gebhart/patrepeval huggingface dataset:
Diagnostic accuracy of coronary angiography and risk factors for post–heart-transplant cardiac allograft vasculopathy (2003)

Cardiac allograft vasculopathy (CAV) is a common cause of death after heart transplantation. Coronary angiography is used to monitor the progress of recipients. Diagnostic accuracy of angiography and risk factors for CAV have not been clearly established. Between August 1979 and January 2002, 566 1-year survivors of heart transplantation underwent 2168 angiograms and were classified as having no CAV (0% stenosis), mild-moderate CAV (up to 70% stenosis), or severe CAV (>70% stenosis). We used serial measurements of stenosis to estimate the diagnostic accuracy of angiography and to assess the following risk factors for CAV onset, progression, and survival: recipient and donor age and sex, preoperative ischemic heart disease (IHD), acute rejection rates, cytomegalovirus (CMV) infection, and serologic status. CAV was diagnosed by angiography in 248 of 556 (45%) 1-year survivors, with a mean onset time of 8.6 years. Patients spent a mean of 3.4 years with mild-moderate disease and 3.4 years with severe disease before death. Angiography specificity was 97.8%, and sensitivity was 79.3%. The following variables were found to significantly increase the risk of CAV onset: recipient age relative rate (95% confidence interval) 1.16 (1.01-1.34), donor age by 1.27 (1.13-1.43), male recipient by 2.00 (1.11-2.57), pretransplant IHD by 1.75 (1.30-2.36), cumulative rejection by 1.13 (1.05-1.21), and CMV infection by 1.42 (1.06-1.92). Acute rejection increased risk of death by 1.48 (1.19-1.85). Angiography is highly specific and moderately sensitive for diagnosis of CAV. Risk of CAV onset is related to donor age and recipient history of pretransplant IHD and is further increased by immune-related insults of acute rejection and CMV infection.
Factors influencing local recurrence of cancer after partial mastectomy (1990)

From 1957 to 1975, 291 patients underwent partial mastectomy for carcinoma of the breast. In a follow-up period of 6 to 25 years, 32 patients had local recurrences. These 32 were matched with 32 patients without local recurrence but who had had the same treatment during the same periods of time for the same clinical stage of disease. Comparisons were made for age of the patient, family history, size of tumor, proximity of tumor to line of resection, involvement of lymph nodes, and prophylactic radiation. The average age of the patients with recurrence was 7 years less than those without, and the incidence of nodal involvement was three times as high in those with local recurrence as in those without. These were the only factors that showed any significant difference between the two groups. When axillary dissection is done in patients treated by partial mastectomy, valuable information is obtained about the likelihood of local recurrence.
Delay-Optimal Burst Erasure Code Construction (2007)

Delay-optimal burst erasure correction codes have the shortest possible decoding delay required to correct all bursts of a given length with a fixed redundancy. We provide a simple construction that yields linear convolutional delay-optimal burst erasure codes for any choice of coding parameters while keeping the finite field small.
Optimal Use of Budget Reserves to Minimize Technical and Management Failure Risks During Complex Project Development (2005)

Project managers are recognizing that adequate resource reserves are a critical success factor in a project development environment that is complex and uncertain. Yet, justifying the need for project reserves is still a challenge, as is the optimal allocation of any available resources to minimize development uncertainties. This paper presents a multiperiod decision model designed to support the management of reserves considering the risks of failures including technical, managerial, i.e., exceeding budget and schedule, or strategic, i.e., meeting budget, schedule, and technical specifications but not achieving the full strategic value of the project. In this paper, we examine the tradeoffs among these risks and their implications for resource allocation during a project's development phase. This decision support model is referred to as Dynamic Advanced Probabilistic Risk Analysis Model. It provides decision makers with a quantitative tool to allocate reserves (beyond the bare-bone minimum project costs) among project reserves, technical reinforcements of the engineered system, and product enhancements, with the advantage of flexibility over time. The model yields first, coarse estimates of the value of deferring some commitments about the product's design until critical uncertainties are resolved and second, an estimate of the optimal amount to be invested in testing and reviews. We show that the greater the uncertainties at the onset of the development phase, the greater the value of this information.
Extending the Applicability of Native Chemical Ligation (1996)

