gebhart/patrepeval huggingface dataset:
Cholinergic Atrial Fibrillation in a Computer Model of a Two-Dimensional Sheet of Canine Atrial Cells With Realistic Ionic Properties (2002)

Classical concepts of atrial fibrillation (AF) have been rooted in Moe's multiple-wavelet hypothesis and simple cellular-automaton computer model. Recent experimental work has raised questions about the multiple-wavelet mechanism, suggesting a discrete "driver region" underlying AF. We reexplored the theoretical basis for AF with a 2-dimensional computer model of a 5x10-cm sheet of atrial cells with realistic ionic and coupling properties. Vagal actions were formulated based on patch-clamp studies of acetylcholine (ACh) effects. In control, a single extrastimulus resulted in a highly meandering unstable spiral wave. Simulated electrograms showed fibrillatory activity, with a dominant frequency (DF, 6.5 Hz) that correlated with the mean rate. Uniform ACh reduced core meander of the spiral wave by approximately 70% (as measured by the standard deviation of spiral-wave tip position) and accelerated the DF to 17.0 Hz. Simulated vagally induced refractoriness heterogeneity caused wavefront breakup as accelerated reentrant activity in regions of short refractoriness impinged on regions unable to respond in a 1:1 fashion because of longer refractoriness. In 7 simulations spanning the range of conditions giving sustained AF, 5 were maintained by single dominant spiral waves. On average, 3.0+/-1.3 wavelets were present (range, 1 to 7). Most wavelets were short-lived and did not contribute to AF maintenance. In contrast to predictions of the multiple-wavelet hypothesis, but in agreement with recent experimental evidence, our model indicates that AF can result from relatively stable primary spiral-wave generators and is significantly organized. Our results suggest that vagal AF may arise from ACh-induced stabilization of the primary spiral-wave generator and disorganization of the heterogeneous tissue response. The full text of this article is available at http://www.circresaha.org.
Improved efficiency sos recruitment system: expression of the mammalian GAP reduces isolation of Ras GTPase false positives (1997)

The Sos recruitment system (SRS) is a novel genetic method for detecting protein-protein interactions. The method is based on localizing Sos, a Ras guanyl nucleotide exchange factor (GEF), to the plasma membrane through interaction between two fusion proteins. Mammalian Ras can bypass the requirement for a functional Ras GEF and represents a predictable false positive in this system. This report demonstrates that introduction of mammalian GTPase activating protein (mGAP) reduces the isolation of Ras false positives in SRS screens of mammalian cDNA libraries, thereby significantly enhancing the efficiency of the system.
Manipulating Angiogenesis (1997)

Considerable progress has been made recently in understanding the molecular mechanisms of angiogenesis, which like most other biological processes is the result of subtle and often complex interactions between molecules that have regulatory (eg, cytokines and their receptors) and effector (eg, extracellular matrix, integrins, and proteases) functions. The title of this review was chosen to reflect a recent trend in which knowledge acquired through a molecular/cell biological approach is being rapidly transferred to the clinical setting. As a result, by manipulating angiogenesis either positively or negatively, considerable therapeutic benefit can now be envisaged in physiological and pathological settings in which neovascularization is a prominent component.
Osteopetrosis in Src-deficient mice is due to an autonomous defect of osteoclasts. (1993)

Osteopetrosis is a bone modeling disorder resulting in excessive accumulation of bone matrix due to defective function of osteoclasts, the cells that resorb bone. Mice carrying a targeted disruption of the gene Src that encodes pp60c-src (Src), a nonreceptor protein tyrosine kinase, develop this phenotype but do not exhibit other overt defects despite the fact that the kinase is normally present in a broad variety of cell types. Because Src is expressed in osteoblasts as well as in osteoclasts and both are required for normal bone resorption, the basic defect could occur in either cell type. In this study we have used in vitro approaches and fetal liver transplantation into irradiated Src- recipients to demonstrate that the inherent defect is with osteoclasts and autonomous of the bone marrow microenvironment. This result (i) identifies a cell type in which Src function is essential and cannot be replaced by other related kinases and (ii) should allow the isolation of a substrate that is specific to Src.
Regulation of collagen gene expression in 3T3-L1 cells. Effects of adipocyte differentiation and tumor necrosis factor .alpha. (1989)

