Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell cycle-specific effects of lovastatin.

Lovastatin (LOV), the drug recently introduced to treat hypercholesteremia, inhibits the synthesis of mevalonic acid. The effects of LOV on the cell cycle progression of the human bladder carcinoma T24 cell line expressing activated p21ras were investigated. At a concentration of 2-10 microM, LOV arrested cells in G1 and also prolonged--or arrested a minor fraction of cells in--the G2 phase of the cell cycle; at a concentration of 50 microM, LOV was cytotoxic. The cytostatic effects were reversed by addition of exogenous mevalonate. Cells arrested in the cycle by LOV were viable for up to 72 hr and did not show any changes in RNA or protein content or chromatin condensation, which would be typical of either unbalanced growth or deep quiescence. The expression of the proliferation-associated nuclear proteins Ki-67 and p105 in these cells was reduced by up to 72% and 74%, respectively, compared with exponentially growing control cells. After removal of LOV, the cells resumed progression through the cycle; they entered S phase asynchronously after a lag of approximately 6 hr. Because mevalonate is essential for the posttranslational modification (isoprenylation) of p21ras, which in turn allows this protein to become attached to the cell membrane, the data suggest that the LOV-induced G1 arrest may be a consequence of the loss of the signal transduction capacity of p21ras. Indeed, while exposure of cells to LOV had no effect on the cellular content of p21ras (detected immunocytochemically), it altered the intracellular location of this protein, causing its dissociation from the cell membrane and translocation toward the cytoplasm and nucleus. However, it is also possible that inhibition of isoprenylation of proteins other than p21ras (e.g., nuclear lamins) by LOV may be responsible for the observed suppression of growth of T24 cells.
Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

Significance Classical atomistic molecular dynamics simulations and free-energy calculations performed on cytochrome c oxidase in an explicit membrane–solvent environment show that the water molecules in the nonpolar cavity near the active site of oxygen reduction reorientate according to the redox state of the enzyme, guiding the path of proton transfer and thereby effectively preventing short-circuit of the proton pump. The results highlight the important role of protein-bound water molecules in biological energy conversion––a notion shared with bacteriorhodopsin, the light-driven proton pump. Molecular oxygen acts as the terminal electron sink in the respiratory chains of aerobic organisms. Cytochrome c oxidase in the inner membrane of mitochondria and the plasma membrane of bacteria catalyzes the reduction of oxygen to water, and couples the free energy of the reaction to proton pumping across the membrane. The proton-pumping activity contributes to the proton electrochemical gradient, which drives the synthesis of ATP. Based on kinetic experiments on the O–O bond splitting transition of the catalytic cycle (A → PR), it has been proposed that the electron transfer to the binuclear iron–copper center of O2 reduction initiates the proton pump mechanism. This key electron transfer event is coupled to an internal proton transfer from a conserved glutamic acid to the proton-loading site of the pump. However, the proton may instead be transferred to the binuclear center to complete the oxygen reduction chemistry, which would constitute a short-circuit. Based on atomistic molecular dynamics simulations of cytochrome c oxidase in an explicit membrane–solvent environment, complemented by related free-energy calculations, we propose that this short-circuit is effectively prevented by a redox-state–dependent organization of water molecules within the protein structure that gates the proton transfer pathway.
Evaluating the Performance of a Visually Guided Hearing Aid Using a Dynamic Auditory-Visual Word Congruence Task