A more general approach to native (amide-forming) chemical ligation of unprotected peptide segments is described that extends the technique beyond the previously reported X-Cys ligation site to now include X-Gly and Gly-X ligation sites. A peptide, [peptide1]αCOSR, is reacted with a second peptide, HSCH2CH2(O)-Nα[peptide2], under conditions promoting thioester exchange. The intermediate thioester-linked product rearranges to form a ligation product linked by an N-substituted amide bond. If desired, the -oxyalkyl substitution on the amide bond can be removed by facile treatment with Zn in acidic medium to give a native peptide bond at the ligation site. The techniques described have been employed to ligate small model peptide segments to yield peptides with native or modified backbones, proving the feasibility of this approach.
The Drosophila saxophone Gene: a Serine-Threonine Kinase Receptor of the TGF-β Superfamily (1994)

The Drosophila decapentaplegic (dpp) gene encodes a transforming growth factor-beta (TGF-beta)-like protein that plays a key role in several aspects of development. Transduction of the DPP signal was investigated by cloning of serine-threonine kinase transmembrane receptors from Drosophila because this type of receptor is specific for the TGF-beta-like ligands. Here evidence is provided demonstrating that the Drosophila saxophone (sax) gene, a previously identified female sterile locus, encodes a TGF-beta-like type I receptor. Embryos from sax mothers and dpp embryos exhibit similar mutant phenotypes during early gastrulation, and these two loci exhibit genetic interactions, which suggest that they are utilized in the same pathway. These data suggest that sax encodes a receptor for dpp.
Anti-stress and Promoting Effect of the Fruit of Morus alba (2005)

Effects of Morus alba fruit extracts on monoamine oxidase (MAO) activity were examined in rats during and after physical exercise. Oral administration of M. alba extract (0.3 g/kg body weight) significantly increased brain MAOA activity but decreased liver MAO-B activity when they were measured using serotonin and benzylamine as substrates. Type of physical exercises had significant effect on MAO activity. Brain MAO-A activity markedly decreased with physical activity-related stress compared to normal group, whereas Liver MAO-B activity increased up to 60 min after exercise. Lactate dehydrogenase (LDH) activity and lactate concentration in blood, clinical indices of physical exercise activities, were also determined for correlation to MAO activities. MAO-A activity of rats subjected to oral administration of M. alba extract and physical exercise increased whereas MAO-B and LDH activities, and lactate level decreased. All indices eventually recovered normal levels. These results suggest M. alba may increase capability of physical activities by modulating MAO activities during exercise.
STUDIES ON REACTIONS RELATING TO CARBOHYDRATES AND POLYSACCHARIDES: XLIV. SYNTHESIS OF ISOMERIC BICYCLIC ACETAL ETHERS (1933)

Two isomeric bicyclic acetal ethers, namely, 3, 5, 7-trioxabicyclo [2, 2, 2] octane and 3, 6, 8-trioxabicyclo [3, 2, 1] octane, have been synthesized by the action of aqueous potassium hydroxide on 1, 3-bromoethylidene glycerol 2-benzoate and 1, 2-bromoethylidene glycerol 3-benzoate respectively. Both isomers are crystalline products possessing similar solubilities in organic solvents and high vapor pressures. They show no indication of interconvertibility on solution in solvents, or under the influence of heat. On hydrolysis they yield glycollic aldehyde and glycerol.A new method for the synthesis of cyclic acetals from simple open-chain acetals is described.
Age- and Stage-dependent Accumulation of Advanced Glycation End Products in Intracellular Deposits in Normal and Alzheimer's Disease Brains (2004)

