gebhart/patrepeval huggingface dataset:
Immunodominant epitopes in nsp2 of porcine reproductive and respiratory syndrome virus are dispensable for replication, but play an important role in modulation of the host immune response (2009)

Non-structural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) is the largest protein of this virus. In addition to its crucial role in virus replication, recent studies have indicated its involvement in modulating host immunity. In this study, each of the six identified immunodominant nsp2 B-cell epitopes (ES2-ES7) was deleted using a type I PRRSV cDNA infectious clone. Deletion of ES3, ES4 or ES7 allowed the generation of viable virus. In comparison with the parental virus, the DeltaES3 mutant showed increased cytolytic activity and more vigorous growth kinetics, whilst the DeltaES4 and DeltaES7 mutants displayed decreased cytolytic activity and slower growth kinetics in MARC-145 cells. These nsp2 mutants were characterized further in a nursery pig disease model. The results showed that the DeltaES4 and DeltaES7 mutants exhibited attenuated phenotypes, whereas the DeltaES3 mutant produced a higher peak viral load in pigs. The antibody response reached similar levels, as measured by IDEXX ELISA at 21 days post-infection, and slightly higher levels of mean virus neutralizing titres were observed from pigs infected by the DeltaES4 and DeltaES7 mutants. The expression of innate and T-helper 1 cytokines was measured in peripheral blood mononuclear cells or virus-infected macrophages. The results consistently showed that interleukin-1beta and tumour necrosis factor alpha expression levels were downregulated in cells that were stimulated (or infected) with the DeltaES3 mutant compared with parental virus and the other nsp2 deletion mutants. These results suggest that certain regions in nsp2 are non-essential for PRRSV replication but may play an important role in modulation of host immunity in vivo.
Perceived barriers to therapeutic hypothermia for patients resuscitated from cardiac arrest: A qualitative study of emergency department and critical care workers* (2010)

This study demonstrated that the systematic adoption of a new intervention, therapeutic hypothermia, is met with interdependent generic, local, and individual barriers. A working awareness of the types of barriers that exist at multiple sites will assist in targeting specific knowledge translation strategies to improve adherence to evidence-based practice.
Sensory and Motor Neuron-derived Factor. A NOVEL HEREGULIN VARIANT HIGHLY EXPRESSED IN SENSORY AND MOTOR NEURONS (1995)

The heregulin family of polypeptides arise as splice variants from a single gene and share a conserved epidermal growth factor (EGF)-like domain thought to be the major determinant of their biological activities. We report here the cloning of a novel member of this family, termed sensory and motor neuron-derived factor or SMDF, which is highly expressed in sensory and motor neurons in human and rodent species. It contains a C-terminal beta-type EGF-like domain and an unique N-terminal sequence which lacks an Ig-like domain and is distinct from all known heregulin variants. Mammalian cell-expressed SMDF activates tyrosine phosphorylation of a 185-kDa protein in cell lines expressing p185erbB2, indicating that it is biologically active. Analyses of expression patterns suggest that, unlike other heregulin variants, SMDF is expressed mainly in the nervous system. In situ hybridization signals with the unique SMDF sequence probe and with a probe to the conserved EGF-like domain are comparable, suggesting that SMDF is the predominant isoform expressed in sensory and motor neurons. Expression of SMDF is maintained in both adult motor neurons and dorsal root ganglion neurons. These findings suggest that SMDF may mediate biological responses such as Schwann cell proliferation and acetylcholine receptor induction in the peripheral nervous system.
Protein kinase C mediates basic fibroblast growth factor protection of endothelial cells against radiation-induced apoptosis. (1994)