Objectives: The “visually guided hearing aid” (VGHA), consisting of a beamforming microphone array steered by eye gaze, is an experimental device being tested for effectiveness in laboratory settings. Previous studies have found that beamforming without visual steering can provide significant benefits (relative to natural binaural listening) for speech identification in spatialized speech or noise maskers when sound sources are fixed in location. The aim of the present study was to evaluate the performance of the VGHA in listening conditions in which target speech could switch locations unpredictably, requiring visual steering of the beamforming. To address this aim, the present study tested an experimental simulation of the VGHA in a newly designed dynamic auditory-visual word congruence task. Design: Ten young normal-hearing (NH) and 11 young hearing-impaired (HI) adults participated. On each trial, three simultaneous spoken words were presented from three source positions (−30, 0, and 30o azimuth). An auditory-visual word congruence task was used in which participants indicated whether there was a match between the word printed on a screen at a location corresponding to the target source and the spoken target word presented acoustically from that location. Performance was compared for a natural binaural condition (stimuli presented using impulse responses measured on KEMAR), a simulated VGHA condition (BEAM), and a hybrid condition that combined lowpass-filtered KEMAR and highpass-filtered BEAM information (BEAMAR). In some blocks, the target remained fixed at one location across trials, and in other blocks, the target could transition in location between one trial and the next with a fixed but low probability. Results: Large individual variability in performance was observed. There were significant benefits for the hybrid BEAMAR condition relative to the KEMAR condition on average for both NH and HI groups when the targets were fixed. Although not apparent in the averaged data, some individuals showed BEAM benefits relative to KEMAR. Under dynamic conditions, BEAM and BEAMAR performance dropped significantly immediately following a target location transition. However, performance recovered by the second word in the sequence and was sustained until the next transition. Conclusions: When performance was assessed using an auditory-visual word congruence task, the benefits of beamforming reported previously were generally preserved under dynamic conditions in which the target source could move unpredictably from one location to another (i.e., performance recovered rapidly following source transitions) while the observer steered the beamforming via eye gaze, for both young NH and young HI groups.
Exposure to prenatal and childhood infections and the risk of schizophrenia: suggestions from a study of sibship characteristics and influenza prevalence.

BACKGROUND It has been proposed that infections, perhaps prenatal exposure to the influenza virus, might increase the risk of schizophrenia. To address this hypothesis, we studied the possible influence on schizophrenia risk of sibship characteristics and ecological influenza prevalence data. Birth order and influenza prevalence were used as proxy measures for exposure to prenatal infection, and sibship size and interval to siblings were used as proxy measures for exposure to common childhood infections. METHODS We established a population-based cohort of 1746366 persons whose mothers were Danish-born women born since 1935 by using data from the Civil Registration System. Schizophrenia in cohort members (n = 2669) and their parents was identified by linkage with the Danish Psychiatric Case Register. Birth order, sibship size, and interval to siblings were calculated for each cohort member based on person-identifiable information on all siblings. The number of notifications of influenza per month in Denmark was obtained from the National Board of Health and Statens Serum Institut. RESULTS There was no association between birth order and schizophrenia risk or between schizophrenia risk and influenza prevalence during any month of prenatal life. Coming from a large sibship was associated with an increased schizophrenia risk. The relative risks were 1.26 (95% confidence interval [CI], 1.11-1.44) and 1.46 (95% CI, 1.22-1.75) for sibships of 4 and 5 or more, respectively, vs. a sibship of 2. Short interval (<2 years) to the nearest older sibling and nearest younger sibling was associated with a risk of 1.22 (95% CI, 1.05-1.38) and 1.15 (95% CI, 1.03-1.28), respectively, compared with longer intervals. CONCLUSIONS Our findings do not support the hypothesis that schizophrenia is associated with prenatal exposure to common infections or influenza. However, they are compatible with the hypothesis that environmental exposure, perhaps to common infections in childhood, may be a risk factor, although other explanations are also possible.
A shared alloantigenic determinant on Ia antigens encoded by the I-A and I-E subregions: evidence for I region gene duplication.

