gebhart/patrepeval huggingface dataset:
Evaluating the Role of Solubility in Oral Absorption of Poorly Water‐Soluble Drugs Using Physiologically‐Based Pharmacokinetic Modeling (2019)

Poor aqueous solubility and dissolution of drug candidates drive key decisions on lead series optimization during drug discovery, on formulation optimization, and clinical studies planning during drug development. The interpretation of the in vivo relevance of early pharmaceutical profiling is often confounded by the multiple factors affecting oral systemic exposure. There is growing evidence that in vitro drug solubility may underestimate the true in vivo solubility and lead to drug misclassification. Based on 10 poorly water-soluble tyrosine kinase inhibitors, this paper demonstrates the use of physiologically-based pharmacokinetic (PK) analysis in combination with early clinical PK data to identify drugs whose absorption is truly limited by solubility in vivo and, therefore, expected to exhibit food effect. Our study supports a totality of evidence approach using early clinical data to guide decisions on conducting drug interaction studies with food and acid-reducing agents.
A computer model of the annihilation of the electric field in an electromagnetic wave by the elastic stress field of a rotated grain (2010)

Resistance to heat was simulated and measured in a computer model as an annihilation of the elastic stress arising from the electric field in the radiation. The elastic stress created from the electromagnetic wave was superimposed with the elastic stresses produced by the rotation of a grain, which was represented in two dimensions as an ellipse in the simulation. Both the tilt angle of the grain with respect to the applied force and the aspect ratio of the grain were varied in the computer program. Results are reported here for a ratio of wavelength to total grain length of 10. Annihilation of an elastic stress from the electric field of up to 80 to 90 percent was seen for aspect ratios of 8/7 to 2 in several ranges of grain tilt angle. For this same range in aspect ratio, steep transitions in the amount of annihilation were seen near the ends of the grain. An elongated grain, with an aspect ratio of 10 and rotating counterclockwise, exhibited extinction of 50 to nearly 90 percent of the electric field near the lower end of the grain throughout the tilt angle range of 5° to 85°.
The potential for poly (ADP-ribose) polymerase inhibitors in cancer therapy (2011)

The modulation of DNA repair pathways for therapeutic benefit in cancer has now become a reality with the development of poly (ADP-ribose) polymerase inhibitors (PARPi). PARP is involved in single-strand DNA breaks, which in the presence of defective homologous recombination repair lead to double-strand DNA breaks, the most lethal form of DNA damage. These agents therefore may be the drugs of choice for BRCA mutant breast and ovarian cancers. PARPi result in synergistic antitumor effects when combined with cisplatin, temozolomide, topoisomerase inhibitors and ionizing radiation. The indications for PARPi lie beyond BRCA mutations and may include genomic and functional defects in DNA repair and damage response pathways. Several PARPi are in the clinical development phase at this time and, given the recent failure of a phase III clinical trial of iniparib in triple-negative breast cancer, the identification of structural and functional differences between these inhibitors becomes critical. Acquired resistance to PARPi is being noted and represents an important limitation in this field. A concise review of the literature in this field is presented.
Transaction management in a distributed database system for local area networks (2003)

The design and implementation of an experimental fault-tolerant distributed database management system is described. The system provides a logically integrated view of data with distribution transparency and a controlled data replication. A commitment protocol used to guarantee atomicity of update operations is discussed. Efficient algorithms used to recover a site from a failure and restore data consistency are described. Recovery can be interleaved with the processing of regular database transactions and does not seriously limit the availability of data. The proposed solutions to the problems of fault recovery are designed to take advantage of the properties of a high-bandwidth local area network.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
High quality and thick GaN substrate epitaxially grown by VPE lateral overgrowth (2002)

We have developed the epitaxial lateral overgrowth (ELO) technique for growing high-quality bulk GaN by using hybrid vapour phase epitaxial growth (HVPE). A remarkable reduction of dislocation density was achieved. The preparation of free-standing GaN wafers was demonstrated.
A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion (2016)

Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although the precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive guidance cues stimulate actin polymerization in neuronal growth cones whereas repulsive cues induce actin disassembly. Contrary to this model, we find that the repulsive guidance cue Slit stimulates the formation and elongation of actin-based filopodia from mouse dorsal root ganglion growth cones. Surprisingly, filopodia form and elongate toward sources of Slit, a response that we find is required for subsequent axonal repulsion away from Slit. Mechanistically, Slit evokes changes in filopodium dynamics by increasing direct binding of its receptor, Robo, to members of the actin-regulatory Ena/VASP family. Perturbing filopodium dynamics pharmacologically or genetically disrupts Slit-mediated repulsion and produces severe axon guidance defects in vivo. Thus, Slit locally stimulates directional filopodial extension, a process that is required for subsequent axonal repulsion downstream of the Robo receptor.
Promoter Effects of Alkali Metal Cations on the Electrochemical Reduction of Carbon Dioxide (2017)

The electrochemical reduction of CO<sub>2</sub> is known to be influenced by the identity of the alkali metal cation in the electrolyte; however, a satisfactory explanation for this phenomenon has not been developed. Here we present the results of experimental and theoretical studies aimed at elucidating the effects of electrolyte cation size on the intrinsic activity and selectivity of metal catalysts for the reduction of CO<sub>2</sub>. Experiments were conducted under conditions where the influence of electrolyte polarization is minimal in order to show that cation size affects the intrinsic rates of formation of certain reaction products, most notably for HCOO<sup>-</sup>, C<sub>2</sub>H<sub>4</sub>, and C<sub>2</sub>H<sub>5</sub>OH over Cu(100)- and Cu(111)-oriented thin films, and for CO and HCOO<sup>-</sup> over polycrystalline Ag and Sn. Interpretation of the findings for CO<sub>2</sub> reduction was informed by studies of the reduction of glyoxal and CO, key intermediates along the reaction pathway to final products. Density functional theory calculations show that the alkali metal cations influence the distribution of products formed as a consequence of electrostatic interactions between solvated cations present at the outer Helmholtz plane and adsorbed species having large dipole moments. The observed trends in activity with cation size are attributed to an increase in the concentration of cations at the outer Helmholtz plane with increasing cation size.
Histamine Releasing Factor/Translationally Controlled Tumor Protein: History, Functions and Clinical Implications (2012)

Histamine Releasing Factor (HRF) also known as Translationally Controlled Tumor Protein (TCTP) is a ubiquitous, novel protein that has both intracellular and extracellular functions. The purpose of this review is to highlight the background history of the molecule, the clinical implications and focus on the extracellular functions. Specifically the cells and the cytokines that are produced when stimulated by HRF/TCTP will be delineated as well as the signal transduction pathway that HRF/TCTP elicits will be described. Originally it was thought that HRF/TCTP interacted with IgE. Subsequently, cells that do not bind IgE also respond to HRF/TCTP and the interaction with IgE was questioned. Now, very recently, HRF/TCTP or at least its mouse counterpart appears to interact with some, but not all IgE and IgG molecules. HRF/TCTP has been shown to activate multiple human cells including basophils, eosinophils, T cells and B cells. Many of the cells that are activated by HRF/TCTP participate in the allergic response, leading to the conclusion that the extracellular functions of HRF/TCTP could exacerbate the allergic, inflammatory response.
Identifying inactive code in product lines with configuration-aware system dependence graphs (2014)

