gebhart/patrepeval huggingface dataset:
Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54 (2003)

Hypogonadotropic hypogonadism is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function. In the absence of pituitary or hypothalamic anatomical lesions and of anosmia (Kallmann syndrome), hypogonadotropic hypogonadism is referred to as isolated hypogonadotropic hypogonadism (IHH). A limited number of IHH cases are due to loss-of-function mutations of the gonadotropin-releasing hormone receptor. To identify additional gene defects leading to IHH, a large consanguineous family with five affected siblings and with a normal gonadotropin-releasing hormone receptor coding sequence was studied. Homozygosity whole-genome mapping allowed the localization of a new locus within the short arm of chromosome 19 (19p13). Sequencing of several genes localized within this region showed that all affected siblings of the family carried a homozygous deletion of 155 nucleotides in the GPR54 gene. This deletion encompassed the splicing acceptor site of intron 4–exon 5 junction and part of exon 5. The deletion was absent or present on only one allele in unaffected family members. GPR54 has been initially identified as an orphan G protein-coupled receptor with 40% homology to galanin receptors. Recently, a 54-aa peptide derived from the KiSS1 protein was identified as a ligand of GPR54. The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.
The Waardenburg syndrome type 4 gene, SOX10, is a novel tumor-associated antigen identified in a patient with a dramatic response to immunotherapy. (2002)

In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that controls the development and postnatal survival of melanocytes. Mutations in SOX10 result in Waardenburg syndrome type 4. The overlapping epitopes AWISKPPGV and SAWISKPPGV, designated SOX10: 332-340 and SOX10: 331-340, respectively, were recognized by tumor-infiltrating lymphocyte clone M37 in an HLA-A2-restricted fashion.
Angiotensin receptors in pulmonary arterial and aortic endothelial cells (1989)

Angiotensin II (ANG II) is formed from angiotensin I by the action of angiotensin-converting enzyme located on the luminal surface of vascular endothelial cells. We determined whether binding sites specific for ANG II exist on pulmonary artery and aortic endothelial cells. The binding of 125I-ANG II to pulmonary artery and aortic endothelial cells was time dependent, saturable, and reversible. Scatchard analysis indicated a single class of high-affinity binding sites with equilibrium dissociation constants (Kd) of 0.85 and 0.81 nM and total binding capacities of 70 and 73 fmol/mg protein in pulmonary artery and aortic endothelial cells, respectively. Angiotensin analogues [Sar1,Ile8]ANG II and [Sar1,Ala8]ANG II, as well as angiotensin I and angiotensin III, competitively displaced 125I-ANG II in both pulmonary artery and aortic endothelial cells. The degree of inhibition of 125I-ANG II binding by these angiotensin analogues and antagonists was comparable except that [Sar1,Ala8]ANG II was 65% less potent than the other antagonists in both cell types. The binding of 125I-ANG II in pulmonary artery and aortic endothelial cells was not affected by vasopressin, substance P, or insulin, suggesting the presence of specific angiotensin receptors on these cells. These receptors appear to recognize the general configuration of angiotensin peptide rather than being specific to ANG II with no major differences between endothelial cells from pulmonary arterial or aortic vessels.
Heating-Induced Evolution of Thiolate-Encapsulated Gold Nanoparticles:  A Strategy for Size and Shape Manipulations (1999)

A heating treatment strategy for inducing size and shape change of composite nanoparticles in solutions is described. The composite nanoparticles are ∼2 nm gold cores encapsulated with alkanethiolate monolayers. The development of abilities in size and shape controls constitutes the motivation of this work. We demonstrated a remarkable evolution of the preformed particles in solutions toward monodispersed larger core sizes with well-defined and highly faceted morphologies. The particles thus evolved were encapsulated with the thiolate shells, and exhibited striking propensities of forming long-range ordered arrays. The morphological and structural evolutions were characterized using transmission electron microscopy, X-ray diffraction, UV−vis and infrared spectroscopies. Although temperature-driven crystal growth is known for nonencapsulated particles, the evolution of the thiolate-encapsulated nanoparticles in solutions into well-defined morphologies represents an intriguing example of temperature manipulations in size monodispersity and shape control.
The Catalyst Precursor, Catalyst, and Intermediate in the RuII‐Promoted Asymmetric Hydrogen Transfer between Alcohols and Ketones (1997)