Two monoclonal antibodies to mouse Ia antigens were produced by fusion of xenoimmune rat spleen cells with the NSI myeloma. These monoclonal antibodies detect polymorphic determinants present on B cells and activated T lymphocytes from mice carrying the H-2b, H-2d, H-2k, H-2r, and H-2q haplotypes but not from mice carrying the H-2s or H-2r haplotypes. Antigenic site number determinations showed the positive haplotypes can be divided into 2 groups. Mice bearing the H-2b, H-2d, and H-2q haplotypes express a high number--40,000 to 80,000--of antigenic sites per B lymphocyte, and monoclonal antibody plus complement can lyse B cells from these mice. In contrast, mice bearing the H-2k and H-2r haplotypes express a low number of antigenic sites--about 5000 per cell. Spleen cells from mice carrying the latter haplotypes are not lysed with monoclonal antibody and complement. Genetic mapping demonstrated that high and low expression map to the I-A and I-E subregions, respectively. The monoclonal antibodies detect an Ia specificity on I-Ab, I-Ad, I-Ed, and I-Ek molecules. These observations were confirmed using several different experimental approaches, i.e., cytotoxicity, fluorescent staining, competitive inhibition of monoclonal antibody binding, and 2-dimensional gel electrophoresis of immunoprecipitates. The avidity for A alpha b A beta b and E alpha k E beta k is 5 to 7 x 10(-9) M-1. The antigenic determinant is heat labile, which suggests that it is not carbohydrate. The results imply that Ia antigens encoded by distinct subregions share sequence homology, which may be a consequence of ancestral gene duplication.
Increased Total Heart Rate Variability and Enhanced Cardiac Vagal Autonomic Activity in Healthy Humans with Sinus Bradycardia

Sinus bradycardia can be defined as a sinus rhythm with a resting heart rate of 60 beats per minute or less. While it is assumed that increased autonomic parasympathetic activity is associated with sinus bradycardia, such an association has yet to be proven. The aims of this study were to compute a number of heart rate variability (HRV) parameters in healthy individuals with sinus bradycardia and determine whether there was a significant vagal component to sinus bradycardia. Forty-three healthy adults with normal sinus rhythm and 25 healthy adults with sinus bradycardia had an electrocardiogram recorded for 20 minutes, from which HRV indices were calculated. Results showed significant increases in SDNN (standard deviation of NN intervals) (P< 0.05), RMSDD (square root of the mean squared differences of successive NN intervals) (P< 0.05), and DFA32 (detrended fluctuation analysis) (P< 0.05) in bradycardic subjects compared with subjects with normal sinus rhythm. There were no significant differences in sympathetic frequency domain indices between the two groups. In conclusion, there were significant increases in total heart variability and increased parasympathetic drive in subjects with bradycardia. Clinically, bradycardia is likely to be cardioprotective in aging populations based upon these HRV findings.
Prognostic value of myeloperoxidase in patients with chest pain.

BACKGROUND Inflammation is linked to adverse outcomes in acute coronary syndromes. Myeloperoxidase, an abundant leukocyte enzyme, is elevated in culprit lesions that have fissured or ruptured in patients with sudden death from cardiac causes. Numerous lines of evidence suggest mechanistic links between myeloperoxidase and both inflammation and cardiovascular disease. METHODS We assessed the value of plasma levels of myeloperoxidase as a predictor of the risk of cardiovascular events in 604 sequential patients presenting to the emergency department with chest pain. RESULTS Initial plasma myeloperoxidase levels predicted the risk of myocardial infarction, even in patients who are negative for troponin T (<0.1 ng per milliliter) at base line (P<0.001). Myeloperoxidase levels at presentation also predicted the risk of major adverse cardiac events (myocardial infarction, the need for revascularization, or death) within 30 days and 6 months after presentation (P<0.001). In patients without evidence of myocardial necrosis (defined as those who were negative for troponin T), the base-line myeloperoxidase levels independently predicted the risk of major adverse coronary events at 30 days (unadjusted 2nd, 3rd, and 4th quartile odds ratios, 2.2 [95 percent confidence interval, 1.1 to 4.6], 4.2 [95 percent confidence interval, 2.1 to 8.4], and 4.1 [95 percent confidence interval, 2.0 to 8.4], respectively) and at 6 months. CONCLUSIONS A single initial measurement of plasma myeloperoxidase independently predicts the early risk of myocardial infarction, as well as the risk of major adverse cardiac events in the ensuing 30-day and 6-month periods. Myeloperoxidase levels, in contrast to troponin T, creatine kinase MB isoform, and C-reactive protein levels, identified patients at risk for cardiac events in the absence of myocardial necrosis, highlighting its potential usefulness for risk stratification among patients who present with chest pain.
Grey Matrix Relational Modeling and Its Application Based on Multivariate Panel Data

