gebhart/patrepeval huggingface dataset:
Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. (1998)

Mutation of the adenomatous polyposis coli (APC) tumor suppressor gene initiates the majority of colorectal (CR) cancers. One consequence of this inactivation is constitutive activation of beta-catenin/Tcf-mediated transcription. To further explore the role of the APC/beta-catenin/Tcf pathway in CR tumorigenesis, we searched for mutations in genes implicated in this pathway in CR tumors lacking APC mutations. No mutations of the gamma-catenin (CTNNG1), GSK-3alpha (GSK3A), or GSK-3beta (GSK3B) genes were detected. In contrast, mutations in the NH2-terminal regulatory domain of beta-catenin (CTNNB1) were found in 13 of 27 (48%) CR tumors lacking APC mutations. Mutations in the beta-catenin regulatory domain and APC were observed to be mutually exclusive, consistent with their equivalent effects on beta-catenin stability and Tcf transactivation. In addition, we found that CTNNB1 mutations can occur in the early, adenomatous stage of CR neoplasia, as has been observed previously with APC mutations. These results suggest that CTNNB1 mutations can uniquely substitute for APC mutations in CR tumors and that beta-catenin signaling plays a critical role in CR tumorigenesis.
Optimal gene partition into operons correlates with gene functional order (2006)

Gene arrangement into operons varies between bacterial species. Genes in a given system can be on one operon in some organisms and on several operons in other organisms. Existing theories explain why genes that work together should be on the same operon, since this allows for advantageous lateral gene transfer and accurate stoichiometry. But what causes the frequent separation into multiple operons of co-regulated genes that act together in a pathway? Here we suggest that separation is due to benefits made possible by differential regulation of each operon. We present a simple mathematical model for the optimal distribution of genes into operons based on a balance of the cost of operons and the benefit of regulation that provides 'just-when-needed' temporal order. The analysis predicts that genes are arranged such that genes on the same operon do not skip functional steps in the pathway. This prediction is supported by genomic data from 137 bacterial genomes. Our work suggests that gene arrangement is not only the result of random historical drift, genome re-arrangement and gene transfer, but has elements that are solutions of an evolutionary optimization problem. Thus gene functional order may be inferred by analyzing the operon structure across different genomes.
Cardiac Ion Channels (2002)

The normal electrophysiologic behavior of the heart is determined by ordered propagation of excitatory stimuli that result in rapid depolarization and slow repolarization, thereby generating action potentials in individual myocytes. Abnormalities of impulse generation, propagation, or the duration and configuration of individual cardiac action potentials form the basis of disorders of cardiac rhythm, a continuing major public health problem for which available drugs are incompletetly effective and often dangerous. The integrated activity of specific ionic currents generates action potentials, and the genes whose expression results in the molecular components underlying individual ion currents in heart have been cloned. This review discusses these new tools and how their application to the problem of arrhythmias is generating new mechanistic insights to identify patients at risk for this condition and developing improved antiarrhythmic therapies.
Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. (1990)

To determine the importance of the third alpha-helix in bovine growth hormone (bGH) relative to growth-related biological activities, the following experimental approach was used: (i) mutagenesis of helix III of bGH to generate an idealized amphiphilic helix; (ii) in vitro expression analyses of the mutated bGH gene in cultured mouse L cells; (iii) mouse liver membrane binding studies of wild-type and mutated bGH; and (iv) expression of the mutated gene in the transgenic mouse. An altered bGH gene (pBGH10 delta 6-M8) was generated that encodes the following changes: glutamate-117 to leucine, glycine-119 to arginine, and alanine-122 to aspartate. The plasmid pBGH10 delta 6-M8 was shown to be expressed in, and its protein product secreted by, mouse L cells. The altered hormone possessed the same binding affinity to mouse liver membrane preparations as wild-type bGH. Transgenic mice containing the mutated bGH gene, however, showed a significant growth-suppressed phenotype. The degree of suppression was directly related to serum levels of the altered bGH molecule.
Structure of the light-emitting moiety of aequorin (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of the light-emitting moiety of aequorinOsamu Shimomura and Frank H. JohnsonCite this: Biochemistry 1972, 11, 9, 1602–1608Publication Date (Print):April 1, 1972Publication History Published online1 May 2002Published inissue 1 April 1972https://pubs.acs.org/doi/10.1021/bi00759a009https://doi.org/10.1021/bi00759a009research-articleACS PublicationsRequest reuse permissionsArticle Views319Altmetric-Citations87LEARN 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 Get e-Alerts
Glossary of terms used in biomolecular screening (IUPAC Recommendations 2011) (2011)

