gebhart/patrepeval huggingface dataset:
Non-Prostanoid Endothelium-Derived Vasoactive Factors (1989)

Endothelium-derived relaxing factor (EDRF) and endothelium-derived contracting factor (EDCF) are released by endothelial cells following stimulation by a wide range of chemical agonists acting on specific endothelial membrane receptors and by physical factors such as shear stress on the vascular wall. It has now been firmly established that EDRF is nitric oxide, whereas EDCF has been recently identified as a 21-residue peptide, endothelin. Circumstantial evidence, however, suggests that there may be more than one EDRF and/or EDCF. EDRF induces relaxation of the underlying vascular smooth muscle by enhancing intracellular cyclic GMP levels. This action is comparable to that of nitrovasodilators, and nitric oxide can, therefore, be regarded as an endogenous nitrovasodilator. The mechanism of action of endothelin is uncertain, but depends on influx of extracellular calcium. The respective roles of EDRF and EDCF in disease are still hypothetical. It is preferable to think in terms of balance (or imbalance) between these two factors which, probably, have a fundamental role, and very likely interact with each other in maintaining and regulating vascular tone in man.
Identification of Novel Ah Receptor Agonists Using a High-Throughput Green Fluorescent Protein-Based Recombinant Cell Bioassay (2001)

The Ah receptor is a ligand-dependent transcription factor that mediates the biological and toxic effects of polycyclic aromatic hydrocarbons and halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). Recent evidence also suggests a role for the AhR in normal physiology and development. Although a variety of structurally diverse chemicals are reported to bind to and activate the AhR, the full spectrum of structural chemical classes that can interact with the AhR remains to be elucidated. Large-scale analysis of the ligand binding specificity of the AhR requires the use of a high-throughput AhR bioassay system for chemical screening. We have utilized a recombinant mouse hepatoma cell line (H1G1.1c3) containing a stably integrated TCDD- and AhR-responsive enhanced green fluorescent protein (EGFP) reporter gene to screen a 1,5-dialkylamino-2,4-dinitrobenzene combinatorial chemical library consisting of 155 parental amines and up to 12 090 combinatorial products in less than 7 days for novel AhR agonists. These analyses have identified numerous parental amines as relatively potent inducers of EGFP (with EC(50)s between 8 and 1000 microM) and also have revealed several novel products of the combinatorial chemical library synthesis with EC(50)s between 10 and 100 microM. Overall, these results have not only allowed the identification of novel activators of the AhR but also demonstrate the utility of the recombinant H1G1.1c3 cell bioassay for high-throughput chemical screening.
Parity logging overcoming the small write problem in redundant disk arrays (1993)

Parity encoded redundant disk arrays provide highly reliable, cost effective secondary storage with high performance for read accesses and large write accesses. Their performance on small writes, however, is much worse than mirrored disks—the traditional, highly reliable, but expensive organization for secondary storage. Unfortunately, small writes are a substantial portion of the I/O workload of many important, demanding applications such as on-line transaction processing. This paper presents parity logging, a novel solution to the small write problem for redundant disk arrays. Parity logging applies journalling techniques to substantially reduce the cost of small writes. We provide a detailed analysis of parity logging and competing schemes—mirroring, floating storage, and RAID level 5— and verify these models by simulation. Parity logging provides performance competitive with mirroring, the best of the alternative single failure tolerating disk array organizations. However, its overhead cost is close to the minimum offered by RAID level 5. Finally, parity logging can exploit data caching much more effectively than all three alternative approaches.
Growth and study of nonlinear optical materials for frequency conversion devices with applications in defence and security (2014)