Though containing plenty of information of the research objects, the multivariate panel data, due to the complex data structure, still bring about difficulty in analyzing and measuring the similarity among the cross-section individuals. To solve the problem, the possibility for the multivariate panel data to be represented as the matrix has been discussed, and the spatial and temporal characteristics of them also has been analyzed. Based on the spatial and temporal characteristics of the multivariate panel data, the grey matrix relation analysis model, which can be applied to measure the similarity of the multivariate panel cross-section data, is built. The model is capable of leading the" horizon" distance, the" increment" distance and the" variation" distance, which of the spatial and temporal characteristics of the panel data, to the grey relational degree model. And it furthers the calculation from the general vector space to the matrix space. In this article, we take traffic accidents in some area in our country as an example. We have studied and analyzed the phenomenon, and we conclude that this model is of applicability.
Statistical hypothesis test for maritime pine forest SAR images classification based on the geodesic distance

This paper introduces a new statistical hypothesis test for image classification based on the geodesic distance. We present how it can be used for the classification of texture image. The proposed method is then employed for the classification of Polarimetric Synthetic Aperture Radar images of maritime pine forests on both simulated data with the PolSARproSim software and real data acquired during the ONERA RAMSES campaign in 2004.
A comparison of controllers for improving the time response of NiTi wires

This paper presents a comparative theoretical study of the performance of a set of controllers for improving the speed of actuators based on shape memory alloys (SMAs), especially on Nitinol (NiTi). To prevent overheating and thermal fatigue, these controllers take into account the maximum heating current at which a NiTi element can safely be heated. The thermal behavior of NiTi is first modeled for calculating the time response and, based on the suggested model, we show that hysteresis due to phase transformation can be neglected for rapid heating, thus simplifying the model to a linear problem. We present then the design and performance of a set of linear controllers. Simulation results show a substantial increase in actuation speed.
Dynamic Decision-making for Emergency Materials Dispatching Based on Fuzzy Demand

This paper aims at solving the emergency material dispatching problem for major disasters.Based on three-level network of the supply points,supply hubs and demand points and under the fuzzy demand conditions and intermodal transportation,it proposes the multi-objective nonlinear integer programming model with the objectives of total transportation time and cost.Decision-makers dynamically give weights to both the objectives thus the flexibility of the model is improved.It finally provides the algorithm and testifies the validity of the model with an example.
Gait Balance and Acceleration of a Biped Robot Based on Q-Learning

This paper presents a method for the biped dynamic walking and balance control using reinforcement learning, which learns dynamic walking without a priori knowledge about the dynamic model. The learning architecture developed is aimed to solve complex control problems in robotic actuation control by mapping the action space from a discretized domain to a continuous one. It employs the discrete actions to construct a policy for continuous action. The architecture allows for the scaling of the dimensionality of the state space and cardinality of the action set that represents new knowledge, or new requirements for a desired task. The balance learning method utilizing the motion of robot arm and leg to shift the zero moment point on the soles of a robot can maintain the biped robot in a static stable state. This balanced algorithm is applied to biped walking on a flat surface and a seesaw and is making the biped's walks more stable. The simulation shows that the proposed method can allow the robot to learn to improve its behavior in terms of walking speed. Finally, the methods are implemented on a physical biped robot to demonstrate the feasibility and effectiveness of the proposed learning scheme.
Waterfilling-based resource allocation techniques in downlink Non-Orthogonal Multiple Access (NOMA) with Single-User MIMO

