gebhart/patrepeval huggingface dataset:
Single Nucleotide Polymorphisms rs2227284, rs2243283 and rs2243288 in the IL-4 Gene Show no Association with Susceptibility to Chronic Hepatitis B in a Chinese Han Population (2014)

Abstract Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of the interleukin-4 (IL-4) gene and outcome of hepatitis B virus (HBV) infection in a Chinese Han population. Methods Total of 501 patients with chronic hepatitis B virus (HBV) infection and 301 controls with selflimiting HBV infection were studied. Three tag SNPs in the IL-4 gene (rs2227284G/T, rs2243283C/G and rs2243288A/G) were genotyped by the Multiplex snapshot technique. The genotype and allele frequencies were calculated and analyzed. Results The three SNPs showed no significant genotype/allele associations with chronic HBV infection. Overall allele P values were: rs2227284, P = 0.655, odds ratio (OR) [95% confidence interval (CI)] = 1.070 (0.793-1.445); rs2243283, P = 0.849, OR (95% CI) = 0.976 (0.758-1.257); rs2243288, P = 0.659, OR (95% CI) = 1.060 (0.818-1.375). Overall genotype P values were: rs2227284, P = 0.771; rs2243283, P = 0.571; rs2243288, P = 0.902. There were no statistically significant differences between patients with chronic HBV infection and controls. Haplotypes generated by these three SNPs also had no significant differences between the two groups. Conclusions The three tag SNPs of IL-4 were not associated with the outcome of HBV infection in the Han Chinese population.
A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in inflammatory arthritis (2006)

Neutrophil recruitment into tissue plays an important role in host defense and disease pathogenesis, including the inflammatory arthritides. A multitude of diverse chemoattractants have been implicated in neutrophil recruitment, suggesting that they have overlapping functions in mediating this critical biological response. However, here we demonstrate a unique, non-redundant role for the leukotriene B4 receptor BLT1 in mediating neutrophil recruitment into the joint in the K/BxN mouse model of inflammatory arthritis. We demonstrate that neutrophil expression of BLT1 was absolutely required for arthritis generation and chemokine production in this model, and that specific BLT1 inhibition reversed established disease. Adoptive transfer of wild-type (WT) neutrophils restored arthritis and chemokine production in BLT1(-/-) mice. Surprisingly, the primary effect of the transferred WT neutrophils into BLT1(-/-) mice was to promote the entry of endogenous BLT1(-/-) neutrophils into the joints of these mice. However, continued joint inflammation was dependent on the presence of WT neutrophils, indicating an ongoing specific requirement for BLT1-activated neutrophils in mediating BLT1(-/-) neutrophil recruitment by other chemoattractants. These experiments demonstrate that neutrophil BLT1 functions in a novel and essential non-cell-autonomous manner to enable the recruitment of additional neutrophils not expressing this receptor, thereby amplifying the inflammatory response in autoantibody-induced arthritis.
Subcarrier multiplexed broad-band service network: a flexible platform for broad-band subscriber services (1993)

The concept of the subcarrier multiplexed broadband service network (SCM-BSN) has been developed in response to the need to provide low-cost integrated broad-band services in the local loop. The SCM-BSN architecture incorporates three elements which have been identified over the past few years as key cost-saving features: passive optical splitting, fiber-to-the-curb, and subcarrier multiplexing of video signals. This paper introduces the SCM-BSN concept, describes a prototype system that has been built at GTE Laboratories, and describes some possible evolutionary scenarios to integrated digital services. While the SCM-BSN prototype system has been designed to provide voice, data, and switched video services using FM-video modulation, the BSN design has been structured to provide for a graceful evolution to other broad-band services including HDTV, digital video, and integrated broad-band services based on ATM transmission. Because of its potentially low-cost and flexibility, SCM-BSN is attractive for local loop services.
Messenger RNAs for trk and the low-affinity NGF receptor in rat basal forebrain (1991)

