gebhart/patrepeval huggingface dataset:
Attenuation of dysfunction in the postischemic 'stunned' myocardium by dimethylthiourea. (1987)

The mechanism for the prolonged contractile dysfunction observed in myocardium reperfused after reversible regional ischemia ("stunned" myocardium) is unclear. Recent studies suggest that myocardial stunning may be mediated by oxygen-derived free radicals, but the precise molecular species involved remain unknown. Thus we explored the role of the highly cytotoxic hydroxyl radical in regional postischemic dysfunction by using dimethylthiourea (DMTU), an effective and highly permeable hydroxyl radical scavenger. Open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery followed by 4 hr of reperfusion received either DMTU (0.5 g/kg iv over 45 min starting 30 min before occlusion, n = 14) or saline (n = 15). Control and treated dogs were comparable with respect to variables that may affect postischemic dysfunction, including heart rate, aortic pressure, left atrial pressure, arterial blood gases and hemoglobin concentration, size of the occluded bed (determined by postmortem perfusion), and collateral blood flow (determined by radioactive microspheres). Regional myocardial function was assessed by measuring wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesis during ischemia. After reperfusion, however, wall thickening (expressed as percent of baseline) was considerably greater in treated as compared with control dogs: 53 +/- 9% (mean +/- SEM) vs 9 +/- 14% (p less than .03) at 1 hr, 55 +/- 9% vs 23 +/- 13% (p less than .05) at 2 hr, 60 +/- 9% vs 28 +/- 14% (p less than .05) at 3 hr, and 67 +/- 5% vs 36 +/- 13% (p less than .05) at 4 hr. Thus DMTU produced a significant and sustained improvement in recovery of contractile function. In concentrations greater than the plasma levels attained in vivo, DMTU did not scavenge either hydrogen peroxide or superoxide anion in vitro. These results suggest that the myocardial dysfunction occurring after a brief episode of regional ischemia is mediated in part by the hydroxyl radical.
Reconstitution of the Third Site of Oxidative Phosphorylation (1971)

Abstract A complex was reconstituted with hydrophobic proteins from bovine heart mitochondrial membranes, cytochrome c, cytochrome oxidase, phospholipids, and coupling factors. These vesicular structures catalyzed oxidative phosphorylation with reduced N-methylphenazinium methyl sulfate as substrate.
Lelystad virus and the porcine epidemic abortion and respiratory syndrome. (1993)

Lelystad virus is the causal agent of a relatively new pig disease, variously known as mystery swine disease, porcine epidemic abortion and respiratory syndrome and porcine reproductive and respiratory syndrome. The virus is a small, enveloped RNA virus, that tentatively can be included in a new virus family, the Arteriviridae. The virus has infected pigs throughout the world and seems to persist in many pig populations and in individual pigs. Clinical signs of an infection with Lelystad virus are characterized by late term abortions and still birth in sows, and respiratory disease in piglets.
Typing a multi-language intermediate code (2001)

The Microsoft .NET Framework is a new computing architecture designed to support a variety of distributed applications and web-based services. .NET software components are typically distributed in an object-oriented intermediate language, Microsoft IL, executed by the Microsoft Common Language Runtime. To allow convenient multi-language working, IL supports a wide variety of high-level language constructs, including class-based objects, inheritance, garbage collection, and a security mechanism based on type safe execution.This paper precisely describes the type system for a substantial fragment of IL that includes several novel features: certain objects may be allocated either on the heap or on the stack; those on the stack may be boxed onto the heap, and those on the heap may be unboxed onto the stack; methods may receive arguments and return results via typed pointers, which can reference both the stack and the heap, including the interiors of objects on the heap. We present a formal semantics for the fragment. Our typing rules determine well-typed IL instruction sequences that can be assembled and executed. Of particular interest are rules to ensure no pointer into the stack outlives its target. Our main theorem asserts type safety, that well-typed programs in our IL fragment do not lead to untrapped execution errors.Our main theorem does not directly apply to the product. Still, the formal system of this paper is an abstraction of informal and executable specifications we wrote for the full product during its development. Our informal specification became the basis of the product team's working specification of type-checking. The process of writing this specification, deploying the executable specification as a test oracle, and applying theorem proving techniques, helped us identify several security critical bugs during development.
Automatic Patch-Based Exploit Generation is Possible: Techniques and Implications (2008)

