gebhart/patrepeval huggingface dataset:
Operating System Transactions (2009)

Applications must be able to synchronize accesses to operating system resources in order to ensure correctness in the face of concurrency and system failures. System transactions allow the programmer to specify updates to heterogeneous system resources with the OS guaranteeing atomicity, consistency, isolation, and durability (ACID). System transactions efficiently and cleanly solve persistent concurrency problems that are difficult to address with other techniques. For example, system transactions eliminate security vulnerabilities in the file system that are caused by time-of-check-to-time-of-use (TOCTTOU) race conditions. System transactions enable an unsuccessful software installation to roll back without disturbing concurrent, independent updates to the file system.
Novel therapies for peripheral T-cell non-Hodgkinʼs lymphomas (2009)

The development of rational combinations of such agents in clinical trials will be required to improve the outcome of these patients.
In vivo multiplexed interrogation of amplified genes identifies GAB2 as an ovarian cancer oncogene (2014)

High-grade serous ovarian cancers are characterized by widespread recurrent copy number alterations. Although some regions of copy number change harbor known oncogenes and tumor suppressor genes, the genes targeted by the majority of amplified or deleted regions in ovarian cancer remain undefined. Here we systematically tested amplified genes for their ability to promote tumor formation using an in vivo multiplexed transformation assay. We identified the GRB2-associated binding protein 2 (GAB2) as a recurrently amplified gene that potently transforms immortalized ovarian and fallopian tube secretory epithelial cells. Cancer cell lines overexpressing GAB2 require GAB2 for survival and show evidence of phosphatidylinositol 3-kinase (PI3K) pathway activation, which was required for GAB2-induced transformation. Cell lines overexpressing GAB2 were as sensitive to PI3K inhibition as cell lines harboring mutant PIK3CA. Together, these observations nominate GAB2 as an ovarian cancer oncogene, identify an alternative mechanism to activate PI3K signaling, and underscore the importance of PI3K signaling in this cancer.
Rheology of dispersions of swollen gel particles (1975)

Abstract A centrifugal technique was used to determine the swelling, Q (g swollen gel/g dry polymer), of crosslinked polyacrylate gel particles in water. Both centrifugal force and time of centrifugation affected the magnitude of Q but under constant centrifuge conditions it was found that Q −1 was proportional to μ 1/2 , μ being the ionic strength. The viscoelastic properties of water dispersions of these gel particles were measured as functions of concentration and ionic strength. Viscosity data were reducible to a normalized master curve by plotting (η sp / c r ) versus c r , where c r is a reduced concentration defined as cQ . Values of shear modulus, G , computed from the first normal stress difference measured at various concentrations and ionic strengths also fell on a single curve when plotted against the reduced concentration, cQ . Comparison of these results with those obtained earlier on a similar polyacrylate dispersion, but one in which as much as 20% of the polyacrylate is in a soluble, uncrosslinked form, shows that the soluble fraction has little effect on the magnitude of the viscosity and, moreover, that the presence or absence of the soluble fraction does not affect the transient stress overshoot phenomenon. As in the earlier work, high absolute values of viscosity occur when cQ ≧ 1, that is when the dispersion consists of close‐packed deformable gel particles in intimate contact with little or no interstitial solvent present.
Mechanism for iron-regulated transcription of the Escherichia coli cir gene: metal-dependent binding of fur protein to the promoters (1989)

The molecular basis for the greatly elevated expression of the cir gene (encoding the colicin I receptor) in cells unable to maintain a critical supply of intracellular iron was investigated by genetic and biochemical means. Deletion analysis of the cloned promoter region allowed delineation of sequences necessary for control of transcription initiating at the two promoters, P1 and P2. Gel retardation assays were used to demonstrate both binding of purified Fur (ferric uptake regulation) protein to the iron control region and lack of binding to DNA fragments which are not involved in cir regulation. An operator sequence spanning 43 to 47 base pairs and completely encompassing the two promoters was identified by DNase I protection experiments (footprinting), with binding occurring in a metal-dependent fashion. Thus, during iron-replete growth, Fur appears to act as a repressor of transcription by blocking formation of a DNA-RNA polymerase complex, analogous to the mechanism previously described for regulation of the aerobactin operon (V. de Lorenzo, S. Wee, M. Herrero, and J.B. Neilands, J. Bacteriol. 169:2624-2630, 1987). Characterized and putative Fur recognition sites from several genes were analyzed and classified by statistical methods.
Freeze-Fracture and Cytochemical Evidence for Structural and Functional Alteration in the Axolemma and Myelin Sheath of Adult Guinea Pig Optic Nerve Fibers After Stretch Injury (1999)

