Miracle-dz/UniFAR-FTUs huggingface dataset:
Quercetin, a bioflavonoid, protects against oxidative stress-related renal dysfunction by cyclosporine in rats.

Nephrotoxicity is the most common and clinically important side effect of cyclosporine (CsA). Recent evidence suggests that reactive oxygen species (ROS) play an important role in CsA nephrotoxicity. This study was designed to demonstrate the role of oxidative stress and its relation to renal dysfunction and to investigate the effects of quercetin, a bioflavonoid with antioxidant properties, in CsA-induced nephrotoxicity. Quercetin (0.5 and 2.0 mg/kg i.p.) was administered 24 h before and concurrently with CsA (20 mg/kg s.c.) for 21 days. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS). Renal function was assessed by estimating plasma creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed histopathologically. Pretreatment with CsA (20 mg/kg s.c.) for 21 days produced elevated levels of TBARS and deteriorated renal function as assessed by increased plasma creatinine, BUN and decreased creatinine and urea clearance as compared to vehicle-treated rats. The kidneys of CsA-treated rats showed severe striped interstitial fibrosis, arteriopathy, glomerular basement thickening, tubular vacuolization and hyaline casts. Quercetin (2 mg/kg) markedly reduced elevated levels of TBARS and significantly attenuated renal dysfunction and morphological changes in CsA-treated rats. It is likely that quercetin, due to its antioxidant properties, prevented CsA-induced ROS and consequently CsA nephrotoxicity. These results clearly demonstrate the pivotal role of oxidative stress and its relation to renal dysfunction, and also point to the therapeutic potential of the natural antioxidant quercetin in CsA-induced nephrotoxicity.
In Search of Recollection and Familiarity Signals in the Hippocampus

fMRI studies of recognition memory have often been interpreted to mean that the hippocampus selectively subserves recollection and that adjacent regions selectively subserve familiarity. Yet, many of these studies have confounded recollection and familiarity with strong and weak memories. In a source memory experiment, we compared correct source judgments (which reflect recollection) and incorrect source judgments (often thought to reflect familiarity) while equating for old–new memory strength by including only high-confidence hits in the analysis. Hippocampal activity associated with both correct source judgments and incorrect source judgments exceeded the activity associated with forgotten items and did so to a similar extent. Further, hippocampal activity was greater for high-confidence old decisions relative to forgotten items even when source decisions were at chance. These results identify a recollection signal in the hippocampus and may identify a familiarity signal as well. Similar results were obtained in the parahippocampal gyrus. Unlike in the medial temporal lobe, activation in prefrontal cortex increased differentially in association with source recollection.
Integrity, Efficacy and Community in the Stories of Political Activists

Narrative interviews were conducted with eight New Zealand long-term political activists to understand how they experienced their activism in relation to the psychological well-being concerns of integrity, efficacy and community. The interviews were analyzed using theory-based thematic analysis, and negative themes were subtracted from positive themes to give a measure of ambivalence. The results indicated that integrity (a sense of being true to oneself and living according to core values) appeared to provide the foundation for the activists' ongoing motivation, with efficacy (a feeling that one has, and can continue to meet new challenges) also playing a key role. Relationships with others (community), especially fellow-activists, were more problematic. The study's implications both for understanding activism and for learning more about the role of subjective experience in people's lives are discussed.
Use of the PFA-100® in the Assessment of Primary, Platelet-Related Hemostasis in a Pediatric Setting