The automatic patch-based exploit generation problem is: given a program P and a patched version of the program P', automatically generate an exploit for the potentially unknown vulnerability present in P but fixed in P'. In this paper, we propose techniques for automatic patch-based exploit generation, and show that our techniques can automatically generate exploits for 5 Microsoft programs based upon patches provided via Windows Update. Although our techniques may not work in all cases, a fundamental tenant of security is to conservatively estimate the capabilities of attackers. Thus, our results indicate that automatic patch-based exploit generation should be considered practical. One important security implication of our results is that current patch distribution schemes which stagger patch distribution over long time periods, such as Windows Update, may allow attackers who receive the patch first to compromise the significant fraction of vulnerable hosts who have not yet received the patch.
Noncovalent association of heavy and light chains of human immunoglobulins. IV. The roles of the CH1 and CL domains in idiotypic expression. (1985)

A rabbit anti-idiotypic antiserum was raised against a monoclonal human IgM kappa(Me) in order to analyze the possible modulation of idiotypic expression by Fab constant domains. IgM(Me) fragments, subunits, and domains were prepared by chemical and enzymatic cleavages. All molecular species were shown to have a well-defined secondary and tertiary structure by circular dichroism. Full recombination between domains and subunits was ascertained by difference spectroscopy. The expression of the idiotype on native and recombined fragments, domains, and subunits was quantitated in a competitive enzyme-linked immunosorbent assay (ELISA). Reduced and alkylated Fab, isolated H and L chains, purified Fv(Me), intact VH and VL domains and H-L, VH-L, VL-H, and VH-VL recombinants were compared on a molar basis to native Fab(Me) for idiotypic expression. VH-specific determinants were found, whereas the L chains were virtually devoid of idiotypic activity. Both the peptic FV(Me) fragment, which is composed of intact VH and VL domains, and the recombined VH-VL heterodimer were found to be fourfold less active for idiotype expression than native Fab(Me). However, full inhibition was achieved at high molar concentrations, suggesting that all the idiotopes present on Fab(Me) were expressed on FV(Me) but with a reduced antigenicity. Comparison of VH-L and VL-H hybrid molecules revealed that the presence of the C mu 1 domain was sufficient to restore full idiotypic expression as compared with native Fab(Me). These data support the hypothesis that the first constant domain of the mu heavy chain alters the quaternary interaction between the variable domains, and therefore modulates the expression of the idiotype through longitudinal interactions that are not affected by reduction of the inter-H-L chain disulfide bond.
Matrix Vesicle Plasma Cell Membrane Glycoprotein-1 Regulates Mineralization by Murine Osteoblastic MC3T3 Cells (1999)

A naturally occurring nonsense truncation mutation of the inorganic pyrophosphate (PPi)-generating nucleoside triphosphate pyrophosphohydrolase (NTPPPH) PC-1 is associated with spinal and periarticular ligament hyperostosis and cartilage calcification in "tiptoe walking" (ttw) mice. Thus, we tested the hypothesis that PC-1 acts directly in the extracellular matrix to restrain mineralization. Cultured osteoblastic MC3T3 cells expressed PC-1 mRNA and produced hydroxyapatite deposits at 12-14 days. NTPPPH activity increased steadily over 14 days. Transforming growth factor-beta and 1,25-dihydroxyvitamin D3 increased PC-1 and NTPPPH in matrix vesicles (MVs). Because PC-1/NTPPPH was regulated in mineralizing MC3T3 cells, we stably transfected or infected cells with recombinant adenovirus, in order to express 2- to 6-fold more PC-1. PC-1/NTPPPH and PPi content increased severalfold in MVs derived from cells transfected with PC-1. Furthermore, MC3T3 cells transfected with PC-1 deposited approximately 80-90% less hydroxyapatite (by weight) than cells transfected with empty plasmid or enzymatically inactive PC-1. ATP-dependent 45Ca precipitation by MVs from cells overexpressing active PC-1 was comparably diminished. Thus, regulation of PC-1 controls the PPi content and function of osteoblast-derived MVs and matrix hydroxyapatite deposition. PC-1 may provide a novel therapeutic target in certain disorders of bone mineralization.
Membrane topology of the Escherichia coli γ-aminobutyrate transporter: implications on the topography and mechanism of prokaryotic and eukaryotic transporters from the APC superfamily (1998)

