Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural bases for the different anti-fibrillatory effects of chloroquine and quinidine.

AIMS Chloroquine, an anti-malarial quinoline, is structurally similar to quinidine. Both drugs have been shown to block ion channels. We tested the hypothesis that chloroquine's mode of interaction with the vestibule of the cytoplasmic domain of the inward rectifier potassium channel Kir2.1 makes it a more effective I(K1) blocker and anti-fibrillatory agent than quinidine. METHODS AND RESULTS We used comparative molecular modelling and ligand docking of the three-dimensional structures of quinidine and chloroquine in the intracellular domain of Kir2.1. Simulations predicted that chloroquine effectively blocks potassium flow by binding at the centre of the ion permeation vestibule of Kir2.1. In contrast, quinidine binds the vestibular side, only partially blocking ion movement. We tested the modelling predictions in Kir2.1-expressing human embryonic kidney (HEK)-293 cells. The half-maximal inhibitory concentration for chloroquine block of I(K1) was 1.2 µM, while that of quinidine was 57 µM. Finally, we used optical mapping of Langendorff-perfused mouse hearts with cardiac-specific Kir2.1 up-regulation to compare the anti-fibrillatory effects of the drugs. In five of six hearts, 10 μM quinidine slowed the frequency but did not terminate the tachyarrhythmia. In five of five hearts, 10 μM chloroquine terminated the arrhythmia, restoring sinus rhythm. CONCLUSION Quinidine only partially blocks I(K1). Chloroquine binds at the centre of the ion permeation vestibule of Kir2.1, which makes it a more effective I(K1) blocker and anti-fibrillatory agent than quinidine. Integrating the structural biology of drug-ion channel interactions with cellular electrophysiology and optical mapping is an excellent approach to understand the molecular mechanisms of anti-arrhythmic drug action and for drug discovery.
Measuring Alexithymia via Trait Approach-I: A Alexithymia Scale Item Selection and Formation of Factor Structure.

INTRODUCTION It is not clear in the literature whether available instruments are sufficient to measure alexithymia because of its theoretical structure. Moreover, it has been reported that several measuring instruments are needed to measure this construct, and all the instruments have different error sources. The old and the new forms of Toronto Alexithymia Scale are the only instruments available in Turkish. Thus, the purpose of this study was to develop a new scale to measure alexithymia, selecting items and constructing the factor structure. METHODS A total of 1117 patients aged from 19 to 82 years (mean = 35.05 years) were included. A 100-item pool was prepared and applied to 628 women and 489 men. Data were analyzed using Explanatory Factor Analysis, Confirmatory Factor Analysis, and Item Response Theory and 28 items were selected. The new form of 28 items was applied to 415 university students, including 271 women and 144 men aged from 18 to 30 (mean=21.44). RESULTS The results of Explanatory Factor Analysis revealed a five-factor construct of "Solving and Expressing Affective Experiences," "External Locused Cognitive Style," "Tendency to Somatize Affections," "Imaginary Life and Visualization," and "Acting Impulsively," along with a two-factor construct representing the "Affective" and "Cognitive" components. All the components of the construct showed good model fit and high internal consistency. The new form was tested in terms of internal consistency, test-retest reliability, and concurrent validity using Toronto Alexithymia Scale as criteria and discriminative validity using Five-Factor Personality Inventory Short Form. CONCLUSION The results showed that the new scale met the basic psychometric requirements. Results have been discussed in line with related studies.
Nonlinear fluid dynamics from gravity

Black branes in AdS5 appear in a four parameter family labeled by their velocity and temperature. Promoting these parameters to Goldstone modes or collective coordinate fields—arbitrary functions of the coordinates on the boundary of AdS5—we use Einstein's equations together with regularity requirements and boundary conditions to determine their dynamics. The resultant equations turn out to be those of boundary fluid dynamics, with specific values for fluid parameters. Our analysis is perturbative in the boundary derivative expansion but is valid for arbitrary amplitudes. Our work may be regarded as a derivation of the nonlinear equations of boundary fluid dynamics from gravity. As a concrete application we find an explicit expression for the expansion of this fluid stress tensor including terms up to second order in the derivative expansion.
The prevention and treatment of obesity.

