Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunopathogenesis of HIV Infection in Cocaine Users: Role of Arachidonic Acid

Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC) has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2), prostaglandin E2 synthetase (PGE2), thromboxane A2 receptor (TBXA2R), cyclopentenone prostaglandins (CyPG), such as 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), 14-3-3 ζ/δ and 5-lipoxygenase (5-LOX) mediated induction of IDC immune dysfunctions in cocaine using HIV positive patients. The plasma levels of AA, PGE2, 15d-PGJ2, 14-3-3 ζ/δ and IDC intracellular COX-2 and 5-LOX expression were assessed in cocaine users, HIV positive patients, HIV positive cocaine users and normal subjects. Results showed that plasma concentration levels of AA, PGE2 and COX-2, TBXA2R and 5-LOX in IDCs of HIV positive cocaine users were significantly higher whereas 15d-PGJ2 and 14-3-3 ζ/δ were significantly reduced compared to either HIV positive subjects or cocaine users alone. This report demonstrates that AA metabolites are capable of mediating the accelerative effects of cocaine on HIV infection and disease progression.
Structural basis for substrate recognition and inhibition of prephenate aminotransferase from Arabidopsis

Aromatic amino acids are protein building blocks and precursors to a number of plant natural products, such as the structural polymer lignin and a variety of medicinally relevant compounds. Plants make tyrosine and phenylalanine by a different pathway from many microbes; this pathway requires prephenate aminotransferase (PAT) as the key enzyme. Prephenate aminotransferase produces arogenate, the unique and immediate precursor for both tyrosine and phenylalanine in plants, and also has aspartate aminotransferase (AAT) activity. The molecular mechanisms governing the substrate specificity and activation or inhibition of PAT are currently unknown. Here we present the X-ray crystal structures of the wild-type and various mutants of PAT from Arabidopsis thaliana (AtPAT). Steady-state kinetic and ligand-binding analyses identified key residues, such as Glu108, that are involved in both keto acid and amino acid substrate specificities and probably contributed to the evolution of PAT activity among class Ib AAT enzymes. Structures of AtPAT mutants co-crystallized with either α-ketoglutarate or pyridoxamine 5'-phosphate and glutamate further define the molecular mechanisms underlying recognition of keto acid and amino acid substrates. Furthermore, cysteine was identified as an inhibitor of PAT from A. thaliana and Antirrhinum majus plants as well as the bacterium Chlorobium tepidum, uncovering a potential new effector of PAT.
A Novel, Rapid Method to Quantify Intraplatelet Calcium Dynamics by Ratiometric Flow Cytometry

Cytosolic free calcium ions represent important second-messengers in platelets. Therefore, quantitative measurement of intraplatelet calcium provides a popular and very sensitive tool to evaluate platelet activation and reactivity. Current protocols for determination of intracellular calcium concentrations in platelets have a number of limitations. Cuvette-based methods do not allow measurement of calcium flux in complex systems, such as whole blood, and therefore require isolation steps that potentially interfere with platelet activation. Flow cytometry has the potential to overcome this limitation, but to date the application of calibrated, quantitative readout of calcium kinetics has only been described for Indo-1. As excitation of Indo-1 requires a laser in the ultraviolet range, such measurements cannot be performed with a standard flow cytometer. Here, we describe a novel, rapid calibration method for ratiometric calcium measurement in platelets using both Ar+-laser excited fluorescence dyes Fluo-4 and Fura Red. We provide appropriate equations that allow rapid quantification of intraplatelet calcium fluxes by measurement of only two standardisation buffers. We demonstrate that this method allows quantitative calcium measurement in platelet rich plasma as well as in whole blood. Further, we show that this method prevents artefacts due to platelet aggregate formation and is therefore an ideal tool to determine basal and agonist induced calcium kinetics.
Computational Characterization of Transient Strain-Transcending Immunity against Influenza A

