Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigation of the in Vitro Metabolism of the Analgesic Flupirtine

The in vitro metabolism of flupirtine, ethyl-N-[2-amino-6-(4-fluorophenylmethyl-amino)pyridine-3-yl]carbamate, a centrally acting analgesic with muscle tone-reducing activity, was studied. Two flupirtine metabolites were already known: the N-acetylated analog D13223 and 4-fluorohippuric acid. The structure of flupirtine suggested that redox chemistry may play a role in metabolism, and cyclic voltammetry studies showed that the drug undergoes facile and irreversible redox reactions. Thus, oxidative metabolism was investigated first. With CYP3A1-induced rat liver microsomes an 18% turnover of flupirtine and a 20 to 25% turnover of D13223 took place over 30 min, but less than 5% turnover of flupirtine was observed with all human liver microsomal preparations tested, evidence that cytochrome P450 does not contribute appreciably to the metabolism in humans. Likewise, no involvement of human monoamine oxidase (isoforms A and B) was found for either flupirtine or D13223. In contrast, flupirtine was an excellent substrate for both human myeloperoxidase and horse radish peroxidase (HRP). These enzymes produced detectable amounts of oxidation products. Incubations of flupirtine with HRP produced an oxidation product that could be trapped with glutathione, the resulting glutathione conjugate was characterized by mass spectrometry and NMR. Metabolism of D13223 by both peroxidases was also observed but to a much lesser extent. Porcine liver esterases cleave the carbamate group of flupirtine, and both human N-acetyltransferases 1 and 2 acetylated the hydrolysis product, presumably descarboethoxyflupirtine, with nearly equal efficiencies to yield D13223. Incubations of human liver microsomes with flupirtine or the metabolite D13223 together with UDP-glucuronic acid gave two isomeric N-glucuronides in both cases.
Allosteric Ligands for the Corticotropin Releasing Factor Type 1 Receptor Modulate Conformational States Involved in Receptor Activation

Allosteric modulators of G-protein-coupled receptors can regulate conformational states involved in receptor activation ( Mol Pharmacol58:1412-1423, 2000 ). This hypothesis was investigated for the corticotropin-releasing factor type 1 (CRF1) receptor using a novel series of ligands with varying allosteric effect on CRF binding (inhibition to enhancement). For the G-protein-uncoupled receptor, allosteric modulation of CRF binding was correlated with nonpeptide ligand signaling activity; inverse agonists inhibited and agonists enhanced CRF binding. These data were quantitatively consistent with a two-state equilibrium underlying the modulation of CRF binding to the G-protein-uncoupled receptor. We next investigated the allosteric effect on CRF-stimulated G-protein coupling. Ligands inhibited CRF-stimulated cAMP accumulation regardless of their effect on the G-protein-uncoupled state. The modulators reduced CRF Emax values, suggesting that they reduced the efficacy of a CRF-bound active state to couple to G-protein. Consistent with this hypothesis, the modulators inhibited binding to a guanine nucleotide-sensitive state. Together, the results are quantitatively consistent with a model in which 1) the receptor exists in three predominant states: an inactive state, a weakly active state, and a CRF-bound fully active state; 2) allosteric inverse agonists stabilize the inactive state, and allosteric agonists stabilize the weakly active state; and 3) antagonism of CRF signaling results from destabilization of the fully active state. These findings imply that nonpeptide ligands differentially modulate conformational states involved in CRF1 receptor activation and suggest that different conformational states can be targeted in designing nonpeptide ligands to inhibit CRF signaling.
Macro Bending Losses in Single-Cell Kagome-Lattice Hollow-Core Photonic Crystal Fibers

We report on numerical and experimental results on macro bending losses in single-cell Kagome-lattice hollow-core photonic crystal fibers. Fibers with different cladding layer numbers have been investigated. Results show that a cladding with at least two rings produces a reduction in bend sensitivity by more than one order of magnitude relative to a single layer cladding. This result is an original way to confirm the main role played by the inhibiting coupling mechanism in such microstructured fibers.
Growth to Value: Option Exercise and the Cross-Section of Equity Returns

