was registered with PROSPERO (CRD42020175466). Findings Of 2870 articles identified, 96 were eligible for inclusion. Most studies that compared ML and regression showed increased performance of ML, and most studies that compared performance with or without SDoH/related variables showed increased performance with them. The most frequently included SDoH variables were race/ethnicity, income, education and marital status. Studies were largely from North America, Europe and China, limiting the diversity of included populations and variance in social determinants. Interpretation Findings show that machine learning models, as well as SDoH and related variables, improve CVD prediction model performance. The limited variety of sources and data in studies emphasize that there is opportunity to include more SDoH variables, especially environmental ones, that are known CVD risk factors in machine learning CVD prediction models. Given their flexibility, ML may provide opportunity to incorporate and model the complex nature of social determinants. Such data should be recorded in electronic databases to enable their use. Funding We acknowledge funding from Blue Cross Blue Shield of Louisiana. The funder had no role in the decision to publish.
Towards Quantum Entanglement Between a Solid-State Spin and a Trapped Ion

We are constructing a system to remotely entangle a single trapped ytterbium ion with a donor qubit in zinc oxide through a photonic link as a step towards the construction of a hybrid quantum system.
l-Cysteine Stimulates the Effect of Vitamin D on Inhibition of Oxidative Stress, IL-8, and MCP-1 Secretion in High Glucose Treated Monocytes.

Objective: Vitamin D deficiency is common in the general population and diabetic patients, and supplementation with vitamin D is widely used to help lower oxidative stress and inflammation. The cytokine storm in SARS-CoV2 infection has been linked with both diabetes and Vitamin D deficiency. This study examined the hypothesis that supplementation with vitamin D, in combination with l-cysteine (LC), is better at reducing oxidative stress and thereby, more effective, at inhibiting the secretion of the pro-inflammatory cytokines, Interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in U937 monocytes exposed to high glucose concentrations. Methods: U937 monocytes were pretreated with 1,25 (OH)2 vitamin D (VD, 10 nM) or LC (250 µM) or VD + LC for 24 h and then exposed to control or high glucose (HG, 25 mM) for another 24 h. Results: There were significantly greater reactive oxygen species (ROS) levels in monocytes treated with HG than those in controls. Combined supplementation with VD and LC showed a more significant reduction in ROS (46%) in comparison with treatment with LC (19%) or VD (26%) alone in monocytes exposed to HG. Similarly, VD supplementation, together with LC, caused a more significant inhibition in the secretion of IL-8 (36% versus 16%) and MCP-1 (46% versus 26%) in comparison with that of VD (10 nM) alone in high-glucose treated monocytes. Conclusions: These results suggest that combined supplementation with vitamin D and LC has the potential to be more effective than either VD or LC alone in lowering the risk of oxidative stress and inflammation associated with type 2 diabetes or COVID-19 infection. Further, this combined vitamin D with LC/N-acetylcysteine may be a potent alternative therapy for SARS-CoV2 infected subjects. This approach can prevent cellular damage due to cytokine storm in comorbid systemic inflammatory conditions, such as diabetes, obesity, and hypertension.
Bayesian subgroup analysis in regression using mixture models

Abstract Heterogeneity occurs in many regression problems, where members from different latent subgroups respond differently to the covariates of interest (e.g., treatments) even after adjusting for other covariates. A Bayesian model called the mixture of finite mixtures (MFM) can be used to identify these subgroups, a key feature of which is that the number of subgroups is modeled as a random variable and its distribution is learned from the data. The Bayesian MFM model was not commonly used in earlier applications largely due to computational difficulties. In comparison, an alternative infinite mixture model called the Dirichlet Process Mixture (DPM) model has been a main Bayesian tool for clustering even though it is a mis-specified model for many applications. The popularity of DPM is partly due to its convenient mathematical properties that enable efficient computing algorithms. A class of Bayesian models tailored to regression problems, the conditional MFMs (cMFM), are described and studied. Computing for the cMFM is developed by extending the efficient MCMC algorithms for general MFMs. Using simulation and real data examples, the cMFM is compared to existing frequentist methods, the conditional DPM, and the original MFM and DPM models that model response and covariates jointly. The cMFM is shown to be favorable in clustering accuracy and is robust to different covariates and noise distributions.
Melatonin improves brain function in a model of chronic Gulf War Illness with modulation of oxidative stress, NLRP3 inflammasomes, and BDNF-ERK-CREB pathway in the hippocampus

