Miracle-dz/UniFAR-FTUs huggingface dataset:
The Conduct of in Vitro Studies to Address Time-Dependent Inhibition of Drug-Metabolizing Enzymes: A Perspective of the Pharmaceutical Research and Manufacturers of America

Time-dependent inhibition (TDI) of cytochrome P450 (P450) enzymes caused by new molecular entities (NMEs) is of concern because such compounds can be responsible for clinically relevant drug-drug interactions (DDI). Although the biochemistry underlying mechanism-based inactivation (MBI) of P450 enzymes has been generally understood for several years, significant advances have been made only in the past few years regarding how in vitro time-dependent inhibition data can be used to understand and predict clinical DDI. In this article, a team of scientists from 16 pharmaceutical research organizations that are member companies of the Pharmaceutical Research and Manufacturers of America offer a discussion of the phenomenon of TDI with emphasis on the laboratory methods used in its measurement. Results of an anonymous survey regarding pharmaceutical industry practices and strategies around TDI are reported. Specific topics that still possess a high degree of uncertainty are raised, such as parameter estimates needed to make predictions of DDI magnitude from in vitro inactivation parameters. A description of follow-up mechanistic experiments that can be done to characterize TDI are described. A consensus recommendation regarding common practices to address TDI is included, the salient points of which include the use of a tiered approach wherein abbreviated assays are first used to determine whether NMEs demonstrate TDI or not, followed by more thorough inactivation studies for those that do to define the parameters needed for prediction of DDI.
Characterization of a Cloned Locust Tyramine Receptor cDNA by Functional Expression in Permanently Transformed Drosophila S2 Cells

Abstract: The cDNA for Tyr‐Loc, a G protein‐coupled receptor that clearly shows homology to a number of mammalian and fruit fly receptors for biogenic amines, was cloned from the nervous system of Locusta migratoria. Functional expression of the cloned cDNA was obtained in cultured insect cells, i.e., in Spodoptera SF9 cells using a baculoviral expression system and in stably transformed Drosophila Schneider 2 (S2) cells. Multiple copies of the receptor expression construct are inserted into the genome of these permanently transformed cells. The expression of the receptor cDNA was driven by the upstream sequences of a Bombyx mori baculoviral immediate early gene. Tyramine shows a much higher binding affinity to this receptor than other possible endogenous ligands. It also reduces forskolin‐induced cyclic AMP production in the permanently transformed S2 cells. The pharmacological profile of the Tyr‐Loc receptor is distinct from that of any locust receptor‐type described so far, but it is similar to that of the Drosophila tyramine/octopamine receptor. In the locust CNS, the Tyr‐Loc mRNA is not present in the distal part of the optic lobes but has a widespread distribution in the brain and the ventral nerve cord.
Stereo Matching Using Sub-segmentation and Robust Higher-Order Graph Cut

This paper provides a novel and efficient approach to dense stereo matching. The first contribution is, rather than applying disparity distribution inside a segment as hard constraint to directly project the likelihood of corresponding candidates to each pixel individually, our method treat segmentation and corresponding disparity distribution as soft constraint, and further partition each segment to sub-over segments which effectively facilitate the assumption of the disparity consistency. The second contribution is we transform this assumption into higher-order-based potential, and it can be minimized effectively through graph cut. The third contribution is the successful combination of several known techniques as one holistic framework. Two test-beds of both Middlebury and challenging real-scene data have been evaluated, results show that it obtains the state-of-the-art results while keeping efficiency.
A Web-Based System for Automatic Language Skill Assessment: EVALING

EVALING is a Leonardo da Vinci project funded by the European Union, involving four European laboratories. The aim of the project is to build an automatic system to evaluate language skills in people's native language. This paper focuses on native French. Other partners are working on their own language and are building specific tests (Italian and German). EVALING is an 'Item Banking' system: exercise database allowing dynamic design of questionnaires. We present a technique based on the use of NPL tools that assure easy and costless updating of these databases. In addition, we underline the interest of Local Grammars (Finite State Transducers) for scoring exercises on language.
MicroRNA Expression Profiling of Oligodendrocyte Differentiation from Human Embryonic Stem Cells

