Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative Stress in the Progression of Alzheimer Disease in the Frontal Cortex

We investigated oxidative stress in human postmortem frontal cortexfrom individuals characterized as mild cognitive impairment (n= 8), mild/moderate Alzheimer disease (n = 4), and late-stage Alzheimer disease (n = 9). Samples from subjects with no cognitive impairment (n = 10) that were age- and postmortem interval-matched with these cases were used as controls. The short postmortem intervalbrain samples were processed for postmitochondrial supernatant, nonsynaptic mitochondria, and synaptosome fractions. Samples were analyzed for several antioxidants (glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, superoxide dismutase, catalase) and the oxidative marker, thiobarbituric acid reactive substances. The tissue was also analyzed for possible changes in protein damage using neurochemical markers for protein carbonyls, 3-nitrotyrosine, 4-hydroxynonenal, andacrolein. All 3 neuropil fractions (postmitochondrial supernatant, mitochondrial, and synaptosomal) demonstrated significant disease-dependent increases in oxidative markers. The highest changes were observed in the synaptosomal fraction. Both mitochondrial and synaptosomal fractions had significant declines in antioxidants (glutathione, glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase). Levels of oxidative markers significantly correlated with Mini-Mental Status Examination scores. Oxidative stress was more localized to the synapses, with levels increasing in a disease-dependent fashion. These correlations implicate an involvement of oxidative stress in Alzheimer disease-related synaptic loss.
Identification of Chimeric Antigen Receptors That Mediate Constitutive or Inducible Proliferation of T Cells

Frigault, Lee, and colleagues compared chimeric antigen receptors (CAR) encoding signaling domains comprising CD28, ICOS, and 4-1BB and found that some CD28 CAR-T cells have antigen-independent constitutive proliferation and cytokine secretion when highly expressed, leading to inferior antitumor effects. This study compared second-generation chimeric antigen receptors (CAR) encoding signaling domains composed of CD28, ICOS, and 4-1BB (TNFRSF9). Here, we report that certain CARs endow T cells with the ability to undergo long-term autonomous proliferation. Transduction of primary human T cells with lentiviral vectors encoding some of the CARs resulted in sustained proliferation for up to 3 months following a single stimulation through the T-cell receptor (TCR). Sustained numeric expansion was independent of cognate antigen and did not require the addition of exogenous cytokines or feeder cells after a single stimulation of the TCR and CD28. Results from gene array and functional assays linked sustained cytokine secretion and expression of T-bet (TBX21), EOMES, and GATA-3 to the effect. Sustained expression of the endogenous IL2 locus has not been reported in primary T cells. Sustained proliferation was dependent on CAR structure and high expression, the latter of which was necessary but not sufficient. The mechanism involves constitutive signaling through NF-κB, AKT, ERK, and NFAT. The propagated CAR T cells retained a diverse TCR repertoire, and cellular transformation was not observed. The CARs with a constitutive growth phenotype displayed inferior antitumor effects and engraftment in vivo. Therefore, the design of CARs that have a nonconstitutive growth phenotype may be a strategy to improve efficacy and engraftment of CAR T cells. The identification of CARs that confer constitutive or nonconstitutive growth patterns may explain observations that CAR T cells have differential survival patterns in clinical trials. Cancer Immunol Res; 3(4); 356–67. ©2015 AACR.
SNPing Away at Candidate Genes

We develop regression methodology to identify subsets of single nucleotide polymorphisms (SNPs) within candidate genes related to quantitative traits and apply our methods to the simulated Genetic Analysis Workshop (GAW) 12 data set. In the data set we find 694 SNP loci with minimum allele frequencies of at least 0.01. We assume an additive casual model between these SNPs and all five quantitative traits. After initial screening using one‐way analysis of variance, we employ a computationally efficient, simulated annealing algorithm to select among all possible subsets of SNP loci, using a generalization of Mallows’ Cp as our optimality criterion. The simple transition kernel we develop evaluates new subsets in O(1), by requiring just three arithmetic operations to calculate the proposed RSS based on the Gauss‐Jordan pivot. We identify an SNP loci located at 6–5782 related to traits 2 and 3 and several sites on gene 2 related to trait 5 using a subsample of 1,000 individuals and the full data set (n = 8,250) for comparison. © 2001 Wiley‐Liss, Inc.
Potential Biases in Feedback Diagnosis from Observational Data: A Simple Model Demonstration