An early feature in the development of adipocytes from fibroblast-like precursor cells is the biogenesis of an extracellular basement membrane (Napolitano, 1963; Kuri-Harcuch et al., 1984). Interactions between components of the basement membrane (e.g., collagens) and the surfaces of differentiating adipocytes are thought to regulate subsequent phases of the developmental program. Since fibroblasts principally secrete type I and III collagens whereas type IV collagen is abundant in basement membrane, it appears that a switch in collagen gene expression is a key element in adipocyte differentiation. Little is known about the mechanisms underlying differentiation-dependent changes in collagen expression or the effects of the potent lipolytic cytokine TNF-alpha on collagen mRNA accumulation in preadipocytes and adipocytes. In this study, 3T3-L1 preadipocytes were found to express mRNAs encoding type I, III, and IV procollagens. When 3T3-L1 cells were stimulated to differentiate into adipocytes, the relative concentrations of type I and type III procollagen mRNAs declined by 80-90%. Parallel decreases in the rates of transcription of the procollagen I and procollagen III genes appear to account for the diminished levels of these mRNAs. In contrast, the relative rate of transcription of the procollagen IV gene increased 2.6-fold during adipocyte development. As a consequence, the abundance of type IV procollagen transcripts was elevated in adipocytes. Tumor necrosis factor alpha (TNF-alpha) is a cytokine that stimulates lipolysis, an apparent "dedifferentiation" of adipocytes, and inhibits transcription of certain adipocyte-specific genes. The effects of TNF-alpha on collagen mRNA levels were dependent upon the state of differentiation of 3T3-L1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Healing of segmental bone defects in rats induced by a ?-TCP-MCPM cement combined with rhBMP-2 (1999)

A beta-tricalcium phosphate-monocalcium phosphate monohydrate (beta-TCP-MCPM) cement was evaluated as an effective carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2) in rat femoral critical-size defects. Hard cement cylinders (4 x 5 mm) impregnated with two different doses of rhBMP-2 (1.26 or 6.28 microg) were implanted into each defect, and the results were compared with those in rats that had implantations of cylinders only. Implantation of the 6.28 microg dose of rhBMP-2 caused a large bone shell to form around the defect, resulting in osseous union in all cases within 3 weeks. Except for beta-TCP granules, the cement was resorbed and replaced by bone tissue at 6 weeks. A torsion test at 9 weeks showed that the failure torque and bone stiffness had recovered 99% and 141%, respectively, compared with the intact contralateral femur. The defects that received 1.26 microg of rhBMP-2 resulted in 40% union and 41% of the failure torque at 9 weeks. However, no instances of union were observed in the defects implanted with cylinders only. In conclusion, the beta-TCP-MCPM cement was shown to be effective as a rhBMP-2 carrier. Combined with rhBMP-2, this cement was rapidly resorbed and completely healed the defects.
Inhibition of Spontaneous Metastasis in a Rat Prostate Cancer Model by Oral Administration of Modified Citrus Pectin (1995)

Further investigations are warranted to determine the following: 1) the role of galectin-3 in normal and cancerous prostate tissues and 2) the ability of modified citrus pectin to inhibit human prostate metastasis in nude mice.
Iron-Catalyzed Cascade Arene−Aldehyde Addition/Cyclizations for the Highly Efficient Synthesis of Xanthenes and Its Analogous: Observation of a C−C Bond Cleavage in Indole-Based Triarylmethanes (2009)

An efficient, general, and one-pot procedure for the synthesis of multisubstituted xanthene derivatives through Fe(III)-catalyzed reactions of 2-aryloxybenzaldehydes with electron-rich arenes has been developed. This method offers several advantages such as high selectivities, mild reaction conditions, and easily accessible starting materials. A mechanistic study revealed that a C-C bond cleavage of a triarylmethane intermediate might be involved in the domino process.
A conus peptide blocks nicotinic receptors of unmyelinated axons in human nerves (2005)