BACKGROUND The high prevalence of obesity (24% of the adult population) and its adverse effects on health call for effective prevention and treatment. METHOD Pertinent articles were retrieved by a systematic literature search for the period 2005 to 2012. A total of 4495 abstracts were examined. 119 publications were analyzed, and recommendations were issued in a structured consensus procedure by an interdisciplinary committee with the participation of ten medical specialty societies. RESULTS Obesity (body-mass index [BMI] ge;30 kg/m2) is considered to be a chronic disease. Its prevention is especially important. For obese persons, it is recommended that a diet with an energy deficit of 500 kcal/day and a low energy density should be instituted for the purpose of weight loss and stabilization of a lower weight. The relative proportion of macronutrients is of secondary importance for weight loss. If the BMI exceeds 30 kg/m2, formula products can be used for a limited time. More physical exercise in everyday life and during leisure time promotes weight loss and improves risk factors and obesity-associated diseases. Behavior modification and behavioral therapy support changes in nutrition and exercise in everyday life. With respect to changes in lifestyle, there is no scientific evidence to support any particular order of the measures to be taken. Weight-loss programs whose efficacy has been scientifically evaluated are recommended. Surgical intervention is more effective than conservative treatment with respect to reduction of bodily fat, improvement of obesity-associated diseases, and lowering mortality. Controlled studies indicate that, within 1 to 2 years, a weight loss of ca. 4 to 6 kg can be achieved by dietary therapy, 2 to 3 kg by exercise therapy, and 20 to 40 kg by bariatric surgery. CONCLUSION There is good scientific evidence for effective measures for the prevention and treatment of obesity.
Outline Shape Retrieval Using Textual Descriptors and Geometric Features

Content_based image retrieval is a promising approach because of its automatic indexing, recognition and retrieval. This paper is a contribution in the field of the content Based Image Retrieval (CBIR). Objects are represented by their outlines shapes (silhouettes) and described following the XLWDOS Textual Description (Larabi et al., 2003). Textual Descriptors are sensitive to noise. The authors have already developed an approach to smooth the outlines at different scales (Aouat & Larabi, 2010). The smoothing is performed by applying a convolution using the Gaussian Filter to process noisy shapes in order to match shapes descriptors. The authors have also applied an indexing process after silhouettes smoothing (Aouat & Larabi, 2009). The approaches (Aouat & Larabi, 2010; Aouat & Larabi, 2009) are very interesting for shape matching and indexing, but unfortunately, they are not appropriate to the recognition and retrieval processes because there is no use of similarity measures. In order to perform the retrieval process and select the best model for a query silhouette, the authors use in this paper Geometric features extracted from Textual Description of Outline Shapes. Outline Shape Retrieval Using Textual Descriptors and Geometric Features
Fully Homomorphic Encryption without Bootstrapping

We present a radically new approach to fully homomorphic encryption (FHE) that dramatically improves performance and bases security on weaker assumptions. A central conceptual contribution in our work is a new way of constructing leveled fully homomorphic encryption schemes (capable of evaluating arbitrary polynomial-size circuits), without Gentry’s bootstrapping procedure. Specifically, we offer a choice of FHE schemes based on the learning with error (LWE) or ring-LWE (RLWE) problems that have 2 security against known attacks. For RLWE, we have: • A leveled FHE scheme that can evaluate L-level arithmetic circuits with O(λ · L) per-gate computation – i.e., computation quasi-linear in the security parameter. Security is based on RLWE for an approximation factor exponential in L. This construction does not use the bootstrapping procedure. • A leveled FHE scheme that uses bootstrapping as an optimization, where the per-gate computation (which includes the bootstrapping procedure) is O(λ), independent of L. Security is based on the hardness of RLWE for quasi-polynomial factors (as opposed to the sub-exponential factors needed in previous schemes). We obtain similar results for LWE, but with worse performance. We introduce a number of further optimizations to our schemes. As an example, for circuits of large width – e.g., where a constant fraction of levels have width at least λ – we can reduce the per-gate computation of the bootstrapped version to O(λ), independent of L, by batching the bootstrapping operation. Previous FHE schemes all required Ω(λ) computation per gate. At the core of our construction is a much more effective approach for managing the noise level of lattice-based ciphertexts as homomorphic operations are performed, using some new techniques recently introduced by Brakerski and Vaikuntanathan (FOCS 2011). ∗Sponsored by the Air Force Research Laboratory (AFRL). Disclaimer: This material is based on research sponsored by DARPA under agreement number FA8750-11-C-0096. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of DARPA or the U.S. Government. Approved for Public Release, Distribution Unlimited. †This material is based on research sponsored by DARPA under agreement number FA8750-11-2-0225. The same disclaimer as above applies. ISSN 1433-8092 Electronic Colloquium on Computational Complexity, Report No. 111 (2011)
Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells

