Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting Metabolic Clearance for Drugs That Are Actively Transported into Hepatocytes: Incubational Binding as a Consequence of in Vitro Hepatocyte Concentration Is a Key Factor s

Incubational binding or the fraction of drug unbound in an in vitro incubation, fu inc , is an important parameter to predict or measure in the pursuit of accurate clearance predictions from in vitro data. Here we describe a method for fu inc determination directly in the hepatocyte intrinsic clearance ( CL int ) assay with emphasis on compounds that are actively transported into hepatocytes, hypothesizing that for such compounds the typical protocol of 1 million hepatocytes/ml systematically underestimates the maximum attainable unbound intracellular drug concentration. Using the transporter substrate atorvastatin as a test compound, incubations were performed and a mathematical model applied to describe metabolism, distribution, and binding at different hepatocyte concentrations. From these investigations it was evident that, since binding is more extensive intracellularly than in the medium, increased partitioning into the cellular volume, due to active uptake, increases the total amount of atorvastatin bound in the incubation. Consequently, a significant lowering of the hepatocyte concentration impacts the free drug concentration in the incubation and increases the observed rate of metabolism and therefore observed CL int (that is, when viewed from the media drug concentration). The applicability of the findings was tested for a series of 11 actively transported zwitterions for which standard rat hepatocyte metabolic CL int data (1 million cells/ml incubation) poorly predicted in vivo clearance (average fold error of 5.4). Using metabolic CL int determined at a lower hepatocyte concentration (0.125 million cells/ml) considerably improved clearance predictions (average fold error of 2.3).
Bioenergy potentials from forestry in 2050 An assessment of the drivers that determine the potentials

The purpose of this study was to evaluate the global energy production potential of woody biomass from forestry for the year 2050 using a bottom-up analysis of key factors. Woody biomass from forestry was defined as all of the aboveground woody biomass of trees, including all products made from woody biomass. This includes the harvesting, processing and use of woody biomass. The projection was performed by comparing the future demand with the future supply of wood, based on existing databases, scenarios, and outlook studies. Specific attention was paid to the impact of the underlying factors that determine this potential and to the gaps and uncertainties in our current knowledge. Key variables included the demand for industrial roundwood and woodfuel, the plantation establishment rates, and the various theoretical, technical, economical, and ecological limitations related to the supply of wood from forests. Forests, as defined in this study, exclude forest plantations. Key uncertainties were the supply of wood from trees outside forests, the future rates of deforestation, the consumption of woodfuel, and the theoretical, technical, economical, or ecological wood production potentials of the forests. Based on a medium demand and medium plantation scenario, the global theoretical potential of the surplus wood supply (i.e., after the demand for woodfuel and industrial roundwood is met) in 2050 was calculated to be 6.1 Gm (71 EJ) and the technical potential to be 5.5 Gm (64 EJ). In practice, economical considerations further reduced the surplus wood supply from forests to 1.3 Gm year (15 EJ year). When ecological criteria were also included, the demand for woodfuel and industrial roundwood exceeded the supply by 0.7 Gm year (8 EJ year). The bioenergy potential from logging and processing residues and waste was estimated to be equivalent to 2.4 Gm year (28 EJ year) wood, based on a medium demand scenario. These results indicate that forests can, in theory, become a major source of bioenergy, and that the use of this bioenergy can, in theory, be realized without endangering the supply of industrial roundwood and woodfuel and without further deforestation. Regional shortages in the supply of industrial roundwood and woodfuel can, however, occur in some regions, e.g., South Asia and the Middle East and North Africa. Climatic Change (2007) 81:353–390 DOI 10.1007/s10584-006-9163-x E. M. W. Smeets (*) : A. P. C. Faaij Copernicus Institute for Sustainable Development and Innovation, Department of Science, Technology and Society, Utrecht University, Heidelberglaan 2, 3584 CS Utrecht, The Netherlands e-mail: e.smeets@chem.uu. nl
Title: Integration of two in-depth quantitative proteomics approaches determines the kallikrein- related peptidase 7 (KLK7) degradome in ovarian cancer cell secretome. Authors and affiliations:

5Present addresses: National Institute of Dental and Craniofacial Research, 30 Convent Drive, Bethesda, Maryland 20892, USA (L.M.S.); Mater Research Institute – The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, 4102, Australia (T.K.); The University of Queensland Diamantina Institute at the Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102, Australia (C.R.S.); Faculty of Biology, Technion Israel institute of Technology, Haifa, 32000 Israel (O.K.). Mol Cell Proteomics Papers in Press. Published on January 31, 2019 as Manuscript RA118.001304
Burns, David and Macias Castillo, Daniel and Wuthrich, Christian (2015) On Mordell–Weil groups and congruences between derivatives of twisted Hasse–Weil

Let A be an abelian variety defined over a number field k and let F be a finite Galois extension of k. Let p be a prime number. Then under certain not-too-stringent conditions on A and F we compute explicitly the algebraic part of the p-component of the equivariant Tamagawa number of the pair ` h(A/F )(1), Z[Gal(F/k)] ́ . By comparing the result of this computation with the theorem of Gross and Zagier we are able to give the first verification of the p-component of the equivariant Tamagawa number conjecture for an abelian variety in the technically most demanding case in which the relevant Mordell-Weil group has strictly positive rank and the relevant field extension is both non-abelian and of degree divisible by p. More generally, our approach leads us to the formulation of certain precise families of conjectural p-adic congruences between the values at s = 1 of derivatives of the Hasse-Weil L-functions associated to twists of A, normalised by a product of explicit equivariant regulators and periods, and to explicit predictions concerning the Galois structure of Tate-Shafarevich groups. In several interesting cases we provide theoretical and numerical evidence in support of these more general predictions.
Muscular Septal Development

Sixty-two chick embryo hearts were studied at incremental stages of development (Hamburger-Hamilton stages 16 to 39) by scanning electron microscopy following 3% glutaraldehyde fixation and critical point drying. Early in cardiac development, the primitive ventricle becomes homogeneously trabeculated with highly organized sheets of myocytes lined by endocardial cells, with the trabeculae generally oriented in the dorsoventral direction. Coalescence of these trabecular sheets begins at stage 26, initially at the area of the bulboventricular flange, and later proceeding caudally toward the floor of the ventricle. The fusion process is finished by stage 30, resulting in a muscular ventricular septum that has now divided the primitive ventricle into right and left ventricles. Further growth of the ventricular septum is by continued fusion of the adjoining trabecular sheets. Remnants of the apposing trabecular sheets are found in the solidified muscular septum in the form of endocardial channels. We suggest that persistent patency of these channels results in muscular ventricular septal defects. (Cite Res 57: 759-766, 1985)
Title: Revisiting the molecular epidemiology of the FXI deficiency: 9 new mutations and an original large 4qTer deletion in western Brittany (France)

Background: Constitutional deficiency in Factor XI (FXI) is a rare bleeding disorder in the general population, with the exception of Ashkenazi Jews. During the last decade, the detection of FXI-deficient patients has shifted from clinical screening identifying mostly severe bleeders to biological screening combining findings of prolonged activated partial thromboplastin time and FXI coagulation activity (FXI:C) below 50 U/dL. Objectives: The goal of this study was to determine the molecular basis of FXI deficiency in western Brittany, France. Patients/Methods: Over the course of 4 years, we detected 98 FXI-deficient patients through biological screening, and 44 patients agreed to participate in this study corresponding to 25 index cases. We developed an efficient mutation detection strategy (combining direct sequencing and QFM-PCR to search for heterozygous rearrangements in a routine setting) that detected F11 mutations in 24 out of the 25 index cases. Results: An unexpected allelic heterogeneity was found, with 14 different single point mutations being detected, among which 9 are new. Moreover, a large heterozygous deletion of the entire F11 gene was detected, then further defined using a CGH array as a 4q34.2 telomeric deletion of 7 Mb containing 77 genes. Conclusion: We propose that the observed recurrent mutations may be considered as genetic tags of a population. This study highlights the importance of screening for large deletions in molecular studies of F11.
OP-BRCM210234 1..14