We propose a general equilibrium model to study the link between the cross section of expected returns and book-to-market characteristics. We model two primitive assets: value assets and growth assets that are options on assets in place. The cost of option exercise, which is endogenously determined in equilibrium, is highly procyclical and acts as a hedge against risks in assets in place. Consequently, growth options are less risky than value assets, and the model features a value premium. Our model incorporates long-run risks in aggregate consumption and replicates the empirical failure of the conditional capital asset pricing model (CAPM) prediction. The model also quantitatively accounts for the pattern in mean returns on book-to-market sorted portfolios, the magnitude of the CAPM-alphas, and other stylized features of the cross-sectional data.
Limited-Domain Speech-to-Speech Translation between English and Pashto

This paper describes a prototype system for near-real-time spontaneous, bidirectional translation between spoken English and Pashto, a language presenting many technological challenges because of its lack of resources, including both data and expert knowledge. Development of the prototype is ongoing, and we propose to demonstrate a fully functional version which shows the basic capabilities, though not yet their final depth and breadth.
Tutorial in biostatistics: the self‐controlled case series method

The self‐controlled case series method was developed to investigate associations between acute outcomes and transient exposures, using only data on cases, that is, on individuals who have experienced the outcome of interest. Inference is within individuals, and hence fixed covariates effects are implicitly controlled for within a proportional incidence framework. We describe the origins, assumptions, limitations, and uses of the method. The rationale for the model and the derivation of the likelihood are explained in detail using a worked example on vaccine safety. Code for fitting the model in the statistical package STATA is described. Two further vaccine safety data sets are used to illustrate a range of modelling issues and extensions of the basic model. Some brief pointers on the design of case series studies are provided. The data sets, STATA code, and further implementation details in SAS, GENSTAT and GLIM are available from an associated website. Copyright © 2005 John Wiley & Sons, Ltd.
Nutritional assessment and lipid profile in HIV-infected children and adolescents treated with highly active antiretroviral therapy.

INTRODUCTION HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART) regimens that include a protease inhibitor (PI) can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336), and 136 (63 - 271) versus control group: 54.5 (20 - 162); p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58) and 36 (23 - 43); control 49.5 (34 - 69); p = 0.004]. CONCLUSIONS HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.
A Review of the Development of Information Technology and Education: The Role of Culture

Many studies have highlighted that IT’s impact on learning outcomes depends on many antecedents. Culture has been identified as one such factor. This paper is a synthesis of three domains – IT, education and culture. It first traces the evolution of IT in education and the relationship between learning theories and IT. Subsequently, the role of culture in the field of IT and education is presented. The paper then proposes that instruction be designed in a culturally sensitive manner. Second, understandings of culture should be allowed to grow in conjunction with developments in IT and education. We hope that these suggestions would generate more research and insight on the intersection of IT, education and culture.
TECHNICAL NOTE: Estimating beef-cattle forage demand: Evaluating the animal unit concept

The objective of this experiment was to evaluate the effect of BW and physiological status of a beef animal on forage intake. The experiment was repeated over 2 yr with 6 replications of 3 treatments per year: cow-calf pair (CCP, BW = 629 kg), nonlactating cow (NLC, BW = 503 kg), and yearling steer (YS, BW = 305 kg). The CCP was treated as one unit, with the sum of cow BW and calf BW comprising CCP BW. Calves averaged 42 d of age and 73 kg at the start of the experiment each year. Animals were housed in individual pens and fed grass hay harvested from subirrigated meadow (11% CP) in quantities sufficient for ad libitum intake. Intake of DM, OM, DM that disappeared in vitro, and NDF were greatest (P 0.05) from each other. When expressed as a percentage of metabolic BW (BW0.75), intake of DM, OM, DM that disappeared in vitro, and NDF were greatest (P < 0.01) for CCP, intermediate for NLC, and least for YS. Results indicate that intake differences among cattle of different physiological states should be considered when calculating forage demand for stocking rate or feeding purposes.
Recognising and Treatment Seeking for Acute Bacterial Meningitis in Adults and Children in Resource-Poor Settings: A Qualitative Study