The enigmatic observation that the rapidly evolving influenza A (H3N2) virus exhibits, at any given time, a limited standing genetic diversity has been an impetus for much research. One of the first generative computational models to successfully recapitulate this pattern of consistently constrained diversity posits the existence of a strong and short-lived strain-transcending immunity. Building on that model, we explored a much broader set of scenarios (parameterizations) of a transient strain-transcending immunity, ran long-term simulations of each such scenario, and assessed its plausibility with respect to a set of known or estimated influenza empirical measures. We evaluated simulated outcomes using a variety of measures, both epidemiological (annual attack rate, epidemic duration, reproductive number, and peak weekly incidence), and evolutionary (pairwise antigenic diversity, fixation rate, most recent common ancestor, and kappa, which quantifies the potential for antigenic evolution). Taking cumulative support from all these measures, we show which parameterizations of strain-transcending immunity are plausible with respect to the set of empirically derived target values. We conclude that strain-transcending immunity which is milder and longer lasting than previously suggested is more congruent with the observed short- and long-term behavior of influenza.
Stretch sensing properties of conductive knitted structures of PEDOT-coated viscose and polyester yarns

Wearable textile-based stretch sensors for health-care monitoring allow physiological and medical evaluation without interfering in the daily routine of the patient. In our previous work, we successfully coated viscose and polyester (PES) fibers with the conjugated polymer poly(3,4-ethylenedioxythiophene) (PEDOT), using a chemical vapor deposition (CVD) process. In the present paper we report the possibility of producing a large quantity of PEDOT-coated conductive fibers with acceptable mechanical strength and frictional properties, so that knitted stretch sensors can be produced. In utilizing these knitted structures we have demonstrated the possibility of producing a textile-based monitoring device which is more readily integrated into wearable clothing than the previous metal-containing structures. The performance of viscose and PES knitted structures as stretch sensors has been investigated using a cyclic tester of our own design. For imitation of respiratory and joint movement, the variation in electrical properties of the knitted structures was examined at 5 to 50% elongation, and the performance of knitted viscose and PES structures was then compared on the basis of the cyclic testing results. In order to determine the effect of washing on PEDOT coatings and the knitted structures, two washing cycles were performed. After washing, the persistence of PEDOT coating on knitted structures was investigated using FT–IR spectroscopy and thermogravimetric analysis. In the case of PES fiber, it was revealed that stretch sensing behavior persisted even after the washing cycles. These structures thus have the potential to be utilized in medical textiles for monitoring the physiological activities of patients, such as breathing rate and joint movement.
Quantification of circulating cell-free DNA to predict patient survival in non-small-cell lung cancer

We used computed tomography (CT) to explore the prognostic value of cell-free (cf) DNA quantification and its predictive efficacy over time after chemotherapy in non-small-cell lung cancer (NSCLC) patients. In total, 177 NSCLC patients were enrolled in a prospective biomarker trial. Consecutive paired blood collection was performed to determine cfDNA concentrations at baseline CT and throughout serial follow-ups. The best cfDNA cut-off value to predict progression-free and overall survival was determined using X-tile analysis. Among 112 chemo-naive patients with stage IV adenocarcinoma, 43 were available for follow-up analysis. Cox regression multivariate analysis indicated that a high cfDNA concentration was an independent negative prognostic factor for progression-free survival (hazard ratio: 2.60; 95% confidence interval: 1.65-4.10; p = 0.008) and overall survival (hazard ratio: 2.63; 95% confidence interval: 1.66-4.17; p < 0.001). However, cfDNA concentration changes during treatment did not correlate with radiological CT responses at first follow-up or best response. No pattern was noted in the percent change in the cfDNA concentration from baseline or subsequently measured level to progression. The serum cfDNA concentration is thus associated with NSCLC patient prognosis, but does not appear to be a clinically valid marker for tumor responses.
Managerial Power, Capital Structure and Firm Value