The voluntary generation of non-overlearned responses is usually assessed with phonemic fluency. Like most frontal tasks, it draws upon different complex processes and systems whose precise nature is still incompletely understood. Many claimed aspects regarding the pattern of phonemic fluency performance and its underlying anatomy remain controversial. Major limitations of past investigations include small sample size, scant analysis of phonemic output and methodologically insufficient lesion analysis approaches. We investigated a large number of patients with focal unilateral right or left frontal (n1⁄4 110) or posterior (n1⁄4100) or subcortical (n1⁄465) lesions imaged with magnetic resonance or computed tomography and compared their performance on the number of overall responses, words produced over time, extremely infrequent/unknown words and inappropriate words generated. We also employed, for the first time parcel-based lesion-symptom mapping, tract-wise statistical analysis as well as Bayesian multi-variate analysis based on meta-analytically defined functional region of interest, including their interactions. We found that left frontal damage was associated with greater impairment than right frontal or posterior damage on overall fluency performance, suggesting that phonemic fluency shows specificity to frontal lesions. We also found that subcorticals, similar to frontals, performed significantly worse than posteriors on overall performance suggesting that subcortical regions are also involved. However, only frontal effects were found for words produced over time, extremely infrequent/unknown and inappropriate words. Parcel-based lesionsymptom mapping analysis found that worse fluency performance was associated with damage to the posterior segment of the left frontal middle and superior gyrus, the left dorsal anterior cingulate gyrus and caudate nucleus. Tract-wise statistical analysis revealed that disconnections of left frontal tracts are critical. Bayesian multi-variate models of lesions and disconnectome maps implicated left middle and inferior frontal and left dorsomedial frontal regions. Our study suggests that a set of well localized left frontal areas together with subcortical regions and several left frontal tracts are critical for word generation. We speculate that a left lateralized network exists. It involves medial, frontal regions supporting the process of ‘energization’ , which sustains activation for the duration of the task and middle and inferior frontal regions concerned with ‘selection’, required due to the competition produced by associated stored words, respectively. The methodology adopted represents a promising and empirically robust approach in furthering our understanding of the neurocognitive architecture underpinning executive processes.
Development and Validation of Breast Cancer Knowledge and Beliefs Questionnaire for Malaysian Student Population

This study aimed to develop and validate a questionnaire on Malaysian students’ knowledge and belief toward breast cancer and breast cancer screening. A cross sectional study was conducted among 792 female undergraduate students in selected public universities in Klang Valley, Malaysia. Convergent and discriminant validity tests were used for assessing construct validity of the questionnaire while the internal reliability of the instrument was checked by Cronbach’s alpha. The average age of respondents was 22 years (21.77± 1.20). Majority of them were single (96.8%), Malay (91.9%), and Muslim (94.6%). This instrument had a good face and content validity. Cronbach’s alpha coefficient for Health Belief Model Scales ranged between 0.73-0.83, indicating acceptable levels of internal consistency. The Kappa value for the knowledge part ranged between 0.52-0.90, also showing acceptable reliability. The developed instrument indicated good construct validity and reliability for Malaysian female students. This instrument can help health care planners and providers to measure levels of knowledge and beliefs of Malaysian women toward breast cancer before planning appropriate intervention. Keyword: Breast cancer, breast cancer screening,
SMART SENSOR AND TRACKING SYSTEM FOR UNDERGROUND MINING

The thesis predominantly discusses a smart sensor and tracking system for underground mining, as developed by the author. The tracking system is developed by two steps, the first of which involves finding an efficient way to measure the distance, and the second of which involves localizing the positions of each miner in real-time. For the first step, a Received Signal Strength Indicator (RSSI) is used to measure the distance between two points by indicating the amount of energy lost during the transmission. Due to environmental and human factors, errors exist when using RSSI to measure distance. Three methods are taken to reduce the error: Gaussian distribution, statistical average and preset points. It can be observed that the average error between actual distance and measured distance is only 0.1145 meters using the proposed model. In regards to the localization, the “3-point localization method” is considered first. With the proposed method, the result of the localization is improved by 0.6 meters, as compared to the “2-point localization method”. The transmission method for the project is then discussed. After comparing several transmission protocols in the market, ZigBee was chosen for the signal transmission. With the Zigbee protocol, up to 65000 nodes can be connected, which are suitable for many miners using the system at the same time. The power supply for the ZigBee protocol is only 1mW for each unit, thus potentially saving a great amount of energy during the transmission. To render the tracking system more powerful, two smart sensors are installed: an MQ-2 sensor and a temperature sensor. The MQ-2 sensor is used to detect the harmful gas and smoke. In the event that the sensor’s detected value is beyond the threshold, it will provide a warning for the supervisor on the ground.
RELATIONSHIP MARKETING PRACTICES AND CUSTOMER REPURCHASE INTENTION OF ONLINE RETAIL FIRMS IN LAGOS, NIGERIA