Recent work in animal models of human diffuse axonal injury has generated the hypothesis that, rather than there being physical disruption of the axolemma at the time of injury, a pertubation of the membrane occurs, which leads, over time, to a dysfunction of the physiology of the axolemmal. This dysfunction is posited to lead to a disruption of ionic homeostasis within the injured axon, leading to secondary axotomy some hours after the initial insult. We decided to test the hypothesis that membrane pump/ion channel activity or function is compromised and this would be reflected in structural changes within the axolemma and myelin sheath. We used freeze fracture and cytochemical techniques to provide evidence for change in membrane structure and the activity of membrane pumps after nondisruptive axonal injury in the adult guinea pig optic nerve. Within 10 min of injury, structural changes occurred in the distribution and number of intramembranous particles (IMPs) in the internodal axolemma. By 4 h, there was novel labeling for Ca-ATPase membrane pump activity at the same site. There was loss of IMPs from the nodal axolemma extending over several hours after injury. There was loss of both membrane pump Ca-ATPase and p-nitro-phenylphosphatase (p-NPPase) activity of the node. There was loss of ecto-Ca-ATPase activity but increased labeling for p-NPPase activity at sites of dissociation of compacted myelin. Quantitative freeze-fracture demonstrated statistically significant changes in membrane structure. We provide support for the hypothesis that structural and functional changes occur in the axolemma and myelin sheath at nondisruptive axonal injury.
Conversion of Fatty Aldehydes to Alka(e)nes and Formate by a Cyanobacterial Aldehyde Decarbonylase: Cryptic Redox by an Unusual Dimetal Oxygenase (2011)

Cyanobacterial aldehyde decarbonylase (AD) catalyzes conversion of fatty aldehydes (R-CHO) to alka(e)nes (R-H) and formate. Curiously, although this reaction appears to be redox-neutral and formally hydrolytic, AD has a ferritin-like protein architecture and a carboxylate-bridged dimetal cofactor that are both structurally similar to those found in di-iron oxidases and oxygenases. In addition, the in vitro activity of the AD from Nostoc punctiforme (Np) was shown to require a reducing system similar to the systems employed by these O(2)-utilizing di-iron enzymes. Here, we resolve this conundrum by showing that aldehyde cleavage by the Np AD also requires dioxygen and results in incorporation of (18)O from (18)O(2) into the formate product. AD thus oxygenates, without oxidizing, its substrate. We posit that (i) O(2) adds to the reduced cofactor to generate a metal-bound peroxide nucleophile that attacks the substrate carbonyl and initiates a radical scission of the C1-C2 bond, and (ii) the reducing system delivers two electrons during aldehyde cleavage, ensuring a redox-neutral outcome, and two additional electrons to return an oxidized form of the cofactor back to the reduced, O(2)-reactive form.
HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro (2008)

Despite 40% heterogeneity between the HIV-1 and HIV-2 integrase genes, the phenotypic susceptibility of clinical HIV-2 isolates to INIs was similar to that of HIV-1. This new class of antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2-infected patients who otherwise have few treatment options.
Proteomic definition of normal human luminal and myoepithelial breast cells purified from reduction mammoplasties (1999)