With the reform of our property rights system, the maturity of the capital market, and the diversification of corporate financing, the capital structure decision has become the major concern of financial management. There are numbers of researches on how to determine the optimal capital structure, what factors affect the capital structure and what the relationship is like between the capital structure and the firm value. Built upon prior literature, this paper investigates how managerial power influences the capital structure with the operation risks and the characteristics of the directors’ structure. We find that the capital structure deviates from the optimal level more in firms with stronger managerial power, and these firms have a stronger discount on such deviation.
Human mesenchymal stem cells as delivery of osteoprotegerin gene: homing and therapeutic effect for osteosarcoma

Biological treatments have been studied extensively and previous studies have proved that osteoprotegerin (OPG) can inhibit the development and progress of human osteosarcoma. However, the utility of biologic agents for cancer therapy has a short half-life, which can hardly deliver to and function in tumor sites efficiently. Mesenchymal stem cells (MSCs) have the potential to migrate to tumor sites. In this study, MSCs transfected with adenoviruses carrying the OPG gene (MSCs-OPG) were used via the tail vein to treat athymic nude mice (nu/nu) bearing osteosarcoma. In vivo and ex vivo images were used to validate the MSCs homing to tumors. The therapeutic effect for osteosarcoma was evaluated by observations on growth of tumors and bone destruction. The results showed that infected MSCs-OPG labeled with red fluorescent protein (RFP) can migrate to tumor sites and express OPG protein. The treatment by MSCs-OPG reduced the tumor growth and inhibited bone destruction in vivo. All these indicated that MSCs can deliver OPG to tumor sites, which could be a new direction of biological treatment for human osteosarcoma.
Minireview MRI-guided gene therapy

MRI has the ability to generate high-contrast and high-resolution images, to obtain multiple diagnostic evaluations of organ function and morphology, and to provide multiple image planes with no risk of ionizing radiation. Recent efforts have focused on using MR technology to monitor gene delivery, to enhance gene transfection/transduction, and to track gene expression. This review summarizes the current status of MRIguided gene therapy. 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
Single-Mother Families: An Interactionist Perspective to Examine Cognitive Functioning in Middle Childhood

Many researchers note that children from single-parent households generally do worse in school than children from two-parent households, possibly because single-parent families are more susceptible to instability due to lack of resources. However, environment and individual differences, such as the mother's resiliency, can provide a buffer for children in single-parent homes. In order to confirm the distinction between how individual and external factors influence single mothers and their effects on their child’s cognitive functioning, the current study had two objectives: to determine (a) individual factors of the single mothers associated with their children’s cognitive functioning in middle childhood; and (b) external factors that impact single mothers and are associated with children’s cognitive functioning. This study used a sample of high-risk single mothers and their children from Welfare, Children, and Families: A Three-City Study. At the Wave 1 data collection the children were ages 2 to 4 and at a follow-up five years later, Wave 3, the children were ages 7 to 10. The mothers’ family background, psychosocial resources, socioeconomic status, family stress, and parenting quality from early childhood were used to predict their children’s cognitive functioning in middle childhood, while controlling for the children’s cognitive functioning at Wave 1. The results show that maternal education (for the applied problem scale: ß=.14, p=.01) and positive parenting (both for the applied problem scale ß=.10, p=.04 and letter-word identification ß=.90, p=.06) during early childhood were related to increases in the child’s cognitive functioning over a five-year period. This argues for resources to increase single mothers’ education and programs to help improve their positive parenting skills. It is hoped that the results of this study can initiate intervention or preventive programs for these mothers and children in the future.
Structural Equation Model of Disability in Low Back Pain