Background Cells of the oligodendrocyte (OL) lineage play a vital role in the production and maintenance of myelin, a multilamellar membrane which allows for saltatory conduction along axons. These cells may provide immense therapeutic potential for lost sensory and motor function in demyelinating conditions, such as spinal cord injury, multiple sclerosis, and transverse myelitis. However, the molecular mechanisms controlling OL differentiation are largely unknown. MicroRNAs (miRNAs) are considered the “micromanagers” of gene expression with suggestive roles in cellular differentiation and maintenance. Although unique patterns of miRNA expression in various cell lineages have been characterized, this is the first report documenting their expression during oligodendrocyte maturation from human embryonic stem (hES) cells. Here, we performed a global miRNA analysis to reveal and identify characteristic patterns in the multiple stages leading to OL maturation from hES cells including those targeting factors involved in myelin production. Methodology/Principal Findings We isolated cells from 8 stages of OL differentiation. Total RNA was subjected to miRNA profiling and validations preformed using real-time qRT-PCR. A comparison of miRNAs from our cultured OLs and OL progenitors showed significant similarities with published results from equivalent cells found in the rat and mouse central nervous system. Principal component analysis revealed four main clusters of miRNA expression corresponding to early, mid, and late progenitors, and mature OLs. These results were supported by correlation analyses between adjacent stages. Interestingly, the highest differentially-expressed miRNAs demonstrated a similar pattern of expression throughout all stages of differentiation, suggesting that they potentially regulate a common target or set of targets in this process. The predicted targets of these miRNAs include those with known or suspected roles in oligodendrocyte development and myelination including C11Orf9, CLDN11, MYTL1, MBOP, MPZL2, and DDR1. Conclusions/Significance We demonstrate miRNA profiles during distinct stages in oligodendroglial differentiation that may provide key markers of OL maturation. Our results reveal pronounced trends in miRNA expression and their potential mRNA target interactions that could provide valuable insight into the molecular mechanisms of differentiation.
A Cross-Cultural Approach to the Study of Educational Leadership: An Emerging Framework1

Although studies of educational leadership have proliferated over the last decade, they have mostly focused on Western school settings. Leadership in non-Western school settings has largely been ignored, so that little is known about the influence of culture on the beliefs and actions of school leaders across national boundaries. This article builds a case for increasing understanding of educational leadership through adopting a comparative cross-cultural lens. It has three interrelated purposes. First, it presents the argument for strengthening a cultural comparative approach to educational leadership. Second, it suggests a framework for comparing cultural influences on educational leadership across national and cultural boundaries. Finally, it recognizes some of the difficulties of conceptualizing and conducting cross-cultural leadership research. Through achieving these purposes we hope to contribute to the ongoing development of understanding of school leadership.
Towards Autonomic Index Maintenance

Automatic index selection has received significant attention in the autonomic computing field. Previous works have focused on providing tools and algorithms to help the DBA in the choice of indices for a given static workload. We present an approach for indexing management that works for workloads that may dynamically change with no human intervention at all. We automatically monitor statements submitted to the database with a built-in component, that interacts directly with the DBMS, creating and dropping indices on-the-fly. This paper presents a mechanism to integrate automatic index management components in relational databases. We discuss the heuristics considered and the observed experimental results for a PostgreSQL implementation. Resumo. A selecao automatica de indices e um topico dos mais relevantes na area de computacao autonoma. Os trabalhos existentes tem foco em ferramentas e algoritmos que ajudem o DBA na escolha de indices para uma dada carga estatica. Nesse trabalho sugerimos uma abordagem para gerencia de indices que funciona para cargas que mudam dinamicamente, sem intervencao humana. Ha um monitoramento automatico dos comandos submetidos para o banco de dados com um componente embutido, que interage diretamente com o SGBD, permitindo a criacao e destruicao de indices com a base em operacao. Este artigo apresenta um mecanismo que integra componentes de gerencia automatica de indices em bases de dados relacionais. Nos discutimos as heuristicas consideradas e tambem os resultados experimentais observados para uma implementacao utilizando PostgreSQL.
Models of conceptual understanding in human respiration and strategies for instruction