The role of CD4+ and CD8+ T cells in mediating pulmonary clearance of a cryptococcal infection was investigated. Intratracheal inoculation of BALB/c and C.B-17 mice with a moderately virulent strain of Cryptococcus neoformans (52D) resulted in a pulmonary infection, which was cleared by a T cell-dependent mechanism. During this clearance, there was a significant influx of both CD4+ and CD8+ T cells into the lungs. Depletion of CD4+ T cells by injections of CD4-specific monoclonal antibody (mAb) prevented pulmonary clearance and also resulted in significant colonization of the brain and spleen of infected mice. CD4 depletion did not prevent the influx of CD8+ T cells into the lungs. Surprisingly, depletion of CD8+ T cells by mAb also ablated pulmonary clearance. CD8-depleted mice also had a small but significant increase in brain and spleen colony-forming unit compared to control mice by the end of the study. CD4+ T cell pulmonary influx was independent of the presence of CD8+ T cells. The lungs of T cell- depleted mice were examined histologically. CD4+ and CD8+ T cells each mediated a degree of inflammatory influx seen in the lungs of infected mice and raised the possibility that CD4+ and CD8+ T cells may synergize to generate the inflammatory response in the lungs. Numerous phagocytized but intact cryptococci were seen in the inflammatory foci of CD8-depleted mice but not in control or CD4-depleted mice. We propose that CD4+ T cells may recruit and activate effector phagocytes while CD8+ T cells predominantly function to lyse cryptococcus-laden unactivated phagocytes similar to the function of CD8+ T cells during listeria and mycobacteria infections.
Turbo-Coded HARQ with Switchable Relaying Mechanism in Single Hop Cooperative Wireless System

Cooperative relaying has recently received significant attention due to its diversity gain, higher QoS, power savings, extended coverage and improved BER as compared to conventional SISO systems. For further improvement in the system performance, Hybrid ARQ proves itself as effective transmission strategy. Exploiting the retransmission nature of Hybrid ARQ, this paper proposes Switchable Relaying Mechanism (SRM) to be used with Turbo codes in a single hop Cooperative System. According to channel conditions, SRM will let the relay to switch its relaying protocol between AAF and DAF. Moreover, retransmission mechanism at destination guarantees improvement of an overall system performance. The proposed Hybrid ARQ-SRM scheme when used with Turbo codes has shown better BER performance as compared to conventional cooperative systems.
Authoring and Living Next-Generation Location-Based Experiences

Authoring location-based experiences involving multiple participants, collaborating or competing in both indoor and outdoor mixed realities, is extremely complex and bound to serious technical challenges. In this work, we present the first results of the MAGELLAN European project and how these greatly simplify this creative process using novel authoring, augmented reality (AR) and indoor geolocalisation techniques.
The Cdc42 Binding and Scaffolding Activities of the Fission Yeast Adaptor Protein Scd2*