Normal human luminal and myoepithelial breast cells separately purified from a set of 10 reduction mammoplasties by using a double antibody magnetic affinity cell sorting and Dynabead immunomagnetic technique were used in two-dimensional gel proteome studies. A total of 43,302 proteins were detected across the 20 samples, and a master image for each cell type comprising a total of 1,738 unique proteins was derived. Differential analysis identified 170 proteins that were elevated 2-fold or more between the two breast cell types, and 51 of these were annotated by tandem mass spectrometry. Muscle-specific enzyme isoforms and contractile intermediate filaments including tropomyosin and smooth muscle (SM22) alpha protein were detected in the myoepithelial cells, and a large number of cytokeratin subclasses and isoforms characteristic of luminal cells were detected in this cell type. A further 134 nondifferentially regulated proteins were also annotated from the two breast cell types, making this the most extensive study to date of the protein expression map of the normal human breast and the basis for future studies of purified breast cancer cells.
Effect of Cross-Linking on Matrix Permeability: A Model for AGE-Modified Basement Membranes (1996)

There is much evidence that basement membranes, such as in the renal glomerulus, act as macromolecular sieves, restricting the passage of proteins. Cross-linking of matrix proteins, as occurs because of advanced glycosylation end products (AGEs) in diabetes, may have an effect on the sieving properties of the basement membrane. To test this hypothesis, Matrigel, a basement membrane-like matrix, was cross-linked with glycolaldehyde and control and cross-linked matrices compared. Control matrices allowed less bovine serum albumin to pass through than did cross-linked matrices, with sieving coefficients (SCs) of 0.38 +/- 0.02 and 0.52 +/- 0.02, respectively (P < 0.0005). The control matrices also allowed less cross-linked albumin through than did the cross-linked matrices: 0.13 +/- 0.01 vs. 0.17 +/- 0.02 (P < 0.002). The SCs of a series of fluorescein isothiocyanate dextrans (four sizes, Mr 16,000- 168,000) were lower for the control matrix than for the cross-linked matrix (P < 0.03). In addition, the SC for glycated albumin (incubated with glucose-6-phosphate) was higher than that of normal albumin for both the control (P < 0.04) and cross-linked matrices (P < 0.001). These data indicate that cross-linking of the matrix increases permeability to macromolecules. Analysis of the data using fiber-matrix theory suggests that the mean fiber radius was increased in the cross-linked matrix. The data also indicate that glycated albumin filters through the matrices more easily than does normal albumin. In relation to the situation seen in vivo, it is possible that glycation of circulating proteins and AGE modification of glomerular basement membrane proteins may both contribute to the proteinuria seen in diabetes.
Effect of Zinc Nutritional Status on Growth, Protein Metabolism and Levels of Indole-3-acetic Acid and other Phytohormones in Bean (Phaseolus vulgarisL.) (1989)

Bean (Phaseolus vulgaris L. var. Prelude) plants were grown for 17 d under controlled environmental conditions with varied Zn supply in the nutrient solution. The concentrations of amino acids; indole-3-acetic acid, IAA; abscisic acid, ABA; isopentenyl adenine, I-Ade; isopentenyl adenosine, I-Ado; zeatin, Z; and zeatin riboside, ZR were determined in various shoot fractions. The growth of plants, especially shoot growth, was severely depressed under conditions of Zn deficiency. Simultaneously, concentrations of soluble protein and chlorophyll decreased, whereas amino acid concentrations increased several-fold. In the Zn-deficient plants, the level of IAA in the shoot tips and young leaves decreased to about 50% of that in Zn-sufficient plants. A similar decrease occurred in the ABA levels of shoot tips. In contrast, Zn deficiency was without effect on cytokinin levels in the leaves. Re-supply of Zn to the deficient plants for up to 96 h significantly increased shoot growth, soluble protein, and IAA levels up to the values of Zn-sufficient plants. Simultaneously, the concentration of amino acids dropped to low levels. The effect of Zn nutritional status on the tryptophan level was parallel to that of most of the other amino acids. The results confirm the role of Zn in protein synthesis and demonstrate that the decrease in IAA level in Zn-deficient plants is not brought about by impaired synthesis of tryptophan. It is also unlikely that in Zn-deficient plants the conversion of tryptophan to IAA is specifically inhibited.
Identification of four epitopes in hepatitis C virus core protein (1993)

