Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison Between Trophic Positions in the Barents Sea Estimated From Stable Isotope Data and a Mass Balance Model

The trophic position concept is central in system ecology, and in this study, trophic position (TP) estimates from stable-isotopes and an Ecopath mass-balance food web model for the Barents Sea were compared. Two alternative models for estimating TP from stable isotopes, with fixed or scaled trophic fractionation were applied. The mass-balance model was parametrized and balanced for year 2000, was comprised of 108 functional groups (Gs), and was based on biomass and diet data largely based on predator stomach data. Literature search for the Barents Sea Large Marine Ecosystem revealed 93 sources with stable isotope data (δ15N values) for 83 FGs, and 25 of the publications had trophic position estimated from nitrogen stable isotopes. Trophic positions estimated from the mass-balance model ranged to 5.1 TP and were highly correlated with group mean δ15N values, and also highly correlated with the original literature estimates of trophic positions from stable isotopes. On average, TP from the mass-balance model was 0.1 TP higher than the original literature TP estimates (TPSIR) from stable isotopes. A trophic enrichment factor (TEF) was estimated assuming fixed fractionation and minimizing differences between trophic positions from Ecopath and TP predicted from δ15N values assuming a baseline value for δ15N calculated for pelagic particulate organic matter at a baseline TP of 1.0. The estimated TEF of 3.0‰ was lower than the most commonly used TEF of 3.4 and 3.8‰ in the literature. The pelagic whales and pelagic invertebrates functional groups tended to have higher trophic positions from Ecopath than from stable isotopes while benthic invertebrate functional groups tended to show an opposite pattern. Trophic positions calculated using the scaled trophic fractionation approach resulted in lower TP than from Ecopath for intermediate TPs and also a larger TP range in the BS. It is concluded that TPs estimated from δ15N values using a linear model compared better to the Ecopath model than the TPs from scaled fractionation approach.
Simulation Modeling of Reduced Glycosylation Effects on Potassium Channels of Mouse Cardiomyocytes

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure and the primary reason for heart transplantation; upward of 70% of DCM cases are considered idiopathic. Our in-vitro experiments showed that reduced hybrid/complex N-glycosylation in mouse cardiomyocytes is linked with DCM. Further, we observed direct effects of reduced N-glycosylation on Kv gating. However, it is difficult to rigorously determine the effects of glycosylation on Kv activity, because there are multiple Kv isoforms in cardiomyocytes contributing to the cardiac excitation. Due to complex functions of Kv isoforms, only the sum of K+ currents (IKsum) can be recorded experimentally and decomposed later using exponential fitting to estimate component currents, such as IKto, IKslow, and IKss. However, such estimation cannot adequately describe glycosylation effects and Kv mechanisms. Here, we propose a framework of simulation modeling of Kv kinetics in mouse ventricular myocytes and model calibration using the in-vitro data under normal and reduced glycosylation conditions through ablation of the Mgat1 gene (i.e., Mgat1KO). Calibrated models facilitate the prediction of Kv characteristics at different voltages that are not directly observed in the in-vitro experiments. A model calibration procedure is developed based on the genetic algorithm. Experimental results show that, in the Mgat1KO group, both IKto and IKslow densities are shown to be significantly reduced and the rate of IKslow inactivation is much slower. The proposed approach has strong potential to couple simulation models with experimental data for gaining a better understanding of glycosylation effects on Kv kinetics.
Efficacy and tolerability of switching to ziprasidone from olanzapine, risperidone or haloperidol: an international, multicenter study