MODELS OF CONCEPTUAL UNDERSTANDING IN HUMAN RESPIRATION AND STRATEGIES FOR INSTRUCTION SEPT 1998 MARY ANNE RAMIREZ, B.Sc., VIRGINIA COMMONWEALTH UNIVERSITY, MEDICAL COLLEGE OF VIRGINIA M.ED., UNIVERSITY OF MASSACHUSETTS AMHERST ED.D. , UNIVERSITY OF MASSACHUSETTS, AMHERST Directed by: Professor John Clement Prior research has indicated that students show little understanding of respiration beyond breathing in and out and the need for air to survive. This occurs even after instruction, with alternative conceptions persisting into adulthood. Whether this is due to specific educational strategies or to the difficulty individuals encounter in understanding complex biological topics, is an important question. The purpose of this study was to obtain a deeper understanding of students’ development of mental models of human respiration. This was carried out through case studies on eight eighth graders. The study was composed of two major parts, one concerned with documenting and analyzing how students learn, and one concerned with measuring the effect of teaching strategies. The results of this study may be particularly significant to biology education. They provide insights into strategies that can be utilized to assist students in understanding a complex system; strategies that may prove useful in studying other complex biological systems. All students in this study were successful in constructing mental models of a complex concept, respiration, and significant differences were obtained on the post test
Goal-oriented cognitive rehabilitation for an individual with Mild Cognitive Impairment: Behavioural and neuroimaging outcomes

An individual, goal-oriented cognitive rehabilitation intervention was conducted with AB, a 77-year-old woman with MCI. Outcomes were evaluated using a client-centred measure of goal achievement and an experimental associative learning task testing a skill practised in the intervention. Pre- and post-intervention fMRI scans were compared to examine changes in brain activation. Following intervention, AB showed improved performance on rehabilitation goals and on the associative learning task. There were significant decreases in brain activation in sensory areas and significant increases in memory-related areas. Both client-centred measures and fMRI may assist in detecting clinically-meaningful changes resulting from cognitive rehabilitation interventions.
An Experimental Approach to O-o Software Process and Product Measurements

This paper reports on an ongoing software measurement experiment which has been set up to monitor and evaluate team based student projects on a progressive basis. Student Assessment-Tutorial Ongoing Proole Sheets (SA-TOPS) have been used to provide a more objective feedback to improve students' learning and for measuring their understanding for grading purposes. The objective of the measurement is to improve the quality of the software process and product by measuring the activities of a scenario based development of an Object-Oriented system by various student teams.
PROTOCOL VULNERABILITIES IN PRACTICE: CAUSES, MODELING AND AUTOMATIC DETECTION *

Starting from practical scenarios we underline that the most relevant security vulnerabilities in practice come from weak protocol design or implementation flaws rather than from weak or flawed cryptography. In particular, we outline security vulnerabilities in several kinds of scenarios starting from well explored fields such as computer networks to less explored ones from the automotive industry and control systems. Some of the security flaws that we discuss are already known while others are new and have been subject of our previous research. Finally, we emphasize that to assure good security, focus should be on assuring correct implementations and proper tools for automatic verification of services.
Phylogenetic position of guinea pigs revisited.

