gebhart/patrepeval huggingface dataset:
Molecular basis of congenital insensitivity to pain with anhidrosis (CIPA): Mutations and polymorphisms inTRKA (NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor (2001)

Congenital insensitivity to pain with anhidrosis (CIPA), also referred to as hereditary sensory and autonomic neuropathy type IV (HSAN-IV), is an autosomal recessive hereditary disorder characterized by recurrent episodic fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. The TRKA (NTRK1) gene located on chromosome 1 (1q21-q22), consists of 17 exons and spans at least 23 kb. TRKA encodes the receptor tyrosine kinase (RTK) for nerve growth factor (NGF) and is the gene responsible for CIPA. Defects in NGF signal transduction at the TRKA receptor lead to failure to support survival of sympathetic ganglion neurons and nociceptive sensory neurons derived from the neural crest. Thirty-seven different TRKA mutations, identified in patients in various countries, including nine frameshift, seven nonsense, seven splice, and 14 missense mutations, are distributed in an extracellular domain involved in NGF binding, as well as in the intracellular signal-transduction domain. Extensive analysis of CIPA mutations and associated intragenic polymorphisms should facilitate detection of CIPA mutations and aid in the diagnosis and genetic counseling of this painless but severe genetic disorder with devastating complications. In addition, naturally occurring TRKA missense mutations with loss of function provide considerable insight into the structure-function relationship in the RTK family. Further, molecular pathology of CIPA would provide unique opportunities to explore critical roles of the autonomic sympathetic nervous system as well as peripheral sensory nervous system that transmit noxious stimuli in humans.
A versatile and safe mobility assistant (2001)

The Bremen autonomous wheelchair implements obstacle avoidance plus driving and routing assistance in a shared-control system. This article shows how the tasks of reliably detecting obstacles in the environment and safely avoiding these obstructions are solved.
Molecular Cloning of Cytidine Monophospho-N-acetylneuraminic Acid Hydroxylase. REGULATION OF SPECIES- AND TISSUE-SPECIFIC EXPRESSION OF N-GLYCOLYLNEURAMINIC ACID (1995)

Cytidine monophospho-N-acetylneuraminic acid (CMP-NeuAc) hydroxylase, which is the key enzyme for the synthesis of N-glycolylneuraminic acid (NeuGc), has been purified from the cytosolic fraction of mouse liver, as described in our previous paper. The amino acid sequences of the purified CMP-NeuAc hydroxylase, and peptides obtained by lysylendopeptidase digestion, were used to synthesize specific oligonucleotide primers. A mouse cDNA clone of the enzyme was obtained by a combination of the polymerase chain reaction and rapid amplification of cDNA ends. The sequence of the clone contained an open reading frame coding for a protein of 577 amino acids with a predicted molecular mass of 66 kDa. The deduced sequence included the amino acid sequences obtained for the purified enzyme and peptides, and a complete match was obtained for 159 residues. The enzyme has neither a signal peptide sequence nor a membrane spanning domain, which is consistent with localization of the enzyme in the cytosol. Transfection of a cDNA construct to COS-1 cells increased the enzyme activity and the amount of NeuGc. Comparison of the sequence with GenBank data indicated that no similar sequence has been reported so far. Northern blot analysis of various mouse tissues with the enzyme cDNA as a probe indicated that expression of NeuGc is related to the level of CMP-NeuAc hydroxylase mRNA. On Southern blot analysis with the same probe, cross-hybridizing bands were detected in the human and fish genomes.
Characterization, performance, and applications of a yeast surface display-based biocatalyst (2015)

Yeast surface display (YSD) of two lipases. Measured expression level and copy number. Synthetic and hydrolytic activity comparable to commercial lipase. Cost analysis of YSD system <italic>vs.</italic> commercial formulations.
Dimension Estimation in Noisy PCA With SURE and Random Matrix Theory (2008)

Principal component analysis (PCA) is one of the best known methods for dimensionality reduction. Perhaps the most important problem in using PCA is to determine the number of principal components (PCs) or equivalently choose the rank of the loading matrix. Many methods have been proposed to deal with this problem but almost all of them fail in the important practical case when the number of observation is comparable to the number of variables, i.e., the realm of random matrix theory (RMT). In this paper we propose to use Stein's unbiased risk estimator (SURE) to estimate, with some assistance from RMT, the number of principal components. The method is applied both on simulated and real functional magnetic resonance imaging (fMRI) data, and compared to BIC and the Laplace method.
Survival of cultured neurons from amyloid precursor protein knock-out mice against Alzheimer's amyloid-beta toxicity and oxidative stress. (1998)

