gebhart/patrepeval huggingface dataset:
TP53 mutations in breast cancer associated with BRCA1 or BRCA2 germ-line mutations: distinctive spectrum and structural distribution. (2001)

Several groups have studied the molecular pathology of inherited breast cancer. By combining several such studies, we show in this study that somatic TP53 abnormalities are more common in breast cancer associated with BRCA1 or BRCA2 germ-line mutations than in sporadic breast cancers (odds ratio, 2.8; P = 0.0003). Then, we compared the spectrum of TP53 mutations for breast cancers in the IARC TP53 mutation database with the 82 mutations reported in BRCA1/2-associated breast cancers. The spectrum differed significantly both in distribution (P < 1 x 10(-6)) and in base changes (P = 0.025). Mutations at A:T bp were more common in BRCA1/2-associated tumors and strand bias suggesting DNA repair abnormalities was found. Changes were common at TP53 codons that are not mutation hotspots. Structural modeling showed that most of these p53 non-hotspot amino acids characterized in breast tumors isolated from patients with deficient BRCA1/2 function are distributed in a region of the protein on the opposite side of the p53 DNA-binding surface. Our results suggest that BRCA1/2 mutations influence the type and distribution of TP53 mutations seen in breast cancer.
Fast search algorithms for reconfiguration problems (2002)

A number of reconfiguration strategies have been proposed for increasing the yield of VLSI chips. In most cases the associated reconfiguration problems are NP-complete. Therefore, exhaustive search algorithms are generally used in order to find a solution when one exists. In this paper we present the notion of admissible sets and show how such sets can be used to significantly reduce the running time of many exhaustive search algorithms for reconfiguration problems. As an example, the authors find a class of admissible sets called excess-k critical sets that can be used in the design of fast search algorithms for the problem of reconfiguring redundant random access memories (RRAMs). They also consider applications to the problems of reconfiguring RRAMs with shared spares and reconfiguring redundant programmable logic arrays (RPLAs). Experimental results indicate that this approach is very powerful.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Expansion of NK Cells with Reduction of Their Inhibitory Ly-49A, Ly-49C, and Ly-49G2 Receptor-Expressing Subsets in a Murine Helminth Infection: Contribution to Parasite Control (2002)

Natural killer cell-associated direct cytotoxicity and cytokine production are crucial mechanisms for early innate host resistance against viruses, bacteria, or protozoa. The engagement of inhibitory NK cell receptors can influence host responses to viruses. However, these receptors have not been investigated to date in parasitic infections, and little is known about the role of NK cells in the defense against helminths. Therefore, we have correlated the frequencies of cells expressing the pan-NK marker DX5 and subsets bearing inhibitory Ly-49 receptors with worm survival and cytokine production during infection with Litomosoides sigmodontis in BALB/c mice (H2(d)), the only fully permissive model of filariasis. A marked influx of DX5(+)/CD3(-) NK cells and DX5(+)/CD3(+) T cells into the pleural cavity, where the parasites were located, was observed. The frequency of pleural NK cells expressing the H2(d)-reactive inhibitory receptors Ly-49A, Ly-49C, or Ly-49G2 declined most strongly compared with spleen and blood. In the peripheral blood, longitudinal analysis revealed an early and stable reduction of Ly-49C(+) and Ly-49G2(+) NK cells, a subsequent significant increase of the entire NK cell and DX5(+)/CD3(+) T cell populations, and a reduction in the Ly-49A(+) subset. The in vivo depletion of NK cells strongly enhanced the worm load and influenced IL-4 and IL-5 plasma levels. These data demonstrate a new role for NK cells in the host defense against filariae and, for the first time, alterations of Ly-49 receptor-expressing NK cell subsets in a parasitic infection.
Microarrays in Clinical Diagnostics (2005)