Abstract Feedbacks are widely considered to be the largest source of uncertainty in determining the sensitivity of the climate system to increasing anthropogenic greenhouse gas concentrations, yet the ability to diagnose them from observations has remained controversial. Here a simple model is used to demonstrate that any nonfeedback source of top-of-atmosphere radiative flux variations can cause temperature variability, which then results in a positive bias in diagnosed feedbacks. This effect is demonstrated with daily random flux variations, as might be caused by stochastic fluctuations in low cloud cover. The daily noise in radiative flux then causes interannual and decadal temperature variations in the model’s 50-m-deep swamp ocean. The amount of bias in the feedbacks diagnosed from time-averaged model output depends upon the size of the nonfeedback flux variability relative to the surface temperature variability, as well as the sign and magnitude of the specified (true) feedback. For model runs produ.
Expression of Rous sarcoma virus transforming protein pp60v-src in Saccharomyces cerevisiae cells

The Rous sarcoma virus (RSV) pp60v-src protein was expressed in Saccharomyces cerevisiae cells either from a plasmid vector carrying the v-src gene or in yeast cells containing a single-copy v-src gene chromosomally integrated. In both yeast strains, v-src gene transcription is regulated by the galactose-inducible GAL10 promoter. Growth in galactose-containing medium resulted in constitutive expression of pp60v-src in the integrated strain and transient expression of higher levels of pp60v-src in the plasmid-bearing strain. The concentration of pp60v-src in the plasmid-bearing strain at its peak of expression was approximately threefold lower than that found in RSV-transformed mammalian cells. pp60v-src synthesized in yeast cells was phosphorylated in vivo on sites within the amino and carboxyl halves of the molecule. In immune complex kinase assays, the yeast pp60v-src was autophosphorylated on tyrosine and was able to phosphorylate exogenous substrates such as casein and enolase. The specific activity of pp60v-src synthesized in yeast cells was approximately 5- to 10-fold higher than that made in mammalian cells. Induction of pp60v-src caused the death of the plasmid-bearing yeast strain and transient inhibition of growth of the single-copy strain. Concomitantly, this induction resulted in high levels of tyrosine phosphorylation of yeast cell proteins. This indicates that pp60v-src functions as a tyrosine-specific phosphotransferase in yeast cells and suggests that hyperphosphorylation of yeast proteins is inimical to cell growth.
URC: Unsupervised regional clustering of remote sensing imagery

Conditional random fields (CRF) have been used extensively for spatially coherent segmentation and classification of images. As a result, may techniques for finding the optimal inference of CRFs have been developed. However, CRFs have seen little use in clustering and segmenting of satellite imagery due to the large number of pixels in satellite images. In this paper we present a means of defining remote sensing imagery as a region based conditional random field (CRF). Unlike the pixel based CRF, our region based CRF can be optimally solved using the latest advancements in CRF inference techniques because the region based CRF is a computationally simpler problem to tackle. To reduce the loss of information when forming the region based CRF, the regions are defined using a superpixel algorithm which decreases the spatial resolution while preserving the original satellite image's structure. Furthermore, unlike previous approaches, we show that the optimal number of clusters in the satellite images can be automatically determined by formulating the number of clusters as part of the CRF cost function. This unsupervised region based approach is a non-parametric formulation which is validated using different imaging modalities: SAR and hyper-spectral imaging.
Chemical-Cue Preferences of Inexperienced Snakes: Comparative Aspects