New insight into the mechanism of catalysis. The purple 16-electron complex 1 and the yellow 18-electron complex 2 directly mediate the asymmetric, RuII-catalyzed hydrogen transfer between secondary alcohols and ketones. Both complexes were characterized by X-ray crystallography.
Algorithms for software and low-cost hardware RAIDs (2002)

RAIDs implemented in disk controllers are called hardware RAIDs. A software RAID, on the other hand, is implemented purely in software running on a host computer. In this paper, we describe algorithms that can be used by software RAIDs. We present one algorithm (parallel algorithm) for achieving fastest possible RAID update response time; we present one algorithm (PGS bit map algorithm) for improved recovery times; we present one algorithm for improved update concurrency; and we present four algorithms (Parity Caching, Delta Parity Caching, Delta Parity and Partial Parity Caching, and Data Prefetching) for improved sequential performance. Many of our algorithms are also appropriate for low-cost hardware RAIDs.
Cell-surface perturbations of the epidermal growth factor and vascular endothelial growth factor receptors by phosphorothioate oligodeoxynucleotides (1997)

Antisense oligodeoxynucleotides offer potential as therapeutic agents to inhibit gene expression. Recent evidence indicates that oligodeoxynucleotides designed to target specific nucleic acid sequences can interact nonspecifically with proteins. This report describes the interactive capabilities of phosphorothioate oligodeoxynucleotides of defined sequence and length with two essential protein tyrosine receptors, flk-1 and epidermal growth factor receptor (EGFR), and their effects on receptor signaling in a transfected and tumor cell line, respectively. Phosphorothioate oligodeoxynucleotides bound to the cell surface, as demonstrated by fluorescence-activated cell-sorter analyses (FACS), and perturbed receptor activation in the presence and absence of cognate ligands, EGF (EGFR) and vascular endothelial growth factor (flk-1), in phosphorylation assays. Certain phosphorothioate oligodeoxynucleotides interacted relatively selectively with flk-1 and partially blocked the binding of specific anti-receptor monoclonal antibodies to target sites. They stimulated EGFR phosphorylation in the absence of EGF but antagonized ligand-mediated activation of EGFR and flk-1. In vivo studies showed that a nonspecific phosphorothioate oligodeoxynucleotide suppressed the growth of glioblastoma in a mouse model of tumorigenesis. These results emphasize the capacity of phosphorothioate oligodeoxynucleotides to interact with cells in a sequence-selective nonantisense manner, while associating with cellular membrane proteins in ways that can inhibit cellular metabolic activities.
Real-Time PCR Assay Targeting IS 481 of Bordetella pertussis and Molecular Basis for Detecting Bordetella holmesii (2001)

Detection of Bordetella holmesii by a real-time PCR assay targeting IS481 of Bordetella pertussis is reported. Sequencing of IS481-specific PCR products from B. pertussis and B. holmesii isolates revealed sequence homology. Restriction fragment length polymorphism demonstrated a low copy number of IS481-like sequences in B. holmesii. These results, and culture of B. holmesii from patients with cough, suggest that the specificity and predictive value of IS481-based PCR assays for pertussis may be compromised.
Characterization of a novel facultative Methylocystis species capable of growth on methane, acetate and ethanol (2010)

A non-motile strain of Methylocystis, strain SB2, isolated from a spring bog in southeast Michigan, had a curved rod morphology with a typical type II intracytoplasmic membrane system. This organism expressed the membrane-bound or particulate methane monooxygenase (pMMO) as well as a chalkophore with high affinity for copper and did not express the cytoplasmic or soluble methane monooxygenase (sMMO). Strain SB2 was found to grow within the pH range of 6-9, with optimal growth at 6.8. Growth was observed at temperatures ranging between 10°C and 30°C, with no growth at 37°C. The DNA G+C content was 62.9 mol%. Predominant fatty acids were 18:1ω7c (72.7%) and 18:1ω9c (24%) when grown on methane. Phylogenetic comparisons based on both pmoA and 16S rRNA sequences indicated that this organism belonged to the Methylocystis genus, and was closely related to Methylocystis rosea SV97(T) and Methylocystis echinoides IMET10491(T) (98% 16S rRNA gene sequence similarity to both strains). DNA : DNA hybridizations indicated that strain SB2 had 70% similarity with M. rosea SV97(T) . Unlike M. rosea SV97(T) , strain SB2 was able to utilize not only methane for growth, but also ethanol and acetate. Furthermore, the predominant fatty acids in strain SB2 were different from those found in M. rosea SV97(T) , i.e. 54.2% and 39.7% of fatty acids are 18:1ω8 and 18:1ω7 in M. rosea SV97(T) , while 18:1ω8 is completely absent in strain SB2.
Impaired adult olfactory bulb neurogenesis in the R6/2 mouse model of Huntington's disease (2010)