Nerve growth factor (NGF) acts by binding to specific sets of neurons. Low-affinity binding (Kd of 10(-9) M) is mediated via a 75 kDa glycoprotein (LNGFR). Recently, a 140 kDa tyrosine protein kinase encoded by the proto-oncogene trk has been found to bind NGF with high affinity (Kd of 10(-11) M) and to evoke neurotrophic responses. In addition, the related trkB protein and the LNGFR have been shown to bind brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) with an affinity of Kd 10(-9) M. We demonstrate the distribution of mRNA encoding the neurotrophin-binding proteins in the forebrain of the 21-day-old Sprague-Dawley rat by in-situ hybridization. Expression of trk and LNGFR mRNA showed co-localization and was restricted to the medial septal nucleus and the nucleus of Broca's diagonal band, suggesting a receptor function in these cells for both proteins encoded. In contrast, expression of trkB was widely spread in many areas. Thus trkB protein might serve general functions in the forebrain.
Hormonal regulation of cholesterol 7 alpha-hydroxylase mRNA levels and transcriptional activity in primary rat hepatocyte cultures. (1992)

In primary cultures of adult rat hepatocytes the level of cholesterol 7 alpha-hydroxylase steady-state mRNA markedly decreased by 72 h. However, the addition of L-thyroxine (T4) and dexamethasone synergistically returned cholesterol 7 alpha-hydroxylase steady-state mRNA levels near to that of cholestyramine-fed animals. The maximal responses to T4 and dexamethasone in serum-free medium were at 1.0 and 0.1 microM, respectively. The addition of T4 in combination with dexamethasone resulted in an 11-fold increase in transcriptional activity of the cholesterol 7 alpha-hydroxylase gene as compared to no addition controls. The specific activities of cholesterol 7 alpha-hydroxylase in microsomes prepared from cultures treated with dexamethasone and T4 were 1.56 +/- 1.17 nmol/h/mg protein which is similar to that of intact liver (1.70 +/- 0.062 nmol/h/mg protein), but lower than cholestyramine-fed animals. Cholesterol 7 alpha-hydroxylase activity was not detectable (less than 0.020 nmol/h/mg protein) at 72 h in cultures without the addition of both dexamethasone and T4. In the presence of optimal concentrations of dexamethasone and T4, glucagon (0.2 microM), or dibutyryl cAMP (50 microM) decreased (90%) cholesterol 7 alpha-hydroxylase mRNA within 6 h. Transcriptional activity decreased (62%) in 6 h following the addition of glucagon (0.2 microM) to the culture medium. The results reported in this paper suggest an important role for multiple hormones in the regulation of cholesterol 7 alpha-hydroxylase in the liver.
OrthoMCL: Identification of Ortholog Groups for Eukaryotic Genomes (2003)

The identification of orthologous groups is useful for genome annotation, studies on gene/protein evolution, comparative genomics, and the identification of taxonomically restricted sequences. Methods successfully exploited for prokaryotic genome analysis have proved difficult to apply to eukaryotes, however, as larger genomes may contain multiple paralogous genes, and sequence information is often incomplete. OrthoMCL provides a scalable method for constructing orthologous groups across multiple eukaryotic taxa, using a Markov Cluster algorithm to group (putative) orthologs and paralogs. This method performs similarly to the INPARANOID algorithm when applied to two genomes, but can be extended to cluster orthologs from multiple species. OrthoMCL clusters are coherent with groups identified by EGO, but improved recognition of "recent" paralogs permits overlapping EGO groups representing the same gene to be merged. Comparison with previously assigned EC annotations suggests a high degree of reliability, implying utility for automated eukaryotic genome annotation. OrthoMCL has been applied to the proteome data set from seven publicly available genomes (human, fly, worm, yeast, Arabidopsis, the malaria parasite Plasmodium falciparum, and Escherichia coli). A Web interface allows queries based on individual genes or user-defined phylogenetic patterns (http://www.cbil.upenn.edu/gene-family). Analysis of clusters incorporating P. falciparum genes identifies numerous enzymes that were incompletely annotated in first-pass annotation of the parasite genome.
Hydrolytic properties of two cellulases of Trichoderma reesei expressed in yeast (1993)

