gebhart/patrepeval huggingface dataset:
Session 6: Is Hypergastrinaemia Dangerous to Man? (1991)

Achlorhydria has been discussed as a possibly dangerous consequence of therapeutic inhibition of gastric acid secretion since the introduction of H2-receptor antagonists. The risk of long-term hypergastrinaemia has only been considered for about 5 years. The reason for this was the demonstration that gastric carcinoids (ECLomas) observed after life-long treatment of rats with the proton pump inhibitor omeprazole could also be produced in rats by other methods leading to long-lasting profound hypergastrinaemia. Such methods were the 80% resection of the oxyntic mucosa or feeding of ranitidine (2000 mg/day) for 2 years. The endocrine tumours corresponded to the gastric carcinoids found in patients with long-lasting hypergastrinaemia due to pernicious anaemia or with a gastrinoma as part of the MEN I syndrome. Neither in animals nor in man could other endocrine tumours or adenocarcinomas of the gastrointestinal tract be related to hypergastrinaemia. Epidemiologic data do not support gastrin dependence of adenocarcinoma of the stomach or the colon. Experimental findings of gastrin effects on tumour growth in vivo and in vitro have been contradictory and may be explained by the presence of gastrin receptors on tumour cells and the role of gastrin as an autocrine growth factor in some of these tumours. Since acid blockade by proton pump inhibitors or H2-receptor blockers dose-dependently increase serum gastrin levels, patients with ranitidine-resistant peptic ulceration receiving long-term treatment with high-dose omeprazole have been followed up with serial gastric biopsy specimens for up to 5 years. Complete healing, moderate hypergastrinaemia, and a slight hyperplasia but no dysplasia of the ECL cells in the oxyntic mucosa have been observed, which seemed to be correlated to chronic gastritis progressing over the years. Despite these negative findings excessive hypergastrinaemia by overdosage of potent drugs for inhibition of gastric secretion should be avoided and monitoring of plasma gastrin levels is recommended in case of long-term treatment.
A comparison of magnetic and electrical stimulation of peripheral nerves (1990)

We compared magnetic stimulation using different coil designs (2 rounded coils and a butterfly-prototype coil) with electrical stimulation of the median and ulnar nerves in 5 normal subjects. Using magnetic stimulation we were able to record technically satisfactory maximal sensory and motor responses only with the butterfly coil. Submaximal electrical stimuli preferentially activated sensory rather than motor axons, but submaximal magnetic stimuli did not. The onset latency, amplitude, area and duration of responses elicited electrically or magnetically with the butterfly coil during routine sensory and motor nerve conduction studies were similar, and motor and sensory conduction velocities were comparable when studied over long segments of nerve. However, the motor conduction velocities with magnetic and electrical stimulation differed by as much as 18 m/sec in the across-elbow segment of ulnar nerve. Thus, recent developments in magnetic stimulator design have improved the focality of the stimulus, but the present butterfly coil design cannot replace electrical stimulation for the detection of focal changes in nerve conduction velocity at common entrapment sites, such as in the across-elbow segment of the ulnar nerve.
A systematic scan of interactions with tyrosine motifs in the erythropoietin receptor using a mammalian 2-hybrid approach (2005)

Signaling via the erythropoietin receptor (EpoR) depends on the interaction of several proteins with phosphorylated tyrosine-containing motifs in its cytosolic domain. Detailed mapping of these interactions is required for an accurate insight into Epo signaling. We recently developed a mammalian protein-protein interaction trap (MAPPIT), a cytokine receptor-based 2-hybrid method that operates in intact Hek293-T mammalian cells. As baits, we used intracellular segments of the EpoR containing 1 or 2 tyrosines. Several known signaling molecules, including cytokine-inducible SH2-containing protein (CIS), suppressor of cytokine signaling-2 (SOCS2), phosphatidylinositol 3'-kinase (PI3-K), phospholipase C-gamma (PLC-gamma), and signal transducer and activator of transcription 5 (STAT5) were used as prey. We also extended the MAPPIT method to enable interaction analysis with wild-type EpoR. In this relay MAPPIT approach, instead of using isolated EpoR fragments as bait, we used the full-length EpoR itself as a "receptor bait." Finally, we introduced MAPPIT in the erythroleukemic TF-1 cell line, which is a more natural setting of the EpoR. With these strategies several known interactions with the EpoR were analyzed and evidence for new interactions was obtained.
Ocular Disposition, Pharmacokinetics, Efficacy and Safety of Nanoparticle-Formulated Ophthalmic Drugs (2007)