These findings suggest that the striatal environment, severely affected in R6/2 mice, is capable of attracting neuroblasts, however this region fails to provide sufficient signals for neuronal maturation. Moreover, in transgenic R6/2 animals, the hostile huntingtin-associated microenvironment in the olfactory bulb interferes with the survival and integration of new mature neurons. Taken together, endogenous cell repair strategies in HD may require additional factors for the differentiation and survival of newly generated neurons both in neurogenic and non-neurogenic regions.
Activation of nuclear factor kappa B and oncogene expression by 12(R)-hydroxyeicosatrienoic acid, an angiogenic factor in microvessel endothelial cells. (1994)

12(R)-Hydroxy-5,8,14(Z,Z,Z)-eicosatrienoic acid (12(R)-HETrE) is an arachidonic acid metabolite formed by the corneal epithelium of several species, porcine leukocytes, and human and rat epidermal cells. It is a potent, stereospecific proinflammatory and angiogenic factor and its synthesis is increased manyfold in inflamed tissues, e.g. cornea and skin. It is possible that the angiogenic activity of 12(R)-HETrE is due to a direct mitogenic effect on microvessel endothelial cells via yet to be elucidated cellular and molecular mechanisms. In the present study, we demonstrated the ability of 12(R)-HETrE to stimulate the growth of quiescent endothelial cells in a time- and concentration-dependent manner with a maximal effect at 0.1 nM. This effect was highly stereospecific since its enantiomer, 12(S)-HETrE, had no effect within the same concentration range. Northern blot analysis and transient transfection experiments with chloramphenicol acetyltransferase constructs of oncogene promoter regions demonstrated significant increases over control (0.5% fetal calf serum) in c-myc-, c-jun, and c-fos mRNA levels and expression in cells treated with 0.1 nM 12(R)-HETrE. Electrophoretic mobility shift assay of nuclear protein extracts from cells treated with 12(R)-HETrE with specific radiolabeled oligonucleotides corresponding to known transcriptional binding sites, including AP-1, AP-2, SP1, TRE, NF kappa B, TFIID, OKT1, CREB, CTF/NF1, and GRE demonstrated a markedly rapid and specific increase in the binding activity of NF kappa B and to a lesser extent, AP-1. No significant increase was observed in the binding of other transcription factors assayed as compared to control (untreated) cells. Since the protooncogenes (c-fos, c-jun, and c-myc) are immediate early response genes that are implicated in the process of cell proliferation and differentiation, and activation of certain transcription factors, in particular NF kappa B, is associated with the immediate response of the cell to an injury, we propose that 12(R)HETrE's mitogenic and angiogenic activities are mediated, in part, via the activation of NF kappa B and expression of these protooncogenes.
Rapid and Sensitive Routine Detection of All Members of the Genus Enterovirus in Different Clinical Specimens by Real-Time PCR (2002)

We developed a rapid and sensitive method for the routine detection of all members of the enterovirus genus in different clinical specimens by using real-time TaqMan quantitative PCR. Multiple primer and probe sets were selected in the highly conserved 5'-untranslated region of the enterovirus genome. Our assay detected all 60 different enterovirus species tested, whereas no reactivity was observed with the viruses from the other genera of the picornaviridae family, e.g., hepatovirus and parechovirus. Weak cross-reactivity was observed with 7 of the 90 different high-titer rhinovirus stocks but not with rhinovirus-positive clinical isolates. Analysis of a well-characterized reference panel containing different enteroviruses at various concentrations demonstrated that the enterovirus real-time TaqMan PCR is as sensitive as most of the currently used molecular detection assays. Evaluation of clinical isolates demonstrated that the assay is more sensitive than the "gold standard" method, i.e., viral culture. Moreover, the PCR assay can be used on different clinical specimens, such as plasma, serum, nose and throat swabs, cerebrospinal fluid, and bronchoalveolar lavage, without apparent inhibition. Our data demonstrate that the real-time TaqMan PCR is a rapid and sensitive assay for the detection of enterovirus infection. The assay has a robust character and is easily standardized, which makes it an excellent alternative for the conventional time-consuming viral culture.
Hepatitis C virus core protein cooperates with ras and transforms primary rat embryo fibroblasts to tumorigenic phenotype (1996)