Two cellulases of the filamentous fungus Trichoderma reesei, cellobiohydrolase II (CBHII, EC 3.2.1.91) and endoglucanase I (EGI, EC 3.2.1.4), produced in recombinant strains of the yeast Saccharomyces cerevisiae, were tested in the hydrolysis of cellulose, xylan and other polymeric substrates. Both enzymes were active against unsubstituted, insoluble cellulose. CBHII had greater activity than EGI against crystalline cellulose, whereas in the case of amorphous substrate the order was reversed. Evidence for synergism was obtained when mixtures of the two enzymes were used with a constant total protein dosage. The EGI was also active against soluble substituted cellulose derivatives, whereas the activity of CBHII against these substrates was insignificant. Both enzymes were active against barley (1-->3,1-->4)-beta-glucan, but were inactive against (1-->3,1-->6)-beta-glucan (laminarin). An apparent low mannan-degrading activity of EGI against locust-bean (Ceratonia siliqua) gum galactomannan was not confirmed when homopolymeric mannan was used as substrate in a prolonged hydrolysis test. EGI exhibited considerably greater activity against insoluble, unsubstituted hardwood xylan than against amorphous cellulose. Soluble 4-O-methyl-glucuronoxylan was also attacked by EGI, although to a somewhat lesser extent than the unsubstituted xylan. By comparison with two purified xylanases of T. reesei, EGI produced xylo-oligosaccharides with a longer mean chain length when acting on both substituted and unsubstituted xylan substrates. CBHII was inactive against xylan.
Admission chemokine (C-C motif) ligand 4 levels predict survival in pediatric septic shock* (2010)

A serum level of chemokine (C-C motif) ligand 4 of < or =140 pg/mL, when obtained within 24 hrs of admission, predicts a very high likelihood of survival in pediatric septic shock. Exclusion of patients with a chemokine (C-C motif) ligand 4 level of < or =140 pg/mL from interventional clinical trials in pediatric septic shock could create a study population in which survival benefit from the study agent could be more readily demonstrated.
Sodium Valproate in Treatment of Epilepsy (1974)

Sodium valproate has a simple chemical structure unlike other anticonvulsants. It has been given to 63 patients with various types of epilepsy whose attacks were frequent and of whom 40 had failed to respond to other anticonvulsants. Fits stopped completely in 27 patients (43%) and 14 (22%) showed a reduction of attacks by more than 50%. The best results were in patients with absences (typical and atypical) associated with spike and wave discharges on the electroencephalogram. Myoclonic epilepsies responded well and improvement occurred with tonic-clonic seizures and focal motor fits. There was little or no improvement in temporal lobe epilepsy. Sodium valproate given alone did not cause unwanted effects but it potentiated many other anticonvulsants. An unusual side effect was temporary hair loss. A number of patients became more alert, school performances improved, and the management of subnormal patients became easier.
Origin of threshold voltage instability in indium-gallium-zinc oxide thin film transistors (2008)

We investigated the impact of the passivation layer on the stability of indium-gallium-zinc oxide (IGZO) thin film transistors. While the device without any passivation layer showed a huge threshold voltage (Vth) shift under positive gate voltage stress, the suitably passivated device did not exhibit any Vth shift. The charge trapping model, which has been believed to be a plausible mechanism, cannot by itself explain this behavior. Instead, the Vth instability was attributed to the interaction between the exposed IGZO backsurface and oxygen and/or water in the ambient atmosphere during the gate voltage stress.
Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization (2013)

Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities of HIV-1-neutralizing antibodies in serum can be elucidated from the serum pattern of neutralization against a diverse panel of HIV-1 isolates. We determined "neutralization fingerprints" for 30 neutralizing antibodies on a panel of 34 diverse HIV-1 strains and showed that similarity in neutralization fingerprint correlated with similarity in epitope. We used these fingerprints to delineate specificities of polyclonal sera from 24 HIV-1-infected donors and a chimeric siman-human immunodeficiency virus-infected macaque. Delineated specificities matched published specificities and were further confirmed by antibody isolation for two sera. Patterns of virus-isolate neutralization can thus afford a detailed epitope-specific understanding of neutralizing-antibody responses to viral infection.
Detection of antibodies to the recombinant P39 protein of Borrelia burgdorferi using enzyme immunoassay and immunoblotting. (1993)

The diagnostic value of serologic tests using the recombinant P39 protein of Borrelia burgdorferi was compared with that of tests prepared from a whole spirochete antigen source. Immunoassays (ELISA and Western blot) prepared from either the recombinant protein or whole spirochetes were evaluated using a test panel comprised of 2 sera groups, one obtained from patients with clinically diagnosed Lyme disease, the other from individuals with no indication of past or current infection with B. burgdorferi. Results obtained indicate that ELISA screening tests relying on the recombinant protein are less sensitive than ELISA tests using whole spirochete antigen preparations. Western blot tests based on the P39 protein were more specific than P39 ELISA yielding no false positive or indeterminate results. These findings suggest that the P39 protein may prove valuable for confirmation testing for Lyme disease.
Neural selective activation and temporal regulation of a mammalian GAP-43 promoter in zebrafish (1994)

Neurons throughout the vertebrate nervous system selectively activate the gene for a growth cone component, GAP-43, during embryonic development, and then decrease its expression abruptly as they form synapses. Distal interruption of mature axons in the central nervous system (CNS) of fish and amphibians, but not in the mammalian CNS reverses the developmental down-regulation of GAP-43 expression. To explore functional conservation and divergence of cis-acting elements that regulate expression of the GAP-43 gene, we studied activation, in transgenic zebrafish embryos, of mammalian GAP-43 genomic sequences fused to a marker gene. The DNA fragments containing the GAP-43 promoter, including a short fragment of 386 base pairs, were preferentially activated in the embryonic fish nervous system at times when extensive neuronal differentiation and neurite outgrowth take place. After 2 days of development, expression of the mammalian transgenes was specifically downregulated in the fish spinal cord but increased in more rostral regions of the CNS. This expression pattern was well correlated with the regulation of the endogenous fish GAP-43 gene revealed by in situ hybridization. Elements of the mammalian gene located a substantial distance upstream of the minimal promoter directed additional expression of the marker gene in a specific set of non-neural cells in zebrafish embryos. Our results indicate that cis-acting elements of the GAP-43 gene, and signaling pathways controlling these elements during embryonic development, have been functionally conserved in vertebrate evolution.
Sustained Reverse Left Ventricular Structural Remodeling With Cardiac Resynchronization at One Year Is a Function of Etiology (2006)

Reverse LV remodeling and symptom benefit with CRT are sustained at 12 months in patients with New York Heart Association class III/IV heart failure but occur to a lesser degree in patients with an ischemic versus a nonischemic etiology, most likely owing to the inexorable progression of ischemic disease.
Risk assessment for indeterminate pulmonary nodules using a novel, plasma-protein based biomarker assay (2018)

The performance of the novel plasma protein biomarker assay supports its use as a noninvasive risk assessment aid for characterizing IPN. The high NPV of the SVM model suggests its application as a rule-out test to increase the confidence of providers to avoid aggressive interventions for their patients for whom the VA model result is an inconclusive, intermediate risk.
A new antitumor antibiotic, chromoxymycin. II. Production, isolation, characterization and antitumor activity. (1986)

Chromoxymycin is a new antitumor antibiotic produced by a new actinomycete named Streptomyces libani subsp. rubropurpureus No. 6362. Chromoxymycin is active against P388 leukemia and B16 melanoma in mice, and has weak antibacterial activity against some Gram-positive bacteria.
Molecular and functional defects in kidneys of mice lacking collagen alpha 3(IV): implications for Alport syndrome. (1996)