Ophthalmic drugs are delivered to ocular tissues predominantly via relatively simple formulations, such as topically dosed water-soluble drug solutions and water-insoluble drug suspensions in ointments. An ideal topical drug delivery system should possess certain desirable properties, such as good corneal and conjunctival penetration, prolonged precorneal residence time, easy instillation, non-irritative and comfortable to minimize lachrymation and reflex blinking, and appropriate rheological properties. In general, ocular efficacy is closely related to ocular drug bioavailability, which may be enhanced by increasing corneal drug penetration and prolonging precorneal drug residence time. To improve ocular bioavailability of topically dosed ophthalmic drugs, a variety of ocular drug delivery systems, such as hydrogels, microparticles, nanoparticles, microemulsions, liposomes and collagen shields, have been designed and investigated. These newer systems may, to some extent, control drug release and maintain therapeutic levels in ocular tissues over a prolonged period of time. This review focuses on the in vitro, ex vivo and in vivo studies of ophthalmic drugs formulated in nanoparticles published over the past two decades. The progress and development issues relating to ocular disposition, pharmacokinetics, efficacy and safety of the nanoparticle-formulated ophthalmic drugs are specifically addressed. Information and discussions summarized in this review are helpful for pharmaceutical scientists to develop better ophthalmic therapeutics.
The OpenCL specification (2009)

This document begins with an overview of basic concepts and the architecture of OpenCL, followed by a detailed description of its execution model, memory model and synchronization support. It then discusses the OpenCL platform and runtime API and is followed by a detailed description of the OpenCL C programming language. Some examples are given that describe sample compute use-cases and how they would be written in OpenCL. The specification is divided into a core specification that any OpenCL compliant implementation must support; a handheld/embedded profile which relaxes the OpenCL compliance requirements for handheld and embedded devices; and a set of optional extensions that are likely to move into the core specification in later revisions of the OpenCL specification.
Enantioselective Ring Opening of Epoxides by Fluoride Anion Promoted by a Cooperative Dual-Catalyst System (2010)

An enantioselective method for the synthesis of beta-fluoroalcohols by catalytic nucleophilic fluorination of epoxides is described. Mild reaction conditions and high selectivity are made possible by the use of benzoyl fluoride as a soluble, latent source of fluoride anion. A chiral amine and chiral Lewis acid serve as cooperative catalysts for desymmetrizations of five- through eight-membered cyclic epoxides, affording products in up to 95% ee. The cocatalytic protocol is also effective for kinetic resolutions of racemic terminal epoxides, which proceed with k(rel) values as high as 300.
Keynote: intelligent video as a force multiplier for crime detection and prevention (2005)

Four of the main crime detection and prevention functions of law enforcement personnel are: physical deterrence; monitoring public areas; responding to crimes; and forensic analysis to pick up the pieces. An acknowledged challenge is the lack of manpower to be effective at these functions. Law enforcement agencies everywhere are embracing new technologies as multipliers to make their existing labour force more effective. One valuable force multiplier technology is intelligent video surveillance (IVS)-computer software that can detect threats, crimes, or events of interest in surveillance video and automatically generate and distribute alerts for those events. This technology exists today and is experiencing commercial success in law enforcement applications world-wide. However, to fully exploit the benefits of such technologies, four specific factors need to converge: more specific IVS applications must be created to solve law enforcement challenges; IVS technology must enable smart devices that can be rapidly and ubiquitously deployed; these devices must proliferate based on applications and infrastructure outside of law enforcement; and law enforcement agencies must adopt new processes and policies to exploit them. This paper discusses these factors and provides examples of successful law enforcement agencies that have adopted and adapted IVS technology.
Ultra-low power precision ISFET readout using global current feedback (2006)