Application engineers frequently create customer-specific products in two stages: the required software components are first selected to create an initial product which is then evolved by refining the selected features and adapting the code to meet the customers' requirements. For instance, developers frequently set configuration options in the code to adjust the product. However, given that such changes are often necessary in the entire code base it is hard to know which part of the code is still relevant for the chosen configuration options. This means that engineers need to understand and maintain a lot of code that is potentially inactive in a particular product variant. Existing approaches provide only partial solutions: for instance, feature-to-code mappings do not adequately consider complex code dependencies of the implemented features. Static analysis techniques provide better results but usually do not consider variability aspects. We present an approach to automatically identify inactive code in product variants using a configuration-aware code analysis technique. We demonstrate the flexibility of our approach by customizing it to a product line of an industry partner in the domain of industrial automation. We further evaluate the approach to demonstrate its effectiveness, accuracy, and performance.
Functional Consequences of Reduction in NMDA Receptor Glycine Affinity in Mice Carrying Targeted Point Mutations in the Glycine Binding Site (2000)

We have used site-directed mutagenesis in conjunction with homologous recombination to generate two mouse lines carrying point mutations in the glycine binding site of the NMDAR1 subunit (Grin1). Glycine concentration-response curves from acutely dissociated hippocampal neurons revealed a 5- and 86-fold reduction in receptor glycine affinity in mice carrying Grin1(D481N) and Grin1(K483Q) mutations, respectively, whereas receptor glutamate affinity remained unaffected. Homozygous mutant Grin1(D481N) animals are viable and fertile and appear to develop normally. However, homozygous mutant Grin1(K483Q) animals are significantly lighter at birth, do not feed, and die within a few days. No gross abnormalities in CNS anatomy were detected in either Grin1(D481N) or Grin1(K483Q) mice. Interestingly, in situ hybridization and Western blot analysis revealed changes in the expression levels of NMDA receptor subunits in Grin1(D481N) mice relative to wild type that may represent a compensatory response to the reduction in receptor glycine affinity. Grin1(D481N) mice exhibited deficits in hippocampal theta burst-induced long-term potentiation (LTP) and spatial learning and also a reduction in sensitivity to NMDA-induced seizures relative to wild-type controls, consistent with a reduced activation of NMDA receptors. Mutant mice exhibited normal prepulse inhibition but showed increased startle reactivity. Preliminary analysis indicated that the mice exhibit a decreased natural aversion to an exposed environment. The lethal phenotype of Grin1(K483Q) animals confirms the critical role of NMDA receptor activation in neonatal survival. A milder reduction in receptor glycine affinity results in an impairment of LTP and spatial learning and alterations in anxiety-related behavior, providing further evidence for the role of NMDA receptor activation in these processes.
Formal Interaction Analysis - A Methodology and Software Tool for the Design and Assessment of Information and Communication Structures for Concurrent Engineering (2007)

. Since the availability of information is a prerequisite for efficient Concurrent Engineering (CE), information and communication structures have to be designed carefully. However, current practice is often based on a trialand -error approach resulting in inefficient communication. Existing methods especially concentrate on which information has to be delivered to whom in terms of output-input relationships. The here presented methodology extends the existing approaches by designing also the communication patterns and selecting the communication means with which the information is communicated. The FIA methodology (Formal Interaction Analysis) provides a systematic approach and decision support for finding the best solution for a specific communication scenario. The paper outlines typical communication problems in product development and explains the basic thinking of FIA. The methodology and its sub steps are described and the supporting software tool is presented. The p...
Text-independent speaker verification with dynamic trajectory model (2003)

A novel approach is presented for text-independent speaker verification. Based on the frequencies of occurrence of Gaussian component strings in the quantized acoustic trajectories, a universal background trajectory model and multiple target trajectory models are created for the background and target speakers separately. Analysis of the speaker entropy in the trajectory space demonstrates that the segmental dynamic trajectory catches speaker-specific information. Experiments are conducted on the telephony speech used in the NIST 1999 speaker verification evaluation and show that the bicomponent strings achieve good performance and may provide complementary information to a general speaker verification system.
Determination of the Sites of Posttranslational Modifications in the Charge Isomers of Bovine Myelin Basic Protein by Capillary Electrophoresis-Mass Spectroscopy (1998)

