Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure-Function Correlation in Glycine Oxidase from Bacillus subtilis*

Structure-function relationships of the flavoprotein glycine oxidase (GO), which was recently proposed as the first enzyme in the biosynthesis of thiamine in Bacillus subtilis, has been investigated by a combination of structural and functional studies. The structure of the GO-glycolate complex was determined at 1.8 Å, a resolution at which a sketch of the residues involved in FAD binding and in substrate interaction can be depicted. GO can be considered a member of the “amine oxidase” class of flavoproteins, such as d-amino acid oxidase and monomeric sarcosine oxidase. With the obtained model of GO the monomer-monomer interactions can be analyzed in detail, thus explaining the structural basis of the stable tetrameric oligomerization state of GO, which is unique for the GR2 subfamily of flavooxidases. On the other hand, the three-dimensional structure of GO and the functional experiments do not provide the functional significance of such an oligomerization state; GO does not show an allosteric behavior. The results do not clarify the metabolic role of this enzyme in B. subtilis; the broad substrate specificity of GO cannot be correlated with the inferred function in thiamine biosynthesis, and the structure does not show how GO could interact with ThiS, the following enzyme in thiamine biosynthesis. However, they do let a general catabolic role of this enzyme on primary or secondary amines to be excluded because the expression of GO is not inducible by glycine, sarcosine, or d-alanine as carbon or nitrogen sources.
Medical diagnosis lost in translation – Analysis of uncertainty and negation expressions in English and Swedish clinical texts

In the English clinical and biomedical text domains, negation and certainty usage are two well-studied phenomena. However, few studies have made an in-depth characterization of uncertainties expressed in a clinical setting, and compared this between different annotation efforts. This preliminary, qualitative study attempts to 1) create a clinical uncertainty and negation taxonomy, 2) develop a translation map to convert annotation labels from an English schema into a Swedish schema, and 3) characterize and compare two data sets using this taxonomy. We define a clinical uncertainty and negation taxonomy and a translation map for converting annotation labels between two schemas and report observed similarities and differences between the two data sets.
Polynomial ring calculus for many-valued logics

This paper discusses a new algebraic proof method for general sentential logics, which is particularly apt for finitely-many-valued logics and for PC, based on reducing polynomials over finite fields. The method can also be extended to cover certain non-finitely valued logics and non-truth-functional logics as well, provided they can be characterized by two-valued dyadic semantics. The resulting mechanizable proof method introduced here is of interest for automatic proof theory, and seems also to be appropriate for investigating questions on complexity.
Association between depression and insomnia subtypes: a longitudinal study on the elderly in Japan.

STUDY OBJECTIVE To examine the association between depression and three subtypes of insomnia, namely, difficulty initiating sleep (DIS), early morning awakening (EMA), and difficulty maintaining sleep (DMS). DESIGN Cross-sectional and longitudinal study. SETTING Community dwellers in Japan. PARTICIPANTS Nationally representative samples of adults aged 65 and over (total N=4,997) were selected by a multistage stratified random sampling method in 1999 and were interviewed face-to-face in 1999, 2001, 2003, and 2006. Those who responded to the 3rd survey conducted in 2003 and the 4th survey conducted in 2006 were used in this study. MEASUREMENT AND RESULTS Depression was evaluated according to the 11-item short form of the CES-D scale at 2 points in time. Insomnia subtypes were assessed by self-reported measures. A logistic regression was employed to examine the association between insomnia subtypes and the presence of depression, controlling for relevant factors. A cross-sectional analysis based on the 2003 data demonstrated statistically significant odds ratios (ORs) for DIS and EMA. In the longitudinal study, DIS at the time of the 3rd survey was found to be significantly related to the presence of depression at the time of the 4th survey, with an odds ratio (95%CI) of 1.592 (1.012 to 2.504). EMA (OR 1.070; 95% CI, 0.664 to 1.723) and DMS (OR 1.215; 95% CI, 0.860 to 1.716), however, were not found to be significantly related to the presence of depression. CONCLUSION The longitudinal study revealed a statistically significant relationship, controlling for other relevant factors, between DIS and the presence of depression three years later, but not between EMA or DMS and depression. Based on our findings, we recommend that the association between insomnia subtypes and depression be studied longitudinally in clinical settings.
Anthropometry and competitive sport in Hungary

