gebhart/patrepeval huggingface dataset:
Effects of salvianolic acid-A on NIH/3T3 fibroblast proliferation, collagen synthesis and gene expression (2000)

AIM:To investigate the mechanisms of salvianolic acid A (SA-A) against liver fibrosis in vitro.METHODS:NIH/3T3 fibroblasts were cultured routinely, and incubated with 10(-4) mol/L-10(-7)mol/L SA-A for 22h. The cell viability was assayed by (3)H proline incorporation, cell proliferation by (3)H TdR incorporation, cell collagen synthetic rate was measured with (3)H proline impulse and collagenase digestion method.The total RNA was prepared from the control cells and the drug treated cells respectively, and alpha(1) I pro-collagen mRNA expression was semi-quantitatively analyzed with RT-PCR.RESULTS:10(-4)mol/L SA-A decreased cell viability and exerted some cytotoxiciy,while 10(-5)mol/L -10(-7)mol/L SA-A did not affect cell viability, but inhibited cell proliferation significantly, and 10(-6)mol/L SA-A had the best effect on cell viability among these concentrations of drugs. 10 (-5)mol/L -10(-6)mol/L SA-A inhibited intracellular collagen synthetic rate, but no significant influence on extracellular collagen secretion. Both 10(-5)mol/L and 10(-6)mol/L SA-A could decrease alpha(1)I pro-collagen mRNA expression remarkably.CONCLUSION:SA-A had potent action against liver fibrosis. It inhibited NIH/3T3 fibroblast proliferation, intracellular collagen synthetic rate and type I procollagen gene expression, which may be one of the main mechanisms of the drug.
NMR methods for the study of protein structure and dynamics (1997)

An understanding of the role played by a protein in cellular function requires a detailed picture of its three-dimensional structure as well as an appreciation of how the structure varies as a function of time as a result of molecular dynamics. Over the past several years, multidimensional, multinuclear solution NMR spectroscopy has become a powerful technology for obtaining both structural and dynamical information on proteins and protein-ligand systems. In the present review, a number of new methodological advances are highlighted that have significantly improved the quality of NMR spectra of biomolecules and have increased the molecular weight limitations previously imposed on NMR-based structural studies of macromolecules. Applications of this technology to a number of protein systems currently studied in my laboratory are presented.
Common DNS Operational and Configuration Errors (1996)

This memo describes errors often found in both the operation of Domain Name System (DNS) servers, and in the data that these DNS servers contain. This memo tries to summarize current Internet requirements as well as common practice in the operation and configuration of the DNS. This memo also tries to summarize or expand upon issues raised in [RFC 1537].
The FKBP12-Rapamycin-binding Domain Is Required for FKBP12-Rapamycin-associated Protein Kinase Activity and G1 Progression (1999)

The immunosuppressant rapamycin, in complex with its cellular receptor FKBP12, targets the cellular protein FKBP12-rapamycin-associated protein/mammalian target of rapamycin/rapamycin and FKBP12 target 1 (FRAP/mTOR/RAFT1) and inhibits/delays G1 cell cycle progression in mammalian cells. As a member of the novel phosphatidylinositol kinase-related kinase family, FRAP's kinase activity is essential for its signaling function. The FKBP12-rapamycin binding (FRB) domain in FRAP is also speculated to play an important role in FRAP function and signaling. However, the biochemical and physiological functions of FRB, as well as the mechanism for rapamycin inhibition, have been unclear. The present study focuses on investigation of FRB's role and the functional relationship between FRB domain and kinase domain in FRAP. Microinjection of purified FRB protein into human osteosarcoma MG63 cells results in a drastic blockage of the G1 to S cell cycle progression; such a dominant negative effect is reversed by a point mutation (Trp2027 --> Phe). The same mutation also abolishes kinase activity of FRAP without affecting ATP binding, and truncation studies suggest that upstream sequences including FRB are required for kinase activity in vitro. Given these data, we propose a model for FRAP function, in which the FRB domain is required for activation of the kinase domain, possibly through the interaction with an upstream activator. In addition, our observations provide direct evidence linking FRAP function to G1 cell cycle progression.
Quantitative analysis of tumor-derived methylated RUNX3 sequences in the serum of gastric cancer patients. (2009)

Quantification of epigenetic changes in serum RUNX3 methylation using RTQ-MSP is useful for the detection and monitoring of gastric cancer.
Species comparison of anatomical and functional immune system development (2003)

The components of the immune system have not been traditionally emphasized as potential target organs in standard developmental and reproductive toxicity (DART) protocols. A number of workshops have been organized in recent years to examine scientific questions that underlie developmental immunotoxicity tests, and the interpretation of results as they relate to human risk assessment. A key question that must be addressed is to determine the most appropriate species and strains to model the developing human immune system. The objective of this review is to compare the anatomical and functional development of the immune system in several species important to either preclinical studies for drug development or safety assessments for chemicals, with what is known in humans. The development of the immune system in humans will be compared to what is known in mice, rats, dogs and nonhuman primates.
Coax via-A technique to reduce crosstalk and enhance impedance match at vias in high-frequency multilayer packages verified by FDTD and MoM modeling (1997)