The posttranslational modifications in each of the 18.5 kDa bovine myelin basic protein charge isomers C-1 to C-6 have been determined by the use of capillary electrophoresis-mass spectroscopy. The pattern of modifications is viewed as being unique to each charge isomer and is thought to reflect a specific placement and function for each isomer in the myelin membrane. Several of the sites of posttranslational phosphorylation were found to differ from a number of the reported sites that were phosphorylated in vitro by various kinases. These differences suggest that an extremely cautious approach be taken in identifying in vivo posttranslationally modified amino acid residues from residues that have been modified in vitro by various kinases. We have identified the following posttranslationally phosphorylated and deamidated, modified sites in the bovine MBP components C1-C6. C1 has no modification; C2 represents a deamidation of Gln 146; in C3, Thr 97 and Ser 164 are phosphorylated; in C4, Ser 54, Thr 97, and Ser 160 are phosphorylated; in C5 Ser 7, Ser 54, Thr 97, and Ser 164 are phosphorylated; and in C6, Ser 7, Ser 54, Thr 97, Ser 160, and Ser 164 are phosphorylated.
Elastic surface waves (1972)

Devices that exploit the properties of elastic surface waves can perform very complex signal-processing functions, identical to those carried out by conventional electromagnetic devices. The great advantage to using surface waves instead of electromagnetic waves is the tremendous reduction in size of surface-wave devices compared to their electromagnetic counterparts. This great reduction in size is the result of the great difference between the elastic and electromagnetic velocities. Surface waves propagate at velocities approximately 105 times slower than electromagnetic velocities; thus, at the same frequency, the elastic wavelength is 105 times shorter than the electromagnetic wavelength. A further advantage is that the energy in the elastic surface wave can readily be sensed anywhere along its path.
The phenotypic distribution and functional profile of tuberculin‐specific CD4 T‐cells characterizes different stages of TB infection (2012)

Functional subsets and phenotype of tuberculin induced CD4 T-cells differ between stages of TB infection. Predominance of TNF-α(+) CD4 T-cells in active infection suggests an increased effort of the immune system to contain disease.
Removal of Carbonaceous Residue with Wet Hydrogen in Greensheet Processing for Multilayer Ceramic Module: II, Reaction in Large Modules Influenced by Pore Diffusion and Mass Transfer (1990)

An experimental and mathematical investigation of the removal of carbonaceous residue deposited on the ceramic substrate in the fabrication of multilayer ceramic modules has been conducted. Such carbonaceous residue is formed when the organic binder is pyrolyzed during the firing of greensheets. This paper is the second of a two‐part series that reports on and discusses the principal findings of the investigation. In this paper we describe the removal of carbonaceous residue from large blocks of the multilayer ceramic module in which the diffusion of gaseous species may play a role. A mathematical model is developed using the Law of Additive Reaction Times for fluid‐solid reactions, which incroporates the effects of intrinsic chemical kinetics, pore diffusion, and external mass transfer. This law gives an approximate solution to the governing equations which describe the removal of carbonaceous residue from the MLC module during firing.
A Case of Anisakiasis Diagnosed after Partial Resection of Ileum Due to Eosinophilic Ascites and Ileal Abscess (2002)

Eosinophilic enteritis is characterized by massive infiltration of eosinophil throughout the entire or each layer of intestinal wall with marked submucosal edema. The etiology of this disease is not clear until now, and parasite infestation should be considered as a cause of eosinophilic enteritis like this case. We experienced a case of eosinophilic enteritis manifested by intermittent periumbilical pain and bloody ascites. After partial resection of ileum, we confirmed the eosinophilic abscess from Anisakis infestation and successfully treated this patient without sequalae and report it with literatures review.
A real time GPRS surveillance system using the embedded system (2004)