The platelet function analyzer, PFA-100, has been designed to provide an in vitro measure of primary hemostasis simply, quickly, quantitatively, and accurately to aid in the routine screening of patients with potential hemorrhagic risk due to abnormal platelet plug formation. The system measures the closure time (CT), or the time taken for platelets in a sample of anticoagulated blood to form a plug that occludes a microscopic aperture cut into a membrane coated with collagen and either epinephrine or ADP. The high shear stresses produced in the analyzer lead to platelet plug formation that is greatly dependent on von Willebrand's factor (vWF). In this article, we detail the system itself and describe our initial studies using the PFA-100 to assess primary hemostasis in pediatric populations. Normal ranges have been established for healthy children and neonates. CTs for healthy children are independent of the needle gauge (21G or 23G) used for blood sampling. They are similar to CTs for healthy adults, but neonates have significantly shorter CTs, likely due to increased levels of vWF. Children with hemophilia have normal CTs, whereas seven out of eight patients with von Willebrand's disease (vWD) have abnormally long CTs. CT reproducibility between duplicate samples is excellent. Our preliminary results indicate that the PFA-100 will be useful in the evaluation of primary hemostasis in children, as well as in adults.
Modeling and Dynamics of the Inward-Facing State of a Na+/Cl− Dependent Neurotransmitter Transporter Homologue

The leucine transporter (LeuT) has recently commanded exceptional attention due mainly to two distinctions; it provides the only crystal structures available for a protein homologous to the pharmacologically relevant neurotransmitter: sodium symporters (NSS), and, it exhibits a hallmark 5-TM inverted repeat (“LeuT-fold”), a fold recently discovered to also exist in several secondary transporter families, underscoring its general role in transporter function. Constructing the transport cycle of “LeuT-fold” transporters requires detailed structural and dynamic descriptions of the outward-facing (OF) and inward-facing (IF) states, as well as the intermediate states. To this end, we have modeled the structurally unknown IF state of LeuT, based on the known crystal structures of the OF state of LeuT and the IF state of vSGLT, a “LeuT-fold” transporter. The detailed methodology developed for the study combines structure-based alignment, threading, targeted MD and equilibrium MD, and can be applied to other proteins. The resulting IF-state models maintain the secondary structural features of LeuT. Water penetration and solvent accessibility calculations show that TM1, TM3, TM6 and TM8 line the substrate binding/unbinding pathway with TM10 and its pseudosymmetric partner, TM5, participating in the extracellular and intracellular halves of the lumen, respectively. We report conformational hotspots where notable changes in interactions occur between the IF and OF states. We observe Na2 exiting the LeuT-substrate- complex in the IF state, mainly due to TM1 bending. Inducing a transition in only one of the two pseudosymmetric domains, while allowing the second to respond dynamically, is found to be sufficient to induce the formation of the IF state. We also propose that TM2 and TM7 may be facilitators of TM1 and TM6 motion. Thus, this study not only presents a novel modeling methodology applied to obtain the IF state of LeuT, but also describes structural elements involved in a possibly general transport mechanism in transporters adopting the “LeuT-fold”.
Early Life Stress in Depressive Patients: HPA Axis Response to GR and MR Agonist

Background: Evidence indicates that early life stress (ELS) can induce persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis to respond to stress in the adult life that leads to depression. These appear to be related to the impairment of HPA hormones through binding to glucocorticoid (GR) and mineralocorticoid receptors (MR). The aim of this study was to evaluate the impact of ELS in HPA axis response to challenges with GR and MR agonists in depressed patients. Methods: We included 30 subjects, 20 patients with current major depression (HAM-D21 ≥ 17). Patients were recruited into two groups according to ELS history assessed by the Childhood Trauma Questionnaire (CTQ). The cortisol measures in the saliva and plasma were evaluated after using (at 10:00 p.m.) placebo, fludrocortisone (MR agonist), or dexamethasone (GR agonist). Results: Depressed patients showed a significantly lower salivary cortisol upon waking after placebo compared with controls. Moreover, cortisol awakening responses (CAR) after MR agonist were found to be lower in depressed patients than in controls. With CTQ scores, HAM-D21, body mass index and CAR after placebo, GR agonist, MR agonist we found in a Linear Regression model that depressive patients with ELS (p = 0.028) show differences between placebo vs. MR agonist (R = 0.51; p < 0.05) but not after GR agonist; in depressive patients, without ELS the data show differences between placebo vs. MR agonist (R = 0.69; p < 0.05); but now as well placebo vs. GR agonist (R = 0.53; p < 0.05). Conclusion: Our findings indicate that MR activity is impaired in depressed patients compared with controls. Furthermore, in spite of the previous limitations described, in depressed patients with ELS, there was suppression by MR agonist, indicating that patients with ELS are sensitive to MR agonists. In contrast with depressed patients without ELS, we find suppression after both MR and GR agonist. These data suggested that in ELS an imbalance exists between MR and GR with MR dysfunction.
Antibody Conjugate Therapeutics: Challenges and Potential