Different species of new-born, previously unfed snakes will respond with tongue flicking and prey-attack behavior to water extracts of the skin substances of various small animals. However, there are clear species differences in the type of extract responded to by previously unfed snakes, even within the same genus. These differences correspond to the normal feeding preferences shown by the various species.
A BIST Pattern Generator Design for Near-Perfect Fault Coverage

A new design methodology for a pattern generator is proposed, formulated in the context of on-chip BIST. The design methodology is circuit-specific and uses synthesis techniques to design BIST generators. The pattern generator consists of two components: a pseudorandom pattern generator (like an LFSR or, preferably, a GLFSR) and a combinational logic to map the outputs of the pseudorandom pattern generator. This combinational logic is synthesized to produce a given set of target patterns by mapping the outputs of the pseudorandom pattern generator. It is shown that, for a particular CUT, an area-efficient combinational logic block can be designed/synthesized to achieve 100 (or almost 100) percent single stuck-at fault coverage using a small number of test the This method is significantly different from weighted pattern generation and can guarantee testing of all hard-to-detect faults without expensive test point insertion. Experimental results on common benchmark netlists demonstrate that the fault coverage of the proposed pattern generator is significantly higher compared to conventional pattern generation techniques. The design technique for the logic mapper is unique and can be used effectively to improve existing pattern generators for combinational logic and scan-based BIST structures.
Fragment‐Based Screen against HIV Protease

We have employed a fragment‐based screen against wild‐type (NL4‐3) HIV protease (PR) using the Active Sight fragment library and X‐ray crystallography. The experiments reveal two new binding sites for small molecules. PR was co‐crystallized with fragments, or crystals were soaked in fragment solutions, using five crystal forms, and 378 data sets were collected to 2.3–1.3 Å resolution. Fragment binding induces a distinct conformation and specific crystal form of TL‐3 inhibited PR during co‐crystallization. One fragment, 2‐methylcyclohexanol, binds in the ‘exo site’ adjacent to the Gly 16 Gly 17 Gln 18 loop where the amide of Gly 17 is a specific hydrogen bond donor, and hydrophobic contacts occur with the side chains of Lys 14 and Leu 63 . Another fragment, indole‐6‐carboxylic acid, binds on the ‘outside/top of the flap’ via hydrophobic contacts with Trp 42 , Pro 44 , Met 46 , and Lys 55 , a hydrogen bond with Val 56 , and a salt‐bridge with Arg 57 . 2‐acetyl‐benzothiophene also binds at this site. This study is the first fragment‐based crystallographic screen against HIV PR, and the first time that fragments were screened against an inhibitor‐bound drug target to search for compounds that both bind to novel sites and stabilize the inhibited conformation of the target.
On the $K$ -Factor Estimation for Rician Channel Simulated in Reverberation Chamber

Reverberation chambers were recently proposed to simulate Rician radio environment with controllable K-factor. The K-factor is also a parameter that may tell how ideal may be a reverberation chamber when it is used for other more conventional purposes. This paper is dedicated to the problem of the correct estimation of K in a reverberation chamber given a set of data measured along a stirring process.
Velocity Not Acceleration of Self-Motion Mediates Vestibular – Visual Interaction

We investigated the influence of vestibular stimulation with different angular accelerations and velocities on the perception of visual motion direction. Constant accelerations resulting in different angular velocities and constant angular velocities obtained at different accelerations were combined in twenty healthy subjects. Random-dot kinematograms with coherently moving pixels and randomly moving pixels were used as visual stimuli during whole-body rotations. The smallest percentage of coherently moving pixels leading to a clear perception of motion direction was taken as the perception threshold. Perception thresholds significantly increased with increasing angular velocity. Increased acceleration, however, had no significant effect on the perception thresholds. We conclude that the achieved angular velocity, and not acceleration, is the predominant factor in the processing of vestibular-visual interaction.
Am I my own worst enemy