Abstract Persistent cognitive and mood dysfunction is the primary CNS symptom in veterans afflicted with Gulf War Illness (GWI). This study investigated the efficacy of melatonin (MEL) for improving cognitive and mood function with antioxidant, antiinflammatory, and pro-cognitive effects in a rat model of chronic GWI. Six months after exposure to GWI-related chemicals and stress, rats were treated with vehicle or MEL (5, 10, 20, 40, and 80 mg/kg) for eight weeks. Behavioral tests revealed cognitive and mood dysfunction in GWI rats receiving vehicle, which were associated with elevated oxidative stress, reduced NRF2, catalase and mitochondrial complex proteins, astrocyte hypertrophy, activated microglia with NLRP3 inflammasomes, elevated proinflammatory cytokines, waned neurogenesis, and synapse loss in the hippocampus. MEL at 10 mg/kg alleviated simple and associative recognition memory dysfunction and anhedonia, along with reduced oxidative stress, enhanced glutathione and complex III, and reduced NLRP3 inflammasomes, IL-18, TNF-α, and IFN-γ. MEL at 20 mg/kg also normalized NRF2 and catalase and increased microglial ramification. MEL at 40 mg/kg, in addition, reduced astrocyte hypertrophy, activated microglia, NF-kB-NLRP3-caspase-1 signaling, IL-1β, MCP-1, and MIP-1α. Moreover, MEL at 80 mg/kg activated the BDNF-ERK-CREB signaling pathway, enhanced neurogenesis and diminished synapse loss in the hippocampus, and improved a more complex hippocampus-dependent cognitive function. Thus, MEL therapy is efficacious for improving cognitive and mood function in a rat model of chronic GWI, and MEL's effect was dose-dependent. The study provides the first evidence of MEL's promise for alleviating neuroinflammation and cognitive and mood impairments in veterans with chronic GWI.
Visual modulation of spectrotemporal receptive fields in mouse auditory cortex

Recent studies have established significant anatomical and functional connections between visual areas and primary auditory cortex (A1), which may be important for perceptual processes such as communication and spatial perception. However, much remains unknown about the microcircuit structure of these interactions, including how visual context may affect different cell types across cortical layers, each with diverse responses to sound. The present study examined activity in putative excitatory and inhibitory neurons across cortical layers of A1 in awake male and female mice during auditory, visual, and audiovisual stimulation. We observed a subpopulation of A1 neurons responsive to visual stimuli alone, which were overwhelmingly found in the deep cortical layers and included both excitatory and inhibitory cells. Other neurons for which responses to sound were modulated by visual context were similarly excitatory or inhibitory but were less concentrated within the deepest cortical layers. Important distinctions in visual context sensitivity were observed among different spike rate and timing responses to sound. Spike rate responses were themselves heterogeneous, with stronger responses evoked by sound alone at stimulus onset, but greater sensitivity to visual context by sustained firing activity following transient onset responses. Minimal overlap was observed between units with visual-modulated firing rate responses and spectrotemporal receptive fields (STRFs) which are sensitive to both spike rate and timing changes. Together, our results suggest visual information in A1 is predominantly carried by deep layer inputs and influences sound encoding across cortical layers, and that these influences independently impact qualitatively distinct responses to sound.
Structure-function analysis of two interacting vaccinia proteins that are critical for viral morphogenesis: L2 and A30.5.

