gebhart/patrepeval huggingface dataset:
Cardiovascular, endocrine, and renal effects of urodilatin in normal humans (1999)

Effects of urodilatin (5, 10, 20, and 40 ng. kg-1. min-1) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13-37%) and increased fractional Li+ clearance (7-22%) and urinary Na+ excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 ng. kg-1. min-1, respectively). Glomerular filtration rate did not increase significantly with any dose. The two lowest doses decreased cardiac output (7 and 16%) and stroke volume (10 and 20%) without changing mean arterial blood pressure and heart rate. The two highest doses elicited larger decreases in stroke volume (17 and 21%) but also decreased blood pressure (6 and 14%) and increased heart rate (15 and 38%), such that cardiac output remained unchanged. Hematocrit and plasma protein concentration increased with the three highest doses. The renin-angiotensin-aldosterone system was inhibited by the three lowest doses but activated by the hypotensive dose of 40 ng. kg-1. min-1. Plasma vasopressin increased by factors of up to 5 during infusion of the three highest doses. Atrial natriuretic peptide immunoreactivity (including urodilatin) and plasma cGMP increased dose dependently. The urinary excretion rate of albumin was elevated up to 15-fold (37 +/- 17 micrograms/min). Use of a newly developed assay revealed that baseline urinary urodilatin excretion rate was low (<10 pg/min) and that fractional excretion of urodilatin remained below 0.1%. The results indicate that even moderately natriuretic doses of urodilatin exert protracted effects on systemic hemodynamic, endocrine, and renal functions, including decreases in cardiac output and renal blood flow, without changes in arterial pressure or glomerular filtration rate, and that filtered urodilatin is almost completely removed by the renal tubules.
Time-of-Flight Mass Spectrometry Of Underivatized Single-Stranded DNA Oligomers by Matrix-Assisted Laser Desorption (1994)

Matrix-assisted laser desorption with concomitant ionization (MALDI) in conjunction with time-of-flight mass spectrometry (TOF-MS) has been used to analyze underivatized random-base single-stranded DNA (ssDNA) oligomers ranging from 10 to 89 nucleotides in length by embedding them in a solid matrix of 3-hydroxypicolinic acid. At 355-nm desorption wavelength, mass spectra of positive and negative ions measured by reflecting and linear time-of-flight mass spectrometers are compared. Results from the linear system show the ionization yield is approximately equal for each polarity. Metastable ion decay is significant for the larger ssDNA oligomer ions, which results in a decrease in signal intensity and the broadening of mass peaks. In order to obtain an acceptable signal-to-noise ratio on a reflecting TOF system, a higher laser irradiance is needed, which consequently causes further degradation of mass resolution. With the apparent advantages of better sensitivity and mass resolution, it is concluded that a linear TOF system is better suited for the mass spectrometric analysis of ssDNA oligomers larger than about a 25-mer. The current system permits one-base resolution up to about a 40-mer. Mass accuracy for a 20-mer or smaller is within +/- 0.05%. Comparison of mass spectra from 5-ns and 35-ps pulse widths at the same energy density shows no significant differences. Mechanisms for oligonucleotide ion production in these experiments are discussed.
Microstructured Cocultures of Cardiac Myocytes and Fibroblasts: A Two-DimensionalIn VitroModel of Cardiac Tissue (2005)

Cardiac myocytes and fibroblasts are essential elements of myocardial tissue structure and function. In vivo, myocytes constitute the majority of cardiac tissue volume, whereas fibroblasts dominate in numbers. In vitro, cardiac cell cultures are usually designed to exclude fibroblasts, which, because of their maintained proliferative potential, tend to overgrow the myocytes. Recent advances in microstructuring of cultures and cell growth on elastic membranes have greatly enhanced in vitro preservation of tissue properties and offer a novel platform technology for producing more in vivo-like models of myocardium. We used microfluidic techniques to grow two-dimensional structured cardiac tissue models, containing both myocytes and fibroblasts, and characterized cell morphology, distribution, and coupling using immunohistochemical techniques. In vitro findings were compared with in vivo ventricular cyto-architecture. Cardiac myocytes and fibroblasts, cultured on intersecting 30-microm-wide collagen tracks, acquire an in vivo-like phenotype. Their spatial arrangement closely resembles that observed in native tissue: Strands of highly aligned myocytes are surrounded by parallel threads of fibroblasts. In this in vitro system, fibroblasts form contacts with other fibroblasts and myocytes, which can support homogeneous and heterogeneous gap junctional coupling, as observed in vivo. We conclude that structured cocultures of cardiomyocytes and fibroblasts mimic in vivo ventricular tissue organization and provide a novel tool for in vitro research into cardiac electromechanical function.
Stimulation of Insulin Release in the Dog by a Nonmetabolizable Amino Acid. Comparison with Leucine and Arginine1 (1971)