A solid-state chemical sensor ion sensitive field effect transistor (ISFET) that operates in weak inversion and interfaces with negative current feedback to maximise linearity is proposed. The power consumption of this circuit when operating in the weak inversion region is in the nanowatt range, which makes it suitable for biomedical applications.
<title>Optimal motion control for teleoperated surgical robots</title> (1993)

This paper addresses the problem of optimal motion control for teleoperated surgical robots, which must maneuver in constrained workspaces. The control problem is determining how best to use the available degrees of freedom of a surgical robot to accomplish a particular task, while respecting geometric constraints on the work volume, robot mechanism, and the specific task requirements. We present a method of formulating desired motions in the task space (task space goals) as instances of a quadratic optimization problem, optionally subject to additional linear constraints. The control formalism applies both to kinematically deficient as well as kinematically redundant mechanisms. Specifically, we discuss the problem as it relates to a representative set of tasks in teleoperated navigation of a laparoscopic camera attached to a surgical robot.
Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis (2012)

Chondrogenesis occurs as a result of mesenchymal cell condensation and chondroprogenitor cell differentiation. Following chondrogenesis, the chondrocytes remain as resting cells to form the articular cartilage or undergo proliferation, terminal differentiation to chondrocyte hypertrophy, and apoptosis in a process termed endochondral ossification, whereby the hypertrophic cartilage is replaced by bone. Human adult articular cartilage is a complex tissue of matrix proteins that varies from superficial to deep layers and from loaded to unloaded zones. A major challenge to efforts to repair cartilage by stem cell-based and other tissue-engineering strategies is the inability of the resident chondrocytes to lay down a new matrix with the same properties as it had when it was formed during development. Thus, understanding and comparing the mechanisms of cartilage remodeling during development, osteoarthritis (OA), and aging may lead to more effective strategies for preventing cartilage damage and promoting repair. The pivotal proteinase that marks OA progression is matrix metalloproteinase 13 (MMP-13), the major type II collagen-degrading collagenase, which is regulated by both stress and inflammatory signals. We and other investigators have found that there are common mediators of these processes in human OA cartilage. We also observe temporal and spatial expression of these mediators in early through late stages of OA in mouse models and are analyzing the consequences of knockout or transgenic overexpression of critical genes. Since the chondrocytes in adult human cartilage are normally quiescent and maintain the matrix in a low turnover state, understanding how they undergo phenotypic modulation and promote matrix destruction and abnormal repair in OA may to lead to identification of critical targets for therapy to block cartilage damage and promote effective cartilage repair.
Low Order PWM Inverter Harmonics Contributions to the Inverter-Fed Induction Machine Fault Diagnosis (2008)

In this paper, the effects of inverter harmonics on motor current fault signatures are studied in detail. It is theoretically and experimentally shown that the fault signatures caused by the inverter harmonics are similar and comparable to those generated by the fundamental harmonic on the line current. Theoretically-derived extended relations including bearing fault, eccentricity, and broken rotor bar relations are found to match experimental results. Furthermore, it is observed and reported that the asymmetries on the rotor caused by broken rotor bars increase the amplitude of even harmonics. To confirm these claims, bearing, eccentricity, and broken rotor bar faults are tested and the line current spectrum of each faulty motor is compared with the healthy one. The proposed additional fault data are expected to contribute positively to the inverter-fed motor fault decision making algorithms.
Histopathology and Immunohistologic Demonstration of the Distribution of Rickettsia typhi in Fatal Murine Typhus (1989)

