gebhart/patrepeval huggingface dataset:
Integrated microRNA-mRNA analysis of pancreatic ductal adenocarcinoma (2015)

The main aim of this study was to explore the underlying molecular mechanisms and potential target molecules of pancreatic adenocarcinoma. The miRNA (GSE32678) and mRNA (GSE32676) expression profiles of patients with pancreatic ductal adenocarcinoma and healthy controls were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNA and differentially expressed genes were identified by analyzing the microarray algorithm after data preprocessing. Functional analysis was conducted by the Database for Annotation, Visualization and Integrated Analysis. miRNA-mRNA regulation pairs were obtained in TarMir database. The node degree of hsa-miR-200c, hsa-miR-429, and hsa-miR-200b (miRNA), and EFNB2, MYRIP, and PHF17 (mRNA) were extremely high in the miRNA-mRNA network, indicating that these miRNA and mRNA may play a key role in the development of pancreatic cancer. Our study screened out some target miRNAs and mRNAs for pancreatic ductal adenocarcinoma, which may be helpful in its diagnosis and treatment.
One-step synthesis of interpenetrating network hydrogels: Environment sensitivities and drug delivery properties (2015)

A novel interpenetrating network hydrogel for drug controlled release, composed of modified poly(aspartic acid) (KPAsp) and carboxymethyl chitosan (CMCTS), was prepared in aqueous system. The surface morphology and composition of hydrogels were characterized by SEM and FTIR. The swelling properties of KPAsp, KPAsp/CMCTS semi-IPN and KPAsp/CMCTS IPN hydrogels were investigated and the swelling dynamics of the hydrogels was analyzed based on the Fickian equation. The pH, temperature and salt sensitivities of hydrogels were further studied, and the prepared hydrogels showed extremely sensitive properties to pH, temperature, the ionic salts kinds and concentration. The results of controlled drug release behaviors of the hydrogels revealed that the introduction of IPN observably improved the drug release properties of hydrogels, the release rate of drug from hydrogels can be controlled by the structure of the hydrogels and pH value of the external environment, a relative large amount of drug released was preferred under simulated intestinal fluid. These results illustrated high potential of the KPAsp/CMCTS IPN hydrogels for application as drug carriers.
Associations Between Periodontal Disease and Risk for Nosocomial Bacterial Pneumonia and Chronic Obstructive Pulmonary Disease. A Systematic Review (2003)

1. Oral colonization by respiratory pathogens, fostered by poor oral hygiene and periodontal diseases, appears to be associated with nosocomial pneumonia. 2. Additional large-scale RCTs are warranted to provide the medical community with further evidence to institute effective oral hygiene procedures in high-risk patients to prevent nosocomial pneumonia. 3. The results associating periodontal disease and COPD are preliminary and large-scale longitudinal and epidemiologic and RCTs are needed.
Adaptive playout mechanisms for packetized audio applications in wide-area networks (2002)

Recent interest in supporting packet-audio applications over wide area networks has been fueled by the availability of low-cost, toll-quality workstation audio and the demonstration that limited amounts of interactive audio can be supported by today's Internet. In such applications, received audio packets are buffered, and their playout delayed at the destination host in order to compensate for the variable network delays. The authors investigate the performance of four different algorithms for adaptively adjusting the playout delay of audio packets in an interactive packet-audio terminal application, in the face of such varying network delays. They evaluate the playout algorithms using experimentally-obtained delay measurements of audio traffic between several different Internet sites. Their results indicate that an adaptive algorithm which explicitly adjusts to the sharp, spike-like increases in packet delay which were observed in the traces can achieve a lower rate of lost packets for both a given average playout delay and a given maximum buffer size.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Growth factors and growth modulators in human uterine endometrium: their potential relevance to reproductive medicine (1994)

Current evidence supports the thesis that GFs play a central role in cyclic mitosis and differentiation of endometrial cellular components, recruitment of macrophages in decidualizing endometrium, endometrial-trophoblast interactions, early pregnancy maintenance, tissue shedding in the absence of implantation, and endometrial functionalis regeneration.
Saturation Mutagenesis of the Yeast his3 Regulatory Site: Requirements for Transcriptional Induction and for Binding by GCN4 Activator Protein (1986)