The novel alpha-conotoxin Vc1.1 is a potential analgesic for the treatment of painful neuropathic conditions. In the present study, the effects of Vc1.1 were tested on the nicotine-induced increase in excitability of unmyelinated C-fiber axons in isolated segments of peripheral human nerves. Vc1.1 in concentrations above 0.1 microM antagonized the increase in axonal excitability produced by nicotine; the maximal inhibition was observed with 10 microM. We also demonstrate immunoreactivity for alpha 3 and alpha 5 subunits of neuronal nicotinic receptors on unmyelinated peripheral human axons. Blockade of nicotinic receptors on unmyelinated peripheral nerve fibers may be helpful in painful neuropathies affecting unmyelinated sympathetic and/or sensory axons.
Structure and Cellular Distribution of Mouse Brain Testican (1996)

The complete deduced primary structure of mouse brain testican has been established from cDNA cloning. The cDNA encodes a polypeptide of 442 amino acids belonging to the proteoglycan family. The mouse brain testican core protein is 95% identical to its human testicular counterpart. In situ hybridization investigations revealed that mouse testican mRNA is mainly present in a subpopulation of pyramidal neurons localized in the CA3 area of the hippocampus. An immunocytochemical approach, with antibodies directed against an overexpressed chimeric antigen, produced in bacterial systems, showed that testican is associated with the postsynaptic region of these pyramidal neurons. Testican includes several putative functional domains related to extracellular or pericellular proteins associated with binding and/or regulatory functions. On the basis of its structural organization and its occurrence in postsynaptic areas, this proteoglycan might contribute to various neuronal mechanisms in the central nervous system.
Bioactive Diterpenoids Isolated from Salvia mellifera (1996)

Eight diterpenoids were isolated from the roots of Salvia mellifera Greene. Their structures were elucidated by comparison to their physical and spectroscopy data with those reported in the literature or that of authentic samples as: abieta-8,11,13-triene, ferruginol, 15-deoxi-fuerstione, taxodione, isotanishinone III, rolyeanone, 7αsl-hydroxi-rolyleanone and demethylsalvicanol. Demethylsalvican-11-12-dione was obtained by oxidation with Ag2O from demethylsalvicanol. Compounds ferruginol, taxodione, isotanshinone III, and 7αsl-hydroxi-royleanone showed cytotoxic activity against both HeLa and Hep-2 cells in culture. Royleanone and demethylsalvican-11-12-dione were active on Hep-2 and HeLa cells respectively. Antimicrobial activity against some Gram (+) bacteria was observed for the diterpenoids ferruginol, taxodione, 7α-hydroxi-royleanone and demethylsalvican-11-12-dione. None of them was active on Gram (−) bacteria or Candida albicans.
The angiotensin-I-converting enzyme inhibitor perindopril suppresses tumor growth and angiogenesis: possible role of the vascular endothelial growth factor. (2001)

Angiotensin-I converting enzyme (ACE) inhibitor is used widely as an antihypertensive agent, and it has been suggested recently that it decreases the risk of cancer (A. F. Lever et al., Lancet, 352: 179-184, 1998). In this study, we examined the effect of several ACE inhibitors and angiotensin-II type 1 receptor (AT(1)-R) antagonists on tumor development and angiogenesis in a murine hepatocellular carcinoma model. Among ACE inhibitors, perindopril appeared to be a potent inhibitor of tumor development and angiogenesis, whereas AT(1)-R antagonists did not exert such an inhibitory effect. The inhibitory effect of perindopril was achieved even on established tumors. The level of the potent angiogenic factor, vascular endothelial growth factor (VEGF), in the tumor was significantly suppressed by perindopril. In vitro studies showed that perindopril-derived active form, perindoprilat, suppressed the endothelial cell tubule formation. Perindoprilat treatment also significantly inhibited VEGF mRNA expression in BNL-HCC cells in vitro. These results showed that the ACE inhibitor perindopril inhibited tumor development and angiogenesis independent from AT(1)-R blockage, and that VEGF alternation may be involved in the mechanism of this inhibitory effect. Because perindopril is widely used in clinical practice, it may represent an effective new strategy for anticancer therapy.
Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes (2011)

Five-year results of SBRT for localized prostate cancer demonstrate the efficacy and safety of shorter courses of high dose per fraction radiation delivered with SBRT technique. Ongoing clinical trials are underway to further explore this treatment approach.
The photoinduced long-lived charge-separated state of Ru(bpy)3–methylviologen with cucurbit[8]uril in aqueous solution (2006)