We have previously demonstrated that hepatitis C virus (HCV) core protein regulates cellular protooncogenes at the transcriptional level; this observation implicates core protein in the alteration of normal hepatocyte growth. In the present study, the transforming potential of the HCV core gene was investigated by using primary rat embryo fibroblast (REF) cells which were transfected with or without cooperative oncogenes. Integration of the HCV core gene resulted in expression of the viral protein in REF stable transformants. REF cells cotransfected with HCV core and H-ras genes became transformed and exhibited rapid proliferation, anchor-independent growth, and tumor formation in athymic nude mice. Results from these studies suggest that the core protein plays an important role in the regulation of HCV-infected cell growth and in the transformation to tumorigenic phenotype. These observations suggest a possible mechanism for this viral protein in the pathogenesis of hepatocellular carcinoma in HCV-infected humans.
Phylogenetic test of the molecular clock and linearized trees. (1995)

To estimate approximate divergence times of species or species groups with molecular data, we have developed a method of constructing a linearized tree under the assumption of a molecular clock. We present two tests of the molecular clock for a given topology: two-cluster test and branch-length test. The two-cluster test examines the hypothesis of the molecular clock for the two lineages created by an interior node of the tree, whereas the branch-length test examines the deviation of the branch length between the tree root and a tip from the average length. Sequences evolving excessively fast or slow at a high significance level may be eliminated. A linearized tree will then be constructed for a given topology for the remaining sequences under the assumption of rate constancy. We have used these methods to analyze hominoid mitochondrial DNA and drosophilid Adh gene sequences.
lnterleukin-1β Converting Enzyme: Biology and the Chemistry of Inhibitors (1995)

Interleukin-1&amp;#946; converting enzyme (ICE) catalyzes processing of biologically inactive pro IL-1&amp;#946; to mature II-1&amp;#946;. IL-1&amp;#946; is implicated in the pathogenesis of a number of inflammatory diseases, suggesting that compounds which inhibit ICE and reduce levels of the mature cytokine may have therapeutic utility. ICE and related homologs also appear to play a role in the pathway leading to apoptosis (programmed cell death), raising the possibility that inhibitors of ICE may be useful in/ &amp;#039; diseases resulting from inappropriate regulation of apoptosis. ICE defines a new class of cysteine protease as confirmed through X-ray crystal structure determination of peptide inhibitor-ICE complexes. The enzyme exists as a (p20)2/(p10)2 tetramer and binds its peptide inhibitors via an extended P-sheet. A variety of strategies for the discovery of inhibitors of ICE have been successfully explored. Peptidyl aspartyl aldehydes and phenylalkyl ketones are potent reversible inhibitors of the enzyme, in analogy with the classic results obtained with other cysteine proteases. Selective irreversible inhibition of ICE is provided by compounds such as aspartyl diazomethyl ketones and aspartyl (arylacyloxy)methyl ketones, which appear to inactivate the enzyme through alkylation of the side chain thiol of Cys285. Several structurally distinct functional groups can replace the (arylacyl)oxy- moiety as a leaving group, including diphenylphosphinic acid and 5-hydroxy-1-phenyl 3- trifluoromethyl-pyrazole. Non-peptidic 3-chloropyridazines have also been described as irreversible inactivators of ICE.
THE CARDIORESPIRATORY EFFECTS OF INCREASED INTRA-ABDOMINAL PRESSURE IN DIAPHRAGMATIC RUPTURE (1992)