Sport anthropometry has developed from the techniques and results of general physical anthropology. Thus, in the beginning, the main questions and methods were also similar to those of general physical anthropology, only the investigated subjects were taken of a different population. Following the initial, mainly descriptive and comparative, phases of data manipulation, the predictive functions of sport anthropometry have also developed. Continuous progress in the methods of sport training, consequently in athletic performances and the changes in athletic rules and equipment, have developed a need for the investigation of such (indirect) human biological factors that may have a role in competitive sport performance. The analytical approach in sport anthropometry has only become dominant during the past 10 years. A clear recognition of the relationship between structural charac- teristics and functions can - beyond the scientific importance of the matter - help sports practice in both the selection of talented youngsters and the process of athletic preparation. The most recent tendencies in sport anthropometry attempt to answer such questions that cannot be connected to the direct and traditional measurements of physical anthropology. An analysis of the relationship between inherited characteristics (physique and metabolic pathways, functional regulation during exercise, etc.) means a new challenge for sport anthropometry.
Microduplications in an autism multiplex family narrow the region of susceptibility for developmental disorders on 15q24 and implicate 7p21

Copy number variations (CNVs) play a crucial role in the intricate genetics of autism spectrum disorders. A region on chromosome 15q24 vulnerable to both deletions and duplications has been previously implicated in a range of phenotypes including autism, Asperger's syndrome, delayed development, and mild to severe mental retardation. Prior studies have delineated a minimal critical region of approximately 1.33 Mb. In this study, a multiplex autism family was evaluated for CNVs using genotyping data from the Illumina 1 M BeadChip and analyzed with the PennCNV algorithm. Variants were then identified that co‐segregate with autism features in this family. Here, we report autistic first cousins who carry two microduplications concordant with disease. Both duplications were inherited maternally and found to be identical by descent. The first is an approximately 10,000 base pair microduplication within the minimal region on 15q24 that falls across a single gene, ubiquitin‐like 7. This is the smallest duplication in the region to result in a neuropsychiatric disorder, potentially narrowing the critical region for susceptibility to developmental and autism spectrum disorders. The second is a novel, 352 kb tandem duplication on 7p21 that replicates part of the neurexophilin 1 and islet cell autoantigen 1 genes. The breakpoint junction falls within the intronic regions of these genes and demonstrates a microhomology of four base pairs. Each of these microduplications may contribute to the complex etiology of autism spectrum disorders. © 2011 Wiley‐Liss, Inc.
Quantitative Determination of Pravastatin in Pharmaceutical Dosage Forms by High-Performance Liquid Chromatography with Ultraviolet Detection

A simple, sensitive and precise high-performance liquid chromatographic formulations assay for pravastatin (PVS) is described. Good chromatographic separation was achieved using a Teknokroma C8 (5 μm, 25cm × 4.6mm) column and a mobile phase consisting of 10mM ammonium acetate: methanol: triethylamine (40:60:0.17 v/v/v) while at a flow-rate of 1.0 mL min-1. PVS was detected at 239 nm and was eluted 2.15 min after injection. No endogenous substances were found to interfere. No internal standard was required. Linearity range for PVS was 0.4-1000 μg mL-1. The determination of intra- and inter-day precision (RSD) was less than 2.94 and 2.97%, at all concentration levels. Statistical treatment of the experimental results indicates that the method is precise and accurate. The proposed method was applied to the determination of the component in commercial tablets with no interference from the excipients. A comparative study between the suggested procedure and the pharmacopoeial method for this compound in the tablets showed no significant difference between the two methods.
A high-resolution morphological and ultrastructural map of anterior sensory cilia and glia in Caenorhabditis elegans

Many primary sensory cilia exhibit unique architectures that are critical for transduction of specific sensory stimuli. Although basic ciliogenic mechanisms are well described, how complex ciliary structures are generated remains unclear. Seminal work performed several decades ago provided an initial but incomplete description of diverse sensory cilia morphologies in C. elegans. To begin to explore the mechanisms that generate these remarkably complex structures, we have taken advantage of advances in electron microscopy and tomography, and reconstructed three-dimensional structures of fifty of sixty sensory cilia in the C. elegans adult hermaphrodite at high resolution. We characterize novel axonemal microtubule organization patterns, clarify structural features at the ciliary base, describe new aspects of cilia–glia interactions, and identify structures suggesting novel mechanisms of ciliary protein trafficking. This complete ultrastructural description of diverse cilia in C. elegans provides the foundation for investigations into underlying ciliogenic pathways, as well as contributions of defined ciliary structures to specific neuronal functions. DOI: http://dx.doi. org/10.7554/eLife.01948. 001
Effect of open-label infusion of an apolipoprotein A-I-containing particle ( CER-001 ) on reverse cholesterol transport and artery wall thickness in patients with familial hypo-alphalipoproteinemia