Biomolecular screening is now a crucial component of the drug discovery process, and this glossary will be of use to practitioners in the field of screening and to those who interact with the screening community. The glossary contains definitions related to various aspects of the screening process such as assay types, data handling, and relevant technologies. Many of the terms used in this discipline are not covered by existing glossaries, and where they are, the definitions are often not appropriate for this field. Where appropriate, this document provides new or modified definitions to better reflect the new context. The field of biomolecular screening is multidisciplinary in nature, and this glossary, containing authoritative definitions, will be useful not only for regular practitioners, but also for those who make use of data generated during the screening process.
Different role of CD30 in the development of acute and chronic airway inflammation in a murine asthma model (2009)

CD30 is a costimulatory molecule of the TNF receptor superfamily, expressed on activated T and B cells. Previously, we have shown in a murine asthma model the crucial role of CD30 signaling for the development of this Th2-cell-mediated disease. In the present study, we investigated the role of CD30 in the maintenance of the immune response. In contrast to the acute model, in the chronic model CD30(-/-) mice developed a severe asthma-like phenotype with eosinophilic inflammation and high serum IgE levels. Collagen content, ECM protein deposition and proliferation of smooth muscle cells as signs for airway remodeling were equally increased in both CD30(-/-) and WT mice. Reduced expression of the costimulatory molecule OX40 on CD3(+) T cells in the acute and up-regulation in the chronic model indirectly supported a compensatory role of OX40 for CD30 signaling. In accordance, application of agonistic OX40 antibody restored the asthma phenotype in CD30(-/-) mice in the acute model, whereas chronic airway inflammation was reduced in the presence of an inhibitory anti-OX40 ligand antibody. These data demonstrate that the crucial role of CD30 signaling in the development of acute asthma may be taken over by other costimulatory molecules like OX40 after long-term exposure to the antigen.
<title>Fiber optic hydrogen detection system</title> (1999)

Commercial and military launch vehicles are designed to use hydrogen as the main propellant, which is very volatile, extremely flammable, and highly explosive. Current detection systems uses Teflon transfer tubes at a large number of vehicle locations through which gas samples are drawn and the stream analyzed by a mass spectrometer. A concern with this approach is the high cost of the system. Also, the current system does not provide leak location and is not in real-time. This system is very complex and cumbersome for production and ground support measurement personnel. The fiber optic micromirror sensor under development for cryogenic environment relies on a reversible chemical interaction causing a change in reflectivity of a thin film of coated Palladium. The magnitude of the reflectivity change is correlated to hydrogen concentration. The sensor uses only a tiny light beam, with no electricity whatsoever at the sensor, leading to devices that is intrinsically safe from explosive ignition. The sensor, extremely small in size and weight detects, hydrogen concentration using a passive element consisting of chemically reactive microcoatings deposited on the surface of a glass microlens, which is then bonded to an optical fiber. The system uses a multiplexing technique with a fiber optic driver-receiver consisting of a modulated LED source that is launched into the sensor, and a photodiode detector that synchronously measures the reflected signal. The system incorporates a microprocessor (or PC) to perform the data analysis and storage, as well as trending and set alarm function. As it is a low cost system with a fast response, many more detection sensors can be used that will be extremely helpful in determining leak location for safety of crew and vehicles during launch operations.
Study of aging effects in a Ti-6AL-4V alloy with Widmanstätten and equiaxed microstructures by non-destructive means (2014)

When the Ti-6Al-4V alloy is over-aged at 500-600°C, nanometer-sized α2 (Ti3Al) phases can be homogeneously precipitated inside α phases, thereby leading to the additional improvement of mechanical properties. The present study was concerned with the effects of over-aging on thermoelectric power (TEP) measurements in a Ti-6Al-4V alloy. Widmanstätten and equiaxed microstructures containing fine &agr2 (Ti3Al) particles were obtaining by over-aging a Ti-6Al-4V alloy. Over-aging heat treatments were conducted at 515°C, 545°C and 575°C for different aging times. In order to find out the factors affecting the variation in the TEP, the over-aging samples were examined by optical microscopy (OM) and (SEM) scanning electron microscopy. In particular, we studied the behavior of the physical material property hardness, an important parameter of the Ti-6Al-4V alloy mechanical properties, with respect to the variation in the aging time and temperature. It was found that the TEP measurements reveal an increase in the magnitude of the absolute TEP value of the over-aged Widmanstätten and equiaxed microstructures with regards to the unaged condition for different aging times, with a somewhat higher value at 515°C.
Tourette's syndrome in children: neurobiological issues in pathophysiology. (2000)