Although the traditional taxonomy, mainly based on comparative morphology, classifies the guinea pig into the order Rodentia (Luckett and Hartenberger 1985; Novacek 1992), the molecular phylogenetics has been challenging this view. The first such attempt was made by Graur, Hide, and Li (1991), who suggested that the order Rodentia may not be monophyletic, and that the guinea-pig-like rodents (Caviomorpha) may be an outgroup to the clade formed by the rat-like rodents (Myomorpha) and Primates. Their suggestion contradicts the traditional classification of the guinea pig into Rodentia (the Myomorpha/Caviomorpha clade). These authors used a maximum-parsimony (MP) method in estimating the tree, but it is known that the MP method is sometimes misleading, particularly when the evolutionary rate differs among lineages (Felsenstein 1978). Therefore, Hasegawa et al. (1992) reexamined the data by a maximum-likelihood (ML) method for protein sequences (Kishino, Miyata, and Hasegawa 1990) that is robust against the violation of rate constancy (e.g., Hasegawa, Kishino, and Saitou 1991; Hasegawa and Fujiwara 1993). They showed that, although the MP analysis supported Graur, Hide, and Li’s tree of the rodent polyphyly with as high as 96% bootstrap probability (BP), the result of ML analysis was equivocal, and therefore they suggested that Graur, Hide, and Li’s tree might represent an example of the fact that unequal evolutionary rates can mislead MP analysis. More extensive ML analyses, mainly of nuclear DNA-encoded proteins, strongly supported the traditional tree (Cao et al. 1994b; Kuma and Miyata 1994). On the basis of phylogenetic analyses of the complete mitochondrial genome from the guinea pig and 14 other eutherian species with opossum as an outgroup, D’Erchia et al. (1996) recently challenged the traditional view again, but proposed the third alternative hypothesis that the guinea pig is closer to the Lagomorpha/Primates/Carnivora/Perissodactyla/Artiodactyla. /Cetacea clade than to Myomorpha. The tree was supported by all of the three major methods of protein phylogeny; i.e., MP, neighbor joining (NJ; Saitou and Nei 1987), and ML (Kishino, Miyata, and Hasegawa 1990; Adachi and Hasegawa 1996a). While D’Erchia et al. (1996) obtained low BP of only 1% for the rodent monophyly hypothesis from their MP analysis, the BP was 10% from their NJ analysis and the traditional tree could not be dismissed. They also applied the protein ML to the
Simple Reconstruction with Titanium Mesh and Radial Forearm Flap after Globe-Sparing Total Maxillectomy: A 5-Year Follow-Up Study

Background: Reconstruction of eye globe–sparing total maxillectomy defects is one of the major challenges to reconstructive surgeons. In 1994, the authors developed an uncomplicated and easy reconstructive method, where a titanium mesh is applied for the support of orbital contents, a radial forearm free flap for covering the mesh and the cheek lining, and an obturator prosthesis for palatal and dental rehabilitation. Methods: Five patients who underwent primary reconstruction with the authors’ method after globe-sparing maxillectomy with loss of the orbital floor from 1994 to 1999 and who were followed up for more than 5 years were retrospectively reviewed for (1) the presence of diplopia, (2) the shape of the reconstructed orbital floor assessed by coronal section magnetic resonance imaging, and (3) the presence of infection/exposure of the titanium mesh. Results: Only one of the five patients developed slight diplopia. Coronal magnetic resonance imaging showed that the orbital floor restored with titanium mesh had in all cases maintained a proper shape and position for more than 5 years. No infection or exposure of the titanium mesh had developed in any of the cases, despite exposure to irradiation of not less than 30 Gy. All the patients had well-retentive obturator prostheses. Conclusion: This long-term follow-up study demonstrated that the authors’ method attained a long-lasting successful outcome functionally and is the method of choice for reconstruction after globe-sparing total maxillectomy.
Speaker recognition using channel factors feature compensation