A series of nonlinear materials including GaAs, GaP, and ZnSe have been examined to determine their suitability for non-linear frequency conversion devices (FCD) and more specifically their use as high power, compact and broadly tunable IR and THz sources for defense and security applications. The more mature GaAs was investigated to reveal the causes for the optical losses that restrict achievement of higher conversion efficiency in quasi-phasematched FCD, while the efforts with GaP were oriented in developing simple, cost effective techniques for fabrication of orientation patterned (OP) templates and optimizing the subsequent thick HVPE growth on these templates. Thus, average growth rates of 50- 70 &mu;m/h were achieved in up to 8-hour long experiments. High optical layer quality was achieved by suitable control of the process parameters. The optimal orientation of the pattern was determined and used as essential feedback aiming to improve the template preparation. This led to the production of the first 300-400 &mu;m thick device quality OPGaP. Efforts to suppress the parasitic nucleation during growths with longer duration or to achieve thicker layers by a 2 step growth process were also made. The main challenge with the newer candidate, OPZnSe, was to establish suitable regimes for hydrothermal growth on plain (001) ZnSe seeds grown by chemical vapor deposition. Two different temperature ranges, 330-350 &deg;C and 290-330 &deg;C, were investigated. The mineralized concentration was also manipulated to accelerate the growth in (111) direction and, thus, to improve the growth in (001) direction. The next material in the line is GaN. The traditional HVPE approach will be combined with a growth at low reactor pressure. Growths will be performed in the next sequence: growth on thin GaN layers grown by MOCVD on sapphire wafers, growth on half-patterned GaN templates with different orientations and, finally, growth on OPGaN templates.
An Emotion-Based Approach to Freedom of Speech (2003)

Free speech law often protects emotional expression. However, we lack an understanding of the scope and limits of protection for emotional expression. This Essay seeks to make progress toward such an understanding because a better understanding and grasp of the nature of emotion itself is crucial to achieving this goal. If we can arrive at an improved understanding of emotions and how they can be expressed, we will be better able to explain when we do and do not constitutionally protect the expression of emotion.
The emerging role of histone lysine demethylases in prostate cancer (2012)

Early prostate cancer (PCa) is generally treatable and associated with good prognosis. After a variable time, PCa evolves into a highly metastatic and treatment-refractory disease: castration-resistant PCa (CRPC). Currently, few prognostic factors are available to predict the emergence of CRPC, and no curative option is available. Epigenetic gene regulation has been shown to trigger PCa metastasis and androgen-independence. Most epigenetic studies have focused on DNA and histone methyltransferases. While DNA methylation leads to gene silencing, histone methylation can trigger gene activation or inactivation, depending on the target amino acid residues and the extent of methylation (me1, me2, or me3). Interestingly, some histone modifiers are essential for PCa tumor-initiating cell (TIC) self-renewal. TICs are considered the seeds responsible for metastatic spreading and androgen-independence. Histone Lysine Demethylases (KDMs) are a novel class of epigenetic enzymes which can remove both repressive and activating histone marks. KDMs are currently grouped into 7 major classes, each one targeting a specific methylation site. Since their discovery, KDM expression has been found to be deregulated in several neoplasms. In PCa, KDMs may act as either tumor suppressors or oncogenes, depending on their gene regulatory function. For example, KDM1A and KDM4C are essential for PCa androgen-dependent proliferation, while PHF8 is involved in PCa migration and invasion. Interestingly, the possibility of pharmacologically targeting KDMs has been demonstrated. In the present paper, we summarize the emerging role of KDMs in regulating the metastatic potential and androgen-dependence of PCa. In addition, we speculate on the possible interaction between KDMs and other epigenetic effectors relevant for PCa TICs. Finally, we explore the role of KDMs as novel prognostic factors and therapeutic targets. We believe that studies on histone demethylation may add a novel perspective in our efforts to prevent and cure advanced PCa.
Hierarchical file organization and its application to similar-string matching (1983)

The automatic correction of misspelled inputs is discussed from a viewpoint of similar-string matching. First a hierarchical file organization based on a linear ordering of records is presented for retrieving records highly similar to any input query. Then the spelling problem is attacked by constructing a hierarchical file for a set of strings in a dictionary of English words. The spelling correction steps proceed as follows: (1) find one of the best-match strings which are most similar to a query, (2) expand the search area for obtaining the good-match strings, and (3) interrupt the file search as soon as the required string is displayed. Computational experiments verify the performance of the proposed methods for similar-string matching under the UNIX™ time-sharing system.
Interactions of 2-Methoxyestradiol, an Endogenous Mammalian Metabolite, with Unpolymerized Tubulin and with Tubulin Polymers (1996)