To compare the effectiveness of a switch from haloperidol (N=99), olanzapine (N=82), or risperidone (N=104) to 12 weeks of treatment with 80–160 mg/day ziprasidone in patients with stable schizophrenia or schizoaffective disorder. Stable outpatients with persistent symptoms or troublesome side effects were switched using one of three 1-week taper/switch strategies as determined by the investigator. Efficacy was assessed using the Brief Psychiatric Rating Scale score, Clinical Global Impression, Positive and Negative Symptom Scale, Montgomery–Åsberg Depression Rating Scale, and the Global Assessment of Functioning Scale, and tolerability by using standard measures of weight change, extrapyramidal symptoms, and laboratory findings. Suboptimal efficacy was the primary reason for switching. The preferred switch strategy was immediate discontinuation, and the preferred dosing regimen was 120 mg/day. Completer rates were 68, 60, and 86% in the haloperidol, risperidone, and olanzapine pre-switch groups, respectively. At week 12, a switch to ziprasidone resulted in statistically significant improvement from baseline on the Brief Psychiatric Rating Scale score, Clinical Global Impression-Improvement, Positive and Negative Symptom Scale, and Global Assessment of Functioning scales, reduction in extrapyramidal symptoms and a neutral impact on metabolic parameters. Switch from olanzapine and risperidone resulted in weight reduction and from haloperidol in some weight increase. In conclusion, oral ziprasidone of 80–160 mg/day with food was a clinically valuable treatment option for stable patients with schizophrenia or schizoaffective disorder experiencing suboptimal efficacy or poor tolerability with haloperidol, olanzapine, or risperidone.
V4Miner, un environnement de programmation visuelle pour la fouille de données

Nous presentons un nouvel environnement de programmation visuelle (V4Miner) pour l'extraction interactive de connaissances a partir de donnees. La plate-forme utilise simultanement un ensemble de methodes de visualisation et d'apprentissage automatique permettant de decouvrir de maniere intuitive, interactive et retroactive des connaissances. La tâche de fouille est exprimee sous la forme d'un flot graphique de donnees ou une methode est representee par un composant graphique de JavaBeans, la communication entre les methodes se base sur un bus de donnees. L'utilisateur peut creer et controler totalement le processus d'extraction de connaissances sans aucune programmation. Notre plate-forme de programmation visuelle permet d'une part de reduire la complexite d'une tâche de fouille de donnees et d'autre part d'ameliorer la qualite et la comprehensibilite des resultats obtenus. Des premiers resultats sont presentes sur des ensembles de donnees du Kent Ridge Bio Medical Dataset Repository.
Design and Characterization of Libraries of Molecular Fragments for Use in NMR Screening against Protein Targets

We have designed four generations of a low molecular weight fragment library for use in NMR-based screening against protein targets. The library initially contained 723 fragments which were selected manually from the Available Chemicals Directory. A series of in silico filters and property calculations were developed to automate the selection process, allowing a larger database of 1.79 M available compounds to be searched for a further 357 compounds that were added to the library. A kinase binding pharmacophore was then derived to select 174 kinase-focused fragments. Finally, an additional 61 fragments were selected to increase the number of different pharmacophores represented within the library. All of the fragments added to the library passed quality checks to ensure they were suitable for the screening protocol, with appropriate solubility, purity, chemical stability, and unambiguous NMR spectrum. The successive generations of libraries have been characterized through analysis of structural properties (molecular weight, lipophilicity, polar surface area, number of rotatable bonds, and hydrogen-bonding potential) and by analyzing their pharmacophoric complexity. These calculations have been used to compare the fragment libraries with a drug-like reference set of compounds and a set of molecules that bind to protein active sites. In addition, an analysis of the overall results of screening the library against the ATP binding site of two protein targets (HSP90 and CDK2) reveals different patterns of fragment binding, demonstrating that the approach can find selective compounds that discriminate between related binding sites.
Comprehensive Metabolomics and Network Pharmacology to Explore the Mechanism of 5-Hydroxymethyl Furfural in the Treatment of Blood Deficiency Syndrome

Radix Rehmanniae (RR, from Radix Rehmanniae (Gaertn.) DC. ) is a natural medicine used in traditional Chinese medicine (TCM) since ancient times for the treatment of blood disorders. RR is steamed to get Rehmanniae Radix Praeparata (RP), which has a tonic effect on blood; the content of 5-hydromethylfurfural (5-HMF) increases more than four times after steaming. Studies have shown that 5-HMF has positive pharmacological effects on cardiovascular and hematological disorders. This study aimed to explore and verify the impact of 5-HMF on rats with chemotherapy-induced blood deficiency syndrome (BDS). Rats were given cyclophosphamide (CP) and acetophenhydrazine (APH) to induce BDS, the coefficients of some organs (liver, spleen, and kidney) were measured, and a routine blood test examined the coefficients of several peripheral blood cells. Metabolomics and network pharmacology were combined to find important biomarkers, targets, and pathways. Western blot was used to detect the expression of CYP17A1 and HSD3B1 proteins in the spleen. All these findings suggested that the 5-HMF significantly increased the number of peripheral blood cells and reversed splenomegaly in rats. In addition, 5-HMF upregulated CYP17A1 and HSD3B1 protein expression in splenic tissues. Also, 5-HMF ameliorated chemotherapy-induced BDS in rats, and its therapeutic mechanism might depend on steroid hormone biosynthesis and other pathways. It acts on blood deficiency via multiple targets and pathways, which is unique to Chinese medicine.
‘Hyper-priming’ in thought-disordered schizophrenic patients

