Miracle-dz/UniFAR-FTUs huggingface dataset:
Thioredoxin-Interacting Protein

OBJECTIVE—In diabetes, glucose toxicity affects different organ systems, including pancreatic islets where it leads to β-cell apoptosis, but the mechanisms are not fully understood. Recently, we identified thioredoxin-interacting protein (TXNIP) as a proapoptotic β-cell factor that is induced by glucose, raising the possibility that TXNIP may play a role in β-cell glucose toxicity. RESEARCH DESIGN AND METHODS—To assess the effects of glucose on TXNIP expression and apoptosis and define the role of TXNIP, we used INS-1 β-cells; primary mouse islets; obese, diabetic BTBR.ob mice; and a unique mouse model of TXNIP deficiency (HcB-19) that harbors a natural nonsense mutation in the TXNIP gene. RESULTS—Incubation of INS-1 cells at 25 mmol/l glucose for 24 h led to an 18-fold increase in TXNIP protein, as assessed by immunoblotting. This was accompanied by increased apoptosis, as demonstrated by a 12-fold induction of cleaved caspase-3. Overexpression of TXNIP revealed that TXNIP induces the intrinsic mitochondrial pathway of apoptosis. Islets of diabetic BTBR.ob mice also demonstrated increased TXNIP and apoptosis as did isolated wild-type islets incubated at high glucose. In contrast, TXNIP-deficient HcB-19 islets were protected against glucose-induced apoptosis as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and caspase-3, indicating that TXNIP is a required causal link between glucose toxicity and β-cell death. CONCLUSIONS—These findings shed new light onto the molecular mechanisms of β-cell glucose toxicity and apoptosis, demonstrate that TXNIP induction plays a critical role in this vicious cycle, and suggest that inhibition of TXNIP may represent a novel approach to reduce glucotoxic β-cell loss.
Treatment‐related alteration of cortisol predicts change in neuropsychological function during acute treatment of late‐life anxiety disorder

Older adults with anxiety disorders are burdened by impairment in neurocognition, which may be mediated by elevated circulating cortisol levels. In a randomized controlled trial of acute serotonin‐reuptake inhibitor treatment for late‐life anxiety disorder, we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function.
Men’s Employment Hours and Time on Domestic Chores in European Countries:

Over the past decades, the gender gap in housework has become smaller and scholars have called on changing structural conditions and on the diffusion of egalitarian gender roles to explain why. In particular, women’s presence in the public sphere is found to be associated with a more egalitarian division of chores between partners. However, despite the large presence of women in the public sphere in many countries, the gender gap in housework has not disappeared. This article asks whether the widespread presence of men in the public sphere is slowing the diffusion of more egalitarian practices of housework division. Using multilevel models on European Social Survey data (2010), the article shows that in countries where men work long standard hours, women perform relatively more housework and men relatively less, highlighting the importance of men’s aggregate behavior in explaining partners’ relative time on housework.
Annual Ambient Black Carbon Associated with Shorter Telomeres in Elderly Men: Veterans Affairs Normative Aging Study

Background Telomere length reflects biological age and is inversely associated with risk of cardiovascular disease (CVD). Ambient air pollution is associated with CVD, but its effect on telomere length is unknown. Objective We investigated whether ambient black carbon (BC), a marker for traffic-related particles, is associated with telomere length in the Normative Aging Study (NAS). Methods Among 165 never-smoking men from the NAS, leukocyte telomere length (LTL) was measured repeatedly approximately every 3 years from 1999 through 2006 using quantitative real-time polymerase chain reaction (qRT-PCR). BC concentration at their residences during the year before each LTL measurement was estimated based on a spatiotemporal model calibrated with BC measurements from 82 locations within the study area. Results The median [interquartile range (IQR)] annual moving-average BC concentration was 0.32 (0.20–0.45) μg/m3. LTL, expressed as population-standardized ratio of telomere repeat to single-copy gene copy numbers, had a geometric mean (geometric SD) of 1.25 (1.42). We used linear mixed-effects models including random subject intercepts and adjusted for several potential confounders. We used inverse probability of response weighting to adjust for potential selection bias due to loss to follow-up. An IQR increase in annual BC (0.25 μg/m3) was associated with a 7.6% decrease (95% confidence interval, −12.8 to −2.1) in LTL. We found evidence of effect modification, with a stronger association among subjects ≥ 75 years of age compared with younger participants (p = 0.050) and statin medications appearing protective of the effects of BC on LTL (p = 0.050). Conclusions Telomere attrition, linked to biological aging, may be associated with long-term exposures to airborne particles, particularly those rich in BC, which are primarily related to automobile traffic.
Algebraic integer based 8×8 2-D DCT architecture for digital video processing