An unmetabolizable synthetic amino acid, 2-aminobicyclo[2,2,1]-heptane-2-carboxylic acid (BCH), leucine, arginine and glucose were administered intravenously to 3 dogs. Chlorpropamide, mannoheptulose and diazoxide were administered before or concomitantly with some of these infusions. BCH induced significant increases in plasma insulin in the chlorpropamide-pretreyted dogs. Insulin release induced by BCH, as well as that by leucine, is (a) accentuated by chlorpropamide, (b) increased or unaffected by mannoheptulose and (c) inhibited by diazoxide. Arginine-induced insulin release is suppressed completely by mannoheptulose. Neither leucine nor BCH increased plasma levels of glucagon. The results of these studies: 1) indicate that BCH is a functional leucine analogue with respect to pancreatic islet cell function, 2) provide direct evidence that amino acids themselves rather than one of their metabolites stimulate insulin release, 3) suggest that the beta cell receptor for stimulation of insulin release by the unmetabolizable amino acid BCH (and leucine) may be a transport receptor site, and 4) provide further evidence that the mechanism by which leucine (and BCH) induce insulin release differs from that by which arginine induces the release of insulin.
Partial redundancy elimination in SSA form (1999)

The SSAPRE algorithm for performing partial redundancy elimination based entirely on SSA form is presented. The algorithm is formulated based on a new conceptual framework, the factored redundancy graph, for analyzing redundancy, and representes the first sparse approach to the classical problem and on methods for its solution. With the algorithm description, theorems and their proofs are given showing that the algorithm produces the best possible code by the criteria of computational optimality and lifetime optimality of the introduced temporaries. In addition to the base algorithm, a practical implementation of SSAPRE that exhibits additional compile-time efficiencies is described. In closing, measurement statistics are provided that characterize the instances of the partial redundancy problem from a set of benchmark programs and compare optimization time spent by an implementation of SSAPRE aganist a classical partial redundancy elimination implementation. The data lend insight into the nature of partial redundancy elimination and demonstrate the expediency of this new approach.
The mass spectrometric analysis of glycoproteins and their glycan structures (2005)

One of the most common post-translational modifications of proteins involves the covalent attachment of N- or O-linked carbohydrates to the protein. Glycan moieties are involved in a wide variety of intracellular, cell-cell and cell-matrix recognition events. The study of glycoprotein-linked carbohydrates remains one of the most challenging tasks given to biochemists and bioanalysts as these molecules can exhibit complex branched structures that can differ in linkage and the level of branching. This is why understanding how glycosylation affects the activities and functions of proteins in health and disease represents a major challenge. Mass spectrometry, is one of the most powerful and versatile techniques for the structural analysis of glycoconjugates. This review summarizes the state of knowledge for the mass spectrometric analysis of glycoproteins and their glycan structures.
Celebrating 25 Years of SPERA (2009)

The Society for the Provision of Education in Rural Australia, or SPERA, draws together educators and other community members, for the common goal of improving learning outcomes of students in rural, regional and remote locations, both on the nation and international scene. Throughout its 25 year history SPERA has sought to influence governments, education policy, educators and communities to ensure students in rural locations have the opportunity to receive and achieve equitable and socially just outcomes through: promoting a positive view of education and training in rural areas and encouraging innovation and initiative in the provision of rural services; supporting and encouraging rural communities and educators to work towards the provision of quality education and training; and providing a framework for the sharing of concerns, issues and experiences relating to education and training in rural areas.
Mercuric chloride-treated brown Norway rats develop widespread tissue injury including necrotizing vasculitis. (1992)

We have identified a syndrome induced by mercuric chloride in BN rats in which there is evidence of tissue injury in many organs, with some features in common with graft-versus-host disease. There is also necrotizing leucocytoclastic vasculitis affecting the gut, and the importance of this is enhanced by the description in the accompanying paper of autoantibodies similar to those found in human systemic vasculitis. Our observations strengthen the analogies between this model and human autoimmune disease.
Mammalian display screening of diverse cystine-dense peptides for difficult to drug targets (2017)

