Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome‐wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis‐regulation of BORCS7, AS3MT, and NT5C2 in the human brain

Chromosome 10q24.32‐q24.33 is one of the most robustly supported risk loci to emerge from genome‐wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele‐specific expression to assess cis‐regulatory effects associated with the two best‐supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis‐effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.
CONTROL OF CELL PROGRESSION THROUGH THE MITOTIC CYCLE BY CARBOHYDRATE PROVISION

A stationary phase in the root meristem of excised pea roots was established by prolonged carbohydrate deprivation in sterile culture medium. When the stationary phase had been established, cells that had collected in the G1 period of the mitotic cycle were induced to enter the S stage by subjection to relatively short intervals of carbohydrate provision (sucrose spurts). Progression and cycle location of the G1 cells induced to enter S were measured with tritiated thymidine and radioautography. The results indicated that the number of G1 cells induced to enter S increased directly with the spurt duration and that cells could be positioned and retained in the S and/or G2 periods by varying the duration of the spurt. The data support the hypothesis that S and maybe M stages have a relatively larger dependence on carbohydrate availability, and presumably a greater energy requirement, than G1 and G2.
A General Purpose Partially Reconfigurable Processor Simulator (PReProS)

An innovative technique to model and simulate partial and dynamic reconfigurable processors is presented in this paper. The basis for development is a SystemC kernel modified for dynamic reconfiguration. The presented approach can either be used at transaction-level, which allows the modeling and simulation of higher-level hardware and embedded software, or at register transfer level (RTL), if the dynamic system behavior is desired to be observed at signal level. The reconfigurable processor can be easily set to model the desired architecture in a behavioral but reasonable way. An example is presented where a XPP processor is implemented and simulated, executing typical applications. The resulting statistics assist either in the choice of the best cost/benefit configuration area that should be available on chip, or in the choice of the target architecture itself.
Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

Background Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-α and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur.
The biophysical and molecular basis of intracellular pH sensing by Na+/H+ exchanger‐3

Epithelial Na+/H+ exchanger‐3 (NHE3) transport is fundamental for renal and intestinal sodium reabsorption. Cytoplasmic protons are thought to serve as allosteric modifiers of the exchanger and to trigger its transport through protein conformational change. This effect presupposes an intracellular pH (pHi) dependence of NHE3 activity, although the biophysical and molecular basis of NHE3 pHi sensitivity have not been defined. NHE3, when complexed with the calcineurin homologous protein‐1 (CHP1), had a shift in pHi sensitivity (0.4 units) toward the acidic side in comparison with NHE3 alone, as measured by oscillating pH electrodes combined with whole‐cell patch clamping. Indeed, CHP1 interaction with NHE3 inhibited NHE3 transport in a pHi ‐dependent manner. CHP1 binding to NHE3 also affected its acute regulation. Intracellular perfusion of peptide from the CHP1 binding region (or pHi modification to reduce the CHP1 amount bound to NHE3) was permissive and cooperative for dopamine inhibition of NHE3 but reversed that of adenosine. Thus, CHP1 interaction with NHE3 apparently establishes the exchanger set point for pHi, and modification in this set point is effective in the hormonal stimuli‐mediated regulation of NHE3. CHP1 may serve as a regulatory cofactor for NHE3 conformational change, dependent on intracellular protonation. —Babich V. , Vadnagara K. , Di Sole, F. The biophysical and molecular basis of intracellular pH sensing by the Na+/H+ exchanger‐3. FASEB J. 27, 4646–4658 (2013). www.fasebj. org
Effects of rho-associated protein kinase inhibitor Y-27632 on intraocular pressure and outflow facility.

PURPOSE To elucidate the roles of Rho-associated protein kinase (ROCK) in regulating intraocular pressure (IOP) and outflow facility in the rabbit eye. METHODS A specific ROCK inhibitor Y-27632 was used. The IOP, the outflow facility, and the pupil diameter were determined before and after the topical, intracameral, or intravitreal administration of Y-27632 in rabbits. Western blot analysis was used to identify specific ROCK isoform in human trabecular meshwork (TM) cells and bovine ciliary muscle (CM) tissues. The cell morphology and distribution of actin filaments and vinculin in TM cells were studied by cell biology techniques. Carbachol (Cch)-induced contraction of isolated bovine CM strips after administration of Y-27632 was measured in a perfusion chamber. RESULTS In rabbit eyes, administration of Y-27632 resulted in a significant decrease in IOP in a dose-dependent manner. An increase of the outflow facility and pupil size dilation was also observed in Y-27632-treated eyes. Western blot analysis revealed the presence of p160ROCK in human TM cells and bovine CM tissues. In cultured human TM cells, exposure to Y-27632 caused retraction and rounding of cell bodies as well as disruption of actin bundles and impairment of focal adhesion formation. Y-27632 in addition inhibited Cch-induced contraction of isolated bovine CM strips. CONCLUSIONS Administration of Y-27632 caused a reduction in IOP and an increase in the outflow facility. The in vitro experiments suggest that the IOP-lowering effects of Y-27632 may be related to the altered cellular behavior of TM cells and relaxation of CM contraction. These studies suggest that ROCK inhibitors may have great potential to be developed for treatment of glaucoma and other ocular diseases.
Southwest Pacific Vertical Structure Influences on Oceanic Carbon Storage Since the Last Glacial Maximum