The Escherichia coli gamma-aminobutyric acid permease (GabP) is a plasma membrane protein from the amine-polyamine-choline (APC) superfamily. On the basis of hydropathy analysis, transporters from this family are thought to contain 12, 13 or 14 transmembrane domains. We have experimentally analysed the topography of GabP by using the cytoplasmically active LacZ (beta-galactosidase) and the periplasmically active PhoA (alkaline phosphatase) as complementary topological sensors. The enzymic activities of 32 GabP-LacZ hybrids and 43 GabP-PhoA hybrids provide mutually reinforcing lines of evidence that the E. coli GabP contains 12 transmembrane segments that traverse the membrane in a zig-zag fashion with both N- and C-termini facing the cytoplasm. Interestingly, the resulting model predicts that the functionally important 'consensus amphipathic region' (CAR) [Hu and King (1998) Biochem. J. 330, 771-776] is at least partly membrane-embedded in many amino acid transporters from bacteria and fungi, in contrast with the apparent situation in mouse cationic amino acid transporters (MCATs), in which this kinetically significant region is thought to be fully cytoplasmic [Sophianopoulou and Diallinas (1995) FEMS Microbiol. Rev. 16, 53-75]. To the extent that conserved domains serve similar functions, the resolution of this topological disparity stands to have family-wide implications on the mechanistic role of the CAR. The consensus transmembrane structure derived from this analysis of GabP provides a foundation for predicting the topological disposition of the CAR and other functionally important domains that are conserved throughout the APC transporter superfamily.
The influence of fibre orientation, extracted from different segments of the human left ventricle, on the activation and repolarization sequence: a simulation study (2007)

The model can be expanded to simulate electrophysiology and contraction in the whole heart geometry. Embedded in a torso model, the impact of fibre orientation on body surface ECGs and their relation to local pseudo-ECGs can be identified.
[Distribution of harringtonine positively and negatively charged liposome in rat tissues]. (1993)

Distribution of harringtonine positively and negatively charged liposome (HL(+), HL(-)) and harringtonine free drug (FH) in rat tissues were measured by HPLC. Their LD50 in mice were compared. The results showed that distribution of HL(+), HL(-), In vivo may be changed, that the amount of HL(+), HL(-) was increased in the liver, lung, and spleen and in these tissues it was 2-30-fold higher than that of HF after iv 2 h. HL(+), HL(-) may aid to permeate through the blood-brain, blood-testicle barrier, and to reduce acute lethal toxicity. Areas under the time curve of HL(+), HL(-) in brain and testis within 2 h were 2-4.5 times as much as those of HF. There were significant differences in the fate between negatively and positively charged liposomes in vivo.
A technique for orthogonal frequency division multiplexing frequency offset correction (1994)

This paper discusses the effects of frequency offset on the performance of orthogonal frequency division multiplexing (OFDM) digital communications. The main problem with frequency offset is that it introduces interference among the multiplicity of carriers in the OFDM signal. It is shown, and confirmed by simulation, that to maintain signal-to-interference ratios of 20 dB or greater for the OFDM carriers, offset is limited to 4% or less of the intercarrier spacing. Next, the paper describes a technique to estimate frequency offset using a repeated data symbol. A maximum likelihood estimation (MLE) algorithm is derived and its performance computed and compared with simulation results. Since the intercarrier interference energy and signal energy both contribute coherently to the estimate, the algorithm generates extremely accurate estimates even when the offset is far too great to demodulate the data values. Also, the estimation error depends only on total symbol energy so it is insensitive to channel spreading and frequency selective fading. A strategy is described for initial acquisition in the event of uncertainty in the initial offset that exceeds 1/2 the carrier spacing, the limit of the MLE algorithm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Voice Coding at Low Bit Rates Australia's Leading Role (1992)