An 81-year-old woman had chills, fever, nausea, vomiting, and epigastric pain. On day 3 she had hematuria and was treated with trimethoprim-sulfamethoxazole. On day 5 she had a cough, hypotension, anemia, azotemia, and elevated hepatic enzyme levels. Her condition deteriorated with thrombocytopenia, anuria requiring dialysis, edema, and hypoalbuminemia. Treatment with chloramphenicol and doxycycline was started on day 10. By day 11, she was in hypotensive shock; on day 12 she had seizures and died. Murine typhus was diagnosed by demonstration of antibodies to Rickettsia typhi by indirect immunofluorescence. Necropsy revealed interstitial pneumonia, pulmonary edema, hyaline membranes, alveolar hemorrhages, petechiae and vasculitis in the central nervous system, interstitial myocarditis, multifocal interstitial nephritis and hemorrhages, splenomegaly, portal triaditis, and mucosal hemorrhages in urinary tract. Immunofluorescent R. typhi were demonstrated in the lungs, brain, kidneys, liver, and heart. This unusual death occurred in an elderly patient without rash who was treated too late with antirickettsial drugs.
Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H] SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes. (1984)

The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-[3H]SKF 10,047 (N-allylnormetazocine) and to dopamine D2 sites was investigated. In guinea pig brain membranes, (+)-[3H]SKF 10,047 bound to a single class of sites with a Kd of 4 X 10(-8) M and a Bmax of 333 fmol/mg of protein. This binding was different from mu, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[3H]SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol greater than perphenazine greater than fluphenazine greater than acetophenazine greater than trifluoperazine greater than molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-[3H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[3H]SKF 10,047 binding sites did not correlate with those for [3H]spiperone (dopamine D2) sites. [3H]-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-SKF 10,047. In the striatum, about half of the saturable [3H]haloperidol binding was to [3H]spiperone (D2) sites and the other half was to sites similar to (+)-[3H]SKF 10,047 binding sites.
Secretory protein targeting in a pituitary cell line: differential transport of foreign secretory proteins to distinct secretory pathways. (1985)

The mouse pituitary cell line, AtT-20, packages the adrenocorticotropic hormone (ACTH) in secretory vesicles and releases it when the cell is stimulated with secretagogues. These cells have the capacity, after transfection with the appropriate DNA, to package heterologous peptide hormones into the regulated secretory vesicles (Moore, H. P. H., M. D. Walker, F. Lee, and R. B. Kelly, 1983, Cell, 35:531-538). To test if other secreted proteins prefer a different route to the surface, we have transfected AtT-20 cells with DNAs coding for a fragment of a membrane protein, the vesicular stomatitis virus G protein from which the membrane spanning domain has been deleted (Rose, J. K., and J. E. Bergmann, 1982, Cell, 17:813-819). We found that the secreted vesicular stomatitis virus G proteins were not transported to the regulated secretory vesicles. Instead they preferentially exited the cell by the constitutive pathway previously found in these cells (Gumbiner, B., and R. B. Kelly, 1982, Cell, 28:51-59). In contrast, human growth hormone transfected into the cells by the same procedure was transported to the regulated pathway with a similar efficiency as the endogenous hormone ACTH. Transport of the secreted G protein to the regulated pathway, if it occurs at all, is at least 30-fold less efficient than peptide hormones. We conclude that the transport machinery in AtT-20 cells must selectively recognize different secreted proteins and sort them into distinct secretory pathways.
Human cholesterol 7α-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype (2002)