An enduring mystery in poxvirology is the mechanism by which virion morphogenesis is accomplished. A30.5 and L2 are two small regulatory proteins that are essential for this process. Previous studies have shown that vaccinia A30.5 and L2 localize to the ER and interact during infection, but how they facilitate morphogenesis is unknown. To interrogate the relationship between A30.5 and L2, we generated inducible complementing cell lines (CV1-HA-L2; CV1-3xFLAG-A30.5) and deletion viruses (vΔL2; vΔA30.5). Loss of either protein resulted in a block in morphogenesis and a significant (>100-fold) decrease in infectious viral yield. Structure-function analysis of L2 and A30.5, using transient complementation assays, identified key functional regions in both proteins. A clustered charge-to-alanine L2 mutant (L2-RRD) failed to rescue a vΔL2 infection and exhibits a significantly retarded apparent molecular weight in vivo (but not in vitro), suggestive of an aberrant post-translational modification. Furthermore, an A30.5 mutant with a disrupted putative N-terminal α-helix failed to rescue a vΔA30.5 infection. Using our complementing cell lines, we determined that the stability of A30.5 is dependent on L2, and that wild-type L2 and A30.5 coimmunoprecipitate in the absence of other viral proteins. Further examination of this interaction, using wild-type and mutant forms of L2 or A30.5, revealed that the inability of mutant alleles to rescue the respective deletion viruses is tightly correlated with a failure of L2 to stabilize and interact with A30.5. L2 appears to function as a chaperone-like protein for A30.5, ensuring that they work together as a complex during viral membrane biogenesis. IMPORTANCE Vaccinia virus is a large, enveloped DNA virus that was successfully used as the vaccine against smallpox. Vaccinia continues to be an invaluable biomedical research tool in basic research and in gene therapy vector and vaccine development. Although this virus has been studied extensively, the complex process of virion assembly, termed morphogenesis, still puzzles the field. Our work aims to better understand how two small viral proteins that are essential for viral assembly, L2 and A30.5, function during early morphogenesis. We show that A30.5 requires L2 for stability and that these proteins interact in the absence of other viral proteins. We identify regions in each protein required for their function and show that mutations in these regions disrupt the interaction between L2 and A30.5 and fail to restore virus viability.
Application of Nonlinear Stochastic Dynamics and Damage Accumulation in Seismic Engineering

The response of a structure, in particular in the inelastic range, is highly dependent on the ground excitation intensity, duration as well as frequency content and its evolution with time. Strong ground motions need to be modeled as nonstationary random processes. Although methods have been proposed to generate nonstationary random processes with evolutionary power spectra, the required parameters are difficult to estimated and the methods are difficult to implement in random vibration response studies. This chapter introduces a new nonstationary ground motion model and its applications. It can be efficiently used in Monte Carlo simulations as well as random vibration response studies. Methods for parameter estimation are also given.
Presynaptic differentiation induced in cultured neurons by local application of basic fibroblast growth factor.

Recent studies have suggested a role for molecules residing at the muscle surface in signaling presynaptic development at the neuromuscular junction (NMJ). Since heparan sulfate-proteoglycan is a major component of the extracellular matrix of skeletal muscle, factors that are bound to this proteoglycan, such as basic fibroblast growth factor (bFGF), are in a strategic position for neuronal signaling. To test this idea, we applied bFGF to cultured Xenopus spinal cord neurons and monitored the change in intracellular Ca2+ level with fura-2 ratio imaging. In one-third of the neurons, local application of bFGF elicited a 30–140% increase in intracellular Ca2+ level. Ca(2+)-free medium or suramin abolished this change. Latex beads coated with bFGF induced clustering of synaptic vesicles at the bead-neurite contacts as evidenced by anti-synaptotagmin antibody labeling and electron microscopy. This response was also blocked by Ca(2+)-free medium and by suramin. Uncoated beads or beads coated with PDGF were ineffective. This induction was also inhibited by a tyrosine kinase inhibitor, tyrphostin RG-50864, suggesting the role of receptor tyrosine kinase activation in this process. In addition, bFGF-coated beads also induced the localization of depolarization-dependent Ca2+ influx to the bead- neurite contacts. In contrast, depolarization caused a distributed Ca2+ elevation in untreated neurites. These results suggest that local presentation of bFGF can mimic the muscle target in signaling the development of both a cytoplasmic and a membranous specialization for excitation-secretion coupling observed at the NMJ.
Interaction with GIS attribute data based on categorical coverages

The human-computer interface is a crucial element in the design of the next generation of Geographic Information Systems (GISs). We discuss the user interface design process by separating the formalization of the problem domain (identifying the objects a user manipulates, and their pertinent operations) from its visualization (describing human-computer interaction techniques such as windows and dialog boxes). This framework is used to examine the process of manipulating attribute data in a GIS on the basis of the common cartographic concept of a categorical coverage. The characteristics of categorical coverage data and the user requirements for interacting with this data are formalized in the form of a set of fundamental objects and operations. A visualization for a windows-icons-menus-pointing devices (WIMP) interface is presented.
Human genome sequence variation and the inherited basis of common disease

