gebhart/patrepeval huggingface dataset:
Critical role for Atm in suppressing V(D)J recombination-driven thymic lymphoma (1999)

Chromosome translocations involving T cell receptor (TCR) loci have been found in tumors from Ataxia telangiectasia (AT) patients and in mouse Atm-/- thymoma, suggesting the involvement of V(D)J recombination in these malignancies. By introducing a RAG-1 deficiency into Atm-/- mice in the presence of a TCR transgene, we show that V(D)J recombination is critical for thymoma development in these mice. Therefore, aberrant V(D)J recombination, normally suppressed by Atm, facilitates tumorigenic events leading to cancer. Because V(D)J recombination is dispensable for lymphomagenesis upon p53 deficiency, this study also indicates that Atm and p53 function by distinct mechanisms in suppressing thymoma.
Overexpression of the c-erbB-2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities. (1997)

Overexpression of the c-erbB-2 gene-encoded p185 has been reported in approximately 30% of human breast cancers and has been correlated with lymph node metastasis and poor prognosis in breast cancer patients. To investigate whether overexpression of p185 can enhance the metastatic potential of human breast cancer cells, we have introduced the human c-erbB-2 gene into the very low p185-expressing MDA-MB-435 human breast cancer cells and established 435.eB transfectants that express higher levels of p185. In this study, we compared the metastatic phenotypes of the parental MDA-MB-435 cells and the 435.eB transfectants. In vivo experimental metastasis assays in which we injected MDA-MB-435 parental cells or 435.eB transfectants into the tail veins of ICR-SCID mice demonstrated that mice injected with p185-overexpressing 435.eB transfectants formed significantly more metastatic tumors than the mice injected with parental and control cells. The changes in experimental metastatic potential in vivo were accompanied by increased invasiveness in vitro. In addition, the secretion of basement membrane-degradative enzymes, which is an important step in the invasion and metastasis process, was also increased in the p185-overexpressing 435.eB transfectants. These results indicated that p185 overexpression can enhance the metastatic potential of MDA-MB-435 human breast cancer cells. To investigate whether enhanced metastatic potential in the p185-overexpressing 435.eB transfectants was the result of increased cancer cell growth and transformation potential, we compared the growth rate, anchorage-independent growth ability, and tumorigenicity of the 435.eB transfectants with that of the parental cells. The transfectants and the parental cells all had similar growth rates and anchorage-independent growth abilities and demonstrated similar tumorigenic potential. These findings suggest that c-erbB-2 is a metastasis-promoting gene for breast cancers that is distinct from other tumor-promoting genes in that the c-erbB-2 gene can enhance the intrinsic metastatic potentials of MDA-MB-435 cells without increasing their transformation abilities.
An Essential Interaction between Distinct Domains of HIV-1 Integrase Mediates Assembly of the Active Multimer (1995)

Integrase mediates integration of the retroviral genome into a host cell chromosome, an essential step in the viral life cycle. In vitro, a stable complex containing only purified human immunodeficiency virus (HIV) integrase and a model viral DNA substrate processively executes the 3'-end processing and DNA joining steps in the integration reaction. We examined the relationship of three essential components of the HIV integrase: the HHCC domain, a putative zinc-finger near the N terminus; the phylogenetically conserved "DD35E" motif, which defines the catalytic domain; and a feature recognized by its sensitivity to the alkylating agent N-ethylmaleimide (NEM). HIV integrase is a multimer, and these three components can be distributed among at least two subunits of the multimeric enzyme. The components function asymmetrically in the active multimer; the DD35E motif and NEM-sensitive site are required in trans to the HHCC region. A divalent cation-dependent interaction involving the NEM-sensitive site of one integrase subunit and the HHCC region of another subunit points to a role for these two features of integrase in multimer assembly. Deletion of the HHCC domain, or modification of integrase with NEM, impaired the assembly of a stable complex between integrase and viral DNA, suggesting that this initial step in the integration pathway requires assembly of the active integrase multimer.
Synthesis of High Molecular Weight Poly(styrene-co-acrylonitrile) Copolymers with Controlled Architecture (2006)