Antibody conjugates are a diverse class of therapeutics consisting of a cytotoxic agent linked covalently to an antibody or antibody fragment directed toward a specific cell surface target expressed by tumor cells. The notion that antibodies directed toward targets on the surface of malignant cells could be used for drug delivery is not new. The history of antibody conjugates is marked by hurdles that have been identified and overcome. Early conjugates used mouse antibodies; cytotoxic agents that were immunogenic (proteins), too toxic, or not sufficiently potent; and linkers that were not sufficiently stable in circulation. Investigators have explored 4 main avenues using antibodies to target cytotoxic agents to malignant cells: antibody-protein toxin (or antibody fragment–protein toxin fusion) conjugates, antibody-chelated radionuclide conjugates, antibody–small-molecule drug conjugates, and antibody-enzyme conjugates administered along with small-molecule prodrugs that require metabolism by the conjugated enzyme to release the activated species. Only antibody-radionuclide conjugates and antibody-drug conjugates have reached the regulatory approval stage, and nearly 20 antibody conjugates are currently in clinical trials. The time may have come for this technology to become a major contributor to improving treatment for cancer patients. Clin Cancer Res; 17(20); 6389–97. ©2011 AACR.
Biologically Induced Reduction in Symmetry: A Study of Crystal Texture of Calcitic Sponge Spicules

Organisms can exert a remark- able degree of control over crystal growth. One way of achieving this is by the ad- sorption of specialized macromolecules on specific planes of the growing crystals. With continued growth of the crystal, the macromolecules are incorporated inside the crystal bulk. Their presence does not change the crystal structure, but creates discontinuities in the perfect lattice. Here we study in detail three unusual cases of reduction in symmetry at the level of crys- tal domain shapes, induced by this con- trolled intercalation. We examined sponge spicules, which are single crystals of Mg- bearing calcite. They were specifically chosen for this study, because their mor- phologies do not reflect the hexagonal symmetry of calcite. Their crystal textures (coherence lengths and angular spreads) were characterized by high-resolution X- ray diffraction with well-collimated syn- chrotron radiation. The results are com- pared to analogous studies of synthetic calcite and Mg-bearing calcite. In all the selected spicules reduction in symmetry is observed in the coherence lengths among symmetry-related crystallographic direc- tions. The reconstructed shapes of the do- mains of perfect structure closely match the specific spicule morphologies. The synthetic crystals show no such reduction in symmetry. Although the manner by which such exquisite control is achieved is not known, we envisage it involving a combination of oriented nucleation with either physical or stereochemically driven adsorption.
Stochastic Gradient Geodesic MCMC Methods

We propose two stochastic gradient MCMC methods for sampling from Bayesian posterior distributions defined on Riemann manifolds with a known geodesic flow, e.g. hyperspheres. Our methods are the first scalable sampling methods on these manifolds, with the aid of stochastic gradients. Novel dynamics are conceived and 2nd-order integrators are developed. By adopting embedding techniques and the geodesic integrator, the methods do not require a global coordinate system of the manifold and do not involve inner iterations. Synthetic experiments show the validity of the method, and its application to the challenging inference for spherical topic models indicate practical usability and efficiency.
Investigating the theory of planned behaviour’s application to binge drinking among university students