The small GTP-binding protein Cdc42, the guanine nucleotide exchange factor Scd1, the p21-activated kinase Shk1, and the adaptor protein Scd2 are involved in the Cdc42-dependent signaling cascade in fission yeast. In the present study, we analyzed the Cdc42 binding and scaffolding activities of Scd2 by co-precipitation assays. We found that two SH3-containing regions, amino acid residues 1–87 (CB1 (Cdc42-binding region 1)) and 110–266 (CB2), of Scd2 can bind to the GTP-bound form of Cdc42. CB2 is cryptic because of the intramolecular binding between the SH3 domain in CB2 (SH3(C)) and the PX domain and binds to Cdc42 only when the Scd2 PB1 domain binds to the PC motif-containing region (residues 760–872) of Scd1. This CB2·Cdc42 association, which would stabilize the open configuration of Scd2, enables the SH3(C) domain to bind to the polyproline motif of Shk1. We also found that the GTP-bound form of Cdc42 binds to the CRIB motif of Shk1 more strongly than to Scd2. Thus, Scd2 functions as a scaffold to form a protein complex, and the GTP-bound Cdc42 might be transferred effectively from the upstream activator Scd1 to the downstream effector Shk1 via Scd2.
Speed-up iterative frequent itemset mining with constraint changes

Mining of frequent itemsets is a fundamental data mining task. Past research has proposed many efficient algorithms for this purpose. Recent work also highlighted the importance of using constraints to focus the mining process to mine only those relevant itemsets. In practice, data mining is often an interactive and iterative process. The user typically changes constraints and runs the mining algorithm many times before being satisfied with the final results. This interactive process is very time consuming. Existing mining algorithms are unable to take advantage of this iterative process to use previous mining results to speed up the current mining process. This results in an enormous waste of time and computation. In this paper, we propose an efficient technique to utilize previous mining results to improve the efficiency of current mining when constraints are changed. We first introduce the concept of tree boundary to summarize useful information available from previous mining. We then show that the tree boundary provides an effective and efficient framework for the new mining. The proposed technique has been implemented in the context of two existing frequent itemset mining algorithms, FP-tree and tree projection. Experiment results on both synthetic and real-life datasets show that the proposed approach achieves a dramatic saving of computation.
Quantitative serial sectioning analysis

A method for serial sectioning is presented that allows one to take about 20 sections per hour with spacings in the range 1–20 µm between sections. The alignment of the cross‐sections is done with a linear variable differential transformer; it is thus independent of the microstructure of the sample and does not rely upon markers implanted in the sample. The alignment errors as well as tilts and rotation errors between sections associated with the new method are found to be negligible. Once all the sections are captured in a computer a three‐dimensional image can be constructed. This image can be viewed interactively and rotated, thus allowing the direct observation of three‐dimensional shapes. It can further be used to determine a vast array of microstructural parameters including those that cannot be determined from planar sections. The technique is illustrated through the reconstruction of the microstructure of a cast standard aluminium alloy specimen.
High-fidelity gene targeting in embryonic stem cells by using sequence replacement vectors

Mutations were targeted to the Hprt locus in murine embryonic stem cells by using sequence replacement vectors. When the vector was designed such that the mutated sequences were flanked on both sides by several kilobases of DNA homologous to the target locus, replacement of chromosomal sequences with the exogenous DNA occurred with precision. If, on the other hand, the target-homologous DNA on one arm of the vector was reduced to below 1 kb in length, the fidelity of recombination was diminished.
Protein Phosphatase 2A Mediates Dormancy of Glioblastoma Multiforme-Derived Tumor Stem-Like Cells during Hypoxia