Objective High mortality burden from Acute Bacterial Meningitis (ABM) in resource-poor settings has been frequently blamed on delays in treatment seeking. We explored treatment-seeking pathways from household to primary health care and referral for ABM in Malawi. Design A cross-sectional qualitative study using narrative in-depth interviews, semi-structured interviews and focus group discussions. Participants Adults and children with proven and probable acute bacterial meningitis and/or their carers; adults from urban and peri-urban communities; and primary health care workers (HCW). Setting Queen Elizabeth Central Hospital (QECH), urban and peri-urban private and government primary health centres and communities in Blantyre District, Malawi. Results Whilst communities associated meningitis with a stiff neck, in practice responses focused on ability to recognise severe illness. Misdiagnosis of meningitis as malaria was common. Subsequent action by families depended on the extent to which normal social life was disrupted by the illness and depended on the age and social position of the sufferer. Seizures and convulsions were considered severe symptoms but were often thought to be malaria. Presumptive malaria treatment at home often delayed formal treatment seeking. Further delays in treatment seeking were caused by economic barriers and perceptions of inefficient or inadequate primary health services. Conclusions Given the difficulties in diagnosis of meningitis where malaria is common, any intervention for ABM at primary level must focus on recognising severe illness, and encouraging action at the household, community and primary health levels. Overcoming barriers to recognition and social constraints at community level require broad community-based strategies and may provide a route to addressing poor clinical outcomes.
Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. The Canadian Collaborative Group for research in schizophrenia.

BACKGROUND The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia. METHODS Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment. RESULTS The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test. CONCLUSIONS These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia.
Direct sequencing of human gut virome fractions obtained by flow cytometry

The sequence assembly of the human gut virome encounters several difficulties. A high proportion of human and bacterial matches is detected in purified viral samples. Viral DNA extraction results in a low DNA concentration, which does not reach the minimal limit required for sequencing library preparation. Therefore, the viromes are usually enriched by whole genome amplification (WGA), which is, however, prone to the development of chimeras and amplification bias. In addition, as there is a very wide diversity of gut viral species, very extensive sequencing efforts must be made for the assembling of whole viral genomes. We present an approach to improve human gut virome assembly by employing a more precise preparation of a viral sample before sequencing. Particles present in a virome previously filtered through 0.2 μm pores were further divided into groups in accordance with their size and DNA content by fluorescence activated cell sorting (FACS). One selected viral fraction was sequenced excluding the WGA step, so that unbiased sequences with high reliability were obtained. The DNA extracted from the 314 viral particles of the selected fraction was assembled into 34 contigs longer than 1,000 bp. This represents an increase to the number of assembled long contigs per sequenced Gb in comparison with other studies where non-fractioned viromes are sequenced. Seven of these contigs contained open reading frames (ORFs) with explicit matches to proteins related to bacteriophages. The remaining contigs also possessed uncharacterized ORFs with bacteriophage-related domains. When the particles that are present in the filtered viromes are sorted into smaller groups by FACS, large pieces of viral genomes can be recovered easily. This approach has several advantages over the conventional sequencing of non-fractioned viromes: non-viral contamination is reduced and the sequencing efforts required for viral assembly are minimized.
A review of ‘green’ strategies to prevent or mitigate microbiologically influenced corrosion

Abstract Two approaches to control microbiologically influenced corrosion (MIC) have been developed that do not require the use of biocides. These strategies include the following: i) use of biofilms to inhibit or prevent corrosion, and ii) manipulation (removal or addition) of an electron acceptor, (e.g. oxygen, sulphate or nitrate) to influence the microbial population. In both approaches the composition of the microbial community is affected by small perturbations in the environment (e.g. temperature, nutrient concentration and flow) and the response of microorganisms cannot be predicted with certainty. The following sections will review the literature on the effectiveness of these environmentally friendly, “green,” strategies for controlling MIC.
Properties of polyethylene films with incorporated benzoic anhydride and/or ethyl and propyl esters of 4-hydroxybenzoic acid and their suitability for food packaging