Studies on the amyloid precursor protein (APP) have suggested that it may be neuroprotective against amyloid-beta (Abeta) toxicity and oxidative stress. However, these findings have been obtained from either transfection of cell lines and mice that overexpress human APP isoforms or pretreatment of APP-expressing primary neurons with exogenous soluble APP. The neuroprotective role of endogenously expressed APP in neurons exposed to Abeta or oxidative stress has not been determined. This was investigated using primary cortical and cerebellar neuronal cultures established from APP knock-out (APP-/-) and wild-type (APP+/+) mice. Differences in susceptibility to Abeta toxicity or oxidative stress were not found between APP-/- and APP+/+ neurons. This observation may reflect the expression of the amyloid precursor-like proteins 1 and 2 (APLP1 and APLP2) molecules and supports the theory that APP and the APLPs may have similar functional activities. Increased expression of cell-associated APLP2, but not APLP1, was detected in Abeta-treated APP-/- and APP+/+ cultures but not in H2O2-treated cultures. This suggests that the Abeta toxicity pathway differs from other general forms of oxidative stress. These findings show that Abeta toxicity does not require an interaction of the Abeta peptide with the parental molecule (APP) and is therefore distinct from prion protein neurotoxicity that is dependent on the expression of the parental cellular prion protein.
A Pilot Study of Adalimumab in Infliximab-Allergic Patients (2004)

The anti-TNF-alpha antibody infliximab (Remicade) is highly effective in the treatment of Crohn's disease. A subset of patients experience allergic reactions as a result of antibodies to infliximab (ATIs). The purpose of the current study is to describe the safety and efficacy of adalimumab (Humira) in patients previously allergic or intolerant to infliximab. Adalimumab is an anti-TNF-alpha agent containing only human peptide sequences. Seven patients have been treated with adalimumab who had experienced immediate- or delayed-hypersensitivity reactions to infliximab and one with infliximab-induced lupus. Except for injection site discomfort, adalimumab was well tolerated without signs or symptoms of allergic reactions. One patient who had previously received pooled human immunoglobulin developed a pruritic rash after each dose of adalimumab. Patients with active disease who had previously experienced a robust response to infliximab responded to adalimumab as reflected by an improvement in Harvey-Bradshaw index and inflammatory markers. Based on these preliminary data, adalimumab may be a safe and effective substitute for infliximab-allergic patients. Individuals who have been exposed to human antibodies may be sensitized to other human antibodies such as adalimumab.
A transmon quantum annealer: decomposing many-body Ising constraints into pair interactions (2016)

Adiabatic quantum computing is an analog quantum computing scheme with various applications in solving optimization problems. In the parity picture of quantum optimization, the problem is encoded in local fields that act on qubits which are connected via local 4-body terms. We present an implementation of a parity annealer with Transmon qubits with a specifically tailored Ising interaction from Josephson ring modulators.
Evidence for accumulated melt beneath the slow–spreading Mid–Atlantic Ridge (1997)

The analysis of data from a multi–component geophysical experiment conducted on a segment of the slow–spreading (20 mm yr-1) Mid–Atlantic Ridge shows compelling evidence for a significant crustal magma body beneath the ridge axis. The role played by a crustal magma chamber beneath the axis in determining both the chemical and physical architecture of the newly formed crust is fundamental to our understanding of the accretion of oceanic lithosphere at spreading ridges, and over the last decade subsurface geophysical techniques have successfully imaged such magma chambers beneath a number of intermediate and fast spreading (60-140 mm yr-1 full rate) ridges. However, many similar geophysical studies of slow–spreading ridges have, to date, found little or no evidence for such a magma chamber beneath them.The experiment described here was carefully targeted on a magmatically active, axial volcanic ridge (AVR) segment of the Reykjanes Ridge, centred on 57° 43′ N. It consisted of four major components: wide–angle seismic profiles using ocean bottom seismometers; seismic reflection profiles; controlled source electromagnetic sounding; and magneto–telluric sounding. Interpretation and modelling of the first three of these datasets shows that an anomalous body lies at a depth of between 2 and 3 km below the seafloor beneath the axis of the AVR. This body is characterized by anomalously low seismic P–wave velocity and electrical resistivity, and is associated with a seismic reflector. The geometry and extent of this melt body shows a number of similarities with the axial magma chambers observed beneath ridges spreading at much higher spreading rates. Magneto–telluric soundings confirm the existence of very low electrical resistivities in the crust beneath the AVR and also indicate a deeper zone of low resistivity within the upper mantle beneath the ridge.
The PPARs:  From Orphan Receptors to Drug Discovery (2000)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTThe PPARs: From Orphan Receptors to Drug Discovery†Timothy M. Willson, Peter J. Brown, Daniel D. Sternbach, and Brad R. HenkeView Author Information Department of Medicinal Chemistry, Glaxo Wellcome Research & Development, Research Triangle Park, North Carolina 27709 Cite this: J. Med. Chem. 2000, 43, 4, 527–550Publication Date (Web):February 24, 2000Publication History Received8 November 1999Published online24 February 2000Published inissue 1 February 2000https://pubs.acs.org/doi/10.1021/jm990554ghttps://doi.org/10.1021/jm990554greview-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views6740Altmetric-Citations1452LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Agonists,Ligands,Lipids,Receptors,Rodent models Get e-Alerts
Oxanilic acids, a new series of orally active antiallergic agents (1975)