A stable 1 : 1 inclusion complex of Ru(bpy)(3)-MV(2+) with cucurbit[8]uril (CB[8]) is formed in aqueous solution; upon light irradiation, a long lived (tau approximately 2 micros) charge-separated state Ru(3+)-MV(+ )-CB[8] is observed.
The bombesin receptor is coupled to a guanine nucleotide-binding protein which is insensitive to pertussis and cholera toxins. (1988)

The neuropeptide bombesin acts on a variety of target cells to stimulate the processes of secretion and cell proliferation. In this study we determined whether bombesin receptors interact with known guanine nucleotide-binding proteins in four different cell types: GH4C1 pituitary cells, HIT pancreatic islet cells, Swiss 3T3 fibroblasts, and rat brain tissue. Maximal concentrations of nonhydrolyzable GTP analogs decreased agonist binding to bombesin receptors in membranes from all four sources. In GH4C1 and HIT cell membranes GTP analogs inhibited bombesin receptor binding with IC50 values of about 0.1 microM, whereas GDP analogs were approximately 10-fold less potent. In contrast, GMP and the nonhydrolyzable ATP analog adenylyl-imidodiphosphate had no effect at 100 microM. Equilibrium binding experiments in GH4C1 and HIT cell membranes indicated a single class of binding sites with a dissociation constant (Kd) for [125I-Tyr4]bombesin of 24.4 +/- 7.0 pM and a binding capacity of 176 +/- 15 fmol/mg protein. Guanine nucleotides decreased the apparent affinity of the receptors without significantly changing receptor number. Consistent with this observation, guanine nucleotides also increased the rate of ligand dissociation. Pretreatment of GH4C1 or HIT cells with either pertussis toxin (100 ng/ml) or cholera toxin (500 ng/ml) for 18 h did not affect agonist binding to membrane bombesin receptors, its regulation by guanine nucleotides, or bombesin stimulation of hormone release. Although pertussis toxin pretreatment has been reported to block bombesin stimulation of DNA synthesis in Swiss 3T3 cells, it did not alter the binding properties of bombesin receptors in Swiss 3T3 membranes or inhibit the rapid increase in intracellular [Ca2+] produced by bombesin in these cells. In summary, our results indicate that the bombesin receptor interacts with a guanine nucleotide-binding protein which exhibits a different toxin sensitivity from those which regulate adenylate cyclase as well as those which couple some receptors to phospholipases.
Thermostable Alkaline Xylanases Produced by Alkaliphilic Strains of Bacillus spp.. (1994)

Land plants are mainly composed of cellulose, hemicellulose and lignin. Xylans are major components of hemicellulosic polysaccharides, and one of the most abundant biopolymers. The main chain of xylans from all land plants is based on a β-1, 4-D-xylopyranosyl linkage. This main chain is substituted with a variable number of neutral or uronic monosaccharide, short oligosaccharide side chains, or non-saccharide substituents. Most of xylans are consequently heteropolysaccharides containing L-arabinofuranose, D-galactopyranose and D-glucuronopyranose. Lignin is one of the non-saccharide substituents. Structure of xylans varies in the nature and degree of branching of the main chain.So-called xylanases hydrolyze the β-1, 4-linked xylopyranosyl main chain of land plant xylans to produce xylose or xylooligosaccharides. Xylanases can hydrolyze not only soluble xylans but also insoluble ones bound to cellulose. Therefore, xylanases can break down xylans remaining in pulp. A part of lignin can be consequently removed from the pulp by treatment with xylanases. This “bio-bleaching” process would possibly decrease the amount of chlorine used for pulp bleaching. Toxic or carcinogenic chlorinated compounds have been produced from wood components with the chlorine and thrown into environments.Xylanases have been isolated from various bacteria and fungi. Most of microbial xylanases show the enzymic activities at acidic or neutral pH regions. We have investigated alkaliphilic microorganisms, that are one of extremophiles, and their enzymes.Several xylanases have been isolated from alkaliphiles during a course of the investigation. Some of them are alkaline-active and thermostable. These alkaline xylanases might be suitable for the bio-bleaching process, because the pulp is generally processed at a high alkaline pH and high temperature condition. This article reviews the β-1, 4-xylanases produced by alkaliphiles that have been isolated.
2-D modeling of laterally acoustically coupled thin film bulk acoustic wave resonator filters (2010)