The theory of planned behaviour (TPB) has been found to predict many health-related behaviours. The aim of this study was to further investigate the factors that predict binge drinking in university students using the TPB, and to further investigate social facilitation and self-efficacy in relation to binge drinking. One hundred and sixty-one university students completed a questionnaire (time 1), measuring attitude, subjective norms, perceived behavioural control (PBC) and binge-drinking intentions, and 2 weeks later (time 2) 142 participants reported their binge-drinking behaviour. Ninety-one participants completed both questionnaires. Multiple regression analyses found partial support for the application of the TPB to binge drinking among university students accounting for 50% of variance in intentions to binge drink and 73% of variance in predicting future binge-drinking behaviour. However, PBC was found to be a non-significant predictor, thus supporting the simpler model of behaviour which excludes this control variable, the theory of reasoned action. Self-efficacy and social facilitation were also significant predictors of binge drinking. These findings indicate that to reduce binge drinking in university students, interventions targeting attitude change, perception of social norms and social facilitation would be most effective. Future research should explore the role of PBC in the TPB to determine its relevance in binge drinking.
The International Journal of Biostatistics Direct Effect Models

The causal effect of a treatment on an outcome is generally mediated by several intermediate variables. Estimation of the component of the causal effect of a treatment that is not mediated by an intermediate variable (the direct effect of the treatment) is often relevant to mechanistic understanding and to the design of clinical and public health interventions. Robins, Greenland and Pearl develop counterfactual definitions for two types of direct effects, natural and controlled, and discuss assumptions, beyond those of sequential randomization, required for the identifiability of natural direct effects. Building on their earlier work and that of others, this article provides an alternative counterfactual definition of a natural direct effect, the identifiability of which is based only on the assumption of sequential randomization. In addition, a novel approach to direct effect estimation is presented, based on assuming a model directly on the natural direct effect, possibly conditional on a subset of the baseline covariates. Inverse probability of censoring weighted estimators, double robust inverse probability of censoring weighted estimators, likelihood-based estimators, and targeted maximum likelihood-based estimators are proposed for the unknown parameters of this novel causal model.
How neurologists think: A cognitive psychology perspective on missed diagnoses

Physicians use heuristics or shortcuts in their decision making to help them sort through complex clinical information and formulate diagnoses efficiently. Practice would come to a halt without them. However, there are pitfalls to the use of certain heuristics, the same ones to which humans are prone in everyday life. It may be possible to improve clinical decision making through techniques that minimize biases inherent in heuristics. Five common clinical heuristics or other sources of cognitive error are illustrated through neurological cases with missed diagnoses, and literature from cognitive psychology and medicine are presented to support the occurrence of these errors in diagnostic reasoning as general phenomena. Articulation of the errors inherent in certain common heuristics alerts clinicians to their weaknesses as diagnosticians and should be beneficial to practice. Analysis of cases with missed diagnoses in teaching conferences might proceed along formal lines that identify the type of heuristic used and of inherent potential cognitive errors. Addressing these cognitive errors by becoming conscious of them is a useful tool in neurologic education and should facilitate a career‐long process of continuous self‐improvement. ANN NEUROL 2010;67:425–433
Effect of lenalidomide therapy on hematopoiesis of patients with myelodysplastic syndrome associated with chromosome 5q deletion

Background Lenalidomide improves erythropoiesis in patients with low/intermediate-1 risk myelodysplastic syndrome and interstitial deletion of the long arm of chromosome 5 [del(5q)]. The aim of this study was to explore the effect of lenalidomide treatment on the reserves and functional characteristics of bone marrow hematopoietic progenitor/precursor cells, bone marrow stromal cells and peripheral blood lymphocytes in patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q). Design and Methods We evaluated the number and clonogenic potential of bone marrow erythroid/myeloid/megakaryocytic progenitor cells using clonogenic assays, the apoptotic characteristics and adhesion molecule expression of CD34+ cells by flow cytometry, the hematopoiesis-supporting capacity of bone marrow stromal cells using long-term bone marrow cultures and the number and activation status of peripheral blood lymphocytes in ten patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q) receiving lenalidomide. Results Compared to baseline, lenalidomide treatment significantly decreased the proportion of bone marrow CD34+ cells, increased the proportion of CD36+/GlycoA+ and CD36−/GlycoA+ erythroid cells and the percentage of apoptotic cells within these cell compartments. Treatment significantly improved the clonogenic potential of bone marrow erythroid, myeloid, megakaryocytic colony-forming cells and increased the proportion of CD34+ cells expressing the adhesion molecules CD11a, CD49d, CD54, CXCR4 and the SLAM antigen CD48. The hematopoiesis-supporting capacity of bone marrow stroma improved significantly following treatment, as demonstrated by the number of colony-forming cells and the level of stromal-derived factor-1α and intercellular adhesion molecule-1 in long-term bone marrow culture supernatants. Lenalidomide treatment also increased the proportion of activated peripheral blood T lymphocytes. Conclusions The beneficial effect of lenalidomide in patients with lower risk myelodysplastic syndrome with del(5q) is associated with significant increases in the proportion of bone marrow erythroid precursor cells and in the frequency of clonogenic progenitor cells, a substantial improvement in the hematopoiesis-supporting potential of bone marrow stroma and significant alterations in the adhesion profile of bone marrow CD34+ cells.
ℓp norm multiple kernel Fisher discriminant analysis for object and image categorisation