Background. A number of studies have suggested that indirect semantic priming is enhanced in thought-disordered schizophrenics. However, research on direct semantic priming has produced conflicting results. The aim of the present study was to resolve some of the ambiguities of previous findings. Methods. For the present study, 44 schizophrenic patients were split according to the presence of associative loosening into a positive thought-disordered (TD) and non-positive thought-disordered (NTD) group. Thirty healthy subjects and 36 psychiatric patients served as controls. Results. Schizophrenics displayed increased indirect semantic priming compared with psychiatric controls. When subtyping the sample, TD-patients exhibited significantly enhanced indirect semantic priming compared with healthy and psychiatric controls as well as NTD-patients. Overall slowing was found to be independent of priming effects. Medication, age and chronicity of the schizophrenic illness did not modulate priming. Conclusions. In line with Spitzer and Maher it is inferred that disinhibited semantic networks underlie formal thought disorder in schizophrenia. For future research, it would be appropriate to: employ indirect semantic priming rather than direct semantic priming conditions; and, pay more attention to potential moderators of the priming effect, most importantly, the prime display duration and the length of the stimulus onset asynchrony.
Prevalence of alcohol dependence and abuse in a general hospital; sensitivity and specificity of MAST.

Aim: Alcohol abuse and dependence is an important public health concern in most countries. It is also a big problem among the hospitalized patients. Method: This study was undertaken to determine the number of the patients with alcohol related problems in a general hospital sample, to compare the prevalence rate among clinics, to determine the sensitivity and specificity of MAST (Michigan Alcoholism Screening Test) for an inpatient sample. The data were collected from 13 inpatient clinics of Ankara Numune Research and Training Hospital. Result: A sample of 800 patients was enrolled in the study. 60 patients were (%7,5) diagnosed alcohol addiction and 11 were (%1,4) diagnosed as alcohol abuse. Alcohol addiction was most common in gastroenterology clinic. MAST sensitivity and specificity were found 0,74 and 0,98 respectively. Conclusion: MAST might be a useful instrument for screening alcohol related problems in a general hospital setting.
Modélisation et résolution de grands problèmes stochastiques combinatoires : application à la gestion de production d'électricité

La Programmation Lineaire en Nombres Entiers (PLNE) est couramment utilisee pour modeliser des problemes d'optimisation du monde industriel, de par la facilite a modeliser des problemes complexes d'optimisation et par l’existence d’une resolution generique par l'algorithme de Branch&Bound (B&B). La resolution B&B est souvent limitee pour des problemes de taille reelle, les methodes heuristiques sont alors utilisees pour trouver des solutions de bonne qualite sans avoir de preuve d'optimalite. Cette these etudie les limites de la resolution exacte et des heuristiques sur des problemes industriels d'EDF, en vue de leur insertion dans le processus decisionnel operationnel. L'application principale concerne la planification des arrets de maintenance et de rechargement des centrales nucleaires, sujet du Challenge ROADEF 2010. Nous avons aussi traite un probleme de production journaliere d'un parc thermique a flammes. La methodologie suivie est analogue pour les deux cas. On modelise tout d'abord le probleme avec une formulation compacte PLNE, pour en analyser les limites de la resolution frontale, avant d’envisager des methodes de decomposition. On derive ensuite les methodes exactes en matheuristiques pour resoudre des instances de taille reelle. Dans cette optique, l'hybridation de Variable Neighborhood Search (VNS) avec des voisinages definis par PLNE a donne des resultats tres probants sur les deux problemes en termes de qualites de solutions. Le fait d'avoir travaille avec des methodes exactes a permis egalement de chiffrer l'impact d'hypotheses de resolutions, de repondre a des considerations operationnelles, mais egalement d'obtenir des bornes inferieures.
Imaging FRET standards by steady‐state fluorescence and lifetime methods