A central goal in medical research is to understand how variation in DNA sequence, environment and behavior combine to cause common human diseases. To date, most progress has been limited to rare conditions in which mutation of a single gene is both necessary and sufficient to cause disease. In common diseases, in contrast, multiple genes combine with environmental influences, meaning that the contribution of any single gene variant is probabilistic rather than deterministic. Where gene effects are partial, rather than complete, their effects can only be demonstrated by measuring frequencies of variants in collections of patients and controls much larger than a single family.
A Defense of Two Optimistic Claims in Ethical Theory

I aim to show that (i) thereare good ways to argue about what has intrinsicvalue; and (ii) good ethical arguments needn’tmake ethical assumptions. I support (i) and(ii) by rebutting direct attacks, by discussingnine plausible ways to argue about intrinsicvalue, and by arguing for pain’s intrinsicbadness without making ethical assumptions. If(i) and (ii) are correct, then ethical theoryhas more resources than many philosophers havethought: empirical evidence, and evidencebearing on intrinsic value. With moreresources, we can hope to base all of our moralbeliefs on evidence rather than on, say,emotion or mere intuition.
Chapter 2 – Applications of ESS in Renewable Energy Microgrids

This chapter discusses several applications of energy storage systems (ESS) in renewable energy microgrids. The configuration of ESS applied in microgrid is introduced at the beginning, including aggregated and distributed ESS. The energy management system includes load leveling and peak shifting features, which are widely used to mitigate load fluctuations and improve power quality. Next, the ESS that is used to suppress fluctuations in renewable sources is introduced, including constant power control, output filtering and ramp-rate control. Uninterruptible Power Systems (UPS) are another important application of ESS in microgrids, especially for the islanded renewable microgrid. The placement of ESS in a microgrid is important for power quality. The method that is used to determine the voltage regulation ability and power quality indices are introduced for the best placement of ESS. Using ESSs for voltage regulation and reactive power support is discussed, including a case study. Finally, a method using an ESS as an operating reserve is introduced.
Limited expression of poliovirus by vaccinia virus recombinants due to inhibition of the vector by proteinase 2A.

Abstract A recombinant vaccinia virus was constructed that expressed poliovirus coat precursor protein P1 fused to about two-thirds of the 2A proteinase. The truncated 2A segment could be cleaved away from the P1 region by coinfecting with poliovirus type 1, 2, or 3 or with human rhinovirus 14 but not with encephalomyocarditis virus. Further cleavage of the vector-derived P1 to yield mature poliovirus capsid proteins was not observed. Attempts to isolate vaccinia virus recombinants containing portions of the poliovirus genome that encompassed the complete gene for proteinase 2A were unsuccessful, unless expression of functional 2A was abolished by insertion of a frameshift mutation. We conclude that an activity of the 2A proteinase, probably its role in translational inhibition, prevented isolation of vaccinia virus recombinants that expressed 2A.
Measurements of Endurance Time for Electrostatic Discharge of Spacecraft Materials: A Defect-Driven Dynamic Model

Electrostatic breakdown leads to the majority of anomalies and failures attributed to spacecraft interactions with the plasma space environment. It is therefore critical to understand how the electrostatic field strength ( $F_{{ESD}}$ ) of spacecraft materials varies due to environmental conditions, such as duration of applied electric field, rate of field change, history of exposure to high fields, and temperature. We have developed a dual-defect, thermodynamic, mean-field trapping model in terms of recoverable and irrecoverable defect modes to predict probabilities of breakdown. Fits to a variety of measurements of the dependence of $F_{ {ESD}}$ of insulating polymers on endurance time, voltage ramp rate, and temperature based on this model yield consistent results. Our experimental results for the prototypical materials, low-density polyethylene and polymer (PI or Kapton HN), suggest that the values of $F_{ {ESD}}$ from standard handbooks, or cursory measurements that have been used routinely in the past, substantially overestimate the field required for breakdown in common spacecraft applications, which often apply subcritical fields for very long time periods as charge accumulates.