In recent decades significant advances in the understanding of neurobiological substrates of Tourette's Syndrome (TS) have led to the formulation of hypotheses regarding the ways in which the most salient features of the syndrome may occur. Pathophysiology of TS involves multiple intertwined neurobiological issues in different areas of the Central Nervous System. This review considers neuroimaging studies (MRI, PET, SPECT) in patients with TS. Neurochemical neurophysiological and electrophysiological studies are also reviewed. The role of the neuroendocrine and neuroimmunologic mechanism on pathogenesis of the disease is discussed. Advances in diagnostic techniques (fMRI, mMRI, PET, SPECT) and in neurophysiological research on neurotransmitter systems will allow us to better understand the pathophysiology of TS and to use more specific treatments.
A three‐dimensional in vitro ovarian cancer coculture model using a high‐throughput cell patterning platform (2011)

In vitro 3D cancer models that provide a more accurate representation of disease in vivo are urgently needed to improve our understanding of cancer pathology and to develop better cancer therapies. However, development of 3D models that are based on manual ejection of cells from micropipettes suffer from inherent limitations such as poor control over cell density, limited repeatability, low throughput, and, in the case of coculture models, lack of reproducible control over spatial distance between cell types (e.g., cancer and stromal cells). In this study, we build on a recently introduced 3D model in which human ovarian cancer (OVCAR-5) cells overlaid on Matrigel™ spontaneously form multicellular acini. We introduce a high-throughput automated cell printing system to bioprint a 3D coculture model using cancer cells and normal fi broblasts micropatterned on Matrigel™ . Two cell types were patterned within a spatially controlled microenvironment (e.g., cell density, cell-cell distance) in a high-throughput and reproducible manner; both cell types remained viable during printing and continued to proliferate following patterning. This approach enables the miniaturization of an established macro-scale 3D culture model and would allow systematic investigation into the multiple unknown regulatory feedback mechanisms between tumor and stromal cells and provide a tool for high-throughput drug screening.
ON THE USE OF GEOMETRIC AND SEMANTIC MODELS FOR COMPONENT-BASED BUILDING RECONSTRUCTION (1999)

3D building data is needed in many application areas. Besides the geometric description an increasing number of applications also demand thematic information about acquired buildings. We present a concept for the automatic extraction of buildings from aerial images. In contrast to other approaches generic building structures both are geometrically reconstructed and semantically classified. A component-based, parameterized building model is employed to control the reconstruction of buildings. This paper describes how geometric and semantic knowledge of buildings is propagated through the different aggregation levels of the building model. Furthermore, it is shown how rules and constraints are derived from the model and exploited at each stage of the reconstruction process. 1 INTRODUCTION 3D building data play an important role for digital city models and geoinformation systems, which are used in numerous application areas: architecture, urban planning, telecommunication and environme...
Identification in pituitary tissue of a peptide alpha-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid. (1983)

An enzymatic activity capable of producing an alpha-amidated peptide product from its glycine-extended precursor has been identified in secretory granules of rat anterior, intermediate, and neural pituitary and bovine intermediate pituitary. High levels of endogenous inhibitors of this alpha-amidation activity have also been found in tissue homogenates. The alpha-amidation activity is totally inhibited by addition of divalent metal ion chelators such as diethyldithiocarbamate, o-phenanthroline, and EDTA; alpha-amidation activity is restored to above control levels upon addition of copper. The alpha-amidation reaction requires the presence of molecular oxygen. Of the various cofactors tested, ascorbic acid was the most potent stimulator of alpha-amidation. The alpha-amidation activity has a neutral pH optimum and is primarily soluble following several cycles of freezing and thawing. Kinetic studies with the bovine intermediate pituitary granule-associated activity demonstrated a linear Lineweaver-Burk plot when D-Tyr-Val-Gly was the varied substrate; the apparent Km and Vmax varied with the concentration of ascorbic acid. The substrate specificity of the alpha-amidation activity appears to be quite broad; the conversion of D-Tyr-Val-Gly into D-Tyr-Val-NH2 is inhibited by the addition of a variety of glycine-extended peptides.
Automatic Quantification of Changes in Bone in Serial MR Images of Joints (2006)

Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions.
Cell-Type Specific and Ligand Specific Enhancement of Cellular Uptake of Oligodeoxynucleoside Methylphosphonates Covalently Linked with a Neoglycopeptide, YEE(ah-GalNAc)3 (1995)