Background Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of High-density lipoprotein (HDL). Patients with the orphan disease familial hypoalphalipoproteinemia (FHA) are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label, uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apolipoprotein-AI containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Methods Subjects received 20 infusions of CER-001 (8mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE) and carotid artery wall dimension by MRI and artery wall inflammation by FDG-PET/CT scan. Results We included seven FHA patients (HDL-c 13.8 [1.8 – 29.1] mg/dl; apoA-I 28.7 [7.9 – 59.1] mg/dl). Following 9 infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 mg/dl and 16.1 mg/dl (p=0.018). CER-001 induced a 44% relative increase (p=0.018) in in vitro cellular cholesterol efflux with a trend towards increased FSE (p=0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared to baseline from 25.0 to 22.8 mm (p=0.043) and target-to-background ratio from 2.04 to 1.81 (p=0.046). Conclusion In FHA-subjects, CER-001 stimulates cholesterol mobilisation and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients. Word count: 209 by gest, on N ovem er 0, 2017 w w w . j.org D ow nladed fom
Interpretable Policies for Dynamic Product Recommendations

In many applications, it may be better to compute a good interpretable policy instead of a complex optimal one. For example, a recommendation engine might perform better when accounting for user profiles, but in the absence of such loyalty data, assumptions would have to be made that increase the complexity of the recommendation policy. A simple greedy recommendation could be implemented based on aggregated user data, but another simple policy can improve on this by accounting for the fact that users come from different segments of a population. In this paper, we study the problem of computing an optimal policy that is interpretable. In particular, we consider a policy to be interpretable if the decisions (e.g., recommendations) depend only on a small number of simple state attributes (e.g., the currently viewed product). This novel model is a general Markov decision problem with action constraints over states. We show that this problem is NP hard and develop a Mixed Integer Linear Programming formulation that gives an exact solution when policies are restricted to being deterministic. We demonstrate the effectiveness of the approach on a real-world business case for a European tour operator's recommendation engine.
The effects of medication and current mood upon facial emotion recognition: findings from a large bipolar disorder cohort study

Objectives: Emotional processing abnormalities have been implicated in bipolar disorder (BD) but studies are typically small and uncontrolled. Here, facial expression recognition was explored in a large and naturalistically recruited cohort of BD patients. Methods: 271 patients with BD completed the facial expression recognition task. The effects of current medication together with the influence of current mood state and diagnostic subtype were assessed whilst controlling for the effects of demographic variables. Results: Patients who were currently receiving treatment with lithium demonstrated significantly poorer accuracy in recognising angry faces, an effect that held in a monotherapy sub-analysis comparing those participants on lithium only and those who were medication-free. Accuracy in recognising angry faces was also lower amongst participants currently taking dopamine antagonists (antipsychotics). Higher levels of current depressive symptoms were linked to poorer accuracy at identifying happy faces. Conclusion: Use of lithium and possibly dopamine antagonists may be associated with reduced processing of anger cues in BD. Findings support the existence of mood-congruent negative biases associated with depressive symptoms in BD. Observational cohort studies provide opportunities to explore the substantial effects of demographic, psychometric and clinical variables on cognitive performance and emotional processing.
Effects of the Peroxisome Proliferator-Activated Receptor-γ Agonist Pioglitazone on Peripheral Vessel Function and Clinical Parameters in Nondiabetic Patients: A Double-Center, Randomized Controlled Pilot Trial

Objective: Despite the advanced therapy with statins, antithrombotics, and antihypertensive agents, the medical treatment of atherosclerotic disease is less than optimal. Therefore, additional therapeutic antiatherosclerotic options are desirable. This pilot study was performed to assess the potential antiatherogenic effect of the peroxisome proliferator-activated receptor-γ agonist pioglitazone in nondiabetic patients. Methods: A total of 54 nondiabetic patients were observed in a prospective, double-blind, placebo-controlled study. Patients were randomized to pioglitazone or placebo. The following efficacy parameters were determined by serial analyses: artery pulse wave analysis and carotid-femoral pulse wave velocity (PWV), static and dynamic retinal vessel function, and the common carotid intima-media thickness (IMT). The main secondary endpoint was the change in different biochemical markers. Results: After 9 months, no relevant differences could be determined in the two treatment groups in PWV (pioglitazone 14.3 ± 4.4 m/s vs. placebo 14.2 ± 4.2 m/s), retinal arterial diameter (pioglitazone 112.1 ± 23.3 µm vs. placebo 117.9 ± 21.5 µm) or IMT (pioglitazone 0.85 ± 0.30 mm vs. placebo 0.79 ± 0.15 mm). Additionally, there were no differences in the change in biochemical markers like cholesteryl ester transfer protein, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein or white blood cell count. Conclusions: Treatment with a peroxisome proliferator-activated receptor-γ agonist in nondiabetic patients did not improve the function of large and small peripheral vessels (PPP Trial, clinicaltrialsregister.eu: 2006-000186-11).
FASY: a fuzzy-logic based tool for analog synthesis