2-Methoxyestradiol (2ME) is an endogenous mammalian catabolite of estradiol with antimitotic activity. Although it is a competitive inhibitor of the binding of colchicine to tubulin, it has unusual effects on glutamate-induced tubulin polymerization. Polymer that was little changed in morphology assembled at a reduced rate and was relatively cold stable. We have now examined interactions of [4-3H]-2ME with unpolymerized tubulin and polymer. The [3H]2ME binds avidly to tubulin even on ice, and it is readily displaced by other colchicine site drugs. An association rate constant on ice of 1.9 x 10(2) M-1s-1 was obtained. Scatchard analysis indicated a single class of binding site and an association equilibrium constant of 5.7 x 10(5) M-1. These values lead to a calculated dissociation rate constant of 3.3 x 10(-4) s-1. In glutamate-induced tubulin assembly, a reaction that requires GTP and leads to the formation of sheets of parallel protofilaments, increasing amounts of [3H]2ME were incorporated into polymer, reaching near-stoichiometry with tubulin at 100 microM 2ME. Equivalent binding of [3H]2ME occurred when the drug was added to preformed polymer, but binding of [3H]2ME to polymer was not readily inhibited by colchicine site drugs. Significant amounts of [3H]2ME were also incorporated into microtubule polymer formed with microtubule-associated proteins, glycerol, or 4-morpholineethanesulfonate buffer, but the stoichiometry was substantially lower than that in the sheet polymer induced by either glutamate or 1,4-piperazineethanesulfonate buffer. The structural differences between the microtubule and sheet polymers leading to these differences in apparent affinity for 2ME are unknown, but presumably interaction of the estrogen metabolite with cellular microtubules has functional significance related to the antimitotic properties of the compound.
Human T Cells Recognize Multiple Epitopes of an Immediate Early/Tegument Protein (IE62) and Glycoprotein I of Varicella Zoster Virus (1991)

Infection with varicella zoster virus (VZV) elicits persistent cell-mediated immunity directed against the immediate early (IE62) protein and the glycoprotein I (gp I) in most healthy subjects. In these experiments, synthetic peptides corresponding to residues of the IE62 protein and gp I were used to identify linear amino acid sequences of these immunogenic VZV proteins that were recognized by peripheral blood T lymphocytes from VZV-immune individuals of known major histocompatibility complex (MHC) type. All of 12 VZV-immune donors had T-cell proliferative responses, defined as a stimulation index (SI) greater than or equal to 2.0, to at least two of ten synthetic IE62 peptides; the mean number of IE62 peptides recognized by T cells from VZV-immune donors was seven. Five of the ten IE62 peptides stimulated T cells from 75% to 83% of the VZV-immune donors; the other five IE62 peptides were recognized by T cells from 42% to 67% of the subjects. All VZV-immune donors also had T proliferation responses to at least two of ten synthetic gp I peptides; the mean number of peptides recognized was six. Six of the ten gp I peptides were recognized by T cells from 67% to 92% of the VZV-immune donors; the frequency of donors responding to the other gp I peptides ranged from 42% to 58%. None of five nonimmune donors demonstrated T-cell proliferation to any of the IE62 or gp I peptides. A combination of two IE62 peptides provided epitopes that could be recognized by T cells from all twelve VZV-immune donors, regardless of DR type. Similarly, one gp I peptide in combination with either of two other gp I peptides induced proliferation of T cells from all immune subjects. Memory T cells with specificity for multiple short amino acid sequences of the IE62 protein and gp I were detected in subjects who had had primary VZV infection more than 20 years earlier. These observations indicate that natural VZV infection elicits a diverse cell-mediated immune response to viral proteins that is not restricted to only one or two immunodominant regions. Although the usefulness of peptide vaccines remains to be established, multiple epitopes of the IE62 protein and gp I were identified that could be presented by antigen-presenting cells (APC) and recognized by T cells from most subjects in an "outbred" human population.
Telepharmacy project aids North Dakota’s rural communities (2006)

Journal Article Telepharmacy project aids North Dakota's rural communities Get access Donna Young Donna Young Search for other works by this author on: Oxford Academic Google Scholar American Journal of Health-System Pharmacy, Volume 63, Issue 19, 1 October 2006, Pages 1776–1780, https://doi.org/10.2146/news060013 Published: 01 October 2006
Expression of HLA-DR and its enhancing molecules in muscle fibers in polymyositis (2000)