A time-multiplexed row-parallel architecture is proposed for the real-time implementation of bivariate algebraic integer (AI) encoded 2-D discrete cosine transform (DCT) of images and video sequences. The architecture is based on the Arai algorithm with AI encoding. This leads to an 8×8 2-D DCT which is entirely free of quantization errors. The error free coefficients may be converted into a regular arithmetic format using a final reconstruction step (FRS) at the output stage. The accuracy of the FRS allows each of the 64 coefficients to have its precision set independent of other coefficients without the leakage of quantization noise between coefficient channels. Our architecture leads to low-noise applications in digital video compression, coding, and other image processing applications that rely on the fast systolic computation of the 2-D DCT. A prototype of the 2-D DCT is physically realized, tested, and verified on chip, using a Xilinx Virtex-4 Sx35-10ff668 device. The maximum clock rate was Fclock = 121 MHz, implying an equivalent frame sample rate of 466 Hz, for an image frame size of 1920×1080, which is a common high definition video format.
Increased River Alkalinization in the Eastern U

The interaction between human activities and watershed geology is accelerating long-term changes in the carbon cycle of rivers. We evaluated changes in bicarbonate alkalinity, a product of chemical weathering, and tested for long-term trends at 97 sites in the eastern United States draining over 260 000 km. We observed statistically significant increasing trends in alkalinity at 62 of the 97 sites, while remaining sites exhibited no significant decreasing trends. Over 50% of study sites also had statistically significant increasing trends in concentrations of calcium (another product of chemical weathering) where data were available. River alkalinization rates were significantly related to watershed carbonate lithology, acid deposition, and topography. These three variables explained ∼40% of variation in river alkalinization rates. The strongest predictor of river alkalinization rates was carbonate lithology. The most rapid rates of river alkalinization occurred at sites with highest inputs of acid deposition and highest elevation. The rise of alkalinity in many rivers throughout the Eastern U.S. suggests human-accelerated chemical weathering, in addition to previously documented impacts of mining and land use. Increased river alkalinization has major environmental implications including impacts on water hardness and salinization of drinking water, alterations of air−water exchange of CO2, coastal ocean acidification, and the influence of bicarbonate availability on primary production.
Trajectories of cognitive decline in Alzheimer's disease

ABSTRACT Background: Late-onset Alzheimer disease (LOAD) is a clinically heterogeneous complex disease defined by progressively disabling cognitive impairment. Psychotic symptoms which affect approximately one-half of LOAD subjects have been associated with more rapid cognitive decline. However, the variety of cognitive trajectories in LOAD, and their correlates, have not been well defined. We therefore used latent class modeling to characterize trajectories of cognitive and behavioral decline in a cohort of AD subjects. Methods: 201 Caucasian subjects with possible or probable Alzheimer's disease (AD) were evaluated for cognitive and psychotic symptoms at regular intervals for up to 13.5 years. Cognitive symptoms were evaluated serially with the Mini-mental State Examination (MMSE), and psychotic symptoms were rated using the CERAD behavioral rating scale (CBRS). Analyses undertaken were latent class mixture models of quadratic trajectories including a random intercept with initial MMSE score, age, gender, education, and APOE ϵ4 count modeled as concomitant variables. In a secondary analysis, psychosis status was also included. Results: AD subjects showed six trajectories with significantly different courses and rates of cognitive decline. The concomitant variables included in the best latent class trajectory model were initial MMSE and age. Greater burden of psychotic symptoms increased the probability of following a trajectory of more rapid cognitive decline in all age and initial MMSE groups. APOE ϵ4 was not associated with any trajectory. Conclusion: Trajectory modeling of longitudinal cognitive and behavioral data may provide enhanced resolution of phenotypic variation in AD.
Performance Evaluation and Benchmarking of an Extended Computational Model of Ant Colony System for DNA Sequence Design