Microarray technology is now well established in laboratories all over the world, both for rapid detection of genetic mutations and, increasingly, for simultaneously analyzing the expression of a large number of proteins. In Microarrays in Clinical Diagnostics, a panel of academic and industrial investigators surveys the new world of microarray technology, describing in step-by-step detail diverse DNA and protein assays in clinical laboratories using state-of-the-art technologies. The advanced tools and methods described are designed for mRNA expression analysis, SNP analysis, identification and quantification of proteins, and for studies of protein-protein interactions. Among the highlights are universal arrays, antibody microarrays, direct labeling approaches, and quality control techniques for protein microarray-based analysis. The protocols follow the successful Methods in Molecular Biology™ series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Authoritative and highly practical, Microarrays in Clinical Diagnostics combines a comprehensive collection of cutting-edge technologies with detailed laboratory methods to help clinical laboratory researchers design and perform microarray experiments for DNA and protein analysis, diagnostic testing, and cancer research
Investigation of the role of a β(1–4) agarase produced by Pseudoalteromonas gracilis B9 in eliciting disease symptoms in the red alga Gracilaria gracilis (2003)

Gracilaria species are an important source of agar. The South African Gracilaria industry has experienced a number of setbacks over the last decade in the form of complete or partial die-offs of the agarophyte growing in Saldanha Bay, which may be attributed to bacterial infection. Since a positive correlation was observed between the presence of agarolytic epiphytes and bacterial pathogenicity, we investigated the role of an agarase in the virulence mechanism employed by a bacterium that elicits disease in Gracilaria gracilis. The recombinant plasmid pDA1, isolated from a Pseudoalteromonas gracilis B9 genomic library, was responsible for the agarolytic activity exhibited by Escherichia coli transformants when grown on solid medium. A BLAST search of the GenBank database showed that an 873 bp ORF (aagA) located on pDA1 had 85 % identity to the beta-agarase (dagA) from Pseudoalteromonas atlantica ATCC 19262(T) (or IAM 12927(T)) at the amino acid level. AagA was purified from the extracellular medium of an E. coli transformant harbouring pDA1 by using a combination of gel filtration and ion-exchange chromatography. AagA has an M(r) of 30 000 on SDS-PAGE. TLC of the digestion products of AagA showed that the enzyme cleaves the beta-(1,4) linkages of agarose to yield predominately neoagarotetraose. Western hybridization confirmed that the cloned agarase was in fact the extracellular beta-agarase of P. gracilis B9. The observed relationship between disease symptoms of G. gracilis and the agarolytic phenotype of P. gracilis B9 was confirmed. Transmission electron microscope examination of cross sections of both healthy G. gracilis and G. gracilis infected with P. gracilis, revealed a weakening of the cell structure in the latter plants. Immunogold-labelled antibodies localized the agarase in situ to the cell walls of bleached G. gracilis. Thus, the weakening observed in the cell structure of G. gracilis infected with P. gracilis can be attributed to degradation of the mucilaginous component of the cell wall of the bleached thalli.
Sensitization to self (virus) antigen by in situ expression of murine interferon-gamma. (1995)

Autoimmune disease results from inflammatory destruction of tissues by aberrant self-reactive lymphocytes. We studied the autoimmune potential of T lymphocytes immunologically ignorant of viral antigens acting as self antigens and whether the host defense molecule IFN-gamma could stimulate these cells to cytotoxic competency. For this purpose, we produced double transgenic mice expressing pancreatic IFN-gamma as well as lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) or glycoprotein (GP) antigen. 100% of the NP+/IFN-gamma+ mice became diabetic before 2 mo of age, while none of the NP single transgenic littermates and only 10% of IFN-gamma single transgenic littermates did. Strikingly, NP+/IFN-gamma+ mice spontaneously developed cytotoxic T lymphocyte activity on LCMV-infected targets and vaccinia virus-NP-infected ones without prior LCMV infection but NP+/IFN-gamma- mice did not, which indicates specific sensitization to the viral antigen by IFN-gamma. These results suggest that lymphocytes ignorant of self antigens can be activated by IFN-gamma released after immunologic stimulation such as viral infection. This mechanism may account for the loss of apparent tolerance to self antigens in autoimmune diseases such as insulin-dependent diabetes mellitus.
On the transfer function calculus for underspread LTV channels (1997)

The freedom in the definition of a time-varying transfer function is formalized by introducing the generalized Weyl correspondence, which includes Zadeh's (1950) function and the Weyl symbol. For slowly time-varying linear systems with properly limited memory (underspread LTV systems) we prove the asymptotic validity of the multiplicative transfer function calculus.
Lincosamide antibiotics stimulate dissociation of peptidyl-tRNA from ribosomes (1993)