Protein:protein interactions are among the most difficult to treat molecular mechanisms of disease pathology. Cystine-dense peptides have the potential to disrupt such interactions, and are used in drug-like roles by every clade of life, but their study has been hampered by a reputation for being difficult to produce, owing to their complex disulfide connectivity. Here we describe a platform for identifying target-binding cystine-dense peptides using mammalian surface display, capable of interrogating high quality and diverse scaffold libraries with verifiable folding and stability. We demonstrate the platform's capabilities by identifying a cystine-dense peptide capable of inhibiting the YAP:TEAD interaction at the heart of the oncogenic Hippo pathway, and possessing the potency and stability necessary for consideration as a drug development candidate. This platform provides the opportunity to screen cystine-dense peptides with drug-like qualities against targets that are implicated for the treatment of diseases, but are poorly suited for conventional approaches.
A Model for Collision Processes in Gases. I. Small Amplitude Processes in Charged and Neutral One-Component Systems (1954)

A kinetic theory approach to collision processes in ionized and neutral gases is presented. This approach is adequate for the unified treatment of the dynamic properties of gases over a continuous range of pressures from the Knudsen limit to the high-pressure limit where the aerodynamic equations are valid. It is also possible to satisfy the correct microscopic boundary conditions. The method consists in altering the collision terms in the Boltzmann equation. The modified collision terms are constructed so that each collision conserves particle number, momentum, and energy; other characteristics such as persistence of velocities and angular dependence may be included. The present article illustrates the technique for a simple model involving the assumption of a collision time independent of velocity; this model is applied to the study of small amplitude oscillations of one-component ionized and neutral gases. The initial value problem for unbounded space is solved by performing a Fourier transformation on the space variables and a Laplace transformation on the time variable. For uncharged gases there results the correct adiabatic limiting law for sound-wave propagation at high pressures and, in addition, one obtains a theory of absorption and dispersion of sound for arbitrary pressures. For ionized gases the difference in the nature of the organization in the low-pressure plasma oscillations and in high-pressure sound-type oscillations is studied. Two important cases are distinguished. If the wavelengths of the oscillations are long compared to either the Debye length or the mean free path, a small change in frequency is obtained as the collision frequency varies from zero to infinity. The accompanying absorption is small; it reaches its maximum value when the collision frequency equals the plasma frequency. The second case refers to waves shorter than both the Debye length and the mean free path; these waves are characterized by a very heavy absorption.
Calcitonin Gene‐Related Peptide ( CGRP ) and Migraine Current Understanding and State of Development (2013)

Calcitonin gene-related peptide (CGRP) is a ubiquitous neuropeptide found at the very centers of the migraine process, both centrally and peripherally. It has been under careful study for approximately 25 years. Several CGRP-receptor antagonists are being evaluated for acute treatment of episodic migraine. Three monoclonal antibodies are being studied for prevention of episodic migraine, and 1 monoclonal antibody is being studied for prevention of chronic migraine. In this review, we discuss the role of CGRP in normal physiology and the consequences of CGRP inhibition for human homeostasis. We then review the current state of development for CGRP-receptor antagonists and CGRP monoclonal antibodies. We close by speculating on the potential clinical role of CGRP antagonism in the acute and preventive treatment of episodic and chronic migraine.
한국 중소제조기업의 국내복귀(U-Turn) 결정요인에 관한 연구 (2014)