In the online retail industry, customer repurchase intention is strategic for business survival. As a result of high competition in the industry, firms are challenged to ensure customer repurchase intention through relationship marketing practices RMP. This study investigated the effect of relationship marketing practices on customer repurchase intention of online retail firms in Lagos State, Nigeria. The study employed a cross-sectional survey research design. Data were gathered from 1970 respondents. The response rate was 85.6%. Stratified random and proportionate sampling techniques were adopted in selecting the respondents. A validated questionnaire was administered to collect data. Data were analyzed using descriptive and inferential statistics. The study found that RMP (website quality, trust, reliability, communication and personalization have positive significant effect on customer repurchase intention of online retail firms. The study also found personalization to be the major contributory RM variable affecting customer repurchase intention. The study recommended that the management of online retail firms should invest more in relationship marketing practices in order to increase customer repurchase intention.
Qualitative Assessment of Bacteria and Fungi in the Indoor Environment of Hospitals of Islamabad, Pakistan

This study was conducted to determine the health risks in the indoor air of the four government hospitals of the Islamabad city, Pakistan. Four different main wards, i.e., general male/female surgical wards, children’s ward and microbiology laboratory were included. The sampling was done in the summer season due to the possibility of maximum recovery of microorganisms. Results showed presence of bacterial and fungal pathogens in the air of hospitals especially in surgical wards of all hospitals. Lowest bacterial counts were recorded in microbiology laboratory. Among bacterial isolates Micrococcus and Staphylococcus aureus were abundantly found in all hospitals as 22.09 % & 21.2 %, respectively followed by gram negative group of bacteria i.e, Enterobacteriaceae spp. (Escherichia coli), Pseudomonas spp. were found to be lowest as 6.5 % of the total bacterial load in all hospitals. Among the fungi Aspergillus (fumigatus, niger, flavus) recovery was the most in the environment of all hospitals with the value of 27.7 % and Tricosporon was observed lowest with the value of 1.15 %. pvalue for total microbial load among the hospitals sampled was not significant.
Therapeutic possibilities of brachial plexus avulsion injuries: clinical and experimental approaches Ph.D. Thesis

s related to the thesis I. Nagy E. , Morvay Z. , Pintér S. : MRI scanning of brachial plexus. XVIII. Magyar Radiológus Kongresszus, Tihany, 1996. május 8-11. Magyar Radiológia (Suppl) 1996. 1. kötet. II. J. A. Simonka, S. Pinter, J. Császár: Combined Brachial Plexus Surgery and Closed Arterial Injuries of the Upper Extremity. Abstract in Swiss Surgery (Suppl) 2/1996. III. Pintér Sándor, Horváth Attila, Kincses László: Plexus brachialis sérülés utáni késői rekonstructio felnőttkorban. Magyar Traumatológia Ortopédia Kézsebészet Plasztikai Sebészet. XLII. évf. (Suppl) 1999. IV. S. Pintér, L. Mendler, E. Zádor, L. Dux: Skeletal muscle adaptation capacities after denervation/reinnervation Neuromuscular Disorders Vol. 13 Nos. 7-8 September 2003 (abstract) IF 3,34. V. Simonka J.A. Kincses L. ,Pintér S. Császár J. Vörös E. : Advantages of the new computer analysed myelo-CT method for evaluation and treatment of avulsion injuries of brachial plexus J.Hand Surg. 2005;30B:S1 71 (abstract) IF 0,759. VI. L. Mendler, S. Pintér, M. Kiricsi, L. Dux Changes in fiber-type composition of re-innervated rat soleus muscle regenerating from notexin-induced necrosis Neuromuscular Disorders Vol 16 (Issues 9-10 Page 693) October 2006 (abstract) IF 3,34. List of abbreviations in the text AchE: acetylcholinesterase ABPI: adult brachial plexus injury ALS: amyotrophic lateral sclerosis BMRC: British Medical Research Council ChAT: cholinacetyltransferase CNS: central nervous system EM: electron microscopy GH: glenohumeral HE: haematoxilin-eosin mRNA: messenger ribonucleic acid NMDA: N-methyl-D-aspatare OBPI: obstetrical brachial plexus injury R L: retrograde labelling SERCA: Sarco/Endoplasmic Reticulum Ca -ATPase TOS: thoracic outlet syndrome MRF myogenic regulatory factor
Information Categories in a Learner’s Glossary Entry