The cardiorespiratory effect of gastric herniation in diaphragmatic rupture with and without increased intra-abdominal pressure (produced by inflation of a pneumatic antishock garment [PASG] to an intraperitoneal pressure of 40 mm Hg) was studied in 16 anesthetized spontaneously breathing (80% oxygen) piglets. Four additional animals had similar measurements after PASG inflation but without diaphragmatic rupture. Arterial blood pressure (BP), cardiac output, arterial blood gases, position of the stomach relative to the diaphragm (as measured on fluoroscopy), and mortality were assessed. Gastric herniation without the PASG (group I: 8 animals) produced slight cardiorespiratory deterioration, with PO2 falling from a baseline measurement of 429 +/- 60 mm Hg to 316 +/- 5 mm Hg at 1 hour. Over this period pH decreased from 7.39 +/- 0.05 to 7.30 +/- 0.02 and PCO2 increased from 39 +/- 5 to 46 +/- 2 mm Hg. With PASG inflation (group II: 8 animals) PO2 decreased to a greater extent, from 410 +/- 30 mm Hg at baseline to 48 +/- 10 mm Hg by 1 hour; pH decreased from 7.38 +/- 0.06 to 6.8 +/- 0.2 and PCO2 increased from 39 +/- 4 to 88 +/- 6 mm Hg. Animals without diaphragmatic rupture (group III: 4 animals) showed a smaller decrease in PO2, from 480 +/- 34 mm Hg at baseline to 320 +/- 50 mm Hg by 1 hour after PASG inflation.(ABSTRACT TRUNCATED AT 250 WORDS)
Frequency domain analysis of an optical FM discriminator (1992)

Measurement of optical phase and frequency deviations using a frequency-domain network analysis approach is described. The frequency domain transfer functions are given which relate the conversion of optical phase, frequency, and intensity modulation into photodetector current after passing through a quadrature biased Mach-Zehnder interferometer. It is shown that the error term in the phase and frequency transfer functions depends only to second order on any accompanying intensity modulation. Experimental data are given illustrating the analytical results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enrichment of Cancer Cells Using Aptamers Immobilized on a Microfluidic Channel (2008)

This work describes the development and investigation of an aptamer modified microfluidic device that captures rare cells to achieve a rapid assay without pretreatment of cells. To accomplish this, aptamers are first immobilized on the surface of a poly(dimethylsiloxane) microchannel, followed by pumping a mixture of cells through the device. This process permits the use of optical microscopy to measure the cell-surface density from which we calculate the percentage of cells captured as a function of cell and aptamer concentration, flow velocity, and incubation time. This aptamer-based device was demonstrated to capture target cells with >97% purity and >80% efficiency. Since the cell capture assay is completed within minutes and requires no pretreatment of cells, the device promises to play a key role in the early detection and diagnosis of cancer where rare diseased cells can first be enriched and then captured for detection.
Intracellular glutathione in the protection from anoxic injury in renal proximal tubules. (1990)

Previous results (Weinberg, J. M., J. A. David, M. Abarzua, and T. Rajan. 1987. J. Clin. Invest. 80:1446-1454) have shown that GSH and glycine (GLY) are cytoprotective during anoxia when added extracellularly. The present studies investigate the role that intracellular GSH plays in this cytoprotection. Proximal renal tubules in suspension prepared with either high (11 +/- 1 nmol/mg protein) or low (6 +/- 1 nmol/mg protein) GSH contents were subjected to 40 min of anoxia and 40 min of reoxygenation. Low GSH tubules were protected from plasma membrane damage during anoxia by exogenous addition of 1 mM GSH or GLY, reducing lactate dehydrogenase (LDH) release from 42 +/- 7 to 14 +/- 1 and 10 +/- 1%, respectively. High GSH tubules were equally protected from anoxic damage without exogenous additions. Since the high GSH content approximates the in vivo values, it may be concluded that GSH may be cytoprotective during anoxia in vivo. However, it is not the intracellular GSH itself that is cytoprotective; rather, this protection resides in the ability to produce GLY, which appears to be the cytoprotective agent. Alanine was also shown to have similar cytoprotective properties, although higher concentrations were required. Sulfhydryl reducing agents such as cysteine and dithiothreitol offered less, but significant protection from anoxic damage. Protection by GSH, GLY, or alanine was not associated with higher ATP levels during anoxia. Tubules that were protected from membrane damage during anoxia recovered oxygen consumption and K and ATP contents significantly better during reoxygenation than unprotected tubules.