High molecular weight styrene−acrylonitrile (SAN) copolymers were prepared under azeotropic conditions (60 mol % of styrene) by ARGET (activators regenerated by electron transfer) ATRP (atom transfer radical polymerization) at 80 °C in anisole. When a normal ATRP of styrene and acrylonitrile was conducted, the molecular weight of the resulting SAN copolymers was limited due to outer-sphere electron-transfer reactions. This was due to oxidation of polystyryl radicals to carbocations or reduction of polyacrylonitirile radicals to carbanions via reactions with Cu(II) and Cu(I) species, respectively. Since ARGET ATRP employs much lower concentrations of copper catalyst, the contributions of these side reactions are reduced, enabling formation of high molecular weight SAN copolymers (Mn ∼ 200 000) with low polydispersity (Mw/Mn < 1.3). Additionally, SAN copolymers with controlled chain architecture were prepared including block copolymers and starlike copolymers.
Linux Vs. Windows NT and OS/2 (1994)

We continue to see media blurbs and ads for both Microsoft's Windows NT and IBM's OS/2. Both promise to be the operating system that we need and to take advantage of the Intel 386 and beyond
NADPH oxidase inhibition attenuates total body irradiation-induced haematopoietic genomic instability (2011)

Ionising radiation (IR) is a known carcinogen and poses a significant risk to the haematopoietic system for the development of leukaemia in part by induction of genomic instability. Induction of chronic oxidative stress has been assumed to play an important role in mediating the effect of IR on the haematopoietic system. However, there was no direct evidence to support this hypothesis prior to our studies. In our recent studies, we showed that exposure of mice to total body irradiation (TBI) induces persistent oxidative stress selectively in haematopoietic stem cells (HSCs) at least in part via up-regulation of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4. Now, we found that post-TBI treatment with diphenylene iodonium (DPI), a pan NOX inhibitor, not only significantly reduces TBI-induced increases in reactive oxygen species (ROS) production, oxidative DNA damage and DNA double-strand breaks in HSCs but also dramatically decreases the number of cells with unstable chromosomal aberrations in the clonal progeny of irradiated HSCs. The effects of DPI are comparable to Mn (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin, a superoxide dismutase mimetic and a potent antioxidant. These findings demonstrate that increased production of ROS by NOX in HSCs mediates the induction of haematopoietic genomic instability by IR and that NOX may represent a novel molecular target to inhibit TBI-induced genomic instability.
Molecular mechanisms and selective influences that shape the kappa gene repertoire of IgM+ B cells. (1997)

To analyze the human kappa chain repertoire and the influences that shape it, a single cell PCR technique was used that amplified Vkappa Jkappa rearrangements from genomic DNA of individual human B cells. More than 350 productive and 250 nonproductive Vkappa Jkappa rearrangements were sequenced. Nearly every functional Vkappa gene segment was used in rearrangements, although six Vkappa gene segments, A27, L2, L6, L12a, A17, and O12/O2 were used preferentially. Of these, A27, L2, L6, and L12a showed evidence of positive selection based on the variable region and not CDR3, whereas A17 was overrepresented because of a rearrangement bias based on molecular mechanisms. Utilization of Jkappa segments was also nonrandom, with Jkappa1 and Jkappa2 being overrepresented and Jkappa3 and Jkappa5 underrepresented in the nonproductive repertoire, implying a molecular basis for the bias. In B cells with two Vkappa Jkappa rearrangements, marked differences were noted in the Vkappa segments used for the initial and subsequent rearrangements, whereas Jkappa segments were used comparably. Junctional diversity was generated by n-nucleotide addition in 60% and by exonuclease trimming in 75% of the Vkappa Jkappa rearrangements analyzed. Despite this large degree of diversity, a strict CDR3 length was maintained in both productive and nonproductive rearrangements. More than 23% of the productive rearrangements, but only 7% of the nonproductive rearrangements contained somatic hypermutations. Mutations were significantly more frequent in Vkappa sequences derived from CD5- as compared with CD5+ B cells. These results document that the gene segment utilization within the Vkappa repertoire is biased by both intrinsic molecular processes as well as selection after light chain expression. Moreover, IgM+ memory cells with highly mutated kappa genes reside within the CD5- but not the CD5+ B cell compartment.
High frequency of altered HLA class I phenotypes in invasive colorectal carcinomas (1998)