본 논문은 기 해외직접투자를 한 한국의 중소제조기업들의 국내복귀(U-Turn) 결정요인에 대하여 연구하였다. 2012년 2월부터 5월까지 해외진출기업에 대한 설문과 인터뷰를 실시하였고 연구방법으로는 구조방정식을 사용하였다. 결정요인은 포터(1991) 등의 선행연구를 참고하여 요소조건, 시장조건, 관련조건, 경영여건으로 구분하였고 분석결과 첫째, 요소조건(원자재, 노동력, 세율, 노동 개방도, 실업률)은 입지이전을 하려는 기업들 중 국내복귀를 하려는 기업들에게 유의적인 영향을 미치지 않았다. 둘째, 시장조건(시장 개방도, 시장 성장성, 시장의 규모, 시장의 질, 소득수준)은 입지이전을 하려는 기업들 중 국내복귀를 하려는 기업들에게 유의적인 영향을 미치지 않았다. 셋째, 관련조건(교육수준, 연구개발, 사회 인프라, 클러스터, 생활환경)은 입지이전을 하려는 기업들 중 국내복귀를 하려는 기업들에게 유의적인 영향을 미쳤다. 넷째, 경영여건(투자개방도, 정부 투명성, 기업 자유도, 국가 안정성, 노사관계)은 입지이전을 하려는 기업들 중 국내복귀를 하려는 기업들에게 유의적인 영향을 미치지 않았다. 연구결과는 기 해외직접투자를 한 기업들 중에서 입지이전을 고려하려는 기업들이 있다면 관련조건이 국내복귀에 유의적인 영향을 미치는 것으로 밝혀졌다. 해외직접투자활동을 펼치고 있는 기업들이 사회인프라, 생활환경, 연구개발등에서 어려움을 겪을 경우 국내복귀를 고려하는 것으로 보아 잠정적인 이들 국내복귀(U-Turn)기업들을 국내로 유치하기 위한 방안을 구체적으로 모색해볼 필요가 있다.
p38 Mitogen-activated Protein Kinase Phosphorylates Cytosolic Phospholipase A2 (cPLA2) in Thrombin-stimulated Platelets (1996)

The Ca2+-sensitive 85-kDa cytosolic phospholipase A2 (cPLA2) is responsible for thrombin-stimulated mobilization of arachidonic acid for the synthesis of thromboxane A2 in human platelets. We have previously shown that thrombin activates p38 kinase, a recently discovered new member of the mitogen-activated protein kinase family (Kramer, R. M., Roberts, E. F., Strifler, B. A., and Johnstone, E. M. (1995) J. Biol. Chem. 270, 27395-27398) and also induces phosphorylation of cPLA2, thereby increasing its intrinsic catalytic activity. In the present study we have examined the role of p38 kinase in the phosphorylation and activation of cPLA2 in stimulated platelets. We have observed that activation of p38 kinase accompanies receptor-mediated events in platelets and coincides with cPLA2 phosphorylation. Furthermore, in the presence of inhibitors of p38 kinase, the proline-directed phosphorylation of cPLA2 was completely blocked in platelets stimulated with the thrombin receptor agonist peptide SFLLRN and was suppressed during the early (up to 2 min) phase of platelet stimulation caused by thrombin. Unexpectedly, we found that prevention of proline-directed phosphorylation of cPLA2 in stimulated platelets did not attenuate its ability to release arachidonic acid from platelet phospholipids. We conclude that: 1) cPLA2 is a physiological target of p38 kinase; 2) p38 kinase is involved in the early phosphorylation of cPLA2 in stimulated platelets; and 3) proline-directed phosphorylation of cPLA2 is not required for its receptor-mediated activation.
Determination of equilibrium binding affinity of distamycin and netropsin to the synthetic deoxyoligonucleotide sequence d(GGTATACC)2 by quantitative DNase I footprinting (1988)

A new method for determining the equilibrium binding constant of antitumor drugs to specific DNA sequences by quantitative DNase I footprinting is presented. The use of a short synthetic DNA oligomer to define a homogeneous population of DNA binding sites enables the calculation of the free drug concentration and the fraction of DNA sites complexed with drug in solution and is described for the first time. Since a 1:1 stoichiometry is observed for each drug-oligomer DNA complex, it becomes possible to calculate equilibrium binding constants in solution. By use of this technique, the binding affinities of the nonintercalating drugs netropsin and distamycin to the synthetic oligonucleotide d(GGTATACC)2 are determined to be Ka (25 degrees C) = 1.0 X 10(5) and 2.0 X 10(5) M-1, respectively. Quantitation of the temperature dependence associated with complex formation results in a determination of standard enthalpies of -3.75 and -8.48 kcal mol-1 for the binding of netropsin and distamycin, respectively. Calculation of other thermodynamic parameters are found to be in agreement with previous studies and indicate that the DNA binding process for these compounds is predominantly enthalpy driven. This method of quantitative DNase I footprinting is demonstrated to be a useful technique for the measurement of drug affinities to specific binding sites on DNA oligomers which are designed and synthesized expressly for this purpose. Applications of the technique to the determination of drug binding affinities at specific sites within native DNA sequences are discussed.
Evaluation of Fluorosurfactant Performance with Super-Critical CO2 Flooding for High Salinity Carbonate Reservoirs (2014)