Expression of the yeast his3 and other amino acid biosynthetic genes is induced during conditions of amino acid starvation. The coordination of this response is mediated by a positive regulatory protein called GCN4, which binds specifically to regulatory sites upstream of all coregulated genes and stimulates their transcription. The nucleotide sequence requirements of the his3 regulatory site were determined by analysis of numerous point mutations obtained by a novel method of cloning oligonucleotides. Almost all single base pair mutations within the nine base pair sequence ATGACTCTT significantly reduce his3 induction in vivo and GCN4 binding in vitro, whereas changes outside this region have minimal effects. One mutation, which generates a sequence that most closely resembles the consensus for 15 coregulated genes, increases both the level of induction and the affinity for GCN4 protein. The palindromic nature of the optimal sequence, ATGACTCAT, suggest that GCN4 protein binds as a dimer to adjacent half-sites that possibly overlap.
Expression and Role of Vascular Endothelial Growth Factor in Liver Regeneration After Partial Hepatectomy in Rats (2001)

Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis, which is essential for both healing of injured tissue and proliferation of carcinoma cells. In this study we elucidated the expression and role of VEGF in rat liver regeneration after partial hepatectomy. VEGF expression was mainly detected in periportal hepatocytes and reached a maximal level 48-72 hr after partial hepatectomy by both immunohistochemistry and in situ hybridization. Similarly, immunohistochemistry for Ki-67 showed that the proliferative activity of sinusoidal endothelial cells was highest in the periportal area and reached a maximal level 72 hr after partial hepatectomy. Moreover, neutralization of VEGF significantly inhibited proliferative activity of hepatocytes (p<0. 0001), as well as sinusoidal endothelial cells (p<0.001), at 48 and 96 hr after partial hepatectomy. Conversely, injection of VEGF significantly promoted proliferative activity of hepatocytes (p<0. 0001) as well as sinusoidal endothelial cells (p<0.0005) at 48 hr after partial hepatectomy. These results suggest that VEGF promotes proliferation of hepatocytes through reconstruction of liver sinusoids by proliferation of sinusoidal endothelial cells. Furthermore, these data point to a new therapeutic strategy, the use of VEGF and other hepatocyte growth factors in fulminant or severe acute hepatitis.
Use of Intron-Disrupted Polyadenylation Sites To Enhance Expression and Safety of Retroviral Vectors (2001)

Normal mRNA polyadenylation signals are composed of an AAUAAA motif and G/U box spaced 20 to 30 bp apart. If this spacing is increased further, then polyadenylation is disrupted. Previously it has been demonstrated that insertion of an intron will similarly disrupt this signal even though such introns are removed during a nuclear splicing reaction (X. Liu and J. Mertz, Nucleic Acids Res. 21:5256-5263, 1993). This observation has led to the suggestion that polyadenylation site selection is undertaken prior to intron excision. We now present results that both support and extend these observations and in doing so create a novel class of retroviral expression vector with improved qualities. We found that when an intron-disrupted polyadenylation signal is inserted within a retroviral expression vector, such a signal, although reformed in the producer cell, remains benign until transduction, where it is then preferentially used. Thus, we demonstrate that upon transduction these vectors now produce a majority of shortened subgenomic species and as a consequence have a reduced tendency for subsequent mobilization from transduced cells. In addition, we demonstrate that the use of this internal signal leads to enhanced expression from such vectors and that this is achieved without any loss in titer. Therefore, split polyadenylation signals confer enhanced performance and improved safety upon retroviral expression vectors into which they are inserted. Such split signals may prove useful for the future optimization of retroviral vectors in gene therapy.
Capillary Electrophoresis as an Assay Method for Monitoring Glycosyltransferase Activity (2003)

