gebhart/patrepeval huggingface dataset:
The Jalapeño dynamic optimizing compiler for Java (1999)

Article The Jalapeño dynamic optimizing compiler for Java Share on Authors: Michael G. Burke IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile , Jong-Deok Choi IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile , Stephen Fink IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile , David Grove IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile , Michael Hind IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile , Vivek Sarkar IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile , Mauricio J. Serrano IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile , V. C. Sreedhar IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile , Harini Srinivasan IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile , John Whaley IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NY IBM Thomas J. Watson Research Center, P.O. Box 704, Yorktown Heights, NYView Profile Authors Info & Claims JAVA '99: Proceedings of the ACM 1999 conference on Java GrandeJune 1999 Pages 129–141https://doi.org/10.1145/304065.304113Online:01 June 1999Publication History 188citation1,125DownloadsMetricsTotal Citations188Total Downloads1,125Last 12 Months19Last 6 weeks5 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Prostate-specific Antigen Expression Is Regulated by an Upstream Enhancer (1996)

Prostate cancer can be detected using assays for blood-borne prostate-specific antigen (PSA), which is the clinically most useful diagnostic marker of malignant disease. This paper characterizes the 5 -flanking prostate-specific enhancer which controls expression of the human PSA gene This enhancer, located between -5824 and -3738, is androgen-responsive and requires a promoter for activity. Inductions of 12-100-fold activity occur at 1 nM concentrations of the testosterone analog R1881. The enhancer demonstrated tissue specificity as judged by transfections of several human cell lines. Electrophoretic mobility shift assays comparing nuclear extracts from breast cancer cells MCF-7, and prostate cancer cells LNCaP, showed three regions of prostate-specific binding. These three regions are -4168 to -4797 (region I), -4710 to 4479 (region II), and -4168 to -3801 (region III). Region III contained a putative androgen response element at -4136 that markedly affected activity if mutated. These data suggest that prostate-specific gene expression may involve interaction of prostate-specific proteins or protein complexes with the enhancer in addition to binding of the androgen receptor to androgen response elements.
Human Tumor-Associated Lea-Lex Hybrid Carbohydrate Antigen IV3(Gal.beta.1.fwdarw.3[Fuc.alpha.1.fwdarw.4]GlcNAc)III3FucnLc4 Defined by Monoclonal Antibody 43-9F: Enzymic Synthesis, Structural Characterization, and Comparative Reactivity with Various Antibodies (1994)

Two Le(a)-cross-reacting monoclonal antibodies (mAbs) were previously established which define complex tumor-associated carbohydrate antigens. The first mAb, 43-9F, was raised against human squamous cell lung carcinoma and shows preferential reactivity with various human cancers over normal cells. Its tumor cell binding activity is best inhibited by a milk oligosaccharide characterized as Le(a)-Le(x) [Mårtensson, S., et al. (1988) Cancer Res. 48, 2125], Gal beta 1-->3[Fuc alpha 1-->4] GlcNAc beta 1-->3Gal beta 1-->4]Fuc alpha 1-->3]-GlcNAc beta 1-->3Gal beta 1-->4Glc (1). The second mAb, ST-421, was raised against human gastric cancer xenograft in nude mice and found to have strong tumor growth-suppressing activity in nude mice. The epitope recognized by ST-421 was chemically identified as Le(a)-Le(a), Gal beta 1-->3 [Fuc alpha 1-->4]GlcNAc beta 1-->3Gal beta 1-->3-[Fuc alpha 1-->4] GlcNAc beta 1-->3Gal beta 1-->4Glc (2) [Stroud, M.R., et al. (1991) J. Biol. Chem. 266, 8439]. Both 43-9F and ST-421 cross-react with Le(a). Identification of the 43-9F antigen as structure 1 (Le(a)-Le(x)) is tentative since it was not based on isolation and chemical characterization of antigen from tumor cells or tissues. We therefore synthesized structure 1 starting from sialyl-nor-hexaosylceramide (VI3NeuAcnLc6), with sequential enzymatic hydrolysis by sialidase and beta-galactosidase followed by addition of beta 1-->3Gal with beta 1-->3 galactosyltransferase. This yielded the hybrid type 1/type 2 chain core structure IV3-(Gal beta 1-->3GlcNAc)nLc4, which was fucosylated with alpha 1-->3/4 fucosyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)
Crystal Structure Analysis of Warfarin Binding to Human Serum Albumin (2001)

Human serum albumin (HSA) is an abundant transport protein found in plasma that binds a wide variety of drugs in two primary binding sites (I and II) and can have a significant impact on their pharmacokinetics. We have determined the crystal structures at 2.5 A-resolution of HSA-myristate complexed with the R-(+) and S-(-) enantiomers of warfarin, a widely used anticoagulant that binds to the protein with high affinity. The structures confirm that warfarin binds to drug site I (in subdomain IIA) in the presence of fatty acids and reveal the molecular details of the protein-drug interaction. The two enantiomers of warfarin adopt very similar conformations when bound to the protein and make many of the same specific contacts with amino acid side chains at the binding site, thus accounting for the relative lack of stereospecificity of the HSA-warfarin interaction. The conformation of the warfarin binding pocket is significantly altered upon binding of fatty acids, and this can explain the observed enhancement of warfarin binding to HSA at low levels of fatty acid.
Transplantation of Adipose Derived Stromal Cells is Associated with Functional Improvement in a Rat Model of Chronic Myocardial Infarction (2008)