Lower atmospheric CO2 concentrations during the Last Glacial Maximum (LGM; 23.0–18.0 ka) have been attributed to the sequestration of respired carbon in the ocean interior, yet the mechanism responsible for the release of this CO2 during the deglaciation remains uncertain. Here we present calculations of vertical differences in oxygen and carbon isotopes (∆δ18O and ∆δ13C, respectively) from a depth transect of southwest Pacific Ocean sediment cores to reconstruct changes in water mass structure and CO2 storage. During the Last Glacial Maximum, ∆δ18O indicates a more homogenous deep Pacific below 1,100 m, whereas regional ∆δ13C elucidates greater sequestration of CO2 in two distinct layers: enhanced CO2 storage at intermediate depths between ~940 and 1,400 m, and significantly more CO2 at 1,600 m and below. This highlights an isolated glacial intermediate water mass and places the main geochemical divide at least 500 m shallower than the Holocene. During the initial stages of the deglaciation in Heinrich Stadial 1 (17.5–14.5 ka), restructuring of the upper ~2,000 m of the southwest Pacific water column coincided with sea‐ice retreat and rapid CO2 release from intermediate depths, while CO2 release from the deep ocean was earlier and more gradual than waters above it. These changes suggest that sea‐ice retreat and shifts in Southern Ocean frontal locations contributed to rapid CO2 ventilation from the Southern Ocean's intermediate depths and gradual ventilation from the deep ocean during the early deglaciation.
Diet Quality Is Associated with All-Cause Mortality in Adults Aged 65 Years and Older123

Diet quality indices assess compliance with dietary guidelines and represent a measure of healthy dietary patterns. Few studies have compared different approaches to assessing diet quality in the same cohort. Our analysis was based on 972 participants of the British Diet and Nutrition Survey of people aged 65 y and older in 1994/1995 and who were followed-up for mortality status until 2008. Dietary intake was measured via a 4-d weighed food record. Three measures of diet quality were used: the Healthy Diet Score (HDS), the Recommended Food Score (RFS), and the Mediterranean Diet Score (MDS). HR for all-cause mortality were obtained using Cox regression adjusted for age, sex, energy intake, social class, region, smoking, physical activity, and BMI. After adjustment for confounders, the MDS was significantly associated with mortality [highest vs. lowest quartile; HR = 0.78 (95% CI = 0.62–0.98)]. Similarly, the RFS was also associated with mortality [HR = 0.67 (95 % CI = 0.52–0.86)]; however, there were no significant associations for the HDS [HR = 0.99 (95% CI = 0.79–1.24)]. The HDS was not a predictor of mortality is this population, whereas the RFS and the MDS were both associated with all-cause mortality. Simple measures of diet quality using food-based indicators can be useful predictors of longevity.
BacMam Virus Transduced Cardiomyoblasts Can Be Used for Myocardial Transplantation Using AP-PEG-A Microcapsules: Molecular Cloning, Preparation, and In Vitro Analysis

The potential of genetically modified cardiomyoblasts in treating damaged myocardium is well known. However, efficient delivery of these cells is of major concern during treatment. The limiting factors are the massive cell death that occurs soon after their intramyocardial transplantation into the beating heart. To address these problems, we generated recombinant baculoviruses (BacMam viruses) which efficiently transduced cardiomyoblast cells under optimized conditions. These genetically modified cells were then protected in a new polymeric microcapsule using poly-ethylene-glycol (PEG), alginate, and poly-L-lysine (PLL) polymers for efficient delivery. Results showed that microcapsules maintain cell viability and support cell proliferation for at least 30 days. The capsules exhibit strong immunoprotective potential and have high mechanical and osmotic stability with more than 70% intact capsules. The encased transduced cells showed a rapid transgene expression inside the capsule for at least 15 days. However, preclinical studies are needed to further explore its long-term functional benefits.
Cross-Cultural Privacy Prediction