Ant colony system (ACS) algorithm is one of the biologically inspired algorithms that have been introduced to effectively solve a variety of combinatorial optimisation problems. In literature, ACS has been employed to solve DNA sequence design problem. The DNA sequence design problem was modelled based on a finite state machine in which the nodes represent the DNA bases {A, C, T, G}. Later in 2011, an extended computational model of finite state machine has been employed for DNA sequence design using ACS. The performance evaluation, however, was limited. In this study, the extended computational model of finite state machine is revisited and an extensive performance evaluation is conducted using 5, 7, 10, 15, 20, 25, 30, 35, and 40 agents/ants, each with 100 independent runs. The performance of the extended computational model is also benchmarked with the existing algorithm such as a Genetic Algorithm (GA), Multi-Objective Evolutionary Algorithm (MOEA), and Particle Swarm Optimisation (PSO). Keywords-Ant Colony System, DNA Sequence Design, Finite State Machine.
Impact of contraindications, barriers to self-care and support on incident peritoneal dialysis utilization.

BACKGROUND Targets for peritoneal dialysis (PD) utilization may be difficult to achieve because many older patients have contraindications to PD or barriers to self-care. The objectives of this study were to determine the impact that contraindications and barriers to self-care have on incident PD use, and to determine whether family support increased PD utilization when home care support is available. METHODS Consecutive incident dialysis patients were assessed for PD eligibility, offered PD if eligible and followed up for PD use. All patients lived in regions where home care assistance was available. RESULTS The average patient age was 66 years. One hundred and ten (22%) of the 497 patients had absolute medical or social contraindications to PD. Of the remaining 387 patients who were potentially eligible for PD, 245 (63%) had at least one physical or cognitive barrier to self-care PD. Patients with barriers were older, weighed less and were more likely to be female, start dialysis as an inpatient and have a history of vascular disease, cardiac disease and cancer. Family support was associated with an increase in PD eligibility from 63% to 80% (P = 0.003) and PD choice from 40% to 57% (P = 0.03) in patients with barriers to self-care. Family support increased incidence PD utilization from 23% to 39% among patients with barriers to self-care (P = 0.009). When family support was available, 34% received family-assisted PD, 47% received home care-assisted PD, 12% received both family- and home care-assisted PD, and 7% performed only self-care PD. Incident PD use in an incident end-stage renal disease (ESRD) population was 30% (147 of the 497 patients). CONCLUSIONS Contraindications, barriers to self-care and the availability of family support are important drivers of PD utilization in the incident ESRD population even when home assistance is available. These factors should be considered when setting targets for PD.
Social network coordination and graph routing

We consider the problem of coordinating robots moving on a network. Each robot is autonomous and needs to visit various sites of the network at various times. The sequence of destinations for each robot changes dynamically and unpredictably. Recently, Onn and Tennenholtz showed that the problem can be solved by introducing a social law on the network, which, once obeyed by all robots, enables each to move to any desired destination without collisions and regardless of the actions of other robots, needing neither central coordination nor mutual communication. This social law can be derived from a suitably defined routing of the graph underlying the network. Here, we study the complexity of routing. We provide an effective characterization of 2‐routable graphs, and by establishing a correspondence between hypergraph coloring and graph routing, we show that computing or approximating an optimal routing is generally hard. We also discuss routing in planar graphs, which often underlie robotic networks and show that the correspondence between coloring and routing together with the Four Color Theorem guarantee the existence of small and effectively computable routings in bipartite planar graphs of small radius. The complexity of routing arbitrary planar graphs remains open. © 2002 Wiley Periodicals, Inc.
Stochastic Resonance Noise Enhanced Spectrum Sensing in Cognitive Radio Networks