We analyzed the expression of HLA class I antigens in 78 tumor tissue samples obtained from patients diagnosed as having colorectal carcinomas. A broad panel of mAbs defining HLA monomorphic, locus-specific and allele-specific determinants was used. In addition, an antibody defining HLA-C locus-specific determinant (L31) was also tested. Previous reports on these tumors indicated HLA class I losses of 30 to 40%. At least 73% of the patients in the present study had a detectable HLA class I alteration. These altered HLA phenotypes were classified as total HLA loss (18%) (phenotype I); HLA-A locus-specific loss (9%) (phenotype IIIa); HLA-B locus-specific loss (8%) (phenotype IIIb); HLA-A and B locus losses (2%) and HLA allelic losses (36%) (phenotype IV). We found no HLA-C locus losses. Autologous peripheral blood lymphocyte HLA class I typing was always necessary to define phenotype IV. We also studied the CD3 zeta chain in tumor tissues to correlate possible changes in the CD3 signal transduction pathway with HLA alterations. The CD3 ratio was frequently altered, but this alteration could not be correlated with tumor HLA phenotypes. The high frequency of HLA class I losses in colorectal carcinomas suggests that this finding is a widespread phenomenon and may be required to escape T-cell recognition. It remains to be determined whether HLA expression is "normal" in the rest of the 27% of our patients.
Cells Capable of Bone Production Engraft from Whole Bone Marrow Transplants in Nonablated Mice (1999)

Allogeneic and autologous marrow transplants are routinely used to correct a wide variety of diseases. In addition, autologous marrow transplants potentially provide opportune means of delivering genes in transfected, engrafting stem cells. However, relatively little is known about the mechanisms of engraftment in transplant recipients, especially in the nonablated setting and with regard to cells not of hemopoietic origin. In particular, this includes stromal cells and progenitors of the osteoblastic lineage. We have demonstrated for the first time that a whole bone marrow transplant contains cells that engraft and become competent osteoblasts capable of producing bone matrix. This was done at the individual cell level in situ, with significant numbers of donor cells being detected by fluorescence in situ hybridization in whole femoral sections. Engrafted cells were functionally active as osteoblasts producing bone before being encapsulated within the bone lacunae and terminally differentiating into osteocytes. Transplanted cells were also detected as flattened bone lining cells on the periosteal bone surface.
Changes in IP3 and cytosolic Ca2+ in response to sugars and non‐sugar sweeteners in transduction of sweet taste in the rat. (1996)

1. The transduction pathways of sweet-sensitive cells in rat circumvallate (CV) taste buds were investigated with assays for inositol 1,4,5-trisphosphate (IP3) and with Ca2+ imaging. Stimulation with the non-sugar sweeteners SC-45647 and saccharin rapidly increased the cellular content of IP3 by 400 pmol (mg protein)-1, while sucrose had a much smaller effect on IP3. As shown previously, sucrose, but not saccharin, increased the content of cyclic adenosine monophosphate (cAMP) of this preparation. 2. Stimulation of isolated CV taste buds with SC-45647 increased the cytosolic Ca2+ concentration ([Ca2+]i) by 56.7 +/- 3.2 nM (n = 181). Due to the non-confocality of the measuring system, these concentrations are underestimates. The increase in [Ca2+]i did not require the presence of extracellular Ca2+, suggesting that the Ca2+ release was from intracellular stores. 3. Individual cells responding to the non-sugar sweeteners with Ca2+ release also responded to sucrose and to forskolin with an increase in [Ca2+]i. Such cells did not respond to the bitter tastant denatonium chloride. 4. Responses to sucrose were abolished by lowering the Ca2+ concentration of the stimulus solution, indicating Ca2+ uptake from the extracellular medium. 5. The responses of sweet-sensitive cells to forskolin were also abolished when Ca2+ ions were omitted from the stimulus solution. They were partially inhibited by the presence of Co2+, Ni2+, D600 (methoxyverapamil) and amiloride, indicating multiple pathways of Ca2+ uptake activated by cAMP. 6. In conclusion, a sweet-sensitive cell of the rat responds to sucrose with an increase in cAMP and Ca2+ uptake, but to non-sugar sweeteners with an increase in IP3 and Ca2+ release. The increase in [Ca2+]i, common to both pathways, is presumably required for synaptic exocytosis and for signal termination.
Extraordinary Mobility in Semiconducting Carbon Nanotubes (2003)