Study Design. The effects of participant characteristics along with descriptions of pain and psychological involvement, such as fear avoidance, were assessed using structural equation modeling (SEM) to identify relationships between these factors and disability as a result of low back pain (LBP). Objective. The aim of this study was to evaluate the relationship between factors related to pain description, participants’ characteristics, psychological involvement, and disability through SEM. Summary of Background Data. LBP is a complex multifactorial condition that can lead to disability. Understanding which factors contribute to disability and how those factors interact is important for predicting and minimizing disability in patients with LBP. Methods. We analyzed data from 156 participants (63% female) with LBP. A stepwise SEM was built with patient characteristics, pain intensity, depression, anxiety, and fear avoidance to predict disability in LBP. Results. Participants were 23–84 years (49.7 ± 15.1 yrs) of age and experienced 0.03 to 300 months duration (25.5 ± 36.4 months) of current LBP. The final model explained 62% of the variance in disability and included female gender, full-time employment, depression, and fear avoidance beliefs as significant predictors. Full-time employment was the only significant predictor that reduced disability; all other significant predictors increased disability in the model. Conclusion. Understanding the relationship between these predictors and disability provides a foundation for predicting and managing disability for individual patients who suffer from LBP. Level of Evidence: 3
Isoproterenol Promotes Rapid Ryanodine Receptor Movement to Bridging Integrator 1 (BIN1)–Organized Dyads

Background— The key pathophysiology of human acquired heart failure is impaired calcium transient, which is initiated at dyads consisting of ryanodine receptors (RyRs) at sarcoplasmic reticulum apposing CaV1.2 channels at t-tubules. Sympathetic tone regulates myocardial calcium transients through &bgr;-adrenergic receptor (&bgr;-AR)–mediated phosphorylation of dyadic proteins. Phosphorylated RyRs (P-RyR) have increased calcium sensitivity and open probability, amplifying calcium transient at a cost of receptor instability. Given that bridging integrator 1 (BIN1) organizes t-tubule microfolds and facilitates CaV1.2 delivery, we explored whether &bgr;-AR–regulated RyRs are also affected by BIN1. Methods and Results— Isolated adult mouse hearts or cardiomyocytes were perfused for 5 minutes with the &bgr;-AR agonist isoproterenol (1 µmol/L) or the blockers CGP+ICI (baseline). Using biochemistry and superresolution fluorescent imaging, we identified that BIN1 clusters P-RyR and CaV1.2. Acute &bgr;-AR activation increases coimmunoprecipitation between P-RyR and cardiac spliced BIN1+13+17 (with exons 13 and 17). Isoproterenol redistributes BIN1 to t-tubules, recruiting P-RyRs and improving the calcium transient. In cardiac-specific Bin1 heterozygote mice, isoproterenol fails to concentrate BIN1 to t-tubules, impairing P-RyR recruitment. The resultant accumulation of uncoupled P-RyRs increases the incidence of spontaneous calcium release. In human hearts with end-stage ischemic cardiomyopathy, we find that BIN1 is also 50% reduced, with diminished P-RyR association with BIN1. Conclusions— On &bgr;-AR activation, reorganization of BIN1-induced microdomains recruits P-RyR into dyads, increasing the calcium transient while preserving electric stability. When BIN1 is reduced as in human acquired heart failure, acute stress impairs microdomain formation, limiting contractility and promoting arrhythmias.
Pancreas Segmentation in CT and MRI Images via Domain Specific Network Designing and Recurrent Neural Contextual Learning