For the past two years, Binary Engineering has been the commercial collaborator with two Australian Universities into research towards improved low bit rate voice coding technology. The purpose of this paper is to describe the background to obtaining the Federal Generic IR and D (GIRD) grant for this work, the results performed to date and the hoped for conclusions by the end of the project, in one years time. Also some tips and pitfalls associated with implementing GIRD grants in general are provided for the benefit of would be applicants for this type of funding.
Alcohol Effects During Acamprosate Treatment: A Dose‐Response Study in Humans (2004)

Acamprosate does not alter alcohol pharmacokinetics, acute physiological or psychomotor alcohol effects, or most subjective alcohol effects.
A Subtype of Diabetes Mellitus Associated with a Mutation of Mitochondrial DNA (1994)

Diabetes mellitus associated with the A-->G mutation at position 3243 of mitochondrial leucine transfer RNA represents a subtype of diabetes found in both patients with IDDM and patients with NIDDM in Japan.
p65 Fragments, homologous to the C2 region of protein kinase C, bind to the intracellular receptors for protein kinase C (1992)

Receptors for activated protein kinase C (RACKs) have been isolated from the particulate cell fraction of heart and brain. We previously demonstrated that binding of protein kinase C (PKC) to RACKs requires PKC activators and is via a site on PKC that is distinct from the substrate binding site. Here, we examine the possibility that the C2 region in the regulatory domain of PKC is involved in binding of PKC to RACKs. The synaptic vesicle-specific p65 protein contains two regions homologous to the C2 region of PKC. We found that three p65 fragments, containing either one or two of these PKC C2 homologous regions, bound to highly purified RACKs. Binding of the p65 fragments and PKC to RACKs was mutually exclusive; preincubation of RACKs with the p65 fragments inhibited PKC binding, and preincubation of RACKs with PKC inhibited binding of the p65 fragments. Preincubation of the p65 fragments with a peptide resembling the PKC binding site on RACKs also inhibited p65 binding to RACKs, suggesting that PKC and p65 bind to the same or nearby regions on RACKs. Since the only homologous region between PKC and the p65 fragments is the C2 region, these results suggest that the C2 region on PKC contains at least part of the RACK binding site.
Inroads Toward Robot-Assisted Cochlear Implant Surgery Using Steerable Electrode Arrays (2010)

Preliminary experimental results using robot-assisted steerable electrode prototype show that it is effective in reducing insertion forces and preventing electrode buckling. A second-generation robot has been designed and constructed for cochlear implant surgery under operating room conditions.
Wide range of Schottky barrier height for metal contacts to GaAs controlled by Si interface layers (1988)

Metal (Au, Cr, and Ti) contacts to n‐type (100) GaAs are described in which the Schottky barrier height φB is controlled by using a very thin Si interface layer to influence the interface Fermi energy EiF. The contact structure consists of a thick metal and an ∼15–30 A Si interface layer that is heavily either p‐type or n‐type. A large 1 eV φB is found for the metal–Si(p‐type)–GaAs structure and a small 0.5 eV φB for the metal–Si(n‐type)–GaAs structure. X‐ray photoemission spectroscopy (XPS) was used to obtain EiF and interface composition during initial contact formation; the φB for the thick contacts was measured by I–V and C–V techniques.
Intradermal naked plasmid DNA immunization: mechanisms of action (2011)

Plasmid DNA is a promising vaccine modality that is regularly examined in prime–boost immunization regimens. Recent advances in skin immunity increased our understanding of the sophisticated cutaneous immune network, which revived scientific interest in delivering vaccines to the skin. Intradermal administration of plasmid DNA via needle injection is a simple and inexpensive procedure that exposes the plasmid and its encoded antigen to the dermal immune surveillance system. This triggers unique mechanisms for eliciting local and systemic immunity that can confer protection against pathogens and tumors. Understanding the mechanisms of intradermal plasmid DNA immunization is essential for enhancing and modulating its immunogenicity. With regard to vaccination, this is of greater importance as this routine injection technique is highly desirable for worldwide immunization. This article will focus on the current understanding of the mechanisms involved in antigen expression and presentation during primary and secondary syringe and needle intradermal plasmid DNA immunization.
Efficient affinity maturation of antibody variable domains requires co-selection of compensatory mutations to maintain thermodynamic stability (2017)