In this immunohistochemical study, the age- and stage-dependent accumulation of advanced glycation end-products (AGEs) in Alzheimer's disease (AD) and their relation to the formation of neurofibrillary tangles and neuronal cell death was investigated. For this purpose, the distribution of AGEs in neurons and glia was analyzed in the auditory association area of superior temporal gyrus (Brodmann area 22) of young and old non-demented controls and compared with early- and late-stage AD. A possible co-localization of AGEs with typical hallmarks of AD, such as hyperphosphorylated tau (as a marker for disturbed kinase/phosphatase activity), nNOS (as a marker for nitroxidative stress) and caspase-3 (as a marker of apoptotic cell death), was also investigated. Our results show that the percentage of AGE-positive neurons (and astroglia) increase both with age and, in AD patients, with the progression of the disease (Braak stages). Interestingly, nearly all if those neurons which show diffuse cytosolic AGE immunoreactivity also contain hyperphosphoryated tau, suggesting a link between AGE accumulation and the formation of early neurofibrillary tangles. Many, but not all, neurons show a co-localization of AGEs with other markers of neurodegeneration, such as nNOS and caspase-3.
Community search assistant (2001)

This paper describes a new software agent, the community search assistant, which recommends related searches to users of search engines. The community search assistant enables communities of users to search in a collaborative fashion. All queries submitted by the community are stored in the form of a graph. Links are made between queries that are found to be related. Users can peruse the network of related queries in an ordered way: following a path from a first cousin, to a second cousin to a third cousin, etc. to a set of search results. The first key idea behind the use of query graphs is that the determination of relatedness depends on the documents returned by the queries, not on the actual terms in the queries themselves. The second key idea is that the construction of the query graph transforms single user usage of information networks (e.g. search) into collaborative usage: all users can tap into the knowledge base of queries submitted by others.
Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. (2001)

The expression of vascular endothelial growth factor (VEGF) by breast tumors has been previously correlated with a poor prognosis in the pathogenesis of breast cancer. Furthermore, VEGF secretion is a prerequisite for tumor development. Although most of the effects of VEGF have been shown to be attributable to the stimulation of endothelial cells, we present evidence here that breast tumor cells are capable of responding to VEGF. We show that VEGF stimulation of T-47D breast cancer cells leads to changes in cellular signaling and invasion. VEGF increases the cellular invasion of T-47D breast cancer cells on Matrigel/ fibronectin-coated transwell membranes by a factor of two. Northern analysis for the expression of the known VEGF receptors shows the presence of moderate levels of Flt-1 and low levels of Flk-1/KDR mRNAs in a variety of breast cancer cell lines. T-47D breast cancer cells bind 125I-labeled VEGF with a Kd of 13 x 10(-9) M. VEGF induces the activation of the extracellular regulated kinases 1,2 as well as activation of phosphatidylinositol 3'-kinase, Akt, and Forkhead receptor L1. These findings in T-47D breast cancer cells strongly suggest an autocrine role for VEGF contributing to the tumorigenic phenotype.
Global Warming and Northern Hemisphere Sea Ice Extent (1999)

Surface and satellite-based observations show a decrease in Northern Hemisphere sea ice extent during the past 46 years. A comparison of these trends to control and transient integrations (forced by observed greenhouse gases and tropospheric sulfate aerosols) from the Geophysical Fluid Dynamics Laboratory and Hadley Centre climate models reveals that the observed decrease in Northern Hemisphere sea ice extent agrees with the transient simulations, and both trends are much larger than would be expected from natural climate variations. From long-term control runs of climate models, it was found that the probability of the observed trends resulting from natural climate variability, assuming that the models' natural variability is similar to that found in nature, is less than 2 percent for the 1978-98 sea ice trends and less than 0.1 percent for the 1953-98 sea ice trends. Both models used here project continued decreases in sea ice thickness and extent throughout the next century.
Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. (1986)