Spectrum sensing is a fundamental technology to detect the presence of primary user in cognitive radio networks. Usually, the requirements for spectrum sensing are very stringent. It requires that the spectrum sensing scheme has a good performance even in extremely low signal-to-noise ratio (SNR) environments. In this paper, we propose a novel spectrum sensing method based on stochastic resonance (SR) noise enhance detection (NED) to meet the requirement. For the proposed SR NED based spectrum sensing scheme, a specific signal-independent SR noise is added to the received signal so that the probability distribution of the detection statistics is modified to match the applied nonlinear suboptimal detector better. The performance of the applied detector can then be significantly improved according to the basic principle of SR NED. Under the constraint of the false alarm probability, the method to find the optimal SR noise is provided for both single node sensing and multiple nodes cooperative sensing by maximizing the probability of detection. For single node sensing, the popular energy detector is considered. For cooperative sensing, both maximal ratio combination (MRC) and equal gain combination (EGC) based energy detectors are investigated. Theoretical analysis and simulations results show that the proposed SR NED based spectrum sensing schemes can achieve much better performance than that of the applied original detectors.
Evidence for a Strong Correlation Between Transcription Factor Protein Disorder and Organismic Complexity

Studies of diverse phylogenetic lineages reveal that protein disorder increases in concert with organismic complexity but that differences nevertheless exist among lineages. To gain insight into this phenomenology, we analyzed all of the transcription factor (TF) families for which sequences are known for 17 species spanning bacteria, yeast, algae, land plants, and animals and for which the number of different cell types has been reported in the primary literature. Although the fraction of disordered residues in TF sequences is often moderately or poorly correlated with organismic complexity as gauged by cell-type number (r2 < 0.5), an unbiased and phylogenetically broad analysis shows that organismic complexity is positively and strongly correlated with the total number of TFs, the number of their spliced variants and their total disordered residues content (r2 > 0.8). Furthermore, the correlation between the fraction of disordered residues and cell-type number becomes stronger when confined to the TF families participating in cell cycle, cell size, cell division, cell differentiation, or cell proliferation, and other important developmental processes. The data also indicate that evolutionarily simpler organisms allow for the detection of subtle differences in the conserved IDRs of TFs as well as changes in variable IDRs, which can influence the DNA recognition and multifunctionality of TFs through direct or indirect mechanisms. Although strong correlations cannot be taken as evidence for cause-and-effect relationships, we interpret our data to indicate that increasing TF disorder likely was an important factor contributing to the evolution of organismic complexity and not merely a concurrent unrelated effect of increasing organismic complexity.
Long-term Administration of Antipsychotic Drugs in Schizophrenia and Influence of Substance and Drug Abuse on the Disease Outcome.

BACKGROUND Many schizophrenic patients with a long-term administration of antipsychotic drugs do not regularly adhere to the prescribed pharmacotherapy. Antipsychotic drugs constitute a palliative, but not a curative treatment, and the long-term effect of these drugs is not secure. Patients tend to consume nicotine and alcohol, as well as some patients consume drugs such as cannabis and amphetamines. OBJECTIVE The objective of this mini-review is to examine the reasons for the high tendency of schizophrenic patients to consume alcohol, nicotine and drugs and in addition to suggest measures to reduce the abuse of substances and drugs. The effects of substances such as alcohol and nicotine and drugs such as cannabis and amphetamines on the disease outcome will be mentioned. METHOD Previous reviews on the psychotic disorders and the pharmacological treatment were used to examine the effects of substances and drugs on schizophrenic symptoms and to investigate appropriate measures to improve medication adherence and the renouncement of consuming substances and drugs. RESULTS A possible coherence between the function of single susceptibility genes and the alteration of neurotransmitters is mentioned. The mechanism of action of the most important secondgeneration antipsychotic drugs and their indications are described. The tendency of schizophrenic patients to consume alcohol and nicotine and in addition the effect of both substances to possibly worsen psychotic symptoms are pointed out. The effect of nicotinergic agonists to support smoking cessation is described. The different compounds of cannabis, tetrahydrocannabidiol (a psychotomimetic) and cannabidiol (exerts antipsychotic actions), are mentioned. Because a reduced adherence to the pharmacotherapy is frequently combined with the abuse of substances, additional drugs, psychoeducation and the administration of long-acting injectable antipsychotic drugs could reduce the abuse of substances and drugs; these strategies could help to maintain the antipsychotic administration. CONCLUSION The abuse of drugs and substances might be combined with a reduced adherence to the antipsychotic pharmacotherapy. Drugs and substances might in some cases worsen the psychotic symptoms. Appropriate measures to reduce substance and drug abuse as well as to improve the adherence to the antipsychotic pharmacotherapy are cognitive behavioral therapy, psychoeducation and the administration of long-acting injectable antipsychotic drugs. Some new drugs, for example the cannabis compound cannabidiol that shows antipsychotic properties and ß-varenicline, a nicotinergic cholinergic agonist, might be administered when substance abuse (cannabis, nicotine) occurs.
Molecular Cloning of a T Cell-specific Adapter Protein (TSAd) Containing an Src Homology (SH) 2 Domain and Putative SH3 and Phosphotyrosine Binding Sites*