A 2-D model is developed for calculating lateral acoustical coupling between adjacent thin film BAW resonators forming an electrical N-port. The model is based on solution and superposition of lateral eigenmodes and eigenfrequencies in a structure consisting of adjacent regions with known plate wave dispersion properties. Mechanical and electrical response of the device are calculated as a superposition of eigenmodes according to voltage drive at one electrical port at a time while extracting current induced in the other ports, leading to a full Y-parameter description of the device. Exemplary cases are simulated to show the usefulness of the model in the study of the basic design rules of laterally coupled thin film BAW resonator filters. Model predictions are compared to an experimental 1.9-GHz band-pass filter based on aluminum nitride thin film technology and lateral acoustical coupling. Good agreement is obtained in prediction of passband behavior. The eigenmode-based model forms a useful tool for fast simulation of laterally coupled acoustic devices. It allows one to gain insight into basic device physics in a very intuitive fashion compared with more detailed but heavier finite element method. Shortcomings of this model and possible improvements are discussed.
Differential Antidiabetic Efficacy of Incretin Agonists Versus DPP-4 Inhibition in High Fat–Fed Mice (2007)

Mice treated with vehicle alone or DA-GIP exhibited progressive weight gain, whereas treatment with Ex-4 or DPP-4i prevented weight gain. Although Ex-4 improved oral glucose tolerance and insulin-to-glucose ratios after an intraperitoneal glucose tolerance test (IPGTT), DPP-4i had no significant effect after IPGTT but improved glucose excursion and insulin levels after an oral glucose tolerance test. The extent of improvement in glycemic control was more sustained with continuous DPP-4 inhibition, as evidenced by loss of glucose control evident 9 h after peptide administration and a significant reduction in A1C observed with DPP-4i but not with DA-GIP or Ex-4 therapy. DA-GIP, but not Ex-4 or DPP-4i, was associated with impairment in insulin sensitivity and increased levels of plasma leptin and resistin. Although none of the therapies increased beta-cell mass, only Ex-4-treated mice exhibited increased pancreatic mRNA transcripts for Irs2, Egfr, and Gck. These findings highlight significant differences between pharmacological administration of incretin receptor agonists and potentiation of endogenous GLP-1 and GIP via DPP-4 inhibition.
Solubility measurement of liquid organic compounds in water. (1985)

A highly accurate and simple method to determine the solubility of liquid organic compounds in water has been developed.The TOC (Total organic carbon) method has revealed that the concentrations of alcohols and benzene in water can be accurately determined of removal procedure of IC (Inorganic carbon) is eliminated, as shown in Table 1.Saturated aqueous solutions of organic co mpounds were obtained as follows: After shaking of a supersaturated aqueous solution, the mixture was allowed to stand until equilibrium was reached. Then an oil drop suspending in the mixture was broken by filtration of the mixture through a glass fiber filter paper (Table 2) moistened with water.
Epinephrine sensitivity with respect to metabolic rate and other variables in women (1983)

A test for determination of epinephrine sensitivity has been worked out using six healthy young women. Variables considered were metabolic rate, heart rate, respiratory frequency, blood pressure, blood glucose, plasma insulin, glycerol, free fatty acids, and lactate. After established basal conditions, epinephrine was infused at rates of 0.01, 0.03, and 0.1 microgram X kg fat-free mass-1 X min-1. Most variables responded to epinephrine in a dose-dependent manner. Physiological threshold plasma concentrations of epinephrine ranged from 95 to 250 pg/ml for different variables. Calculated maximal responses ranged from approximately -15% to +900% of basal values and infusion rates giving half-maximal responses from approximately 15 to 190 ng X kg fat-free mass-1 X min-1. On an average, metabolic rate increased by 8, 16, and 29%, respectively, at the three infusion rates, and the maximal metabolic response was calculated to be approximately 35%. The error in determining epinephrine-induced increments in metabolic rate was 7% of the response. As calculated from nonprotein RQ, carbohydrate oxidation increased and lipid oxidation decreased rapidly during the first 10 min of epinephrine infusion. Later, fat oxidation became more important. Results on epinephrine plasma metabolic clearance rate agreed with earlier results in the literature.