Purpose – This study aims to compare the experiences of workers who perceive themselves as both targets and aggressors (aggressor‐targets) with the experiences of other workers.Design/methodology/approach – The paper reports on the results of a cross‐sectional self‐report questionnaire‐based study (n=180). Findings – Aggressor‐targets reported performing more aggressive behaviors than did pure bullies. They also engaged in multiple types of coping strategies, but did so ineffectively as evidenced by their high levels of negative health outcomes.Practical implications – It is possible that aggressor‐targets employed many coping behaviors as a means of dealing with their situation, but they had some difficulty doing so without assistance. Consequently, aggressor‐targets may be open to intervention efforts. Since this group constitutes the largest percentage of bullies and was responsible for most of the reported bullying acts, examining their experiences may help organizations reduce the overall incidence of.
Vehicular fuel composition and atmospheric emissions in South China: Hong Kong, Macau, Guangzhou, and Zhuhai

Vehicular emission is an important source of air pollutants in urban cities in the Pearl River Delta (PRD) re- gion of South China. In order to study the impact of evapo- rative loss of vehicular fuel on air quality, several commonly used fuel samples were collected in four main cities in the PRD region - Hong Kong, Guangzhou, Macau and Zhuhai, and analyzed for their volatile organic compounds (VOCs) composition. Source profiles of vapors of the vehicular fu- els used in these cities were constructed and are believed to be the first reported for the PRD region. The C 8-C10 hy- drocarbons were the main constituents of diesel. Different from diesel, gasoline used in the PRD region was mainly comprised of lighter C4-C7 hydrocarbons, with toluene and i-pentane being the two most abundant species. The toluene content in the Hong Kong and Macau gasoline samples were higher than that in Guangzhou and Zhuhai, while the re- verse was true for the benzene content. The benzene levels in Guangzhou and Zhuhai exceeded the maximum allowable benzene levels for Mainland China unleaded gasoline. Liq- uefied Petroleum Gas (LPG) samples were collected only in Hong Kong and were comprised mainly of n-butane, propane and i-butane. Traffic samples indicated that evaporative loss and vehicular combustion were the primary contributors to elevated VOC levels in roadside atmospheres. Significant i-pentane and toluene concentrations were observed in road- side atmospheres in all four cities. Ratio of i-pentane in gaso- line vapors to that in roadside samples were calculated and this showed that the degree of evaporative loss were higher in Guangzhou and Zhuhai than that in Hong Kong and Macau. We suggest the difference is due to the better maintenance and more new cars in Hong Kong and Macau. From tunnel samples collected in Hong Kong in two different years, we found that the relative amount of propane, i-butane, and n- butane increased between 2001 to 2003, consistent with the
Mapping practice onto theory: the speech and language practitioner's construction of receptive language impairment.

BACKGROUND Receptive language impairment (RLI) is one of the most significant indicators of negative sequelae for children with speech and language disorders. Despite this, relatively little is known about the most effective treatments for these children in the primary school period. AIMS To explore the relationship between the reported practice of speech and language practitioners and the underlying rationales for the therapy that they provide. METHODS & PROCEDURES A phenomenological approach was adopted, drawing on the experiences of speech and language practitioners. Practitioners completed a questionnaire relating to their practice for a single child with receptive language impairment within the 5-11 age range, providing details and rationales for three recent therapy activities. The responses of 56 participants were coded. All the children described experienced marked receptive language impairments, in the main associated with expressive language difficulties and/or social communication problems. OUTCOME & RESULTS The relative homogeneity of the presenting symptoms in terms of test performance was not reflected in the highly differentiated descriptions of intervention. One of the key determinants of how therapists described their practice was the child's age. As the child develops the therapists appeared to shift from a 'skills acquisition' orientation to a 'meta-cognitive' orientation, that is they move away from teaching specific linguistic behaviours towards teaching children strategies for thinking and using their language. A third of rationales refer to explicit theories but only half of these refer to the work of specific authors. Many of these were theories of practice rather than theories of deficit, and of those that do cite specific theories, no less than 29 different authors were cited many of whom might best be described as translators of existing theories rather than generators of novel theories. CONCLUSIONS While theories of the deficit dominate the literature they appear to play a relatively small part in the eclectic practice of speech and language therapists. Theories of therapy may develop relatively independent of theories of deficit. While this may not present a problem for the practitioner, whose principal focus is remediation, it may present a problem for the researcher developing intervention efficacy studies, where the theory of the deficit will need to be well-defined in order to describe both the subgroup of children under investigation and the parameters of the deficit to be targeted in intervention.
THREE-DIMENSIONAL MHD SIMULATION OF THE CALTECH PLASMA JET EXPERIMENT: FIRST RESULTS