A large number of oxanilic acid esters and N-heteroaryl oxamic acid esters were prepared and found to have antiallergic activity using the rat passive cutaneous anaphylaxis (PCA) test. Many of the oxanilic acid esters are active orally, with the most active species having an aryl 2'-carbamoyl group and a 3'-methoxy group. Hydrolysis of the ester from the oxanilic ester moiety causes a loss of oral activity.
Automated Multivariate Optimization Tool for Energy Analysis (2006)

article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this work, or allow others to do so, for United States Government purposes. Building energy simulations are often used for trial-and-error evaluation of “what-if ” options in building design—a limited search for an optimal solution, or “optimization. ” Computerized searching has the potential to automate the input and output, evaluate many options, and perform enough simulations to account for the complex interactions among combinations of options. This paper describes ongoing efforts to develop such a tool. The optimization tool employs multiple modules, including a graphical user interface, a database, a preprocessor, the EnergyPlus simulation engine, an optimization engine, and a simulation run manager. Each module is described and the overall application architecture is summarized.
Repair of Ischemic Heart Disease with Novel Bone Marrow-Derived Multipotent Stem Cells (2005)

Congestive heart failure is a growing, worldwide epidemic. The major causes of heart failure are related to irreversible damage resulting from myocardial infarction (heart attack). The long-standing axiom has been that the myocardium has a limited capacity for self-repair or regeneration; and the irreversible loss of cardiac muscle and accompanying contraction and fibrosis of myocardial scar tissue, sets into play a series of events, namely, progressive ventricular remodeling of nonischemic myocardium that ultimately leads to progressive heart failure. The loss of cardiomyocyte survival cues is associated with diverse pathways for heart failure, underscoring the importance of maintaining the number of viable cardiomyocytes during heart failure progression. Currently, no medication or procedure used clinically has shown efficacy in replacing the myocardial scar with functioning contractile tissue. Therefore, given the major morbidity and mortality associated with myocardial infarction and heart failure, new approaches have been sought to address the principal pathophysiologic deficits responsible for these conditions, resulting from the loss of cardiomyocytes and viable blood vessels. Recently, the identification of stem cells from bone marrow capable of contributing to tissue regeneration has ignited significant interest in the possibility that cell therapy could be employed therapeutically for the repair of damaged myocardium. In this review, we will discuss the currently available bone marrow-derived stem progenitor cells for myocardial repair and focus on the advantages of using recently identified novel bone marrow-derived multipotent stem cells (BMSC).
Mechanism of Margination in Confined Flows of Blood and Other Multicomponent Suspensions (2012)

Flowing blood displays a phenomenon called margination, in which leukocytes and platelets are preferentially found near blood vessel walls, while erythrocytes are depleted from these regions. Here margination is investigated using direct hydrodynamic simulations of a binary suspension of stiff (s) and floppy (f) capsules, as well as a stochastic model that incorporates the key particle transport mechanisms in suspensions-wall-induced hydrodynamic migration and shear-induced pair collisions. The stochastic model allows the relative importance of these two mechanisms to be directly evaluated and thereby indicates that margination, at least in the dilute case, is largely due to the differential dynamics of homogeneous (e.g. s-s) and heterogeneous (s-f) collisions.
A practical and enantioselective synthesis of glycosphingolipids and related compounds. Total synthesis of globotriaosylceramide (Gb3) (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA practical and enantioselective synthesis of glycosphingolipids and related compounds. Total synthesis of globotriaosylceramide (Gb3)K. C. Nicolaou, T. Caulfield, H. Kataoka, and T. KumazawaCite this: J. Am. Chem. Soc. 1988, 110, 23, 7910–7912Publication Date (Print):November 1, 1988Publication History Published online1 May 2002Published inissue 1 November 1988https://pubs.acs.org/doi/10.1021/ja00231a071https://doi.org/10.1021/ja00231a071research-articleACS PublicationsRequest reuse permissionsArticle Views943Altmetric-Citations113LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Polyols of a cascade type as a water-solubilizing element of carborane derivatives for boron neutron capture therapy (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolyols of a cascade type as a water-solubilizing element of carborane derivatives for boron neutron capture therapyHisao Nemoto, J. Gerald Wilson, Hiroyuki Nakamura, and Yoshinori YamamotoCite this: J. Org. Chem. 1992, 57, 2, 435Publication Date (Print):January 1, 1992Publication History Published online1 May 2002Published inissue 1 January 1992https://pubs.acs.org/doi/10.1021/jo00028a010https://doi.org/10.1021/jo00028a010research-articleACS PublicationsRequest reuse permissionsArticle Views921Altmetric-Citations73LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease (2000)