In this paper, we generalise multiple kernel Fisher discriminant analysis (MK-FDA) such that the kernel weights can be regularised with an ℓp norm for any p ≥ 1, in contrast to existing MK-FDA that uses either l1 or l2 norm. We present formulations for both binary and multiclass cases and solve the associated optimisation problems efficiently with semi-infinite programming. We show on three object and image categorisation benchmarks that by learning the intrinsic sparsity of a given set of base kernels using a validation set, the proposed ℓp MK-FDA outperforms its fixed-norm counterparts, and is capable of producing state-of-the-art performance. Moreover, we show that our ℓp MK-FDA outperforms the ℓp multiple kernel support vector machine (ℓp MK-SVM) which has been recently proposed. Based on this observation and our experience with single kernel FDA and SVM, we argue that the almost century-old FDA is still a strong competitor of the popular SVM.
Automation in Immunohematology

There have been rapid technological advances in blood banking in South Asian region over the past decade with an increasing emphasis on quality and safety of blood products. The conventional test tube technique has given way to newer techniques such as column agglutination technique, solid phase red cell adherence assay, and erythrocyte-magnetized technique. These new technologies are adaptable to automation and major manufacturers in this field have come up with semi and fully automated equipments for immunohematology tests in the blood bank. Automation improves the objectivity and reproducibility of tests. It reduces human errors in patient identification and transcription errors. Documentation and traceability of tests, reagents and processes and archiving of results is another major advantage of automation. Shifting from manual methods to automation is a major undertaking for any transfusion service to provide quality patient care with lesser turnaround time for their ever increasing workload. This article discusses the various issues involved in the process.
THE [Ne iii] JET OF DG Tau AND ITS IONIZATION SCENARIOS

Forbidden neon emission from jets of low-mass young stars can be used to probe the underlying high-energy processes in these systems. We analyze spectra of the jet of DG Tau obtained with the Very Large Telescope/X-Shooter spectrograph in 2010. [Ne iii] is clearly detected in the innermost 3″ microjet and the outer knot located at . The velocity structure of the inner microjet can be decomposed into the low-velocity component at km s−1 and the high-velocity component (HVC) at km s−1. Based on the observed [Ne iii] flux and its spatial extent, we suggest the origins of the [Ne iii] emission regions and their relation with known X-ray sources along the jet. The flares from the hard X-ray source close to the star may be the main ionization source of the innermost microjet. The fainter soft X-ray source at from the star may provide sufficient heating to help to sustain the ionization fraction against recombination in the flow. The outer knot may be reionized by shocks faster than 100 km s−1 such that [Ne iii] emission reappears and the soft X-ray emission at is produced. Velocity decomposition of the archival Hubble Space Telescope spectra obtained in 1999 shows that the HVC had been faster, with a velocity centroid of km s−1. Such a decrease in velocity may potentially be explained by the expansion of the stellar magnetosphere, changing the truncation radius and thus the launching speed of the jet. The energy released by magnetic reconnections during relaxation of the transition can heat the gas up to several tens of megakelvin and provide the explanation for on-source keV X-ray flares that ionize the neon microjet.