At nonpermissive temperatures the peptidyl-tRNA hydrolase of pth(Ts) bacterial mutants is inactivated, and cells accumulate peptidyl-tRNA and die. Doses of erythromycin, lincomycin, or clindamycin that inhibited the growth of antibiotic-hypersensitive DB-11 pth+ cells accelerated the killing of DB-11 pth(Ts) cells at nonpermissive temperatures. Erythromycin and lincomycin also stimulated the accumulation of peptidyl-tRNA. Lincomycin and clindamycin stimulated peptidyl-tRNA dissociation from ribosomes.
NetB, a Pore-Forming Toxin from Necrotic Enteritis Strains of Clostridium perfringens (2010)

The Clostridium perfringens necrotic enteritis B-like toxin (NetB) is a recently discovered member of the β-barrel pore-forming toxin family and is produced by a subset of avian C. perfringens type A strains. NetB is cytotoxic for avian cells and is associated with avian necrotic enteritis. This review examines the current state of knowledge of NetB: its role in pathogenesis, its distribution and expression in C. perfringens and its vaccine potential.
ChemInform Abstract: Synthesis and Pharmacological Activity of 2‐Arylethenylthiazol‐4‐acetic Acids and ‐4‐carboxylic Acids. (1986)

Two new series of 2-aryletenylthiazolo-4-acetic (IV-XII) and 4-carboxylic (XIII-XXI) acids substituted with alkoxy groups in the benzene ring were synthesized. The compounds were subjected to comparative tests of antiinflammatory, analgesic and antipyretic activity.
Association of chromosome 11 locus D11S12 with histology, stage, and metastases in lung cancer. (1998)

We have reported frequent allele loss for the marker D11S12 on chromosome band 11p15.5 in human lung cancer. The smallest common region of allele loss has been refined to approximately 500 kb and is confined between D11S1758 and D11S860. Here, we investigated the association of D11S12 allele loss with epidemiologic, pathologic, and clinical parameters. Analysis of allele loss was performed by Southern blotting on a cohort of 156 patients with lung cancer, and data were interpreted with the use of a phosphorimager. Results were statistically compared with retrospectively collected variables. D11S12 allele loss was found in 88% of small cell carcinomas, 57% of squamous cell carcinomas, and 40% of adenocarcinomas. Allele loss was associated with tumor stage (p = 0.04) and was more frequent in tumors that had already metastasized. These results suggest that a gene in the D11S12 region may be responsible for the metastatic potential of lung cancer. The functional status of this gene may thus be of future value in guiding clinicians on decisions regarding adjuvant and neoadjuvant therapies for patients with lung cancer.
Viral complementation allows HIV-1 replication without integration (2008)

This novel mode of retroviral replication allows survival of viruses which would otherwise be lost because of a failure to integrate, amplifies the effective amount of cellular coinfection, increases the replicating HIV-1 gene pool, and enhances the opportunity for diversification through errors of polymerization and recombination.
Nonsense-mediated mRNA decay factors act in concert to regulate common mRNA targets (2005)

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades mRNAs containing nonsense codons, and regulates the expression of naturally occurring transcripts. While NMD is not essential in yeast or nematodes, UPF1, a key NMD effector, is essential in mice. Here we show that NMD components are required for cell proliferation in Drosophila. This raises the question of whether NMD effectors diverged functionally during evolution. To address this question, we examined expression profiles in Drosophila cells depleted of all known metazoan NMD components. We show that UPF1, UPF2, UPF3, SMG1, SMG5, and SMG6 regulate in concert the expression of a cohort of genes with functions in a wide range of cellular activities, including cell cycle progression. Only a few transcripts were regulated exclusively by individual factors, suggesting that these proteins act mainly in the NMD pathway and their role in mRNA decay has not diverged substantially. Finally, the vast majority of NMD targets in Drosophila are not orthologs of targets previously identified in yeast or human cells. Thus phenotypic differences observed across species following inhibition of NMD can be largely attributed to changes in the repertoire of regulated genes.
Stimulation of Human and Rat Islet β-Cell Proliferation with Retention of Function by the Homeodomain Transcription Factor Nkx6.1 (2008)