The variability of the channel and environment is one of the most important factors affecting the performance of text-independent speaker verification systems. The best techniques for channel compensation are model based. Most of them have been proposed for Gaussian Mixture Models, while in the feature domain typically blind channel compensation is performed. The aim of this work is to explore techniques that allow more accurate channel compensation in the domain of the features. Compensating the features rather than the models has the advantage that the transformed parameters can be used with models of different nature and complexity, and also for different tasks. In this paper we evaluate the effects of the compensation of the channel variability obtained by means of the channel factors approach. In particular, we compare channel variability modeling in the usual Gaussian Mixture model domain, and our proposed feature domain compensation technique. We show that the two approaches lead to similar results on the NIST 2005 Speaker Recognition Evaluation data. Moreover, the quality of the transformed features is also assessed in the Support Vector Machines framework for speaker recognition on the same data, and in preliminary experiments on Language Identification.
Astroglial‐Induced In Vitro Angiogenesis: Requirements for RNA and Protein Synthesis

Astrocytes are believed to affect microvascular endothelial cell differentiation in brain and retina. Bovine retinal microvessel endothelial cells formed capillary‐like structures when cocultured with C6 astroglial cells or in the absence of C6 cells in response to the reconstituted basement membrane protein Matrigel. Using quantitative computer‐assisted image analysis, the requirements for RNA and protein synthesis in these two complementary models of in vitro microvessel morphogenesis were examined. Astroglial‐dependent capillary‐like structure formation was inhibited by up to 87% in a dose‐dependent fashion by cycloheximide (0.01–0.1 μg/ml), puromycin (0.1–0.25 μg/ml), and actinomycin D (0.01– 0.025 μg/ml). In contrast, the astroglial‐independent process in response to Matrigel was not affected by these metabolic inhibitors. These findings suggest that capillary‐like structures form in response to astroglial cells in two distinct sequential stages. The first consists of inductive astroglial‐endothelial interactions requiring both RNA and protein synthesis. This initiates endogenous endothelial morphogenic events that do not appear to require RNA or protein synthesis, consistent with posttranslational regulatory mechanisms. The first astroglial‐dependent step is relevant to the regulation of microvessel formation in brain and retina, whereas the second may represent a morphogenic pathway common to micro‐vessel formation in many tissues.
Uniform and Reliable GaN p-i-n Ultraviolet Avalanche Photodiode Arrays

GaN p-i-n ultraviolet avalanche photodiodes (UV-APDs) were fabricated from epitaxial structures grown on low-dislocation-density free-standing GaN substrates to form 4 × 4 UV-APD arrays with a device size of 75 × 75 μm<sup>2</sup>. The devices in the UV-APD array showed a uniform and reliable distribution of breakdown voltage (V<sub>BR</sub>) and leakage current density. The average V<sub>BR</sub> of the 16 devices in one of the UV-APD arrays was 96±0.6 V, and the average dark current density (J<sub>R_Dark</sub>) and photocurrent density (J<sub>R_Photo</sub>) were measured to be (6.5±1.8)×10<sup>-7</sup> and (5.7±1.1)×10<sup>-6</sup> A/cm<sup>2</sup> at the reverse bias voltage of V<sub>R</sub> = 48 V (50% of the average onset point of V<sub>BR</sub>), respectively. The reliable device performance was confirmed by performing multiple reverse bias I-V scans for the selected devices in the UV-APD array. We also observed the significantly enhanced spectral responsivity from the 142 to 5485 mA/W due to the strong carrier impact ionization at high reverse bias.
Bitslice software implementation of KeeLoq as a side-channel countermeasure

Bitslice is a non-conventional way to implement algorithms using a scalar processor as a SIMD. It involves breaking down the algorithm into logical bit operations so that N parallel <operations are possible on a single N-bit microprocessor. It is applied to encryption algorithms, processing N consecutive blocks simultaneously, to achieve high throughput. Security applications using the KeeLoq algorithm are not suitable to traditional bitslice implementations because usually there are no N blocks to be processed. We propose a KeeLoq bitslice implementation, derived from its Algebraic Normal Form, for a single input block as a countermeasure against side-channel attacks. Our experimental results show there is no timing information leaked with an improvement factor of 3.01 in executed cycles. However, the implementation is still vulnerable to differential side-channel analysis, so we propose a secured variation that increases the resistance against differential power analysis without timing leakage, with a lower improvement factor of 1.21 in executed cycles.