Glycobiology has rapidly developed into an important area of research devoted to the understanding and analysis of the interactions that carbohydrates have with other biomolecules. To accompany the rapid development of this field, better techniques for the analysis of the biosynthesis of complex carbohydrates are required. To investigate interactions between proteins and carbohydrates, an adequate supply of carbohydrate ligand must be obtained. Isolation of biologically active carbohydrates is possible, but only in small amounts. Recent efforts in the cloning of glycosyltransferase genes from a variety of sources has opened the possibility of enzymatic synthesis or chemienzymatic synthesis of a larger number of relevant oligosaccharides (1–4, ).
Antagonists of the Receptor-G Protein Interface Block Gi-coupled Signal Transduction (1998)

The carboxyl terminus of heterotrimeric G protein alpha subunits plays an important role in receptor interaction. We demonstrate that peptides corresponding to the last 11 residues of Galphai1/2 or Galphao1 impair agonist binding to A1 adenosine receptors, whereas Galphas or Galphat peptides have no effect. Previously, by using a combinatorial library we identified a series of Galphat peptide analogs that bind rhodopsin with high affinity (Martin, E. L., Rens-Domiano, S., Schatz, P. J., and Hamm, H. E. (1996) J. Biol. Chem. 271, 361-366). Native Galphai1/2 peptide as well as several analogs were tested for their ability to modulate agonist binding or antagonist-agonist competition using cells overexpressing human A1 adenosine receptors. Three peptide analogs decreased the Ki, suggesting that they disrupt the high affinity receptor-G protein interaction and stabilize an intermediate affinity state. To study the ability of the peptides to compete with endogenous Galphai proteins and block signal transduction in a native setting, we measured activation of G protein-coupled K+ channels through A1 adenosine or gamma-aminobutyric acid, type B, receptors in hippocampal CA1 pyramidal neurons. Native Galphai1/2, peptide, and certain analog peptides inhibited receptor-mediated K+ channel gating, dependent on which receptor was activated. This differential perturbation of receptor-G protein interaction suggests that receptors that act on the same G protein can be selectively disrupted.
Differential induction of heat shock, SOS, and oxidation stress regulons and accumulation of nucleotides in Escherichia coli (1987)

Heat and various inhibitory chemicals were tested in Escherichia coli for the ability to cause accumulation of adenylylated nucleotides and to induce proteins of the heat shock (htpR-controlled), the oxidation stress (oxyR-controlled), and the SOS (lexA-controlled) regulons. Under the conditions used, heat and ethanol initiated solely a heat shock response, hydrogen peroxide and 6-amino-7-chloro-5,8-dioxoquinoline (ACDQ) induced primarily an oxidation stress response and secondarily an SOS response, nalidixic acid and puromycin induced primarily an SOS and secondarily a heat shock response, isoleucine restriction induced a poor heat shock response, and CdCl2 strongly induced all three stress responses. ACDQ, CdCl2, and H2O2 each stimulated the synthesis of approximately 35 proteins by factors of 5- to 50-fold, and the heat shock, oxidation stress, and SOS regulons constituted a minor fraction of the overall cellular response. The pattern of accumulation of adenylylated nucleotides during these treatments was inconsistent with a simple role for these nucleotides as alarmones sufficient for triggering the heat shock response, but was consistent with a role in the oxyR-mediated response.
Derivation and analysis of a filtered backprojection algorithm for cone beam projection data (1991)

The authors address the problem of three-dimensional image reconstruction from cone beam projections. Modifying a result due to A.A. Kirillov (Soviet Math. Dokl., vol. 2, p.268-9, 1961), the authors derive an inversion formula for the case where the cone vertices form an unbounded curve. For the special case in which the cone vertices form a circle, an approximate reconstruction formula is developed and shown to be essentially equivalent to the practical cone-beam algorithm of L.A. Feldkamp et al. (1984). For this approximate inverse, the authors derive the resulting spatially varying point spread function, examine the effect of bandlimiting due to sampling, and compare the resulting image quality as a function of the radius of the circle formed by the cone vertices.
Comparison of three human-murine heteromyeloma cell lines for formation of human hybridomas after electrofusion with human peripheral blood lymphocytes from meningococcal cases and carriers (1995)