Abstract The influence of cultural background on people’s privacy decisions is widely recognized. However, a cross-cultural approach to predicting privacy decisions is still lacking. Our paper presents a first integrated cross-cultural privacy prediction model that merges cultural, demographic, attitudinal and contextual prediction. The model applies supervised machine learning to users’ decisions on the collection of their personal data, collected from a large-scale quantitative study in eight different countries. We find that adding culture-related predictors (i.e. country of residence, language, Hofstede’s cultural dimensions) to demographic, attitudinal and contextual predictors in the model can improve the prediction accuracy. Hofstede’s variables - particularly individualism and indulgence - outperform country and language. We further apply generalized linear mixed-effect regression to explore possible interactions between culture and other predictors. We find indeed that the impact of contextual and attitudinal predictors varies between different cultures. The implications of such models in developing privacy-enabling technologies are discussed.
Varenicline Treatment of Concurrent Alcohol and Nicotine Dependence in Schizophrenia: A Randomized, Placebo-Controlled Pilot Trial

Abstract Alcohol and nicotine dependence are common in schizophrenia. Varenicline is effective in smoking cessation and has also been shown to decrease alcohol consumption in smokers. The present pilot study assessed the safety and effectiveness of varenicline for treatment of concurrent nicotine and alcohol dependence in schizophrenia. Outpatients with schizophrenia or schizoaffective disorder and concurrent alcohol and nicotine dependence were enrolled in this 8-week, double-blind, randomized, placebo-controlled trial. Alcohol use and smoking were assessed using self-report (Timeline Follow-Back) and biological measures. Adverse events were recorded. Changes in the number of standard drinks per week and cigarettes per week were compared in the 2 groups. Because of safety concerns or loss to follow-up, of 55 patients enrolled, only 10 started study medication, 5 each on varenicline and placebo. Gastrointestinal adverse effects, such as severe abdominal pain, limited study completion to only 4 subjects. Number of standard alcoholic drinks consumed per week decreased by [mean (SD)] 16.6 (20.1) in the varenicline group and by 2.4 (27.4) in the placebo group. Mean (SD) number of cigarettes smoked per week decreased by 66 (65) in the varenicline group and by 47 (77) in the placebo group. Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia may be problematic because of safety concerns limiting recruitment and poor tolerability (gastrointestinal adverse effects) limiting retention. There was no increased number of serious neuropsychiatric adverse events in the varenicline group. Based on this small sample, concurrent alcohol and nicotine dependence in schizophrenia may present special obstacles to successful treatment with varenicline.
Tuberculous hepatitis in renal transplant recipients following alemtuzumab induction therapy

Mycobacterium tuberculosis infection is one of many opportunistic infections in renal transplant recipients, arising either from reactivation of latent infection or de novo infection, occasionally donor derived. M. tuberculosis hepatitis has never been reported in patients who have received alemtuzumab as part of their renal transplant management. We describe 2 patients who underwent deceased‐donor renal transplantation following alemtuzumab induction therapy and presented with a febrile syndrome, subsequently diagnosed as tuberculous hepatitis, one with disseminated disease. Both responded well to treatment without significant side effects, resulting in excellent graft function. The importance of chemoprophylaxis should be emphasized to minimize the risk of developing active tuberculosis in patients with latent tuberculosis infection undergoing solid organ transplantation.
Compact Switchable Bandpass Filter and Its Application to Switchable Diplexer Design

This later firstly presents a quasi-elliptic bandpass filter (QE-BPF) which consists of a pair of shorted stepped-impedance resonator (SSIR) and a dual-mode resonator (DMR). Then, a 900 MHz switchable bandpass filter (SW-BPF) and a 1250 MHz SW-BPF are designed by loading p-i-n diodes at two open ends of DMR or SSIRs. Finally, a common-T junction constructed by two T-networks is used to combine the above designed 900 and 1250 MHz SW-BPFs to constitute a switchable diplexer. The fabricated QE-BPF, two SW-BPFs and switchable diplexer exhibit wide bandwidth, low insertion loss, sharp passband selectivity, high port isolation and compact size.
EspA Acts as a Critical Mediator of ESX1-Dependent Virulence in Mycobacterium tuberculosis by Affecting Bacterial Cell Wall Integrity