Strategies for treating Alzheimer's disease (AD) include therapies designed to decrease senile plaque (SP) formation and/or promote clearance of SPs, but clinical trials of these treatments are limited by the lack of effective methods to monitor changes in plaque burden in the brains of living AD patients. However, because SPs are extracellular deposits of amyloid-beta peptides (Abeta), it may be possible to eventually develop radioligands that cross the blood-brain barrier (BBB) and label SPs so they can be visualized by current imaging methods. As a first step toward the generation of such a radioligand, we developed a probe, [(trans,trans)-1-bromo-2, 5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB)], and we report here that BSB has the following properties essential for a probe that can detect SPs in vivo. First, BSB sensitively labels SPs in AD brain sections. Second, BSB permeates living cells in culture and binds specifically to intracellular Abeta aggregates. Third, after intracerebral injection in living transgenic mouse models of AD amyloidosis, BSB labels SPs composed of human Abeta with high sensitivity and specificity. Fourth, BSB crosses the BBB and labels numerous AD-like SPs throughout the brain of the transgenic mice after i.v. injection. Thus, we conclude that BSB is an appropriate starting point for future efforts to generate an antemortem diagnostic for AD.
Antagonists of Growth Hormone-Releasing Hormone Inhibit the Growth of U-87MG Human Glioblastoma in Nude Mice (2000)

Antagonists of growth hormone-releasing hormone(GH-RH)inhibit the growth of various cancers by mechanisms that involve the suppression of the insulin-like growth factor (IGF)-I and/or IGF-II. In view of the importance of the IGF system in glioma tumorigenesis, the effects of GH-RH antagonists MZ-5-156 and JV-1-36 were investigated in nude mice bearing subcutaneous and orthotopic xenografts of U-87MG human glioblastomas. After 4 weeks of therapy with MZ-5-156 or JV-1 -36 at the dose of 20 microg/day per animal, the final volume of subcutaneous U-87MG tumors was significantly (P < .01) decreased by 84% and 76%, respectively, as compared with controls. Treatment with GH-RH antagonists also reduced tumor weight and the levels of mRNA for IGF receptor type I (IGFR-I). A reduction in the mRNA levels for IGF-II was found in tumors of mice treated with MZ-5-156. Treatment with MZ-5-156 or JV-1 -36 also extended the survival of nude mice implanted orthotopically with U-87MG glioblastomas by 81% (P < .005) and 18%, respectively, as compared with the controls. Exposure in vitro to GH-RH antagonists MZ-5-156 or JV-1 -36 at 1 microM concentration for 24 hours decreased the tumorigenicity of U-87MG cells in nude mice by 10% to 30% and extended the latency period for the development of subcutaneous palpable tumors by 31% to 56%, as compared with the controls. Exposure of U-87MG cells to GH-RH antagonists in vitro also resulted in a time-dependent increase in the mRNA levels of IGFR-II or a decrease in the mRNA levels of IGFR-I. mRNA for GH-RH was detected in U-87MG cells and xenografts implying that GH-RH may play a role in the pathogenesis of this tumor. Our results suggest that GH-RH antagonists MZ-5-156 and JV-1-36 inhibit the growth of U-87MG human glioblastoma by mechanisms that involve the suppression of IGF system. Antagonistic analogs of GH-RH merit further development for the treatment of malignant glioblastoma.
Two 7α‐hydroxylase enzymes in bile acid biosynthesis (1998)

The addition of a 7-hydroxyl group is an early and often rate-limiting step in the synthesis of bile acids. This reaction is catalysed by two cytochrome P450 enzymes known as cholesterol 7 alpha-hydroxylase and oxysterol 7 alpha-hydroxylase. cDNAs encoding these proteins have been isolated and used to define two evolutionarily conserved pathways that produce 7 alpha-hydroxylated bile acids.