Semiconducting carbon nanotube transistors with channel lengths exceeding 300 microns have been fabricated. In these long transistors, carrier transport is diffusive and the channel resistance dominates the transport. Transport characteristics are used to extract the field-effect mobility (79 000 cm2/Vs) and estimate the intrinsic mobility (>100 000 cm2/Vs) at room temperature. These values exceed those for all known semiconductors, which bodes well for application of nanotubes in high-speed transistors, single- and few-electron memories, and chemical/biochemical sensors.
Complete Genomic Sequence of the Filamentous Nitrogen-fixing Cyanobacterium Anabaena sp. Strain PCC 7120 (2001)

The nucleotide sequence of the entire genome of a filamentous cyanobacterium, Anabaena sp. strain PCC 7120, was determined. The genome of Anabaena consisted of a single chromosome (6,413,771 bp) and six plasmids, designated pCC7120alpha (408,101 bp), pCC7120beta (186,614 bp), pCC7120gamma (101,965 bp), pCC7120delta (55,414 bp), pCC7120epsilon (40,340 bp), and pCC7120zeta (5,584 bp). The chromosome bears 5368 potential protein-encoding genes, four sets of rRNA genes, 48 tRNA genes representing 42 tRNA species, and 4 genes for small structural RNAs. The predicted products of 45% of the potential protein-encoding genes showed sequence similarity to known and predicted proteins of known function, and 27% to translated products of hypothetical genes. The remaining 28% lacked significant similarity to genes for known and predicted proteins in the public DNA databases. More than 60 genes involved in various processes of heterocyst formation and nitrogen fixation were assigned to the chromosome based on their similarity to the reported genes. One hundred and ninety-five genes coding for components of two-component signal transduction systems, nearly 2.5 times as many as those in Synechocystis sp. PCC 6803, were identified on the chromosome. Only 37% of the Anabaena genes showed significant sequence similarity to those of Synechocystis, indicating a high degree of divergence of the gene information between the two cyanobacterial strains.
A Pneumatically Actuated Micro Valve With A Silicone Rubber Membrane For Integration With Fluid-handling Systems (2005)

A valve concept with a silicone rubber membrane has been demonstrated in silicon micromachining technology. The extreme flexibility of the silicone rubber membrane makes it possible to fabricate very small valves with a minimum of dead volume and a large opening. Valves with a membrane design of 225 /spl mu/m x 125/spl mu/m and valve seats with a length of 10 /spl mu/m have been fabricated. A pressure drop on a water flow with open valves of 100 Pa//spl mu/l/min has been measured. No leakage at all could be detected. The valve system has been tested to withstand up to 500 KPa pressure difference over the membrane.
Nuclear localization signals overlap DNA- or RNA-binding domains in nucleic acid-binding proteins (1995)

Journal Article Nuclear localization signals overlap DNA- or RNA-binding domains in nucleic acid-binding proteins Get access Eric C. LaCasse, Eric C. LaCasse Departments of Medicine and Biochemistry, University of Ottawa, Loeb Institute for Medical ResearchOttawa Civic Hospital, Ottawa, Canada + Present address: Ontario Cancer Institute, 500 Sherbourne Street, Toronto, Ontario M4X 1K9, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Yvonne A. Lefebvre Yvonne A. Lefebvre * Departments of Medicine and Biochemistry, University of Ottawa, Loeb Institute for Medical ResearchOttawa Civic Hospital, Ottawa, Canada * To whom correspondence should be addressed at: Division of Endocrinology and Metabolism, Ottawa Civic Hospital, 1053 Carting Avenue, Ottawa, Ontario, Canada K1Y4E9 Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 23, Issue 10, 25 May 1995, Pages 1647–1656, https://doi.org/10.1093/nar/23.10.1647 Published: 25 May 1995 Article history Received: 09 February 1995 Revision received: 30 March 1995 Accepted: 30 March 1995 Published: 25 May 1995
Implementation of Training Convolutional Neural Networks (2015)