A novel, structurally defined, and homogeneous oligodeoxynucleoside methylphosphonate (oligo-MP) neoglycopeptide conjugate, [YEE(ah-GalNAc)3]-SMCC-AET-pUmpT7, has been synthesized. The linkage between the carbohydrate ligand and the oligo-MP is a metabolically stable thioether. Experiments establish that uptake of this conjugate by human hepatocellular carcinoma (Hep G2) is cell-type specific when compared with its uptake by human fibrosarcoma (HT 1080) and human promyleocytic leukemia (HL-60). Uptake of the conjugate with Hep G2 cells can be totally inhibited by the addition of a 100-fold excess of free YEE(ah-GalNAc)3 in the culture medium indicating the observed cell uptake is ligand specific. The conjugate is rapidly taken in by Hep G2 cells in a linear fashion reaching a saturation plateau of 26 pmol per 10(6) cells after 24 h. Conjugation of oligo-MPs to ligands for hepatic carbohydrate receptors, such as YEE(ah-GalNAc)3, represents an efficient and ligand-specific method for the intracellular delivery of oligo-MPs.
A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. (1995)

Thiopurine S-methyltransferase (TPMT; S-adenosyl-L-methionine:thiopurine S-methyltransferase, EC 2.1.1.67) activity exhibits genetic polymorphism, with approximately 0.33% of Caucasians and African-Americans inheriting TPMT deficiency as an autosomal recessive trait. To determine the molecular genetic basis for this polymorphism, we cloned the TPMT cDNA from a TPMT-deficient patient who had developed severe hematopoietic toxicity during mercaptopurine therapy. Northern blot analysis of RNA isolated from leukocytes of the deficient patient demonstrated the presence of TPMT mRNAs of comparable size to that in subjects with high TPMT activity. Sequencing of the mutant TPMT cDNA revealed a single point mutation (G238-->C), leading to an amino acid substitution at codon 80 (Ala80-->Pro). When assessed in a yeast heterologous expression system, this mutation led to a 100-fold reduction in TPMT catalytic activity relative to the wild-type cDNA, despite a comparable level of mRNA expression. A mutation-specific PCR amplification method was developed and used to detect the G238-->C mutation in genomic DNA of the propositus and her mother. This inactivating mutation in the human TPMT gene provides insights into the genetic basis for this inherited polymorphism in drug metabolism.
The Scaffold Protein Homer1b/c Links Metabotropic Glutamate Receptor 5 to Extracellular Signal-Regulated Protein Kinase Cascades in Neurons (2005)

Group I metabotropic glutamate receptors (mGluRs) increase cellular levels of inositol-1,4,5-triphosphate (IP3) and thereby trigger intracellular Ca2+ release. Also, group I mGluRs are organized with members of Homer scaffold proteins into multiprotein complexes involved in postreceptor signaling. In this study, we investigated the relative importance of the IP3/Ca2+ signaling and novel Homer proteins in group I mGluR-mediated activation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured rat striatal neurons. We found that selective activation of mGluR5, but not mGluR1, increased ERK1/2 phosphorylation. Whereas the IP3/Ca2+ cascade transmits a small portion of signals from mGluR5 to ERK1/2, the member of Homer family Homer1b/c forms a central signaling pathway linking mGluR5 to ERK1/2 in a Ca2+-independent manner. This was demonstrated by the findings that the mGluR5-mediated ERK1/2 phosphorylation was mostly reduced by a cell-permeable Tat-fusion peptide that selectively disrupted the interaction of mGluR5 with the Homer1b/c and by small interfering RNAs that selectively knocked down cellular levels of Homer1b/c proteins. Furthermore, ERK1/2, when only coactivated by both IP3/Ca2+- and Homer1b/c-dependent pathways, showed the ability to phosphorylate two transcription factors, Elk-1 and cAMP response element-binding protein, and thereby facilitated c-Fos expression. Together, we have identified two coordinated signaling pathways (a conventional IP3/Ca2+ vs a novel Homer pathway) that differentially mediate the mGluR5-ERK coupling in neurons. Both the Ca2+-dependent and -independent pathways are corequired to activate ERK1/2 to a level sufficient to achieve the mGluR5-dependent synapse-to-nucleus communication imperative for the transcriptional regulation.
Chromosome 8q24 risk variants in hereditary and non‐hereditary prostate cancer patients (2008)

Our study further supports the presence of PCa susceptibility loci at 8q24, particular at Region 2, and also provides evidence that these SNPs play an important role in familial prostate cancer. Large family-based studies are needed to confirm our novel findings.
Cut-off frequency in radially inhomogeneous single-mode fibre (1977)

The limit for single-mode operation in a graded-index fibre has been obtained by calculating the normalised cut-off frequency of the TE01 mode, The affect of diffusion at the core-cladding boundary has been estimated.