Basic fibroblast growth factor (bFGF) was found to protect bovine aortic endothelial cells against the lethal effects of ionizing radiation by inhibiting the programmed cell death (apoptosis) induced in these cells by radiation exposure. The involvement of the bFGF receptor tyrosine kinase in this function was demonstrated by abrogation of the radioprotective effect of bFGF by a specific inhibitor of the bFGF receptor tyrosine kinase, the tyrphostin AG213. The downstream signaling after stimulation of the bFGF receptor tyrosine kinase in bovine aortic endothelial cells involved translocation of the alpha isotype of cytoplasmic protein kinase C (PKC) into the membrane and its activation within 30 s after bFGF stimulation. The involvement of PKC in the radioprotective effect conferred by bFGF was suggested by the demonstration that nonspecific PKC activation by short-term exposure (30 min) to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA; 30 ng/ml) mimicked the radioprotective effect of bFGF. Furthermore, treatment of the cells with the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (20 microM) abrogated the radioprotective effect of bFGF, as was observed after the depletion of cellular PKC by overnight preincubation with high-dose TPA (200 nM). Agarose gel electrophoresis of DNA extracted from irradiated bovine aortic endothelial cells showed that both TPA (30 ng/ml; 30 min) and bFGF (1 ng/ml) inhibited the apoptotic degradation of DNA induced in these cells by radiation exposure (500 cGy). Both the bFGF- and the TPA-mediated inhibition of apoptosis could be reversed by the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (20 microM). These data demonstrate the involvement of PKC in the inhibition of radiation-induced apoptosis by bFGF and the rescue of endothelial cells from this mode of radiation-induced cell death.
Recombinant Human Growth Hormone Accelerates Wound Healing in Children with Large Cutaneous Burns (1994)

Our results indicate that both forms of rhGH are effective in reducing donor site healing time compared with placebo and suggest that accelerating wound healing is of clinical benefit because the patients' own skin becomes rapidly available for harvest and autografting. With this increase in the rate of wound healing, the total length of hospital stay can be reduced by more than 25%.
Er-diffused Ti:LiNbO3 waveguide laser of 1563 and 1576 nm emission wavelengths (1992)

The first continuous wave (cw) and pulsed mode operation of an Er-diffused Ti:LiNbO3 monomode waveguide laser at 1563 nm (E⊥ c) and 1576 nm (E∥ c) wavelengths is reported. A tunable Tl:KCl color center laser was used as a pump source. With π-polarized (Ep∥ c) pump radiation of 1479 nm wavelength an oscillation threshold of 13 mW coupled pump power was achieved for the 1576 nm emission line. Above 25 mW pump power additional lasing at 1563 nm wavelength was observed. σ-polarized (Ep⊥ c) pumping led to a single line emission at 1563 nm throughout with the highest cw output power of 3 mW and a slope efficiency of 3%. Time averaged emission linewidths of about 0.6 nm were measured for both wavelengths at about two times the threshold pump power level. With pulsed excitation of about 1 W coupled peak power output pulses of up to 200 mW peak power were measured.
110nm NROM technology for code and data flash products (2004)

A novel NROM generation with a bit size of 0,043 /spl mu/m/sup 2//bit at a 110nm design rule is introduced. The concept features mainstream CMOS type cell devices in conjunction with a metal contact based virtual ground array architecture. The new technology node serves both advanced code flash products and file storage memories up to 2 Gbit/die.
(S)-1-[3-Hydroxy-2-(Phosphonylmethoxy)propyl]cytosine (Cidofovir): Results of a Phase I/II Study of a Novel Antiviral Nucleotide Analogue (1995)

Cidofovir, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine, is a novel antiviral nucleotide analogue with potent in vitro and in vivo activity against cytomegalovirus (CMV) and other herpesviruses. Thirty-one human immunodeficiency virus-seropositive patients with asymptomatic CMV excretion were evaluated in a phase I/II study with 2 regimens of cidofovir: cidofovir alone at doses of 0.5, 1.0, 3.0, or 10.0 mg/kg/week (20 patients) and cidofovir at 3.0, 5.0, or 7.5 mg/kg with concomitant oral probenecid, saline prehydration, extended dosing intervals, and drug interruption for proteinuria (19 patients). Prolonged and dose-dependent anti-CMV effect was observed with all cidofovir regimens > or = 3.0 mg/kg. The dose-limiting toxicity of cidofovir was dose- and schedule-dependent nephrotoxicity. Four of 20 patients had serum creatinine levels > or = 2.0 mg/dL after a mean cumulative exposure of 14.8 mg/kg cidofovir alone; however, none of 19 patients receiving the modified regimen had elevated creatinine (mean cidofovir exposure, 32.2 mg/kg). The clinical efficacy of cidofovir and its potential for cumulative nephrotoxicity needs further study in patients with end-organ CMV disease.
Nuclear factor-kappa B p65 mediates the assembly and activation of the TNF-responsive element of the murine monocyte chemoattractant-1 gene. (1999)