Magnetic fields are believed to play an essential role in astrophysical jets with observations suggesting the presence of helical magnetic fields. Here, we present three-dimensional (3D) ideal MHD simulations of the Caltech plasma jet experiment using a magnetic tower scenario as the baseline model. Magnetic fields consist of an initially localized dipole-like poloidal component and a toroidal component that is continuously being injected into the domain. This flux injection mimics the poloidal currents driven by the anode–cathode voltage drop in the experiment. The injected toroidal field stretches the poloidal fields to large distances, while forming a collimated jet along with several other key features. Detailed comparisons between 3D MHD simulations and experimental measurements provide a comprehensive description of the interplay among magnetic force, pressure, and flow effects. In particular, we delineate both the jet structure and the transition process that converts the injected magnetic energy to other forms. With suitably chosen parameters that are derived from experiments, the jet in the simulation agrees quantitatively with the experimental jet in terms of magnetic/kinetic/inertial energy, total poloidal current, voltage, jet radius, and jet propagation velocity. Specifically, the jet velocity in the simulation is proportional to the poloidal current divided by the square root of the jet density, in agreement with both the experiment and analytical theory. This work provides a new and quantitative method for relating experiments, numerical simulations, and astrophysical observation, and demonstrates the possibility of using terrestrial laboratory experiments to study astrophysical jets.
Title Validity of electron beam computed tomography for coronaryartery disease : asystematic review and meta-analysis

Background: Electron beam computed tomography (EBCT) is a method for measuring coronary calcification and has been promoted as a possible non-invasive screening/diagnostic tool for coronary artery disease (CAD). Our objective was to carry out a systematic review and metaanalysis of EBCT for the screening of asymptomatic patients and the diagnosis of symptomatic patients for CAD. Methods: Studies were identified from the PUBMED, MEDLINE, EMBASE, Current
Acute Hypoxia Stimulates Intracellular Peroxynitrite Formation Associated With Pulmonary Artery Smooth Muscle Cell Proliferation

There is separate evidence for peroxynitrite formation and hypoxia-induced cell proliferation in several models of hypoxic pulmonary hypertension. We therefore hypothesized that the stimulation of pulmonary artery smooth muscle cells (PASMCs) proliferation by hypoxia is due to peroxynitrite formation. The effect of hypoxia alone and in combination with ≤0.2 μM peroxynitrite on PASMCs was investigated in explants from bovine lungs grown in 1%, 5%, or 10% oxygen for 24 hours with or without peroxynitrite. At 0.1% fetal bovine serum, DNA synthesis of PASMCs (assessed by 3H thymidine incorporation) was increased by transient exposure to 0.2 μM peroxynitrite (by 158% ± 14%, P < 0.01) or to 24 hours of hypoxia (5% oxygen) (by 221% ± 17%, P < 0.01). Results were similar at 2.5% fetal bovine serum. Treatment of PASMCs with 0.2 μM peroxynitrite or 5% O2 hypoxia caused a significant increase in nitrotyrosine formation to a similar extent and intensity. The proliferative response to 0.2 μM peroxynitrite or to the combination of peroxynitrite plus 5% O2 was similar to the effect of 5% O2 alone and was abolished by simultaneous treatment with peroxynitrite scavenger—ebselen (5 μM). Our present data indicate that hypoxia can initiate peroxynitrite-induced proliferative events and suggest a mechanism for the vascular hypertrophy associated with pulmonary hypertension.