Mycobacterium tuberculosis (Mtb) requires the ESX1 specialized protein secretion system for virulence, for triggering cytosolic immune surveillance pathways, and for priming an optimal CD8+ T cell response. This suggests that ESX1 might act primarily by destabilizing the phagosomal membrane that surrounds the bacterium. However, identifying the primary function of the ESX1 system has been difficult because deletion of any substrate inhibits the secretion of all known substrates, thereby abolishing all ESX1 activity. Here we demonstrate that the ESX1 substrate EspA forms a disulfide bonded homodimer after secretion. By disrupting EspA disulfide bond formation, we have dissociated virulence from other known ESX1-mediated activities. Inhibition of EspA disulfide bond formation does not inhibit ESX1 secretion, ESX1-dependent stimulation of the cytosolic pattern receptors in the infected macrophage or the ability of Mtb to prime an adaptive immune response to ESX1 substrates. However, blocking EspA disulfide bond formation severely attenuates the ability of Mtb to survive and cause disease in mice. Strikingly, we show that inhibition of EspA disulfide bond formation also significantly compromises the stability of the mycobacterial cell wall, as does deletion of the ESX1 locus or individual components of the ESX1 system. Thus, we demonstrate that EspA is a major determinant of ESX1-mediated virulence independent of its function in ESX1 secretion. We propose that ESX1 and EspA play central roles in the virulence of Mtb in vivo because they alter the integrity of the mycobacterial cell wall.
Spectrally-normalized margin bounds for neural networks

This paper presents a margin-based multiclass generalization bound for neural networks that scales with their margin-normalized "spectral complexity": their Lipschitz constant, meaning the product of the spectral norms of the weight matrices, times a certain correction factor. This bound is empirically investigated for a standard AlexNet network trained with SGD on the mnist and cifar10 datasets, with both original and random labels; the bound, the Lipschitz constants, and the excess risks are all in direct correlation, suggesting both that SGD selects predictors whose complexity scales with the difficulty of the learning task, and secondly that the presented bound is sensitive to this complexity.
Nutritional Ecology of the Formosan Subterranean Termite (Isoptera: Rhinotermitidae): Feeding Response to Commercial Wood Species

Abstract The feeding preferences of the Formosan subterranean termite, Coptotermes formosanus Shiraki, were tested in three separate experiments on 28 different wood species. Experiment 1 was a multiple-choice test designed to test relative preferences among 24 wood species commercially available in New Orleans, LA. Experiment 2 was a similar study designed to test relative preferences among 21 wood species shown or reported to be unpalatable to the Formosan subterranean termite. Experiment 3 was a no-choice test to examine the feeding deterrence of the 10 least preferred wood species. Preference was determined by consumption rates. Birch (Betula alleghaniensis Britton), red gum (Liquidambar styraciflua L.), Parana pine [Araucaria angustifolia (Bert.)], sugar maple (Acer saccharum Marsh.), pecan (Carya illinoensis Wangenh.), and northern red oak (Quercus rubra L.) were the most preferred species by C. formosanus in order of consumption rate. All of these species were significantly more preferred than southern yellow pine (Pinus taeda L.), widely used for monitoring. Sinker cypress [ = old growth bald cypress, Taxodium distichum (L.)], western red cedar (Thuja plicata Donn), Alaskan yellow cedar (Chamaecyparis nootkatensis D. Don), eastern red cedar (Juniperus virginiana L.), sassafras [Sassafras albidum (Nutt.)], Spanish cedar (Cedrella odorata L.), Honduras mahogany (Swietenia macrophyla King), Indian rosewood (Dalbergia latifolia Roxb.), Honduras rosewood (D. stevensonii Standl.), and morado (Machaerium sp.) induced significant feeding deterrence and mortality to C. formosanus. The last eight species produced 100% mortality after 3 mo.
Multiple-Kernel Based Vehicle Tracking Using 3D Deformable Model and Camera Self-Calibration

Tracking of multiple objects is an important application in AI City geared towards solving salient problems related to safety and congestion in an urban environment. Frequent occlusion in traffic surveillance has been a major problem in this research field. In this challenge, we propose a model-based vehicle localization method, which builds a kernel at each patch of the 3D deformable vehicle model and associates them with constraints in 3D space. The proposed method utilizes shape fitness evaluation besides color information to track vehicle objects robustly and efficiently. To build 3D car models in a fully unsupervised manner, we also implement evolutionary camera self-calibration from tracking of walking humans to automatically compute camera parameters. Additionally, the segmented foreground masks which are crucial to 3D modeling and camera self-calibration are adaptively refined by multiple-kernel feedback from tracking. For object detection/classification, the state-of-the-art single shot multibox detector (SSD) is adopted to train and test on the NVIDIA AI City Dataset. To improve the accuracy on categories with only few objects, like bus, bicycle and motorcycle, we also employ the pretrained model from YOLO9000 with multi-scale testing. We combine the results from SSD and YOLO9000 based on ensemble learning. Experiments show that our proposed tracking system outperforms both state-of-the-art of tracking by segmentation and tracking by detection.