TNF-alpha transcriptionally regulates murine monocyte chemoattractant protein-1 (MCP-1) expression. Three approaches were used to determine the mechanism by which TNF regulates MCP-1. Mutation analysis showed that two distal kappa B sites, a novel dimethylsulfate-hypersensitive sequence, and a promoter proximal SP-1 site were required for TNF induction. Although the kappa B sites and the hypersensitive sequence function as a NF-kappa B-mediated enhancer, regulating induction by TNF, stereospecific alignment of the kappa B sites was not critical. Trans-activation studies conducted by cotransfection of p50 and/or p65 expression vectors with MCP-1 constructions showed that TNF regulates MCP-1 through NF-kappa B. Examination of MCP-1 induction in NF-kappa B-disrupted embryonic fibroblasts showed that p65 was necessary for both the induction and the TNF-induced protein occupancy of the enhancer in vivo. The action of the antioxidant inhibitor of NF-kappa B activation, pyrrolidine dithiocarbamate, in wild-type and NF-kappa B mutant cells was examined. The results suggested that TNF activates NF-kappa B through both pyrrolidine dithiocarbamate-sensitive and -insensitive mechanisms. This study illustrates the crucial role for NF-kappa B p65 in the induction of the MCP-1 gene by TNF and in the assembly of a NF-kappa B dependent enhancer in vivo.
Specificity Determinants for the Pyruvate Dehydrogenase Component Reaction Mapped with Mutated and Prosthetic Group Modified Lipoyl Domains (2000)

Efficient catalysis in the second step of the pyruvate dehydrogenase (E1) component reaction requires a lipoyl group to be attached to a lipoyl domain that displays appropriately positioned specificity residues. As substrates, the human dihydrolipoyl acetyltransferase provides an N-terminal (L1) and an inner (L2) lipoyl domain. We evaluated the specificity requirements for the E1 reaction with 27 mutant L2 (including four substitutions for the lipoylated lysine, Lys(173)), with three analogs substituted for the lipoyl group on Lys(173), and with selected L1 mutants. Besides Lys(173) mutants, only E170Q mutation prevented lipoylation. Based on analysis of the structural stability of mutants by differential scanning calorimetry, alanine substitutions of residues with aromatic side chains in terminal regions outside the folded portion of the L2 domain significantly decreased the stability of mutant L2, suggesting specific interactions of these terminal regions with the folded domain. E1 reaction rates were markedly reduced by the following substitutions in the L2 domain (equivalent site-L1): L140A, S141A (S14A-L1), T143A, E162A, D172N, and E179A (E52A-L1). These mutants gave diverse changes in kinetic parameters. These residues are spread over >24 A on one side of the L2 structure, supporting extensive contact between E1 and L2 domain. Alignment of over 40 lipoyl domain sequences supports Ser(141), Thr(143), and Glu(179) serving as specificity residues for use by E1 from eukaryotic sources. Extensive interactions of the lipoyl-lysine prosthetic group within the active site are supported by the limited inhibition of E1 acetylation of native L2 by L2 domains altered either by mutation of Lys(173) or enzymatic addition of lipoate analogs to Lys(173). Thus, efficient use by mammalian E1 of cognate lipoyl domains derives from unique surface residues with critical interactions contributed by the universal lipoyl-lysine prosthetic group, key specificity residues, and some conserved residues, particularly Asp(172) adjacent to Lys(173).
Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor (1991)

1. The action of analogues and C-terminal fragments of neuropeptide Y (NPY) was examined on excitatory synaptic transmission in area CA1 of the rat hippocampal slice in vitro, by use of intracellular and extracellular recordings, to determine by agonist profile the NPY receptor subtype mediating presynaptic inhibition. 2. Neither NPY, analogues nor fragments of NPY affected the passive or active properties of the post-synaptic CA1 pyramidal neurones, indicating their action is at a presynaptic site. 3. The full-sequence analogues, peptide YY (PYY) and human NPY (hNPY), were equipotent with NPY at the presynaptic receptor, while desamido hNPY was without activity. 4. NPY2-36 was equipotent with NPY. Fragments as short as NPY 13-36 were active, but gradually lost activity with decreasing length. NPY 16-36 had no effect on extracellular field potentials, but still significantly inhibited excitatory postsynaptic potential amplitudes. Fragments shorter than NPY 16-36 had no measurable effect on synaptic transmission. 5. The presynaptic NPY receptor in hippocampal CA1 therefore shares an identical agonist profile with the presynaptic Y2 receptor at the peripheral sympathetic neuroeffector junction.
Focal Atrial Tachycardia II: Management (2006)