Large-scale crosstalk at vias and poor via electrical performance are major drawbacks in state-of-the-art high-frequency multilayer first- or second-level integrated-circuit/monolithic-microwave integrated-circuit (IC/MMIC) packages. The coax via design modeled in this paper breaks new ground in achieving more than 30-dB ultrawide-band crosstalk reduction and providing an enhanced impedance match.
Zollinger–Ellison Syndrome (1987)

The Zollinger-Ellison syndrome, although uncommon, is not rare, and most patients with the disorder present with clinical manifestations similar to those of patients with common peptic ulcer. Early studies emphasized death due to complications of massive gastric acid hypersecretion. However, with the availability of potent antisecretory agents to control acid secretion, death is now more frequently associated with the metastatic potential of slowly growing but malignant gastrinomas. Therefore, physicians should maintain a high degree of suspicion of the Zollinger-Ellison syndrome in assessing patients with either chronic peptic ulcer or unexplained secretory diarrhea. An evaluation aimed at early diagnosis of the Zollinger-Ellison syndrome should be instituted in such patients and should begin with a determination of the fasting serum gastrin level. At least 50 percent of patients with gastrinoma will have nondiagnostic serum gastrin concentrations and will therefore require provocative testing to establish the correct diagnosis. After the presence of the syndrome is established, patients should be treated with a potent antisecretory agent in doses sufficient to reduce basal acid output to less than 10 mmol in the hour preceding administration of the next dose. Although some patients may be maintained satisfactorily in this manner for extended periods, an approach aimed at tumor localization and extirpation is recommended in most patients. Preoperative evaluation should begin with CT scanning with intravenous contrast material. Selective angiography, and occasionally, portal venous sampling for gastrin, should be performed if the location and extent of tumor remain in question. If metastatic disease is demonstrated, or if MEN-I is present, surgery aimed at tumor resection, although it is occasionally effective, will probably be unsuccessful. Because of the considerable morbidity and mortality associated with pancreatoduodenectomy, it should not be performed for unresectable tumor in the head of the pancreas. In other patients with the Zollinger-Ellison syndrome, exploratory surgery should be performed; this should include a careful search for, and resection of, all pancreatic and extrapancreatic gastrinomas. With this approach, it is likely that at least 20 percent of all patients with the Zollinger-Ellison syndrome can be cured.
The Crystal Structure of Human Placenta Growth Factor-1 (PlGF-1), an Angiogenic Protein, at 2.0 Å Resolution (2001)

The angiogenic molecule placenta growth factor (PlGF) is a member of the cysteine-knot family of growth factors. In this study, a mature isoform of the human PlGF protein, PlGF-1, was crystallized as a homodimer in the crystallographic asymmetric unit, and its crystal structure was elucidated at 2.0 A resolution. The overall structure of PlGF-1 is similar to that of vascular endothelial growth factor (VEGF) with which it shares 42% amino acid sequence identity. Based on structural and biochemical data, we have mapped several important residues on the PlGF-1 molecule that are involved in recognition of the fms-like tyrosine kinase receptor (Flt-1, also known as VEGFR-1). We propose a model for the association of PlGF-1 and Flt-1 domain 2 with precise shape complementarity, consider the relevance of this assembly for PlGF-1 signal transduction, and provide a structural basis for altered specificity of this molecule.
Milolides G−N, New Briarane Diterpenoids from the Western Pacific Octocoral Briareum stechei (2002)

Twelve new briarane diterpenes, designated milolides (1-12), and one known diterpene, 9-deacetylstylatulide lactone (13), were isolated from the Micronesian octocoral Briareum stechei collected at Yap, Federated States of Micronesia. Their structures were determined from spectral data.
Chapter 2. Physical methods. Part (ii) Electron spin resonance spectroscopy (1970)

B. C. Gilbert, Annu. Rep. Prog. Chem., Sect. B: Org. Chem., 1970, 67, 18 DOI: 10.1039/OC9706700018
Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17 (1998)