Imaging fluorescence resonance energy transfer (FRET) between molecules labeled with fluorescent proteins is emerging as a powerful tool to study changes in ions, ligands, and molecular interactions in their physiological cellular environment. Different methods use either steady‐state fluorescence properties or lifetime to quantify the FRET rate. In addition, some provide the absolute FRET efficiency whereas others are simply a relative index very much influenced by the actual settings and instrumentation used, which makes the interpretation of a given FRET rate very difficult. The use and exchange of FRET standards in laboratories using these techniques would help to overcome this drawback. We report here the construction and systematic evaluation of FRET standard probes of varying FRET efficiencies. The standards for intramolecular FRET were protein fusions of the cyan and yellow variants of A. victoria green fluorescent protein (ECFP and citrine) joined by short linkers or larger protein spacers, or ECFP tagged with a tetracysteine motif and labeled with the biarsenical fluorochrome, FlAsH. Negative and positive controls of intermolecular FRET were also used. We compared these FRET standards with up to four FRET quantification methods: ratioing of acceptor to donor emission, donor intensity recovery upon acceptor photobleach, sensitized emission after spectral unmixing of raw images, and fluorescence lifetime imaging (FLIM). The latter was obtained with a frequency‐domain setup able to provide high quality lifetime images in less than a second, and is thus very well suited for live cell studies. The FRET rates or indexes of the standards were in good agreement regardless of the method used. For the CFP‐tetraCys/FlAsH pair, the rate calculated from CFP quenching was faster than that obtained by FLIM. Microsc. Res. Tech., 2007. © 2007 Wiley‐Liss, Inc.
A Phase I study of cis‐malonato[(4R,5R)‐4,5‐bis(aminomethyl)‐1,3‐dioxolane] platinum(II) in patients with advanced malignancies

A Phase I study of cis‐malonato[(4R,5R)‐4,5‐bis(aminomethyl)‐1,3‐dioxolane] platinum(II) (SKI 2053R), a new platinum derivative, was performed to determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLTs), and the pharmacokinetic profile of SKI 2053R in patients with advanced, refractory malignancies.
The β-Barrel Outer Membrane Protein Assembly Complex of Neisseria meningitidis

ABSTRACT The evolutionarily conserved protein Omp85 is required for outer membrane protein (OMP) assembly in gram-negative bacteria and in mitochondria. Its Escherichia coli homolog, designated BamA, functions with four accessory lipoproteins, BamB, BamC, BamD, and BamE, together forming the β-barrel assembly machinery (Bam). Here, we addressed the composition of this machinery and the function of its components in Neisseria meningitidis, a model organism for outer membrane biogenesis studies. Analysis of genome sequences revealed homologs of BamC, BamD (previously described as ComL), and BamE and a second BamE homolog, Mlp. No homolog of BamB was found. As in E. coli, ComL/BamD appeared essential for viability and for OMP assembly, and it could not be replaced by its E. coli homolog. BamE was not essential but was found to contribute to the efficiency of OMP assembly and to the maintenance of OM integrity. A bamC mutant showed only marginal OMP assembly defects, but the impossibility of creating a bamC bamE double mutant further indicated the function of BamC in OMP assembly. An mlp mutant was unaffected in OMP assembly. The results of copurification assays demonstrated the association of BamC, ComL, and BamE with Omp85. Semi-native gel electrophoresis identified the RmpM protein as an additional component of the Omp85 complex, which was confirmed in copurification assays. RmpM was not required for OMP folding but stabilized OMP complexes. Thus, the Bam complex in N. meningitidis consists of Omp85/BamA plus RmpM, BamC, ComL/BamD, and BamE, of which ComL/BamD and BamE appear to be the most important accessory components for OMP assembly.
The role of chloride anion and CFTR in killing of Pseudomonas aeruginosa by normal and CF neutrophils