Over the last decade there have been significant changes in the treatment of focal atrial tachycardia (AT). This review concentrates on the different approaches to the treatment of focal AT. Initial therapies included antiarrhythmic medications and surgery. However, with the advent of radiofrequency ablation, and the poor efficacy of pharmacological therapy, there has been a shift toward a primary ablative approach. Several different mapping techniques have been proposed. The different techniques, including P-wave morphology and advanced three-dimensional mapping, are discussed in this review.
Direct genetic analysis by matrix-assisted laser desorption/ionization mass spectrometry (1999)

An approach to analyzing single-nucleotide polymorphisms (SNPs) found in the human genome has been developed that couples a recently developed invasive cleavage assay for nucleic acids with detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The invasive cleavage assay is a signal amplification method that enables the analysis of SNPs by MALDI-TOF MS directly from human genomic DNA without the need for initial target amplification by PCR. The results presented here show the successful genotyping by this approach of twelve SNPs located randomly throughout the human genome. Conventional Sanger sequencing of these SNP positions confirmed the accuracy of the MALDI-TOF MS analysis results. The ability to unambiguously detect both homozygous and heterozygous genotypes is clearly demonstrated. The elimination of the need for target amplification by PCR, combined with the inherently rapid and accurate nature of detection by MALDI-TOF MS, gives this approach unique and significant advantages in the high-throughput genotyping of large numbers of SNPs, useful for locating, identifying, and characterizing the function of specific genes.
Analysis of Sindbis virus promoter recognition in vivo, using novel vectors with two subgenomic mRNA promoters (1991)

Four types of Sindbis virus vectors, each carrying two promoters for subgenomic mRNA synthesis, were designed to measure relative promoter strengths and to survey potential contextual effects on promoter strengths. One of the promoters in each vector was used as the reference promoter, while the other was the one being tested. We used these vectors to measure the relative strengths of four promoters: the minimal promoter, an extended sequence believed to have full promoter activity, and two mutant promoters, one with an inactivating 3-nucleotide insertion called CR4.1 and the other with a 4-nucleotide deletion called delta 4. The strengths of the promoters were measured by quantitating the RNA transcribed from each promoter in vivo and also by assaying for chloramphenicol acetyltransferase activity encoded by one of the two transcripts. We found that the relative strengths of the promoters were similar in different contexts. The complete promoter was 6-fold more active, the delta 4 promoter was (surprisingly) about twice as active, and the CR4.1 promoter was 100-fold less active than the minimal promoter. At least two contextual effects were identified that can alter the activity of one or both promoters in the vectors. One effect is that given identical promoters, the 3'-proximal promoter on the minus-strand template can be more active than the 5'-proximal promoter. This may be due to preferential association of one or more components of the transcription complex for the 3' end of the minus-strand template. A second effect is promoter competition, particularly when the promoters are closely spaced.
2-Pyridyl Cyanate: A Useful Reagent for the Preparation of Nitriles (1996)

Abstract The reaction of Grignard reagents with 2-pyridyl cyanate affords to give nitrites in high yields.
Thrombin is an extracellular signal that activates intracellular death protease pathways inducing apoptosis in model motor neurons. (1998)