Three types of information categories are proposed in a learner‟s glossary entry: conceptual, lexical and pragmatic. The glossary is envisaged as a knowledge-oriented terminological collection which provides quick access to the conceptual structure of a narrow domain, the head terms functioning in it, their definitions, collocations, translations and contextual use. The conceptual information is identified by analyzing the conceptual relations using a classification scheme of the general aspects of the basic concept (top term). The top-down procedure continues with establishing the system-structuring characteristics with possible graphic representation of types. The lexical information refers to terminological collocations identified by a lexico-semantic analysis. The pragmatic information is provided by corpusextracted contexts and translation equivalents specified by a systematicity-based terminological contrastive analysis. A model is proposed for organizing the data obtained in a learner‟s glossary entry. It is concluded that the proposed model allows maximum concentration of terminological knowledge applicable in technical translation.
The field of the paper ： Genetic engineering 1 Alterations of microRNAs expression profiles in small extracellular vesicle after 2 traumatic brain injury in mice 3

27 Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity 28 worldwide. Tools available for diagnosis and therapy are limited. Small extracellular 29 vesicle (sEV) microRNAs (miRNAs) play an important role in TBI disease 30 progression. This study aimed to investigate the alterations in sEV miRNAs 31 expression in the mouse brain extracellular space after TBI. Twenty-four C57BL/6J 32 mice were randomly divided into two groups (12/group). The TBI group was 33 subjected to all surgical procedures and fluid percussion injury (FPI). The sham group 34 only underwent surgery. Brain specimens were collected 3 h after TBI/sham. The 35 brain sEV were isolated. Differentially expressed miRNAs were identified. A total of 36 50 miRNAs were observed to be differentially expressed (fold change ≥1.5 and 37 P <0.05) after TBI, including 5 upregulated and 45 downregulated. The major 38 enriched Gene Ontology terms were metabolic processes, cell, intracellular, organelle, 39 cytoplasm, axon, binding, protein kinase activity, protein binding, and protein 40 dimerization activity. The KEGG pathway analysis predicted that the pathways 41 affected by the variation of miRNAs in sEVs after TBI included the Wnt signaling 42 pathway and NF-κB signaling pathway. The changes in five miRNAs were confirmed 43 by qRT-PCR. In conclusion, this study demonstrated the differential expression of a 44 series of miRNAs in brain sEV after TBI, which might be correlated with post-TBI 45 physiological and pathological processes. The findings might also provide novel 46 targets for further investigating the molecular mechanisms underlying TBI and 47 potential therapeutic interventions.
A general projection framwork for constrained smoothing

There are a wide array of smoothing methods available for finding structure in data. A general framework is developed which shows that many of these can be viewed as a projection of the data, with respect to appropriate norms. The underlying vector space is an unusually large product space, which allows inclusion of a wide range of smoothers in our setup (including many methods not typically considered to be projections). We give several applications of this simple geometric interpretation of smoothing. A major payoff is the natural and computationally frugal incorporation of constraints. Our point of view also motivates new estimates and helps understand the finite sample and asymptotic behavior of these estimates.