A growth factor (HGF) stimulating DNA synthesis of adult rat hepatocytes in primary culture was found in rat platelets. HGF was purified from rat platelets to homogeneity by a three-step procedure: stimulation of its release from platelets by thrombin, cation-exchanger fast protein liquid chromatography on a Mono S column, and heparin-Sepharose chromatography. HGF was clearly distinguishable from the platelet-derived growth factor (PDGF) by fast protein liquid chromatography. HGF was a heat- and acid-labile cationic protein that was inactivated by reduction with dithiothreitol. Its molecular mass was estimated to be 27 kDa by NaDodSO4/PAGE and its amino acid composition was very different from that of PDGF. The purified HGF stimulated DNA synthesis in adult rat hepatocytes at 2 ng/ml and was maximally effective at 20 ng/ml; its effect was additive or synergistic with those of insulin and EGF, depending on their combinations. HGF did not stimulate DNA synthesis of Swiss 3T3 cells, while PDGF did not stimulate that of hepatocytes. Thus, HGF showed clearly different cell specificity from PDGF in its growth-promoting activities. These findings indicate that HGF is a growth factor in platelets for mature hepatocytes.
Cyclic Nucleotide-dependent Vasorelaxation Is Associated with the Phosphorylation of a Small Heat Shock-related Protein (1997)

Activation of cyclic nucleotide-dependent signaling pathways leads to the relaxation of various smooth muscles. One of the major phosphorylation events associated with cyclic nucleotide-dependent vasorelaxation in bovine trachealis and carotid artery smooth muscle is the phosphorylation of two 20-kDa phosphoproteins with pI values of 5.7 and 5.9 (previously designated pp8 and pp3, respectively). The present studies sought to determine the identities of pp3 and pp8 in vascular smooth muscle. The phosphopeptide maps for the pp8 and pp3 proteins were similar. Preparative two-dimensional gel electrophoresis and amino acid sequencing of a peptide fragment of the pp3 protein revealed a sequence identical to a 20-kDa heat shock-related protein (HSP20) previously purified from skeletal muscle. Western blot and immunoprecipitation analysis with anti-HSP20 antibodies demonstrated that the pp3 and pp8 proteins are phosphorylated forms of HSP20. In addition, HSP20 could be phosphorylated in vitro by both cAMP-dependent protein kinase and cGMP-dependent protein kinase. These data suggest that the phosphorylation of the heat shock-related protein HSP20 is associated with cyclic nucleotide-dependent relaxation of vascular smooth muscle.
Adhesion: Molecules and Mechanics (1994)

There is a difference between adhesion at the molecular level and adhesion in engineering. There is no doubt that molecules of solid materials stick together and can be separated mechanically. The problem is explaining the connection between molecular attractions and mechanical measurements. False ideas such as keying and gluing require critical assessment because they confuse molecules and mechanics. Mechanisms such as adhesive hysteresis, stringing, and clustering deserve evaluation. A rational theory of these phenomena should be based on the theoretical concept of reversible work of adhesion and on the measured quantity of adhesive energy, which includes the extra energy required to restructure the interface as surfaces move.
Human platelet heparanase: purification, characterization and catalytic activity (1998)

Heparan sulphate (HS) is an important component of the extracellular matrix (ECM) and the vasculature basal lamina (BL) which functions as a barrier to the extravasation of metastatic and inflammatory cells. Platelet-tumour cell aggregation at the capillary endothelium results in activation and degranulation of platelets. Cleavage of HS by endoglycosidase or heparanase activity produced in relatively large amounts by the platelets and the invading cells may assist in the disassembly of the ECM and BL, and thereby facilitate cell migration. Using a recently published rapid, quantitative assay for heparanase activity towards HS [Freeman, C. and Parish, C.R. (1997), Biochem. J., 325, 229-237], human platelet heparanase has now been purified 1700-fold to homogeneity in 19% yield by a five column procedure, which consists of concanavalin A-Sepharose, Zn2+-chelating-Sepharose, Blue A-agarose, octyl-agarose and gel filtration chromatography. The enzyme, which was shown to be an endoglucuronidase that degrades both heparin and HS, has a native molecular mass of 50 kDa when analysed by gel filtration chromatography and by SDS/PAGE. Platelet heparanase degraded porcine mucosal HS in a stepwise fashion from a number average molecular mass of 18.5 to 13, to 8 and finally to 4.5 kDa fragments as determined by gel filtration analysis. Bovine lung heparin was degraded from 8.9 to 4.8 kDa while porcine mucosal heparin was degraded from 8.1 kDa to 3.8 and finally to 2.9 kDa fragments. Studies of the enzyme's substrate specificity using modified heparin analogues showed that substrate cleavage required the presence of carboxyl groups, but O- and N-sulphation were not essential. Inhibition studies demonstrated an absolute requirement for the presence of O-sulphate groups. Platelet heparanase was inhibited by heparin analogues which also inhibited tumour heparanase, suggesting that sulphated polysaccharides which inhibit tumour metastasis may act to prevent both tumour cell and platelet heparanase degradation of endothelial cell surface HS and the basal laminar.
Combination Chemoprevention of HER2/neu-Induced Breast Cancer Using a Cyclooxygenase-2 Inhibitor and a Retinoid X Receptor–Selective Retinoid (2008)