As for data surveillance, the general packet radio service (GPRS) is the best candidate for always-on connection to any moving vehicles or individuals from the ground up to a few thousand feet above ground. Due to the inherent characteristics of GPRS, the client circuit design requires a central processing unit (CPU) with an appropriate operating system (OS) to activate point-to-point protocol (PPP) as well as IP addressed transmission control protocol (TCP/IP). This paper presents a system designed for clients to carry out GPRS connection, and send GPS and other data to a server system. For surveillance purpose, a geographic information system (GIS) is applied to track the clients on the electronic map. The system architecture and design concept are discussed. Circuit implementation and real world tests are demonstrated and verified. The data transmission delay is estimated within 0.75 seconds, while the surveillance period can be controlled from 5 to 120 seconds. The proposed system has been tested in ground vehicles to ultra light aircraft at 1000 feet with most areas in Taiwan.
Corrected Fluorescence Spectra of Polynuclear Materials and Their Principal Applications (1973)

Abstract Corrected fluorescence spectra are presented for 20 polynuclear aromatic compounds. The applications of corrected spectra, as well as instrumentation and techniques for providing these spectra, are described.
A phylogeny of legumes (Leguminosae) based on analysis of the plastid <i>mat</i><i>K</i> gene resolves many well‐supported subclades within the family (2004)

Phylogenetic analysis of 330 plastid matK gene sequences, representing 235 genera from 37 of 39 tribes, and four outgroup taxa from eurosids I supports many well-resolved subclades within the Leguminosae. These results are generally consistent with those derived from other plastid sequence data (rbcL and trnL), but show greater resolution and clade support overall. In particular, the monophyly of subfamily Papilionoideae and at least seven major subclades are well-supported by bootstrap and Bayesian credibility values. These subclades are informally recognized as the Cladrastis clade, genistoid sensu lato, dalbergioid sensu lato, mirbelioid, millettioid, and robinioid clades, and the inverted-repeat-lacking clade (IRLC). The genistoid clade is expanded to include genera such as Poecilanthe, Cyclolobium, Bowdichia, and Diplotropis and thus contains the vast majority of papilionoids known to produce quinolizidine alkaloids. The dalbergioid clade is expanded to include the tribe Amorpheae. The mirbelioids include the tribes Bossiaeeae and Mirbelieae, with Hypocalypteae as its sister group. The millettioids comprise two major subclades that roughly correspond to the tribes Millettieae and Phaseoleae and represent the only major papilionoid clade marked by a macromorphological apomorphy, pseudoracemose inflorescences. The robinioids are expanded to include Sesbania and members of the tribe Loteae. The IRLC, the most species-rich subclade, is sister to the robinioids. Analysis of the matK data consistently resolves but modestly supports a clade comprising papilionoid taxa that accumulate canavanine in the seeds. This suggests a single origin for the biosynthesis of this most commonly produced of the nonprotein amino acids in legumes.
Dexterity is impaired at both hands following unilateral subcortical middle cerebral artery stroke (2007)

Dexterity was investigated in right-handed subjects in the subacute phase of a first unilateral subcortical middle cerebral artery stroke affecting the left or right hemisphere and right-handed healthy subjects. Dexterity was quantified at both hands by kinematic recordings of finger and hand tapping, a reach-to-grasp movement, quantitative analysis of grip forces in a grasp-lift task and clinical rating scales. Stroke subjects exhibited significant deficits in timing and coordination of tapping movements at both the contralesional and ipsilesional hands, irrespective of the hemisphere affected. Likely for the reach-to-grasp and grasp-lift movements a bilateral impairment was found in stroke subjects. In particular, slowing of hand transport towards the object, deficient timing and scaling of grasp formation, discoordination between grip and lift forces and inefficient scaling of grip forces were observed. The severity of impairment was independent of the hemisphere affected and evident for both the reach (involving more proximal muscles of the arm) and grasp (involving more distal muscles of the arm and hand) components of the task. Strong correlations were found between clinical scores of hand function and loss of sensibility with the deficits in timing, coordination and efficiency of movement of the contralesional and ipsilesional hand. These data provide evidence that dexterity is impaired at both hands after subcortical middle cerebral artery stroke.