Purpose The hypoxic microenvironment of glioblastoma multiforme (GBM) is thought to increase resistance to cancer therapies. Recent evidence suggests that hypoxia induces protein phosphatase 2A (PP2A), a regulator of cell cycle and cell death. The effects of PP2A on GBM tumor cell proliferation and survival during hypoxic conditions have not been studied. Experimental Design Expression of PP2A subunits and HIF-α proteins was measured in 65 high-grade astrocytoma and 18 non-neoplastic surgical brain specimens by western blotting. PP2A activity was measured by an immunoprecipitation assay. For in vitro experiments, GBM-derived tumor stem cell-like cells (TSCs) were exposed to severe hypoxia produced by either CoCl2 or 1% O2. PP2A activity was inhibited either by okadaic acid or by shRNA depletion of the PP2A C subunit. Effects of PP2A activity on cell cycle progression and cell survival during hypoxic conditions were assessed using flow cytometry. Results In our patient cohort, PP2A activity was positively correlated with HIF-1∝ protein expression (P = 0.002). Patients with PP2A activity levels above 160 pMP had significantly worse survival compared to patients with levels below this threshold (P = 0.002). PP2A activity was an independent predictor of survival on multivariable analysis (P = 0.009). In our in vitro experiments, we confirmed that severe hypoxia induces PP2A activity in TSCs 6 hours after onset of exposure. PP2A activity mediated G1/S phase growth inhibition and reduced cellular ATP consumption in hypoxic TSCs. Conversely, inhibition of PP2A activity led to increased cell proliferation, exhaustion of intracellular ATP, and accelerated P53-independent cell death of hypoxic TSCs. Conclusions Our results suggest that PP2A activity predicts poor survival in GBM. PP2A appears to reduce the metabolic demand of hypoxic TSCs and enhances tumor cell survival. Modulation of PP2A may be a potential target for cancer therapy.
Reliability and validity of a self-reported measure of medication adherence in patients with type 2 diabetes mellitus in Korea

Objective This study examined the psychometric properties of the Korean version of the eight-item Morisky Medication Adherence Scale (MMAS-8) to measure adherence to diabetes medication in patients with type 2 diabetes mellitus. Methods The English version of the MMAS-8 was translated into Korean and administered to patient with type 2 diabetes mellitus via face-to-face interviews, conducted by an independent interviewer. Patient characteristics and glycosylated haemoglobin (HbA1c) levels were assessed at the same clinic visit. A proportion of patients was randomly selected for 2-week test-retest reliability via telephone interviews. Convergent validity of the MMAS-8 against a four-item MMAS, correlations with HbA1c levels and construct validity of the MMAS-8 were evaluated. Results In total, 317 patients were included; 70 completed the 2-week test–retest interview. Internal consistency reliability was moderate and test–retest reliability of the MMAS-8 was excellent, although a ceiling effect was detected. Good convergent validity was shown by the high correlation of the new scale scores with the original MMAS-4. A significant association was found between MMAS-8 scores and HbA1c levels. Using glycaemic control as a gold standard, sensitivity was 74.1% and specificity was 38.3%. Explanatory factor analysis identified three dimensions of the scale. Conclusions In light of acceptable reliability and validity, the MMAS-8 is a simple and quick method for the assessment of medication adherence among patient with type 2 diabetes mellitus, in a busy clinic setting.
Endothelins Promote the Activation of Astrocytes in Rat Neostriatum through ETB Receptors

The effects of endothelin (ET)‐3 and an ETB receptor agonist on astrocytic activation in rat caudate putamen were examined by an immunohistochemical staining of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes. A single injection of 40 pmol ET‐3 into rat caudate putamen increased the number of GFAP positive cells compared to that in the contralateral saline‐injected side. Ala1,3,11,15‐ET‐1 (40 pmol), an ETB receptor agonist, also increased the number of striatal GFAP positive cells. The increases in GFAP positive cells were maximum (about 150% of the control side) in 1–2 weeks after injections of the ETs, and then reduced in 4 weeks. A continuous infusion of BQ788, an ETB receptor antagonist (23 nmol/day), into the lateral ventricle of the cerebrum antagonized the effect of Ala1,3,11,15‐ET‐1, while 80788 also reduced the number of GFAP positive cells in saline‐injected caudate putamen. Intrastriatal injection of 40 pmol Ala1,3,11,15‐ET‐1 did not affect the number of cells stained by B4 isolectin from Griffonia simplicifolia, which labels activated microglia/macrophages. Intraperitoneal administration of 5 mg/kg per day chloroquine and 0.2 mg/kg per day colchicine did not affect the action of Ala1,3,11,15‐ET‐1. These results suggest that activation of ETB receptors is involved in the induction of reactive astrocytes.