The inducible prostaglandin synthase isoform cyclooxygenase-2 (COX-2) is overexpressed in approximately 40% of human breast carcinomas and in precancerous breast lesions, particularly in association with overexpression of human epidermal growth factor receptor 2 (HER2/neu). Experimental breast cancer can be suppressed by pharmacologic inhibition or genetic ablation of Cox-2, suggesting potential clinical utility of COX-2 inhibitors with respect to breast cancer. Importantly, several clinical trials have found reduced colorectal adenoma formation in individuals administered selective COX-2 inhibitors. However, such trials also identified increased cardiovascular risk associated with COX-2 inhibitor use. The goal of this research was to test whether improved chemopreventive efficacy could be achieved by combining submaximal doses of a selective COX-2 inhibitor and a retinoid X receptor-selective retinoid (rexinoid). The rate of HER2/neu-induced mammary tumor formation was substantially delayed by coadministration of the COX-2 inhibitor celecoxib (500 ppm in diet) and the rexinoid LGD1069 (10 mg/kg body weight; oral gavage) to MMTV/neu mice. Median time to tumor formation was increased from 304 to >600 days (P < 0.0001). The combination was substantially more effective than either drug individually. Similarly, potent suppression of aromatase activity was observed in mammary tissues from the combination cohort (44% of control; P < 0.001). Regulation of aromatase expression and activity by COX-derived prostaglandins is well established. Interestingly however, single agent LGD1069 significantly reduced mammary aromatase activity (71% of control; P < 0.001) without modulating eicosanoid levels. Our data show that simultaneous blockade of COX/prostaglandin signaling and retinoid X receptor-dependent transcription confers potent anticancer efficacy, suggesting a novel avenue for clinical evaluation.
Vesicle accumulation and exocytosis at sites of plasma membrane disruption. (1995)

Plasma membrane disruptions are resealed by an active molecular mechanism thought to be composed, in part, of kinesin, CaM kinase, snap-25, and synaptobrevin. We have used HRP to mark the cytoplasmic site of a mechanically induced plasma membrane disruption. Transmission electron microscopy revealed that vesicles of a variety of sizes rapidly (s) accumulate in large numbers within the cytoplasm surrounding the disruption site and that microvilli-like surface projections overlie this region. Scanning electron microscopy confirmed that tufts of microvilli rapidly appear on wounded cells. Three assays, employing the membrane specific dye FM1-43, provide quantitative evidence that disruption induces Ca(2+)-dependent exocytosis involving one or more of the endosomal/lysosomal compartments. Confocal microscopy revealed the presence in wounded cells of cortical domains that were strikingly depleted of FM dye fluorescence, suggesting that a local bolus of exocytosis is induced by wounding rather than global exocytosis. Finally, flow cytometry recorded a disruption-induced increase in cell forward scatter, suggesting that cell size increases after injury. These results provide the first direct support for the hypothesis that one or more internal membrane compartments accumulate at the disruption site and fuse there with the plasma membrane, resulting in the local addition of membrane to the surface of the mechanically wounded cell.