Bile acid synthesis plays a critical role in the maintenance of mammalian cholesterol homeostasis. The CYP7A1 gene encodes the enzyme cholesterol 7alpha-hydroxylase, which catalyzes the initial step in cholesterol catabolism and bile acid synthesis. We report here a new metabolic disorder presenting with hyperlipidemia caused by a homozygous deletion mutation in CYP7A1. The mutation leads to a frameshift (L413fsX414) that results in loss of the active site and enzyme function. High levels of LDL cholesterol were seen in three homozygous subjects. Analysis of a liver biopsy and stool from one of these subjects revealed double the normal hepatic cholesterol content, a markedly deficient rate of bile acid excretion, and evidence for upregulation of the alternative bile acid pathway. Two male subjects studied had hypertriglyceridemia and premature gallstone disease, and their LDL cholesterol levels were noticeably resistant to 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. One subject also had premature coronary and peripheral vascular disease. Study of the kindred, which is of English and Celtic background, revealed that individuals heterozygous for the mutation are also hyperlipidemic, indicating that this is a codominant disorder.
Determination of the hydrodynamic parameters of an underwater vehicle during small scale, nonuniform, 1-dimensional translation (2002)

The hover and tight maneuvering regime of an underwater vehicle is difficult to characterize hydrodynamically. Characterization in a reliable model is necessary for successful control of the vehicle during task performance. A 1-dimensional system identification procedure for this regime is described. The experimental set up is simple and noncritical. The analysis is performed by minimizing the error between the trajectories of the vehicle and several numerical models during a free decay. Minimization is controlled by the Nelder-Meade simplex algorithm. Agreement with the work of other researchers is strong. The procedure is flexible and may be extended to coupled models with 4 degrees of freedom.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A monolithically integrated InGaAs-InP p-i-n/JFET focal plane array (1996)

We describe a monolithic InGaAs-InP focal plane array for near-infrared imaging. The array consists of an InGaAs p-i-n diode as a photodetector integrated with an InP junction field effect transistor (JFET) as a switching element for each pixel. In order to minimize the drain and gate leakage to achieve high-detection sensitivity, a novel -p-encapsulation" JFET was employed. Arrays as large as 16/spl times/16 were fabricated, consisting of 528 devices integrated into a single array with >99% individual device yield. This array represents significant progress in InP-based materials and integration technologies.
An evaluation of some conflation algorithms for information retrieval (1981)

The characteristics of conflation algorithms are discussed and examples given of some algorithms which have been used for information retrieval systems. Comparative experiments with a range of keyword dictionaries and with the Cranfield document test collection suggest that there is relatively little difference in the performance of the algorithms despite the widely disparate means by which they have been developed and by which they operate.
Regulatory T Cells (2010)

Regulatory T cells inhibit cellular immunity and represent an obstacle for the development of cancer immunotherapy. The understanding of Treg cellular biology has exponentially increased during the last 10 years, driven primarily by elegant in vivo studies of mouse models systems and in vitro studies of human cells. Numerous clinical strategies are under active investigation to achieve Treg depletion or inhibition in patients with cancer, including low-dose cyclophosphamide and interleukin-2 or anti-interleukin-2R immunotoxins. To date, only modest results have been reported in patients. Our preliminary data suggest that the antihuman CD25 monoclonal daclizumab may be useful as an alternative approach for in vivo Treg depletion, but the mechanism of action of this effect remains to be elucidated. Certain immune modulatory agents may indirectly affect Tregs in patients with cancer but not necessarily in the desired direction for the therapeutic setting. More sophisticated techniques that have become available for Treg analysis in patients will assist in this important translational effort.
ChemInform Abstract: STUDIES IN POTENTIAL FILARICIDES‐ PART X. SYNTHESIS OF 2‐SUBSTITUTED 1,3,4,6,11,11A‐HEXAHYDRO‐2H‐PYRAZINO(1,2‐B)ISOQUINOLIN‐6‐ONES (1977)

Abstract LiBH 4 ‐Reduktion des aus dem Dihydroisocarbostyril (I) und Brom‐äthylacetat erhältlichen Diesters (II) gibt den Bisalkohol (III), der über das entsprechende Dichlorderivat mit Äthylamin zu dem Hexahydropyrazinoisochinolinon (IVa) cyclisiert wird.