Pallido-ponto-nigral degeneration (PPND) is one of the most well characterized familial neurodegenerative disorders linked to chromosome 17q21-22. These hereditary disorders are known collectively as frontotemporal dementia (FTD) and parkinsonism linked to chromosome 17 (FTDP-17). Although the clinical features and associated regional variations in the neuronal loss observed in different FTDP-17 kindreds are diverse, the diagnostic lesions of FTDP-17 brains are tau-rich filaments in the cytoplasm of specific subpopulations of neurons and glial cells. The microtubule associated protein (tau) gene is located on chromosome 17q21-22. For these reasons, we investigated the possibility that PPND and other FTDP-17 syndromes might be caused by mutations in the tau gene. Two missense mutations in exon 10 of the tau gene that segregate with disease, Asn279(Lys) in the PPND kindred and Pro301(Leu) in four other FTDP-17 kindreds, were found. A third mutation was found in the intron adjacent to the 3' splice site of exon 10 in patients from another FTDP-17 family. Transcripts that contain exon 10 encode tau isoforms with four microtubule (MT)-binding repeats (4Rtau) as opposed to tau isoforms with three MT-binding repeats (3Rtau). The insoluble tau aggregates isolated from brains of patients with each mutation were analyzed by immunoblotting using tau-specific antibodies. For each of three mutations, abnormal tau with an apparent Mr of 64 and 69 was observed. The dephosphorylated material comigrated with tau isoforms containing exon 10 having four MT-binding repeats but not with 3Rtau. Thus, the brains of patients with both the missense mutations and the splice junction mutation contain aggregates of insoluble 4Rtau in filamentous inclusions, which may lead to neurodegeneration.
The natural chemopreventive compound indole-3-carbinol: state of the science. (2006)

The hydrolysis product of glucobrassicin, indole-3-carbinol (I3C), is metabolized to a variety of products, including the dimeric 3,3'-diindolylmethane (DIM). Both I3C and DIM exert a variety of biological and biochemical effects. Most of these effects appear to occur because I3C modulates several nuclear transcription factors. I3C induces phase I and phase II enzymes that metabolize carcinogens, including estrogens. Administration of either I3C or DIM results in increased 2-hydroxylation of estrogens. I3C also enhances DNA repair by affecting several of the proteins involved in this process. I3C induces both G1 cell cycle arrest and apoptosis. All of these activities lead to anticancer effects. Although I3C has been shown to protect against tumor induction by some carcinogens, it has also been observed to promote tumor development in animal models. In humans, I3C and DIM affect the metabolism of estrogens. Concerns have been raised that I3C might increase the formation of estrogen metabolites that induce or promote cancer, but this has not been demonstrated. I3C has been found to be effective in treating some cases of recurrent respiratory papillomatosis, and it may have other clinical uses.
Small Business Clusters in Oklahoma: MAR or Jacobs Effects? (2010)

One of the main factors that act as catalysts for small business creation seems to be the existence of business clusters. This study uses both standard and spatial statistics methodologies and tools to analyze the dynamics of small business clusters and the degree to which it is influenced by Marshall-Arrow-Romer or Jacobs effects. The study contributes to better understanding of the influence that industrial diversity or specialization has on the growth of the number of small businesses and, consequently, on small businesses cluster formation. Maybe the most significant finding of this study is that the evidence suggests that Marshall-Arrow-Romer effects are preponderant. Indeed, the study finds significant MAR dynamic effects for the period under scrutiny, as well as Marshall-Arrow-Romer static effects for 2005.
Conformational effects on retinoid receptor selectivity. 1. Effect of 9-double bond geometry on retinoid X receptor activity (1993)

A major challenge is the development of retinoids with selective biological activities. Recently, studies on retinoid response mechanisms indicate that retinoids activate two classes of nuclear receptor proteins, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Here, we analyze the activity of a series of (E)- and (Z)-stilbenecarboxylic acids for gene transcriptional activation of the RARs and RXR-alpha to determine the optimum pharmacophore for receptor activation. The data obtained indicate that RAR and RXR response pathways can be separated by using the appropriate ligand. The conformations of (Z)-4-[2-(5-,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)prop en-1-yl]benzoic acid (Z)-4-[1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)propen-2-yl]benzoic acid were examined by experimental and theoretical methods to establish the appropriate conformation of the latter that specifically activated the retinoid RXR. A palladium(0)-catalyzed aryl bromide-arylboronic acid coupling under nonanhydrous conditions was used to construct a biaryl bond in the conformationally restricted retinoid 2'- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthaleny)biphenyl-4-c arboxylic acid, which had RXR activity.
Integral image compression based on optical characteristic (2011)

The large amount of image data from the captured three-dimensional integral image requires to be presented with adequate resolution. It is therefore necessary to develop compression algorithms that take advantage of the characteristics of the recorded integral image. In this study, the authors propose a new compression method that is adapted to integral imaging. According to the optical characteristics of integral imaging, most of the information of each elemental image is overlapped with that of its adjacent elemental images. Thus, the method is to achieve image compression by taking a sample from the elemental image sequence for every m elemental image to get image compression. Experimental results that are presented to illustrate the proposed compression technique prove that the proposed technique can improve the compression ratio of integral imaging.
Voltage control in power system using expert system based on SCADA system (2003)