Benzoic anhydride and ethyl and propyl esters of 4-hydroxybenzoic acid (ETP and PRP, respectively, also termed parabens) incorporated into low density polyethylene (LDPE) film were studied with regard to migration into food and food simulants at 6°C and 25°C, and changes in selected properties of the film were investigated. Antimicrobials were incorporated into polymer film in concentrations of 5g/kg and 10g/kg. The addition of parabens into the polymer was more difficult than benzoic anhydride due to their volatility. For benzoic anhydride, 30–40% and 10–20% of the added amount was found to leach from the film into aqueous and olive oil food simulants, respectively. The migration into both water and olive oil followed a very similar course in the case of parabens. Migration levels over 90% and in the range of 70% to 80%, relative to the amount of agent in the film, were determined for ETP and PRP respectively. The incorporation of antimicrobials into the film significantly changed the functional characteristics of the packaging material, i.e. permeability of oxygen, carbon dioxide and water vapour, tensile strength, coefficient of friction, sealing strength and transparency. Shelf life tests with packaged cheese and toasted bread demonstrated the efficiency of the film containing 10g/kg of BA against mould growth on the food surface during storage at 6°C.
Image colorization using similar images

We present a new example-based method to colorize a gray image. As input, the user needs only to supply a reference color image which is semantically similar to the target image. We extract features from these images at the resolution of superpixels, and exploit these features to guide the colorization process. Our use of a superpixel representation speeds up the colorization process. More importantly, it also empowers the colorizations to exhibit a much higher extent of spatial consistency in the colorization as compared to that using independent pixels. We adopt a fast cascade feature matching scheme to automatically find correspondences between superpixels of the reference and target images. Each correspondence is assigned a confidence based on the feature matching costs computed at different steps in the cascade, and high confidence correspondences are used to assign an initial set of chromatic values to the target superpixels. To further enforce the spatial coherence of these initial color assignments, we develop an image space voting framework which draws evidence from neighboring superpixels to identify and to correct invalid color assignments. Experimental results and user study on a broad range of images demonstrate that our method with a fixed set of parameters yields better colorization results as compared to existing methods.
Breathfinding: A Wireless Network That Monitors and Locates Breathing in a Home

This paper explores using RSS measurements on the links between commercial wireless devices to locate where a breathing person is located and to estimate their breathing rate, in a home, while the person is sitting, lying down, standing, or sleeping. Prior RSS-based device-free localization methods required calibration measurements to be able to locate stationary people, or did not require calibration but only located people who moved. We collect RSS measurements multiple short (3-7 minute) tests and during a longer 66 minute test, and show the location of the breathing person can be estimated, to within about 2 m average error. We describe a detector that distinguishes between sample times during which a person is moving and sample times during which a person is breathing but otherwise motionless. This detector enables removal of motion interference, i.e., RSS changes due to movements other than a person's breathing, and more accurately estimate a person's breathing rate. Being able to locate and monitor a breathing person, without calibration, is important for applications in search and rescue, health care, and security.
Transport Control Protocol for Cognitive Radio Ad Hoc Networks

The rapid demand for wireless communication networks in the last few decades has lead to spectrum scarcity, Hence there is need of efficient spectrum utilization is occurs. Cognitive radio is a novel technology which improve the spectrum resource utilization and allows a cognitive radio transceiver to detect and sense the available spectrum. Cognitive Radio (CR) networks allow users to transmit in the licensed spectrum bands, without degrading the performance of the Primary Users (PUs). Routing in CRN is a challenging task due to the variations in spectrum availability with time and periodic spectrum sensing undertaken by the CR users. In this paper we investigate the effect of TCP in CR ad hoc network environment and proposes multipath routing protocol, that uses on-demand distance vector routing, called Ad hoc On-demand Multipath Distance Vector (AOMDV) Routing Protocol. We analyze its performance using Network simulator (NS-2) software tool. Simulation gives effective result of cognitive radio ad hoc networks and analyzed the parameter delay, throughput and energy.