Chloride anion is essential for myeloperoxidase (MPO) to produce hypochlorous acid (HOCl) in polymorphonuclear neutrophils (PMNs). To define whether chloride availability to PMNs affects their HOCl production and microbicidal capacity, we examined how extracellular chloride concentration affects killing of Pseudomonas aeruginosa (PsA) by normal neutrophils. PMN‐mediated bacterial killing was strongly dependent on extracellular chloride concentration. Neutrophils in a chloride‐deficient medium killed PsA poorly. However, as the chloride level was raised, the killing efficiency increased in a dose‐dependent manner. By using specific inhibitors to selectively block NADPH oxidase, MPO, and cystic fibrosis transmembrane conductance regulator (CFTR) functions, neutrophil‐mediated killing of PsA could be attributed to three distinct mechanisms: CFTR‐dependent and oxidant‐dependent; chloride‐dependent but not CFTR‐ and oxidant‐dependent; and independent of any of the tested factors. Therefore, chloride anion is involved in oxidant‐ and nonoxidant‐mediated bacterial killing. We previously reported that neutrophils from CF patients are defective in chlorination of ingested bacteria [ 1 ], suggesting that the chloride channel defect might impair the MPO‐hydrogen peroxide‐chloride microbicidal function. Here, we compared the competence of killing PsA by neutrophils from normal donors and CF patients. The data demonstrate that the killing rate by CF neutrophils was significantly lower than that by normal neutrophils. CF neutrophils in a chloride‐deficient environment had only one‐third of the bactericidal capacity of normal neutrophils in a physiological chloride environment. These results suggest that CFTR‐dependent chloride anion transport contributes significantly to killing PsA by normal neutrophils and when defective as in CF, may compromise the ability to clear PsA.
Pharmacogenetic Treatments for Drug Addiction: Cocaine, Amphetamine and Methamphetamine

Background: Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders. Objectives: To review how genetic variation affects responses to cocaine, amphetamine, and methamphetamine and how this information may guide pharmacotherapy. Methods: We performed a cross-referenced literature search on pharmacogenetics, cocaine, amphetamine, and methamphetamine. Results: We describe functional genetic variants for enzymes dopamine-beta-hydroxylase (DβH), catechol-O-methyltransferase (COMT), and dopamine transporter (DAT1), dopamine D4 receptor, and brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP; C-1021T) in the DβH gene is relevant to paranoia associated with disulfiram pharmacotherapy for cocaine addiction. Individuals with variable number tandem repeats (VNTR) of the SLC6A3 gene 3′-untranslated region polymorphism of DAT1 have altered responses to drugs. The 10/10 repeat respond poorly to methylphenidate pharmacotherapy and the 9/9 DAT1 variant show blunted euphoria and physiological response to amphetamine. COMT, D4 receptor, and BDNF polymorphisms are linked to methamphetamine abuse and psychosis. Conclusions: Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting DβH and DAT1 respectively. Altered subjective effects for amphetamine in DAT1 VNTR variants suggest a ‘protected’ phenotype. Scientific Significance: Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment.
A Free Market Economy Model for Resource Management in Wireless Sensor Networks

This paper presents a free market economy model that can be used to facilitate fully distributed autonomous control of resources in massive heterogeneous wireless sensor networks (WSNs). In the future, it is expected that WSNs will exist as part of the global Internet of Things (IoT), and different WSNs can work together in a massive network of heterogeneous WSNs in order to solve common problems. Control of valuable processing, sensing and communication resources, determining which nodes will remain awake during specific time periods in order to provide sensing services, and determining which nodes will forward other nodes’ packets are difficult problems that must be dealt with. It is proposed that just as the free market economy model enables the global human society to function reasonably well when individuals simply attempt to trade money and services in order to maximize their individual profits, and a similar model and mechanism should enable a massive network of heterogeneous WSNs to function well in a fully distributed autonomous manner. The main contributions of this paper are the introduction of the free market economy model for use with WSNs, the formal definition of a maximum profit price problem for multihop packet relaying, and the proposal of a distributed genetic algorithm for the solution of the maximum profit price problem. Simulation results show that the proposed distributed solution produces results that are 70% - 80% similar to a pareto optimal solution for this problem.