Polymyositis (PM) is an autoimmune inflammatory muscle disease of unknown cause in which cellular immunity is thought to play an important pathogenic role. Class II major histocompatibility complex (class II MHC: human leukocyte antigen (HLA)-DR operates as a cofactor of antigen presentation in immunological responses. There has been a major debate over whether muscle fibers themselves synthesize and express HLA-DR molecules and play a role in antigen presentation in PM pathogenesis. In this study, we demonstrated that most muscle fibers from patients with PM synthesized and expressed HLA-DR molecules on their surface. Human leukocyte antigen-DR expression was highly specific to PM. In addition, class II transactivator (CIITA), human leukocyte antigen DM (HLA-DM), and invariant chain (Ii), which are indispensable for expression of mature HLA-DR molecules and for antigen processing and presentation, were co-expressed. One of the cytokines that could induce this expression is interferon-gamma (IFN-gamma), released by activated lymphocytes. Our results indicate that in PM muscle fibers synthesize and express HLA-DR molecules and may contribute to the inflammatory responses together with lymphocytes.
Detection of 16S rDNA of CandidatusLiberibacter asiaticus in Orange Juice by Quantitative Real-time PCR (2012)

Orange juice processed from Huanglongbing (HLB) affected fruit is often associated with bitter taste and/or off-flavor. HLB disease in Florida is associated with CandidatusLiberibacter asiaticus (CLas), a phloem limited bacterium. The current standard to confirm CLas for citrus trees is to take samples from midribs of leaves, which are rich in phloem tissues, and use quantitative real-time polymerase chain reaction (qPCR) test to detect 16S rDNA gene of CLas. It is extremely difficult to detect CLas in orange juice because of the low CLas population, high sugar and pectin concentration, low pH and possible existence of an inhibitor to DNA amplification. The objective of this research was to improve extraction of DNA from orange juice, and detection of CLas by qPCR.
The CRES gene: a unique testis-regulated gene related to the cystatin family is highly restricted in its expression to the proximal region of the mouse epididymis. (1992)

As a result of examining regional-specific gene expression in the mouse epididymis, a novel cystatin-related epididymal specific (CRES) gene was identified. Substantial homology between the CRES gene and members of the cystatin family of cysteine proteinase inhibitors was observed at the amino acid level. This homology included the presence of four highly conserved cysteine residues in exact alignment with the cystatins as well as other regions of sequence characteristic of the cystatins. However, unlike the cystatins, the CRES gene does not contain specific highly conserved sequence motifs thought to be necessary for cysteine proteinase inhibitory activity. Also, in contrast to the ubiquitous expression of the cystatin C gene, Northern blot analysis and in situ hybridization demonstrated that the CRES gene is very restricted in its expression. The 0.75-kilobase CRES transcript is dramatically restricted to the very proximal caput region of the epididymis with 15- to 20-fold less expression in the testis and no expression detected in any of the other 24 tissues examined. In addition, the CRES transcript disappears 2-3 weeks after castration, suggesting a dependence on androgens. However, its expression remained undetectable even after the administration of testosterone or dihydrotestosterone. Unilateral castration also resulted in the disappearance of the CRES mRNA from the castrate epididymis, but not from the intact epididymis, suggesting that testicular factors or hormones other than androgens may be involved in the regulation of CRES gene expression. Therefore, the unique sequence of the CRES gene as well as its highly restricted expression and unusual regulation by the testis suggests that it has a very specialized role in the epididymis.
Leukoregulin is a potent inducer of hyaluronan synthesis in cultured human orbital fibroblasts (1995)

Leukoregulin, a 50-kDa glycoprotein lymphokine, can regulate the extracellular matrix in dermal fibroblasts. Here we investigate the effects of leukoregulin on the synthesis of glycosaminoglycans in human orbital fibroblasts. We demonstrate that leukoregulin enhances the incorporation of [3H]glucosamine into glycosaminoglycans. The effect is dose dependent in the concentration range tested (0.1-2 U/ml), is maximal at 1 U/ml, and is time dependent. [3H]glycosaminoglycan accumulation is enhanced 7.67 +/- 1.23-fold (SE, n = 7) in orbital fibroblast strains. Pulse-chase studies indicate that this enhanced accumulation is not a result of a decreased rate of macromolecular degradation. Radiolabeled material induced by leukoregulin is sensitive to Streptomyces hyaluronidase digestion. Dexamethasone (10(-8) M) and cycloheximide (10 micrograms/ml) can block the cytokine's stimulation of hyaluronan synthesis. [35S]sulfate incorporation into glycosaminoglycan is unaffected by leukoregulin. In dermal fibroblasts, leukoregulin increased hyaluronan synthesis 3.66 +/- 0.37-fold (n = 5 strains, P < 0.02 compared with orbit). The increase in hyaluronan synthesis in orbital fibroblasts is substantially greater than that observed previously with other cytokines, making leukoregulin a candidate molecular trigger in Graves' ophthalmopathy.
Efficacy and Safety of the Once-Daily GLP-1 Receptor Agonist Lixisenatide in Monotherapy (2012)