Abstract The ability of antibodies to accumulate affinity-enhancing mutations in their complementarity-determining regions (CDRs) without compromising thermodynamic stability is critical to their natural function. However, it is unclear if affinity mutations in the hypervariable CDRs generally impact antibody stability and to what extent additional compensatory mutations are required to maintain stability during affinity maturation. Here we have experimentally and computationally evaluated the functional contributions of mutations acquired by a human variable (V H ) domain that was evolved using strong selections for enhanced stability and affinity for the Alzheimer’s Aβ42 peptide. Interestingly, half of the key affinity mutations in the CDRs were destabilizing. Moreover, the destabilizing effects of these mutations were compensated for by a subset of the affinity mutations that were also stabilizing. Our findings demonstrate that the accumulation of both affinity and stability mutations is necessary to maintain thermodynamic stability during extensive mutagenesis and affinity maturation in vitro , which is similar to findings for natural antibodies that are subjected to somatic hypermutation in vivo . These findings for diverse antibodies and antibody fragments specific for unrelated antigens suggest that the formation of the antigen-binding site is generally a destabilizing process and that co-enrichment for compensatory mutations is critical for maintaining thermodynamic stability.
Depolarized MUC1 Expression Is Closely Associated With Hypoxic Markers and Poor Outcome in Resected Non–Small Cell Lung Cancer (2011)

MUC1 is transmembrane mucin aberrantly overexpressed in various cancers. However, little is known about how MUC1 expression is associated with hypoxia, glucose metabolism, and epidermal growth factor receptor (EGFR) pathway, which are related to cancer progression. The aim of this study is to evaluate the relationship between MUC1 expression and these molecular markers in lung cancer. Of all 126 patients, high-grade polarized expression (HP), low-grade polarized expression (LP), and depolarized expression (DP) group were 50 (39.7%), 35 (27.8%), and 41 (32.5%), respectively. Depolarized MUC1 expression was significantly associated with poor outcome and was closely correlated with glucose metabolism (Glut1), hypoxia (HIF-1α), angiogenesis (vascular endothelial growth factor and microvessel density), amino acid metabolism (LAT1), and EGFR expression. High-grade polarized MUC1 expression was associated with favorable prognosis and adenocarcinoma. Depolarized MUC1 expression was significantly associated with poor outcome. Glucose metabolism, hypoxia, angiogenesis, amino acid metabolism, and EGFR pathway may play an important role in the development of depolarized MUC1 expression.
Abstract #1070: Targeting cancer stem cells and vasculatures by a novel anti-dll4 antibody inhibits pancreatic tumor growth and delays tumor recurrence (2009)

Clinical management of pancreatic cancer is very challenging and this disease remains the fourth most common cause of cancer-related deaths. It has been suggested that cancer stem cells drive tumor growth and progression and are preferentially resistant to current therapies. Delta-like 4 ligand (DLL4) is an important component of Notch-mediated stem cell self-renewal and vascular development. We hypothesized that targeting cancer stem cells and the tumor vasculature by interfering with the DLL4/Notch pathway will improve treatment outcome. We developed anti-DLL4 antibodies with potent binding and blocking activities that recognize either human or murine DLL4 to investigate the role of DLL4 in pancreatic cancer. In vivo studies using primary pancreatic xenograft tumor models showed that anti-DLL4 was efficacious as a single agent and in combination with gemcitabine against both high and low grade pancreatic tumors. Gene expression analysis showed that anti-DLL4 affected vascular-related genes in the stroma and Notch target genes in the tumor and stroma. Histologic analysis indicated that the anti-DLL4-mediated anti-tumor effects were associated with a decrease in cell proliferation and an increase in vascular density, hypoxia, apoptosis and differentiation. These effects were further enhanced by the combination treatment with gemcitabine. Furthermore, inclusion of anti-DLL4 delayed pancreatic tumor recurrence following termination of gemcitabine. A tumorigenicity study indicated that treatment with anti-DLL4 decreased cancer stem cell frequency as measured by in vivo limiting dilution assay, whereas gemcitabine alone was ineffective. The combination of anti-DLL4 and gemcitabine further decreased cancer stem cell frequency compared to single agents. Our findings provide a rationale for targeting cancer stem cells and the vasculature through interference with the DLL4/Notch pathway as a therapeutic approach in cancer treatment. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1070.