Peripheral blood lymphocytes from meningitis patients and healthy meningococcal carriers were fused by electrofusion with the three human-murine heteromyeloma cell lines CB-F7, K6H6B5 and H7NS. 934 hybridomas producing human immunoglobulins were obtained in 30 fusions. Heteromyeloma K6H6B5 yielded a significantly higher proportion of hybridomas producing IgG antibodies than did the two other cell lines. CB-F7 and K6H6B5 yielded comparable numbers of hybridomas whose supernatants reacted with homologous bacteria, whereas the cell line H7NS was less efficient.
Effect of in Vitro Virus Infection on Response of Human Monocytes and Lymphocytes to Mitogen Stimulation (1978)

Abstract Viral infection and immunization can depress certain immune functions, including in vitro transformation response of lymphocytes to mitogens and antigens. Since optimal lymphocyte response occurs only in the presence of macrophages, we sought to determine whether the depression of transformation response could result from macrophage dysfunction induced by the viral infection. Highly purified human macrophages and lymphocytes were infected in vitro with influenza A virus. There was no significant difference in transformation response between uninfected and infected lymphocytes either alone or when combined with uninfected macrophages, suggesting, by exclusion, a macrophage defect. Direct evidence for macrophage dysfunction was provided by the observation that virus-infected macrophages were significantly less effective than uninfected macrophages in enhancing the transformation response of either uninfected (p &amp;lt; 0.025) or infected (p &amp;lt; 0.01) lymphocytes. Adverse effects of virus infection could not be attributed to an effect of the virus cultivation medium, to cell separation procedures, or to changes in cell viability. Adverse effects on macrophage function were evident as early as 24 hr after virus infection and were directly related to the virus inoculum. Depressed enhancement of response by macrophages was demonstrated to a greater extent with suboptimal than optimal dose phytohemagglutinin stimulation, and was shown by using allogenic as well as autologous macrophages. Macrophage phagocytosis of staphylococci was similarly depressed but not eliminated by virus infection. Depressed transformation of unseparated mononuclear leukocytes was only manifested when virus infection occurred before or at the time of phytohemagglutinin stimulation, again suggesting a primary effect on macrophages. The inability of virus-infected human macrophages to enhance lymphocyte response to mitogen can account for the depression of human lymphocyte transformation seen during influenza virus infection. Viral infection had no adverse effect on lymphocyte response per se.
The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain (1991)

TTF-1, a homeodomain-containing transcription factor, which is required for the specific expression of the thyroglobulin and thyroperoxidase gene promoters in differentiated thyroid cell lines, is expressed at the very beginning of rat thyroid differentiation. TTF-1 mRNA is detected in the endodermal cells of the thyroid rudiment in the rat embryo and precedes the expression of the two known target genes by 5 days. No delay is observed between the appearance of TTF-1 mRNA and protein, which shows a clear nuclear localization. In the adult thyroid, TTF-1 is present only in the endoderm-derived follicular cells. Two additional domains of expression of TTF-1 have been observed, the lung and restricted areas of the brain. In the lung, TTF-1 mRNA and protein are also present at the earliest stages of differentiation and are later confined to the bronchial epithelium. In the brain, TTF-1 appears to be restricted to structures of diencephalic origin, including the developing neurohypophysis. The early detection of TTF-1 in the endodermal cells of the thyroid and lung anlage and in restricted neuroblast populations indicates that TTF-1 may have a role in cell determination in these three systems and that additional mechanisms may be involved in the activation of thyroid-specific gene expression.
Combinatorial Synthesis of Small Organic Molecules (1996)