Automatic pancreas segmentation in radiology images, eg. , computed tomography (CT) and magnetic resonance imaging (MRI), is frequently required by computer-aided screening, diagnosis, and quantitative assessment. Yet pancreas is a challenging abdominal organ to segment due to the high inter-patient anatomical variability in both shape and volume metrics. Recently, convolutional neural networks (CNNs) have demonstrated promising performance on accurate segmentation of pancreas. However, the CNN-based method often suffers from segmentation discontinuity for reasons such as noisy image quality and blurry pancreatic boundary. From this point, we propose to introduce recurrent neural networks (RNNs) to address the problem of spatial non-smoothness of inter-slice pancreas segmentation across adjacent image slices. To inference initial segmentation, we first train a 2D CNN sub-network, where we modify its network architecture with deep-supervision and multi-scale feature map aggregation so that it can be trained from scratch with small-sized training data and presents superior performance than transferred models. Thereafter, the successive CNN outputs are processed by another RNN sub-network, which refines the consistency of segmented shapes. More specifically, the RNN sub-network consists convolutional long short-term memory (CLSTM) units in both top-down and bottom-up directions, which regularizes the segmentation of an image by integrating predictions of its neighboring slices. We train the stacked CNN-RNN model end-to-end and perform quantitative evaluations on both CT and MRI images.
Measuring Whitespace Patterns as an Indication of Plagiarism

There are several different methods of comparing source code from different programs to find copying1. Perhaps the most common method is comparing source code statements, comments, strings, identifiers, and instruction sequences. However, there are anecdotes about the use of whitespace patterns in code. These virtually invisible patterns of spaces and tabs have been used in litigation to imply copying, but no formal study has been performed that shows that these patterns can actually identify copied code. This paper presents a detailed study of whitespace patterns and the uniqueness of these patterns in different programs.
Deducing the role of functionalizing macromolecules in the nucleation of colloidal nanoparticles

Although polymers are widely employed to impart specific function to surfaces, techniques to characterize the adsorbed molecule are limited and usually indirect. We present two independent dynamic NMR studies to deduce the manner in which adsorbed polyvinylpyrrolidone (PVP) attaches to the surface of ZnO colloidal nanoparticles and directs particle precipitation. In our colloidal system, the conformation of the polymer molecule on the particle surface—loosely described as trains, loops, or tails—can be elucidated by probing the nuclear response of the solvent or the polymer to pulsed magnetic fields. The dynamic 1H-NMR signal of polymer-juxtaposed solvent molecules are monitored in our first approach, in which we monitor both spin-lattice (also known as T1) and spin-spin (also known as T2) relaxation behavior of the solvent, as the ease of solvent relaxation varies with proximity to the nanoparticle surface. In a second approach, the proton signal of the polymer is monitored over time. The rationale of this approach is that the signal of particle-bound polymer moieties will be lost faster than that of unbound polymer ones. Determining the signal of spin-echo and solid-echo processes enables calculation of polymer bound fraction. The ZnO nanoparticle platforms are synthesized by the hydrolysis and condensation of zinc oxide precursors in PVP-containing solutions. Particle size distribution is determined by dynamic light scattering (DLS), as well as extrapolation from UV-visible absorption spectra. Three specific PVP concentrations are chosen in producing ZnO particles. Synthesis in solutions of high PVP concentration produces comparable results between the hydrodynamic radius and the extrapolated UV-visible radius, whereas at low polymeric concentrations, the difference between the two radii increases, suggesting a change in the conformation of adsorbed polymer on the nanoparticle surface under varying concentration. Dynamic NMR T1 analysis reveals a loss of solvent mobility at higher polymer concentrations. In a separate experiment, we investigate the effect of the Zn precursor cations on the solvation of PVP, by using DLS to measure the hydrodynamic radius of the interpenetrating PVP in propanol, in the presence and absence of the zinc cation precursor. The results suggest that the zinc precursor ions pull the PVP chains closer, most likely due to the pyrrolidone rings on the polymers, and reduce the radius of gyration of polymer globules at high PVP concentrations. These results validate a model of highly dense polymer globules serving as reactors for ZnO nanoparticle precipitation, in which the high density of pyrrolidone rings in the globule hinders the diffusion of Zn+2by electrostatic interaction. At high concentrations, large PVP globules appear to trap the reactant species and adsorb in a train conformation on the surface of precipitating ZnO nanoparticles. At low concentrations, the sizes of PVP globules are comparable to that of the evolving ZnO nanoparticles, and PVP adsorbs in looped and tail-only conformation.