This paper presents the type of expert system for controlling the 22 kV voltage levels of a power system in the northern region of Thailand based on the SCADA system. At present, for the operation, the operators have to make decisions by their knowledge and experience to control the voltage. This expert system is obtained for alleviation of voltage violation in the day-to-day operation of a distribution substation in the system, and for processing the data from the SCADA for helping the operator detect buses experiencing abnormal conditions. This expert system focused on shunt reactive compensating devices and transformer tap change to select the most effective control for keeping the bus voltage in the entire system within limits. This study selected 6 distribution substations to be tested with this expert system. The performance of the expert system is compared with the operator control in the terms of voltage deviation indices, numbers of tap changing and minimizing losses.
The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique. (1987)

The nonobese diabetic mouse is recognized as an important animal model for human insulin-dependent diabetes mellitus. One of the components of susceptibility to this disease has been mapped to the major histocompatibility complex. In this study, full-length cDNA clones encoding the I-A alpha and beta chains from the nonobese diabetic mouse have been isolated and sequenced. They are identical to the sequences previously determined from the H-2d haplotype except for the sequence encoding the first external domain, the leader peptide, and the 5' untranslated region of the I-A beta chain molecule. Most strikingly, there are five consecutive nucleotide substitutions which lead to two radical amino acid changes in a region that is conserved between human and mouse. We suggest that the unique structure of the first external I-A beta chain domain is a major determinant in the disease susceptibility that maps to the major histocompatibility complex of the nonobese diabetic mouse.
Fibrinolysis: an unfinished agenda (2000)

There has been a recent decline in interest in fibrinolysis, suggesting that its physiological basis is sufficiently understood and that therapeutic thrombolysis has reached its limit. The importance of the subject has not diminished since cardiovascular disease is now a leading health problem even in developing countries. Certain highlights and inconsistencies are reviewed. The clinical trials of tissue plasminogen activator (t-PA) revealed a major discrepancy between its fibrinolytic efficacy and its clinical benefit (the 't-PA paradox') that is unexplained. Dose-finding studies also showed that the fibrinolytic efficacy of t-PA required significant nonspecific plasminogen activation. Furthermore, the longstanding belief that t-PA is responsible for physiological fibrinolysis and urokinase-type PA (u-PA) for pericellular plasminogen activation is belied by extensive experimental animal data, but these findings have had little impact on traditional thinking. As a result, the mechanisms responsible for the u-PA paradigm of fibrinolysis have received little attention. Clinical experience with pro-u-PA remains limited and most clinical trials have used infusion rates at which pro-u-PA is largely converted systemically to urokinase. This is due to the unanticipated instability of pro-u-PA in plasma at pharmacological concentrations. Insufficient understanding of basic mechanisms of fibrinolysis has handicapped the design of chimeric or mutant activators. It is submitted that physiological fibrinolysis remains to be better defined, and that it is premature to conclude that therapeutic thrombolysis will be inevitably accompanied by side effects that undermine this method of inducing reperfusion.
Androgen-Estrogen Metabolism in Women with Upper BodyVersusLower Body Obesity* (1990)

Androgen and estrogen production rates were examined in 29 morbidly obese women with upper or lower body obesity. Although blood production rates of testosterone (T), dihydrotestosterone, and androstenedione (A4) were elevated in all of these women, those with upper body obesity (waist-height ratios, greater than 0.85) had higher T and production rates than women with lower body obesity (waist-height ratio less than 0.75). A4 was equally elevated in women with upper and lower body obesity. Peripheral aromatization of A4 to estrone (E1) averaged 1.67% in women with upper body obesity, but was elevated at 2.54% in women with lower body obesity. Urinary E1 production rates averaged 466 +/- 295 nmol/day (172 +/- 109 micrograms/day) in women with upper body obesity. Thus, women with lower body obesity had higher E1 production rates due entirely to increased peripheral aromatization. Women with upper body obesity were observed to have higher serum T and estradiol (E2) levels than women with lower body obesity. Further, upper body obesity was associated with decreased levels of sex hormone-binding globulin (16.1 +/- 5.7 nmol/L vs. 18.9 +/- 6.1 in women with lower body obesity). As a result, free T levels averaged 98.8 +/- 39.2 pmol/L in women with upper body obesity vs. 82.2 +/- 33 in women with lower body obesity. Similarly, serum free E2 levels were higher in women with upper body vs. lower body obesity. The data demonstrate that sex hormone production and metabolism are different in morbidly obese women with these differing phenotypes. Women with upper body obesity have higher androgen production rates and higher free T and free E2 levels, whereas women with lower body obesity make increased amounts of E1 from peripheral aromatization. The biological significance of increased aromatization may be offset by increased free E2 levels in women with upper body obesity.
Immunologic Adsorbents (1951)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.