Collagen IV is a major structural component of all basal laminae (BLs). Six collagen IV alpha chains are present in mammals; alpha 1 and alpha 2(IV) are broadly expressed in embryos and adults, whereas alpha 3-6(IV) are restricted to a defined subset of BLs. In the glomerular BL of the kidney, the alpha 1 and alpha 2(IV) chains are replaced by the alpha 3-5(IV) chains as development proceeds. In humans, mutation of the collagen alpha 3, alpha 4, or alpha 5(IV) chain genes results in a delayed onset renal disease called Alport syndrome. We show here that mice lacking collagen alpha 3(IV) display a renal phenotype strikingly similar to Alport syndrome: decreased glomerular filtration (leading to uremia), compromised glomerular integrity (leading to proteinuria), structural changes in glomerular BL, and glomerulonephritis. Interestingly, numerous changes in the molecular composition of glomerular BL precede the onset of renal dysfunction; these include loss of collagens alpha 4 and alpha 5(IV), retention of collagen alpha 1/2(IV), appearance of fibronectin and collagen VI, and increased levels of perlecan. We suggest that these alterations contribute, along with loss of collagen IV isoforms per se, to renal pathology.
Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus (2011)

Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1-H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58-72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ(2) = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs.
Ba 679 Br, a new long-acting antimuscarinic bronchodilator: a pilot dose-escalation study in COPD (1993)

Preclinical studies with Ba 679 Br have demonstrated a significantly longer duration of action than ipratropium bromide. Following inhalation of single doses, no systemic antimuscarinic effects were noted at doses likely to be bronchodilating in man. The objective of the present pilot-study of Ba 679 Br was to establish the dose-range for its bronchodilatory activity in a small number of chronic obstructive pulmonary disease (COPD) patients, before initiating a formal dose- and time-response study. Employing an open cross-over design, the efficacy of Ba 679 Br was tested, following single inhalational administration of five doses of increasing magnitude on separate days in six patients with COPD. A piezoelectric crystal was used, in order to nebulize an aqueous solution into a mist suitable for inhalation. There was a mean increase in forced expiratory volume in one second (FEV1) of 36% 30 min after inhaling ipratropium bromide 40 micrograms. Pulmonary function tests (FEV1, and specific airways conductance (sGaw)) were performed, at regular time intervals up to 24 h after test drug inhalation. The bronchodilatory activity of Ba 679 Br appeared to be dose-related in the dose-range tested (10-160 micrograms). A peak response was reached in 1.5-2 h, and persisted for 10-15 h in the majority of patients with return to baseline FEV1 approximately 19 h after dosing. No changes in physical examination, electrocardiogram (ECG) and laboratory safety tests from predose values were noted, and no serious adverse events were reported by the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Modification of the signal sequence cleavage site of listeriolysin O does not affect protein secretion but impairs the virulence of Listeria monocytogenes (2003)

Listeriolysin O (LLO, hly-encoded), a major virulence factor secreted by the bacterial pathogen Listeria monocytogenes, is synthesized as a precursor of 529 residues. To impair LLO secretion, the four residues of the predicted signal sequence cleavage site (EA-KD) were deleted and the mutant LLO protein was expressed in a hly-negative derivative of L. monocytogenes. Unexpectedly, the mutant protein was secreted in normal amounts in the culture supernatant and was fully haemolytic. N-terminal sequencing of the secreted LLO molecule revealed that N-terminal processing of the preprotein occurred three residues downstream of the natural cleavage site. L. monocytogenes expressing this truncated LLO showed a reduced capacity to disrupt the phagosomal membranes of bone marrow macrophages and of hepatocytes; and the mutant strain showed a 100-fold decrease in virulence in the mouse model. These results suggest that the first N-terminal residues of mature LLO participate directly in phagosomal escape and bacterial infection.