Deep learning refers to the shining branch of machine learning that is based on learning levels of representations. Convolutional Neural Networks (CNN) is one kind of deep neural network. It can study concurrently. In this article, we gave a detailed analysis of the process of CNN algorithm both the forward process and back propagation. Then we applied the particular convolutional neural network to implement the typical face recognition problem by java. Then, a parallel strategy was proposed in section4. In addition, by measuring the actual time of forward and backward computing, we analysed the maximal speed up and parallel efficiency theoretically.
Exercise Training, Lipid Regulation, and Insulin Action: A Tangled Web of Cause and Effect (2009)

Lipids are a strong mediator of coronary artery disease and cardiovascular risk. Although the effects of exercise to improve high-density lipoprotein (HDL) cholesterol and serum triglycerides (TGs) have been known for some time, the effects of different amounts and intensities of exercise on fasting and postprandial serum lipids are little understood. Normal lipid physiology is perturbed in insulin resistant states, where inhibition of lipolysis is impaired, particularly in the postprandial period when excursions in insulin and serum TGs are particularly high. In our STRRIDE (Studies of a Targeted Risk Reduction Intervention through Defined Exercise) study, three important metabolic cardiovascular risk-related variables were improved more by moderate intensity than vigorous-intensity exercise. Moderate-intensity exercise was significantly more effective at lowering TGs and improving insulin sensitivity than was vigorous exercise. Additionally, a composite score for metabolic syndrome improved significantly with low-amount/moderate, but did not with low-amount/vigorous-intensity exercise. That all three of these strong, independent, cardiovascular risk factors were significantly affected by moderate-intensity exercise suggests that regular walking exercise might be as effective, if not more so, than more vigorous exercise in favorably modifying cardiovascular risk. Despite the impressive effects of regular exercise on fasting lipids and atherogenic dyslipidemia, they are more impressive when compared with the trajectory of changes that occur in individuals that remain inactive, without regular exposure to regular exercise. A scientific priority for future investigations should be to study the independent and combined effects of exercise intensity and amount on exercise responses through a direct comparison between two groups matched on amount but differing in intensity.
Game Theory and The Law (2002)

Preface Introduction: Understanding Strategic Behavior Bibliographic Notes Simultaneous Decisionmaking and the Normal Form Game The Normal Form Game Using Different Games to Compare Legal Regimes The Nash Equilibrium Civil Liability, Accident Law, and Strategic Behavior Legal Rules and the Idea of Strict Dominance Collective Action Problems and the Two-by-Two Game The Problem of Multiple Nash Equilibria Summary Bibliographic Notes Dynamic Interaction and the Extensive Form Game The Extensive Form Game and Backwards Induction A Dynamic Model of Preemption and Strategic Commitment Subgame Perfection Summary Bibliographic Notes Information Revelation, Disclosure Laws, and Renegotiation Incorporating Beliefs into the Solution Concept The Perfect Bayesian Equilibrium Solution Concept Verifiable Information, Voluntary Disclosure, and the Unraveling Result Disclosure Laws and the Limits of Unraveling Observable Information, Norms, and the Problem of Renegotiation Optimal Incentives and the Need for Renegotiation Limiting the Ability of Parties to Renegotiate Summary Bibliographic Notes Signaling, Screening, and Nonverifiable Information Signaling and Screening Modeling Nonverifiable Information Signals and the Effects of Legal Rules Information Revelation and Contract Default Rules Screening and the Role of Legal Rules Summary Bibliographic Notes Reputation and Repeated Games Backwards Induction and Its Limits Infinitely Repeated Games, Tacit Collusion, and Folk Theorems Reputation, Predation, and Cooperation Summary Bibliographic Notes Collective Action, Embedded Games, and the Limits of Simple Models Collective Action and the Role of Law Embedded Games Understanding the Structure of Large Games Collective Action and Private Information Collective Action Problems in Sequential Decisionmaking Herd Behavior Summary Bibliographic Notes Noncooperative Bargaining Modeling the Division of Gains from Trade Legal Rules as Exit Options Bargaining and Corporate Reorganizations Collective Bargaining and Exit Options Summary Bibliographic Notes Bargaining and Information Basic Models of the Litigation Process Modeling Separate Trials for Liability and Damages Information and Selection Bias Discovery Rules and Verifiable Information Summary Bibliographic Notes Conclusion: Information and the Limits of Law Notes References Glossary Index