Adapter proteins link catalytic signaling proteins to cell surface receptors or downstream effector proteins. In this paper, we present the cDNA sequence F2771, isolated from an activated CD8+ T cell cDNA library. The F2771 cDNA encodes a novel putative adapter protein. The predicted amino acid sequence includes an SH2 domain as well as putative SH3 and phosphotyrosine binding interaction motifs, but lacks any known catalytic domains. The expression of the gene is limited to tissues of the immune system and, in particular, activated T cells. The protein expressed by F2771 cDNA in transfected COS cells is localized in the cytoplasm. A polyclonal antiserum raised against an F2771-encoded peptide reacts with a tyrosine-phosphorylated 52-kDa protein expressed in phytohemagglutinin-stimulated peripheral blood mononuclear cells. The gene is localized to chromosome 1q21, a region often found to be aberrant in lymphomas. The T cell-specific expression and the rapid induction of mRNA expression upon receptor binding, as well as the lack of catalytic domains in the presence of protein interaction domains, indicate that the F2771 gene encodes a novel T cell-specific adapter protein (TSAd) involved in the control of T cell activation.
Clonal chromosome anomalies and propensity to myeloid malignancies in congenital amegakaryocytic thrombocytopenia (OMIM 604498)

Congenital amegakaryocytic thrombocytopenia (CAMT, OMIM 604498) is an autosomal recessive disorder characterized by absent or reduced number of megakaryocytes in the bone marrow (BM) since birth, elevated serum levels of thrombopoietin (TPO), and very low platelet count. Prognosis of CAMT patients
PD-L1/B7H-1 Inhibits the Effector Phase of Tumor Rejection by T Cell Receptor (TCR) Transgenic CD8+ T Cells

Although increased circulating tumor antigen-specific CD8+ T cells can be achieved by vaccination or adoptive transfer, tumor progression nonetheless often occurs through resistance to effector function. To develop a model for identifying mechanisms of resistance to antigen-specific CTLs, poorly immunogenic B16-F10 melanoma was transduced to express the Kb-binding peptide SIYRYYGL as a green fluorescent protein fusion protein that should be recognized by high-affinity 2C TCR transgenic T cells. Although B16.SIY cells expressed high levels of antigen and were induced to express Kb in response to IFN-γ, they were poorly recognized by primed 2C/RAG2−/− T cells. A screen for candidate inhibitory ligands revealed elevated PD-L1/B7H-1 on IFN-γ-treated B16-F10 cells and also on eight additional mouse tumors and seven human melanoma cell lines. Primed 2C/RAG2−/−/PD-1−/− T cells showed augmented cytokine production, proliferation, and cytolytic activity against tumor cells compared with wild-type 2C cells. This effect was reproduced with anti-PD-L1 antibody present during the effector phase but not during the priming culture. Adoptive transfer of 2C/RAG2−/−/PD-1−/− T cells in vivo caused tumor rejection under conditions in which wild-type 2C cells or CTLA-4-deficient 2C cells did not reject. Our results support interfering with PD-L1/PD-1 interactions to augment the effector function of tumor antigen-specific CD8+ T cells in the tumor microenvironment.