Non-Orthogonal Multiple Access (NOMA) has proven itself as a serious candidate for multiple access schemes in the 5th generation of wireless communication systems. In this paper, we propose new resource allocation techniques that allow the coupling of NOMA with multiple-input-multiple-output (MIMO) systems. As in most of downlink NOMA systems, the proportional fairness (PF) scheduler is used. As for power allocation (PA), most previous works assume an equal PA between antennas and subbands, which is sub-optimal. In this paper, we first propose a technique to reduce the complexity of the PF scheduler, and then we introduce an iterative waterfilling-based power allocation to the Single-User MIMO (SU-MIMO) case. Extensive simulations show that the novel PA technique improves the quality of experience of users suffering from bad channel conditions, as well as the user fairness.
Factors influencing antiretroviral treatment suboptimal adherence among perinatally HIV-infected adolescents in Thailand

Background Existing studies have suggested decreased adherence and rebound in mortality in perinatally HIV-infected adolescents receiving antiretroviral therapy (ART) as compared to adults and young children. Methods We used both quantitative and qualitative approaches to identify factors influencing adherence among perinatally infected adolescents in Thailand. We analyzed data from 568 pairs of perinatally infected adolescents (aged 12–19) and their primary caregivers in the Teens Living With Antiretrovirals (TEEWA) study, a cross-sectional survey conducted in 2010–2012. We also conducted 12 in-depth interviews in 2014 with infected adolescents or their primary caregivers to elicit experiences of living with long-term ART. Results From the quantitative analysis, a total of 275 (48.4%) adolescents had evidence of suboptimal adherence based on this composite outcome: adolescents self-reported missing doses in the past 7 days, caregiver rating of overall adherence as suboptimal, or latest HIV-RNA viral load ≥1000 copies/ml. In multivariate logistic regression analysis, younger age, having grandparents or extended family members as the primary caregiver, caregiver-assessed poor intellectual ability, having a boy/girlfriend, frequent online chatting, self-reported unhappiness and easiness in asking doctors questions were significantly associated with suboptimal adherence. From the in-depth interviews, tensed relationships with caregivers, forgetfulness due to busy schedules, and fear of disclosing HIV status to others, especially boy/girlfriends, were important contributors to suboptimal adherence. Social and emotional support and counseling from peer group was consistently reported as a strong adherence-promoting factor. Conclusion Our findings highlight unique barriers of ART adherence among the perinatally infected adolescents. Future interventions should be targeted at helping adolescents to improve interpersonal relationships and build adaptive skills in recognizing and addressing challenging situations related to ART taking.
Divergent effects of GM‐CSF and TGFβ1 on bone marrow‐ derived macrophage arginase‐1 activity, MCP‐1 expression, and matrix‐metalloproteinase‐12: a potential role during arteriogenesis

Granulocyte/macrophage‐colony stimulating factor (GM‐CSF) and transforming growth factor (TGF)β1 induce arteriogenesis in a nonischemic model of femoral artery ligation. Moreover, clinical trials demonstrated an improved collateralization after injection of bone marrow cells. In the present study, the expression of arteriogenic factors in bone marrow‐derived macrophages (BMDM) was measured to verify the potential of these cells to influence collateral artery growth. GM‐CSF induced in BMDM the expression of monocyte chemoattractive protein (MCP)‐1, matrix‐metalloproteinase (MMP)‐12, and arginase‐1–the latter also showing a remarkable increase in activity. During in vivo induced arteriogenesis, the accumulation rate of macrophages around proliferating collaterals was significantly increased. We also show that MCP‐1 is found to be mainly expressed in the media of the vessel wall, MMP‐12 in macrophages of the adventitia, and arginase at both locations. This study provides for the first time a comprehensive analysis of GM‐CSF/TGFβ1‐regulated arteriogenic factors in BMDM and supports the hypothesis that arteriogenesis is a multistage mechanism, including monocyte/macrophage adhesion and transmigration, pro‐arteriogenic cytokine expression, degradation of connective tissue, and collagen synthesis regulation. Selective modulation of these mechanisms as well as cell‐based therapies supplying arteriogenic factors in vivo point toward new strategies to influence collateral artery growth.