Apoptosis, often also termed "programmed cell death", occurs in normal development in the brain and spinal cord. Important to concepts of disease and potential intervention is the exciting finding that apoptosis is also found after neurotrauma and in a number of neurodegenerative diseases. Although the precise mechanism of neuronal cell loss remains unknown, much emphasis has been placed recently on the activation of cell death protease cascades within the cell. How these cascades may be activated, especially from extracellular influences, is currently poorly understood. Thrombin, the multifunctional coagulation protease, is an early phase modulator at sites of tissue injury and has been shown to induce cell death in neurons by an apoptotic mechanism by activating its receptor, PAR-1. Using a model motor neuronal cell line, NSC19, which we have shown undergoes apoptosis after treatment with classic apoptosis inducers such as the topoisomerase inhibitors camptothecin and etoposide, we unambiguously found that nanomolar thrombin induced characteristic signs of apoptosis. Strikingly, endonucleolysis was accompanied by an increase in caspase-3-like activity in cellular extracts, which correlated with both detection of caspase-induced signature cleavage of the cortical cytoskeleton component nonerythroid spectrin (alpha-fodrin) and identification of increased accessibility of a caspase cleavage domain, using an antibody (Ab127) made against a synthetic peptide KGDEVD. Demonstrating that thrombin activation of death proteases was linked to cell death, we were able to inhibit thrombin-induced apoptosis by using a caspase family inhibitor, benzyloxycarbonyl-Asp-(oMe)-fluoromethyl ketone (Boc-D-FMK). These novel results demonstrate that thrombin serves as an extracellular "death signal" to activate intracellular protease pathways. These pathways lead to apoptotic cell death and can be modulated by inhibiting caspase activity downstream to PAR-1.
Expression of matrix metalloproteinases 7 and 2 in human renal cell carcinoma. (2003)

Matrix metalloproteinases (MMPs) are associated with invasion and metastasis of several malignant tumors in human. Especially so MMP-7, as it is mainly produced by the cancer cell itself. However, the expression of MMP-7 in renal cell carcinoma (RCC) has not been investigated. We examined expressions of MMP-7 and MMP-2 in RCC, and compared them with the clinicopathological characteristics in RCC. Tumor samples from 20 patients with RCC, who had surgery performed at Osaka City University Medical School Hospital, were immunohistochemically stained. Expression of MMP-2 was significantly stronger in advanced stage and in high grade tumors than in low stage and low grade tumors. MMP-7 was also expressed in RCCs, with its expression especially and significantly stronger in high grade than in low grade tumors (p=0.004). However, there was no significant difference of MMP-7 expression between advanced and low stages (p=0.1859). This increased expression of MMP-7 in high grade RCC might be associated with tumor invasion and metastasis.
Self-healing superhydrophobic materials (2012)

Development of materials with self-healing properties is highly important task. This review covers recent development in the design of materials with durable, easy repairable and self-healing superhydrophobic properties.
Varicosities of Intraretinal Ganglion Cell Axons in Human and Nonhuman Primates (2003)

The results demonstrated that intraretinal ganglion cell axons are predominantly varicose fibers in both human and nonhuman primates. Size variations exist within a single axon's diameter and thereby affect the patterns of diameter distribution seen in transverse-cut preparations. The mitochondria-rich varicosities and the presence of intercellular junctions suggest that the varicosities may be functional sites that serve local high-energy demands of unmyelinated fibers and signal transmission.
Prolonging hormone sensitivity in prostate cancer xenografts through dual inhibition of AR and mTOR (2010)

This study suggests that dual inhibition of AR and mTOR in castration-resistant xenograft models can restore sensitivity of tumours to anti-androgen therapy. Furthermore, after bicalutamide failure, dual inhibition with VN/124-1 and everolimus was the most effective treatment.
NIM811, a Cyclophilin Inhibitor, Exhibits Potent In Vitro Activity against Hepatitis C Virus Alone or in Combination with Alpha Interferon (2006)

Host factors involved in viral replication are potentially attractive antiviral targets that are complementary to specific inhibitors of viral enzymes, since resistant mutations against the latter are likely to emerge during long-term treatment. It has been reported recently that cyclosporine, which binds to a family of cellular proteins, cyclophilins, inhibits hepatitis C virus (HCV) replication in vitro. Here, the activities of various cyclosporine derivatives were evaluated in the HCV replicon system. There was a strong correlation between the anti-HCV activity and cyclophilin-binding affinity of these compounds. Of these, NIM811 has been selected as a therapeutic candidate for HCV infection, since it binds to cyclophilins with higher affinity than cyclosporine but is devoid of the significant immunosuppressive activity associated with cyclosporine. NIM811 induced a concentration-dependent reduction of HCV RNA in the replicon cells with a 50% inhibitory concentration of 0.66 microM at 48 h. Furthermore, a greater than three-log(10) viral RNA reduction was achieved after treating the cells with as little as 1 microM of NIM811 for 9 days. In addition, the combination of NIM811 with alpha interferon significantly enhanced anti-HCV activities without causing any increase of cytotoxicity. Taken together, these promising in vitro data warrant clinical investigation of NIM811, an inhibitor of novel mechanism, for the treatment of hepatitis C.