We identified four epitopes in hepatitis C virus core protein by using the algorithm of Jameson and Wolf. G15V (amino acids [aa] 31 to 45) appears to be the immunodominant epitope, since it was able to detect antibodies to the core protein in all 40 patients and in 44 of 45 recombinant immunoblot assay-confirmed positive blood donors. This epitope is associated with a low frequency of false-positive results, as found with 522 negative blood donors. A strong reactivity was also observed with the Q15V epitope (aa 7 to 21), although this was associated with low specificity. Occasional reactivity to the R15P (aa 49 to 63) and P15R (aa 99 to 113) epitopes was observed. Q15V and G15V detected antibodies to core protein earlier than the other two epitopes.
Type 1 Diabetes Is Associated With Increased Cyclooxygenase- and Cytokine-Mediated Inflammation (2005)

These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF(2alpha) and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.
Identification of active site residues in mevalonate diphosphate decarboxylase: Implications for a family of phosphotransferases (2004)

A combination of sequence homology analyses of mevalonate diphosphate decarboxylase (MDD) proteins and structural information for MDD leads to the hypothesis that Asp 302 and Lys 18 are active site residues in MDD. These residues were mutated to replace acidic/basic side chains and the mutant proteins were isolated and characterized. Binding and competitive displacement studies using trinitrophenyl-ATP, a fluorescent analog of substrate ATP, indicate that these mutant enzymes (D302A, D302N, K18M) retain the ability to stoichiometrically bind nucleotide triphosphates at the active site. These observations suggest the structural integrity of the mutant MDD proteins. The functional importance of mutated residues was evaluated by kinetic analysis. The 10(3) and 10(5)-fold decreases in k(cat) observed for the Asp 302 mutants (D302N and D302A, respectively) support assignment of a crucial catalytic role to Asp 302. A 30-fold decrease in activity and a 16-fold inflation of the K(m) for ATP is documented for the K18M mutant, indicating that Lys 18 influences the active site but is not crucial for reaction chemistry. Demonstration of the influence of conserved aspartate 302 appears to represent the first documentation of the functional importance of a residue in the MDD catalytic site and affords insight into phosphotransferase reactions catalyzed by a variety of enzymes in the galactokinase, homoserine kinase, mevalonate kinase, phosphom-evalonate kinase (GHMP kinase) family.
Macrophages and Fc-receptor interactions contribute to the antitumour activities of the anti-CD40 antibody SGN-40 (2008)

SGN-40 is a therapeutic antibody targeting CD40, which induces potent anti-lymphoma activities via direct apoptotic signalling cells and by cell-mediated cytotoxicity. Here we show antibody-dependent cellular phagocytosis (ADCP) by macrophages to contribute significantly to the therapeutic activities and that the antitumour effects of SGN-40 depend on Fc interactions.
Constellation-code division multiplex for digital HDTV (2003)

Constellation-code-division multiplexing (C-CDM), in which subchannels divide the constellation signal point codewords and the subchannel error probability are changed by varying the distances between signal point codewords in the constellation diagram, is described. Quadrature amplitude modulation (QAM) multiplexed by the C-CDM method is called shifted rectangle QAM (SRQAM). SRQAM provides a set of terrestrial digital HDTV broadcasting coverage areas with multiple layers of error probability. By calculating the error probability, coverage areas can be simulated and compared with areas obtained for the proposed 32 QAM. The results show that HDTV area is reduced by 15%, but EDTV area is increased by 32%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ring-Opening Polymerization of the Cyclic Ester Amide Derived from Adipic Anhydride and 1-Amino-5-pentanol (2003)