The homeodomain transcription factor Nkx6.1 plays an important role in pancreatic islet beta-cell development, but its effects on adult beta-cell function, survival, and proliferation are not well understood. In the present study, we demonstrated that treatment of primary rat pancreatic islets with a cytomegalovirus promoter-driven recombinant adenovirus containing the Nkx6.1 cDNA (AdCMV-Nkx6.1) causes dramatic increases in [methyl-(3)H] thymidine and 5-bromo-2'-deoxyuridine (BrdU) incorporation and in the number of cells per islet relative to islets treated with a control adenovirus (AdCMV-betaGAL), whereas suppression of Nkx6.1 expression reduces thymidine incorporation. Immunocytochemical studies reveal that >80% of BrdU-positive cells in AdCMV-Nkx6.1-treated islets are beta cells. Microarray, real-time PCR, and immunoblot analyses reveal that overexpression of Nkx6.1 in rat islets causes concerted upregulation of a cadre of cell cycle control genes, including those encoding cyclins A, B, and E, and several regulatory kinases. Cyclin E is upregulated earlier than the other cyclins, and adenovirus-mediated overexpression of cyclin E is shown to be sufficient to activate islet cell proliferation. Moreover, chromatin immunoprecipitation assays demonstrate direct interaction of Nkx6.1 with the cyclin A2 and B1 genes. Overexpression of Nkx6.1 in rat islets caused a clear enhancement of glucose-stimulated insulin secretion (GSIS), whereas overexpression of Nkx6.1 in human islets caused an increase in the level of [(3)H]thymidine incorporation that was twice the control level, along with complete retention of GSIS. We conclude that Nkx6.1 is among the very rare factors capable of stimulating beta-cell replication with retention or enhancement of function, properties that may be exploitable for expansion of beta-cell mass in treatment of both major forms of diabetes.
The New α-Amino Acid Nω-Hydroxy-nor-l-arginine:  a High-Affinity Inhibitor of Arginase Well Adapted To Bind to Its Manganese Cluster (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTThe New α-Amino Acid Nω-Hydroxy-nor-l-arginine: a High-Affinity Inhibitor of Arginase Well Adapted To Bind to Its Manganese ClusterJ. Custot, C. Moali, M. Brollo, J. L. Boucher, M. Delaforge, D. Mansuy, J. P. Tenu, and J. L. ZimmermannView Author Information Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS Université René Descartes, 45 rue des Saints-Pères 75270 Paris Cedex 06, France CNRS, URA 1116, Bât. 432 Université Paris XI, 91405 Orsay, France CEA/Saclay, Département de Biologie Cellulaire et Moléculaire, Section de Bioénergétique Bât. 532, 91191 Gif Sur Yvette, France Cite this: J. Am. Chem. Soc. 1997, 119, 17, 4086–4087Publication Date (Web):April 30, 1997Publication History Received28 January 1997Published online30 April 1997Published inissue 1 April 1997https://pubs.acs.org/doi/10.1021/ja970285ohttps://doi.org/10.1021/ja970285orapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views1673Altmetric-Citations80LEARN 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:Anatomy,Electron paramagnetic resonance spectroscopy,Inhibitors,Rodent models,Transition metals Get e-Alerts
Association of Cytochromes P450 with Their Reductases:  Opposite Sign of the Electrostatic Interactions in P450BM-3 As Compared with the Microsomal 2B4 System (2000)