Once-daily lixisenatide monotherapy significantly improved glycemic control with a pronounced postprandial effect (75% reduction in glucose excursion) and was safe and well tolerated in type 2 diabetes.
Detection of oligoclonal IgG bands in unconcentrated CSF in multiple sclerosis and other neurological diseases by isoelectric focusing on ultrathin-layer polyacrylamide gel immunofixation and silver staining. (1989)

Isoelectric focusing of proteins (IEF) in ultrathin-layer polyacrylamide gel (0.4 mm, PAG), followed by direct immunofixation with monospecific antiserum and silver staining, is a highly specific, sensitive and simple method for the demonstration of oligoclonal IgG in unconcentrated cerebrospinal fluid (CSF) samples (5-10 microliters). For the present method, the optimal concentrations of IgG in CSF samples are about 0.025-0.030 g/l, corresponding to the applied amount of 125-150 mg. In our testing of this method, oligoclonal IgG bands in CSF specimens were clearly demonstrated in 52 (96%) of 54 patients with clinically established definite diagnosis of multiple sclerosis (MS), in 4 (40%) of 10 patients with infectious diseases of the CNS, and in 9 patients (25%) of 38 with other neurological diseases. Abnormal patterns were also demonstrated in the serum of patients with MS (43%). Intrathecally synthesized IgG was mathematically calculated in 43 (80%) out of 54 patients with MS. This method appears to be a useful alternative for the demonstration of oligoclonal IgG bands in the unconcentrated CSF, especially when questionable or negative results arise by routine electrophoretic technique for oligoclonal bands detection.
Fibroblast Growth Factor Receptor-1 Is Essential for In Vitro Cardiomyocyte Development (2003)

Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling plays a crucial role in mesoderm formation and patterning. Heartless mutant studies in Drosophila suggest that FGFR1, among the different FGFRs, may play a role in cardiogenesis. However, fgfr1-/- mice die during gastrulation before heart formation. To establish the contribution of FGFR1 in cardiac development, we investigated the capacity of murine fgfr1+/- and fgfr1-/- embryonic stem (ES) cells to differentiate to cardiomyocytes in vitro. Clusters of pulsating cardiomyocytes were observed in >90% of 3-dimensional embryoid bodies (EBs) originated from fgfr1+/- ES cells at day 9 to 10 of differentiation. In contrast, 10% or less of fgfr1-/- EBs showed beating foci at day 16. Accordingly, fgfr1-/- EBs were characterized by impaired expression of early cardiac transcription factors Nkx2.5 and d-Hand and of late structural cardiac genes myosin heavy chain (MHC)-alpha, MHC-beta, and ventricular myosin light chain. Homozygous fgfr1 mutation resulted also in alterations of the expression of mesoderm-related early genes, including nodal, BMP2, BMP4, T(bra), and sonic hedgehog. Nevertheless, fgfr1+/- and fgfr1-/- EBs similarly express cardiogenic precursor, endothelial, hematopoietic, and skeletal muscle markers, indicating that fgfr1-null mutation exerts a selective effect on cardiomyocyte development in differentiating ES cells. Accordingly, inhibitors of FGFR signaling, including the FGFR1 tyrosine kinase inhibitor SU 5402, the MEK1/2 inhibitor U0126, and the protein kinase C inhibitor GF109 all prevented cardiomyocyte differentiation in fgfr1+/- EBs without affecting the expression of the hematopoietic/endothelial marker flk-1. In conclusion, the data point to a nonredundant role for FGFR1-mediated signaling in cardiomyocyte development.