Abstract Combinatorial synthesis has developed within a few years from a laboratory curiosity to a method that is taken seriously in drug research. Rapid progress in molecular biology and the resulting ability to determine the activity of new substances extremely efficiently have led to a change in paradigm for the synthesis of test compounds: in addition to the conventional procedure of synthesizing one substance after another, new methods allowing simultaneous creation of many structurally defined substances are becoming increasingly important. A characteristic of combinatorial synthesis is that a reaction is performed with many synthetic building blocks at once—in parallel or in a mixture— rather than with just one building block. All possible combinations are formed in each step, so that a large number of products, a so‐called library, is obtained from only a few reactants. Several methods have been developed for combinatorial synthesis of small organic molecules, based on research into peptide library synthesis: single substances are produced by highly automated parallel syntheses, and special techniques enable targeted synthesis of mixtures with defined components. Many structures can be obtained by combinatorial synthesis, and the size of the libraries created ranges from a few individual compounds to many thousand substances in mixtures. This article gives an overview of the combinatorial syntheses of small organic molecules reported to date, performed both in solution and on a solid support. In addition, different techniques for identification of active compounds in mixtures are presented, together with ways to automate syntheses and process the large amounts of data produced. An overview of pionering companies active in this area is also given. The final outlook attempts to predict the future development of this exponentially growing area and the influence of this new thinking in other areas of chemistry.
Constraints of Opsin Structure on the Ligand-binding Site: Studies with Ring-fused Retinals¶ (2002)

Ring-fused retinal analogs were designed to examine the hula-twist mode of the photoisomerization of the 9-cis retinylidene chromophore. Two 9-cis retinal analogs, the C11-C13 five-membered ring-fused and the C12-C14 five-membered ring-fused retinal derivatives, formed the pigments with opsin. The C11-C13 ring-fused analog was isomerized to a relaxed all-trans chromophore (lambda(max) > 400 nm) at even -269 degrees C and the Schiff base was kept protonated at 0 degrees C. The C12-C14 ring-fused analog was converted photochemically to a bathorhodopsin-like chromophore (lambda(max) = 583 nm) at -196 degrees C, which was further converted to the deprotonated Schiff base at 0 degrees C. The model-building study suggested that the analogs do not form pigments in the retinal-binding site of rhodopsin but form pigments with opsin structures, which have larger binding space generated by the movement of transmembrane helices. The molecular dynamics simulation of the isomerization of the analog chromophores provided a twisted C11-C12 double bond for the C12-C14 ring-fused analog and all relaxed double bonds with a highly twisted C10-C11 bond for the C11-C13 ring-fused analog. The structural model of the C11-C13 ring-fused analog chromophore showed a characteristic flip of the cyclohexenyl moiety toward transmembrane segments 3 and 4. The structural models suggested that hula twist is a primary process for the photoisomerization of the analog chromophores.
Heparin-binding protein: A diagnostic marker of acute bacterial meningitis* (2011)

Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.
Increased Production of Tumor Necrosis Factor-α by Glial Cells Exposed to Simulated Ischemia or Elevated Hydrostatic Pressure Induces Apoptosis in Cocultured Retinal Ganglion Cells (2000)

Although glial cells in the optic nerve head undergo a reactivation process in glaucoma, the role of glial cells during glaucomatous neurodegeneration of retinal ganglion cells is unknown. Using a coculture system in which retinal ganglion cells and glial cells are grown on different layers but share the same culture medium, we studied the influences of glial cells on survival of retinal ganglion cells after exposure to different stress conditions typified by simulated ischemia and elevated hydrostatic pressure. After the exposure to these stressors, we observed that glial cells secreted tumor necrosis factor-α (TNF-α) as well as other noxious agents such as nitric oxide into the coculture media and facilitated the apoptotic death of retinal ganglion cells as assessed by morphology, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and caspase activity. The glial origin of these noxious effects was confirmed by passive transfer experiments. Furthermore, retinal ganglion cell apoptosis was attenuated ∼66% by a neutralizing antibody against TNF-α and 50% by a selective inhibitor of inducible nitric oxide synthase (1400W). Because elevated intraocular pressure and ischemia are two prominent stress factors identified in the eyes of patients with glaucoma, these findings reveal a novel glia-initiated pathogenic mechanism for retinal ganglion cell death in glaucoma. In addition, these findings suggest that the inhibition of TNF-α that is released by reactivated glial cells may provide a novel therapeutic target for neuroprotection in the treatment of glaucomatous optic neuropathy.