Abstract Super-Critical CO2 flooding combined with surfactants is one of the latest methods being used for Enhanced Oil Recovery. This overcomes the shortcomings associated with CO2 gas injection like gravity override and viscous fingering to an appreciable extent. It restricts the mobility of the injected fluid leading to higher contact with the resident crude resulting in better sweep efficiency. A number of surfactants have been tested with CO2 to appraise performance in different scenarios. However there have been problems of surfactant instability at real reservoir conditions i.e. at high temperature and high salinity. Adsorption of surfactants on the rock surface is another issue that usually decreases the effectiveness of the system. In the core-flood experiments performed in this work, an amine oxide-based amphoteric fluorosurfactant has been injected with super critical CO2 for the first time on foot long carbonate cores saturated with high saline formation water (Total Dissolved Solids &amp;gt; 200,000 ppm). High temperature (90°C) and pressure (2500 psi) were applied coupled with 5 days of aging time with reservoir crude to recreate actual reservoir environment. Different injection strategies were studied including co-injection of super-critical CO2 and surfactant solution, and alternating injection of super-critical CO2 and surfactant solution in different ratios, and then compared to find out the optimum injection strategy. Results from the study exhibit a significant increase in the oil recovery due to this CO2-surfactant system as well as foam generation in high saline environment for the co-injection scheme. This research provides a new and viable option for CO2-Surfactant flooding especially for high salinity carbonate reservoirs. It displays the usefulness of the surfactant even at very low concentrations, thus mitigating the high cost of this type of surfactants. Furthermore, this surfactant does not contain environment harmful substances making it a greener substitute to conventional hydrocarbon surfactants.
Identification of a General Transcription Factor TFIIAα/β Homolog Selectively Expressed in Testis (1999)

In this paper we describe the isolation of a cDNA that encodes a human TFIIAalpha/beta-like factor (ALF). The open reading frame of ALF predicts a protein of 478 amino acids that contains characteristic N- and C-terminal conserved domains separated by an internal nonconserved domain. In addition, a rare ALF-containing cDNA, which possesses an extended N terminus (Stoned B/TFIIAalpha/beta-like factor; SALF) has also been identified. The results of Northern and dot blot analyses show that ALF is expressed almost exclusively in testis; in contrast, TFIIAalpha/beta and TFIIAgamma are enriched in testis but are also widely expressed in other human tissues. Recombinant ALF (69 kDa) and TFIIAgamma (12 kDa) polypeptides produced in Escherichia coli form an ALF/gamma complex that can stabilize TBP-TATA interactions in an electrophoretic mobility shift assay. The ALF/gamma complex is also able to restore transcription from the adenovirus major late promoter using HeLa cell nuclear extracts that have been depleted of TFIIA. Overall, the data show that ALF is a functional homolog of human general transcription factor TFIIAalpha/beta that may be uniquely important to testis biology.
Neutrophil Sequestration and Migration in Localized Pulmonary Inflammation: Capillary Localization and Migration across the Interalveolar Septum (1993)

Recent studies have raised the possibility that biophysical properties of the neutrophil, specifically cell size and deformability, along with the unique hemodynamic properties of the pulmonary microvasculature may be important determinants of neutrophil transit through the lung and lead to significant retention in capillaries. Additionally, accumulating evidence supports the concept that leukocytes may emigrate into inflammatory lesions through the pulmonary capillary wall, quite unlike the situation in the systemic circulation where the predominant site of margination and emigration is the postcapillary venule. To confirm and extent this suggestion, morphometric techniques were employed to determine the location and kinetics of neutrophil movement from the vascular compartment to the alveolar space in response to an inflammatory reaction initiated by local instillation of fragments of the activated form of the fifth component of complement (C5f). We found that the site of neutrophil sequestration and probable migration was almost exclusively the capillary. Neutrophil sequestration appeared first in the capillaries of the interalveolar septae, with negligible accumulation in arterioles and venules (less than that in interalveolar septae by a factor of 10(4) when corrected for the relevant surface areas). Accumulation in the airspaces lagged behind that in the interalveolar septa by about 60 min, placing an upper time-limit on the emigration process across the epithelial barriers. Interestingly, neutrophils samples by bronchoalveolar lavage represented only 1 to 2% of those neutrophils shown to be present in the airspaces of the lung by morphometric assessment, suggesting that bronchoalveolar lavage may sample only a subpopulation of the emigrated cells.(ABSTRACT TRUNCATED AT 250 WORDS)