The ring-opening polymerization of the cyclic ester amide (cEA, 2) (systematic name, 1-oxa-7-aza-cyclotridecane-8,13-dione)prepared from adipic anhydride and 1-amino-5-pentanolin the melt at temperatures above 145 °C with Bu2Sn(OMe)2, Ti(OBu)4, Al(O-sec-Bu)3, or Sn(octoate)2 as initiator yields the poly(ester amide) (PEA, 3) (systematic name, poly(5-(5-oxypentylcarbamoyl)pentanoate) with regular microstructure. This poly(ester amide) is a semicrystalline material with a melting point of 108 °C. The elementary chain growth reaction proceeds by a coordination insertion mechanism in analogy to the polymerization of lactones. The monomer-to-initiator ratio and the conversion determine the number-average molecular weight. By using hydroxy telechelic poly(ethylene oxide) with Sn(octoate)2 as initiator poly(ester amide)-block-poly(ethylene oxide) and poly(ester amide)-block-poly(ethylene oxide)-block-poly(ester amide) were obtained. Kinetic studies for different monomer-to-initiator ratios, different temperatures and initiators reveal that the ring-opening polymerization is a first-order reaction with respect to the monomer and shows no termination and transfer reactions.
A novel function of the herpes simplex virus type 1 Fc receptor: participation in bipolar bridging of antiviral immunoglobulin G (1989)

We describe a novel function of the Fc receptor of herpes simplex virus type 1 (HSV-1), its ability to participate in antibody bipolar bridging. This refers to the binding of a single immunoglobulin G (IgG) molecule by its Fab end to its antigenic target and by its Fc end to an Fc receptor (FcR). We demonstrate that various immune IgG antibodies, including polyclonal rabbit antibodies to HSV-1 glycoproteins gC1 and gD1 and monoclonal human antibody to gD1 blocked rosetting of IgG-coated erythrocytes at IgG concentrations 100- to 2,000-fold lower than required for rosette inhibition with nonimmune IgG. Steric hindrance did not account for the observed differences between immune and nonimmune IgG since rabbit anti-gC1 F(ab')2 fragments did not block rosetting. Murine anti-gC1 or anti-gD1 IgG, a species of IgG incapable of binding by its Fc end to the HSV-1 FcR, also did not block rosetting. When cells were infected with a gC1-deficient mutant, anti-gC1 IgG inhibited rosetting to the same extent as nonimmune IgG. This indicates that binding by the Fab end of the IgG molecule was required for maximum inhibition of rosetting. Bipolar bridging was shown to occur even when small concentrations of immune IgG were present in physiologic concentrations of nonimmune IgG. The biologic relevance of antibody bipolar bridging was evaluated by comparing antibody- and complement-dependent virus neutralization of an FcR-negative mutant and its parent HSV-1 strain. By engaging the Fc end of antiviral IgG, the parent strain resisted neutralization mediated by the classical complement pathway. These observations provide insight into the role of the HSV-1 FcR in pathogenesis and may help explain the function of FcR detected on other microorganisms.
Enhanced Nrf2 Activity Worsens Insulin Resistance, Impairs Lipid Accumulation in Adipose Tissue, and Increases Hepatic Steatosis in Leptin-Deficient Mice (2012)

The study herein determined the role of nuclear factor erythoid 2-related factor 2 (Nrf2) in the pathogenesis of hepatic steatosis, insulin resistance, obesity, and type 2 diabetes. Lep(ob/ob)-Keap1-knockdown (KD) mice, which have increased Nrf2 activity, were generated. Markers of obesity and type 2 diabetes were measured in C57Bl/6J, Keap1-KD, Lep(ob/ob), and Lep(ob/ob)-Keap1-KD mice. Lep(ob/ob)-Keap1-KD mice exhibited less lipid accumulation, smaller adipocytes, decreased food intake, and reduced lipogenic gene expression. Enhanced Nrf2 activity impaired insulin signaling, prolonged hyperglycemia in response to glucose challenge, and induced insulin resistance in Lep(ob/ob) background. Nrf2 augmented hepatic steatosis and increased lipid deposition in liver. Next, C57Bl/6J and Keap1-KD mice were fed a high-fat diet (HFD) to determine whether Keap1 and Nrf2 impact HFD-induced obesity. HFD-induced obesity and lipid accumulation in white adipose tissue was decreased in Keap1-KD mice. Nrf2 activation via Keap1-KD or sulforaphane suppressed hormone-induced differentiation and decreased peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein α, and fatty acid-binding protein 4 expression in mouse embryonic fibroblasts. Constitutive Nrf2 activation inhibited lipid accumulation in white adipose tissue, suppressed adipogenesis, induced insulin resistance and glucose intolerance, and increased hepatic steatosis in Lep(ob/ob) mice.