The role of electrostatic interactions in the association of P450s with their nicotinamide adenine dinucleotide phosphate- (NADPH) dependent flavoprotein reductases was studied by fluorescence resonance energy transfer. The fluorescent probe 7-(ethylamino)-3-(4'-maleimidylphenyl)-4-methylcoumarin maleimide (coumarylphenylmaleimide, CPM) was introduced into the flavoprotein molecule at a 1:1 molar ratio. The interaction of P450 2B4 and NADPH-P450 reductase (CPR) from rabbit liver microsomes was compared with that of the isolated heme domain (BMP) and the flavoprotein domain (BMR) of P450BM-3. The cross-pairs of the components were also studied. Increasing ionic strength (0.05-0.5 M) was shown to result in the dissociation of the CPR-P450 2B4 complex with the dissociation constant increasing from 0.01 to 0.09 microM. This behavior is consistent with the assumption that charge pairing between CPR and P450 2B4 is involved in their association. In contrast, the electrostatic component of the interaction of the partners in P450BM-3 was shown to have an opposite sign. The isolated BMP and BMR domains have very low affinity for each other and the dissociation constant of their complex decreases from 8 to 3 microM with increasing ionic strength (0.05-0.5 M). Importantly, the BMP-CPR and P450 2B4-BMR "mixed", heterogeneous pairs behave similarly to the pairs of BMP and P450 2B4 with their native electron donors. Therefore, the observed difference in the interaction mechanisms between these two systems is determined mainly by the different structure of the heme proteins rather than their flavoprotein counterparts. P450BM-3 is extremely efficient and highly coupled, with the reductase and the P450 domains tethered to one another. Therefore, in contrast to P450 2B4-CPR binding, very tight binding between the P450BM-3 redox partners would be of no value in the synchronization of complex formation during catalytic turnover.
Degradation and intracellular accumulation of a residualizing hyaluronan derivative by liver endothelial cells (1993)

The release and intracellular accumulation of 125I-hyaluronan degradation products was studied in cultured liver endothelial cells with hyaluronan oligosaccharides (relative molecular mass = approximately 44,000) uniquely modified and radiolabeled at the terminal reducing sugar. Two methods were combined to measure 125I-hyaluronan degradation by liver endothelial cells. (a) Cetylpyridinium chloride precipitation of hyaluronan oligosaccharides was used as a rapid, convenient assay to monitor the appearance of hyaluronan degradation products. Hyaluronan oligosaccharides less than 54 to 60 monosaccharides in length were not precipitated with cetylpyridinium chloride and thus were assessed as degraded. (b) Gel filtration chromatography was used to estimate the size range of oligosaccharides produced by liver endothelial cells. After internalization of 125I-hyaluronan, liver endothelial cells released radioactive degradation products into the culture media after a lag period of 2.5 to 3.0 hr. The intracellular accumulation of degraded 125I-hyaluronan was linear for at least 2 hr even though no degradation products were released. The long lag before release of degraded 125I-hyaluronan is likely caused by the modified chemical structure at the reducing end of the hyaluronan derivative; the derivative acts like a residualizing label. After this lag the release of degraded 125I-hyaluronan proceeded linearly for up to 12 hr. The extracellular 125I-hyaluronan degradation products eluted with a distribution coefficient of 1.3 on a gel filtration column. The major intracellular 125I-labeled degradation product showed the same retardation (distribution coefficient = 1.3). This retention may be caused by the hydrophobic aromatic and alkyl modifications to the former reducing sugar, also characteristics of a residualizing label. In addition, at least two larger minor intermediates were observed intracellularly. The rate of intracellular 125I-hyaluronan degradation was dependent on hyaluronan concentration and reached a maximal rate (159 molecules/cell/sec) at 2 x 10(-7) mol/L. This was about half the maximal rate of endocytosis (285 molecules/cell/sec) at a hyaluronan concentration of 1.3 x 10(-7) mol/L. The apparent ligand concentration that gives half-maximal responses for endocytosis and intracellular degradation was 0.6 x 10(-7) and 1.0 x 10(-7) mol/L, respectively.
A client-based transaction system to maintain data integrity (1979)

This paper describes a technique for maintaining data integrity that can be implemented using capabilities typically found in existing file systems. Integrity is a property of a total collection of data. It cannot be maintained simply by using reliable primitives for reading and writing single units—the relations between the units are important also. The technique suggested in this paper ensures that data integrity will not be lost as a result of simultaneous access or as a result of crashes at inopportune times. The approach is attractive because of its relative simplicity and its modest demands on the underlying file system. The paper gives a detailed description of how consistent, atomic transactions can be implemented by client processes communicating with one or more file server computers. The discussion covers file structure, basic client operations, crash recovery, and includes an informal correctness proof.