A CAD tool for analog circuit synthesis is presented. This tool, called FASY, uses fuzzy-logic based reasoning to select one topology among a fixed set of alternatives. For the selected topology, a two-phase optimizer sizes all elements to satisfy the performance constraints minimizing a cost function. In FASY, the decision rules used in the topology selection process are introduced by an expert designer or automatically generated by means of a learning process that uses the optimizer mentioned above. The capability of learning topology selection rules by experience, is unique in FASY. Practical examples demonstrate the tool ability of this tool to learn topology selection rules and to synthesize analog cells with different circuit topologies.
LIF Upregulates Expression of NK-1R in NHBE Cells

Leukemia inhibitory factor (LIF), a cytokine at the interface between neurobiology and immunology, is mainly mediated through JAK/STAT pathway and MAPK/ERK pathway. Evidence suggested LIF is related to the higher expression of neurokinin-1 receptor (NK-1R) in asthma. In this study, the immunohistochemistry stain showed the expressions of NK-1R, LIF, p-STAT3, and p-ERK1/2 in the lung tissues of allergic rats were increased compared with the controls, and the main positive cell type was airway epithelial cell. Normal human bronchial epithelial cells were treated with LIF in the presence or absence of AG490 (JAK2 inhibitor), PD98059 (MEK inhibitor), and the siRNA against STAT3. Western blot and RT-PCR indicated that LIF induced the expression of NK-1R, which was inhibited by the inhibitors mentioned above. No significant interaction was found between JAK/STAT pathway and MAPK/ERK pathway. In summary, bronchial epithelial cell changes in asthma are induced by LIF which promotes the expression of NK-1R, and JAK/STAT pathway and MAPK/ERK pathway may participate in this process.
Measuring dissimilarity between respiratory effort signals based on uniform scaling for sleep staging

Polysomnography (PSG) has been extensively studied for sleep staging, where sleep stages are usually classified as wake, rapid-eye-movement (REM) sleep, or non-REM (NREM) sleep (including light and deep sleep). Respiratory information has been proven to correlate with autonomic nervous activity that is related to sleep stages. For example, it is known that the breathing rate and amplitude during NREM sleep, in particular during deep sleep, are steadier and more regular compared to periods of wakefulness that can be influenced by body movements, conscious control, or other external factors. However, the respiratory morphology has not been well investigated across sleep stages. We thus explore the dissimilarity of respiratory effort with respect to its signal waveform or morphology. The dissimilarity measure is computed between two respiratory effort signal segments with the same number of consecutive breaths using a uniform scaling distance. To capture the property of signal morphological dissimilarity, we propose a novel window-based feature in a framework of sleep staging. Experiments were conducted with a data set of 48 healthy subjects using a linear discriminant classifier and a ten-fold cross validation. It is revealed that this feature can help discriminate between sleep stages, but with an exception of separating wake and REM sleep. When combining the new feature with 26 existing respiratory features, we achieved a Cohen’s Kappa coefficient of 0.48 for 3-stage classification (wake, REM sleep and NREM sleep) and of 0.41 for 4-stage classification (wake, REM sleep, light sleep and deep sleep), which outperform the results obtained without using this new feature.
Metabolic phenotype of clinical and environmental Mycobacterium avium subsp. hominissuis isolates

Background Mycobacterium avium subsp. hominissuis (MAH) is an emerging opportunistic human pathogen. It can cause pulmonary infections, lymphadenitis and disseminated infections in immuno-compromised patients. In addition, MAH is widespread in the environment, since it has been isolated from water, soil or dust. In recent years, knowledge on MAH at the molecular level has increased substantially. In contrast, knowledge of the MAH metabolic phenotypes remains limited. Methods In this study, for the first time we analyzed the metabolic substrate utilization of ten MAH isolates, five from a clinical source and five from an environmental source. We used BIOLOG Phenotype MicroarrayTM technology for the analysis. This technology permits the rapid and global analysis of metabolic phenotypes. Results The ten MAH isolates tested showed different metabolic patterns pointing to high intra-species diversity. Our MAH isolates preferred to use fatty acids such as Tween, caproic, butyric and propionic acid as a carbon source, and L-cysteine as a nitrogen source. Environmental MAH isolates resulted in being more metabolically active than clinical isolates, since the former metabolized more strongly butyric acid (p = 0.0209) and propionic acid (p = 0.00307). Discussion Our study provides new insight into the metabolism of MAH. Understanding how bacteria utilize substrates during infection might help the developing of strategies to fight such infections.