These results indicate that transplantation of adipose derived cells in chronic infarct provides a superior benefit to cardiac pre-differentiated ADSC and BM-MNC.
Pilot Study Using Molecular Profiling of Patients' Tumors to Find Potential Targets and Select Treatments for Their Refractory Cancers (2010)

Purpose To compare the progression-free survival (PFS) using a treatment regimen selected by molecular profiling (MP) of a patient's tumor with the PFS for the most recent regimen on which the patient had experienced progression (ie, patient as his own control). Patients and Methods Patients with refractory metastatic cancer had tissue samples submitted for MP in two formats including formalin-fixed tissue for immunohistochemistry and fluorescent in situ hybridization assays and immediately frozen tissue for oligonucleotide microarray (MA) gene expression assays (all performed in a Clinical Laboratory Improvement Amendments [ CLIA ] –certified laboratory). The MP approach was deemed of clinical benefit for the individual patient who had a PFS ratio (PFS on MP-selected therapy/PFS on prior therapy) of ≥ 1.3. Results In 86 patients who had MP attempted, there was a molecular target detected in 84 (98%). Sixty-six of the 84 patients were treated according to MP results. Eighteen (27%) of 66 patients had a PFS ratio of ≥ 1.3 (95% CI, 17% to 38%; one-sided, one-sample P = .007). Therefore, the null hypothesis (that ≤ 15% of this patient population would have a PFS ratio of ≥ 1.3) was rejected. Conclusion It is possible to identify molecular targets in patients' tumors from nine different centers across the United States. In 27% of patients, the MP approach resulted in a longer PFS on an MP-suggested regimen than on the regimen on which the patient had just experienced progression. Issues to be considered in interpretation of this study include limited prior experience with patients as their own controls as a study end point and overall patient attrition.
Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: Induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal (1997)

We have recently shown that VEGF functions as a survival factor for newly formed vessels during developmental neovascularization, but is not required for maintenance of mature vessels. Reasoning that expanding tumors contain a significant fraction of newly formed and remodeling vessels, we examined whether abrupt withdrawal of VEGF will result in regression of preformed tumor vessels. Using a tetracycline-regulated VEGF expression system in xenografted C6 glioma cells, we showed that shutting off VEGF production leads to detachment of endothelial cells from the walls of preformed vessels and their subsequent death by apoptosis. Vascular collapse then leads to hemorrhages and extensive tumor necrosis. These results suggest that enforced withdrawal of vascular survival factors can be applied to target preformed tumor vasculature in established tumors. The system was also used to examine phenotypes resulting from over-expression of VEGF. When expression of the transfected VEGF cDNA was continuously "on," tumors became hyper-vascularized with abnormally large vessels, presumably arising from excessive fusions. Tumors were significantly less necrotic, suggesting that necrosis in these tumors is the result of insufficient angiogenesis.
Butyrate-Producing Probiotics Reduce Nonalcoholic Fatty Liver Disease Progression in Rats: New Insight into the Probiotics for the Gut-Liver Axis (2013)

Nonalcoholic fatty liver disease (NAFLD) includes simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The gut-derived endotoxin plays an essential role in the pathophysiological development and progression of NAFLD. By using rat models of choline-deficient/L-amino acid-defined (CDAA)-diet-induced NAFLD, we examined whether MIYAIRI 588--a butyrate-producing probiotic--prevents the progression of pathophysiological changes from steatosis to hepatocarcinogenesis. In vivo experiments showed that treatment with MIYAIRI 588 reduced CDAA-diet-induced hepatic lipid deposition and significantly improved the triglyceride content, insulin resistance, serum endotoxin levels, and hepatic inflammatory indexes. We also found that MIYAIRI 588 substantially increased the activation of hepatic adenosine 5'-monophosphate-activated protein kinase (AMPK) and AKT and the expression of lipogenesis- or lipolysis-related proteins. MIYAIRI 588 also improved CDAA-diet-induced delocalization and substantially decreased the expression of the tight-junction proteins intestinal zonula occluden-1 and occludin in CDAA-diet-fed rats. Further, the MIYAIRI 588-treated rats also showed remarkable induction of nuclear factor erythoid 2-related factor 2 (Nrf2) and its targeted antioxidative enzymes, which suppressed hepatic oxidative stress. In vitro studies revealed that treatment with sodium butyrate (NaB) also activated AMPK and AKT and enhanced Nrf2 expression by precluding ubiquitination, thereby increasing the half-life of the Nrf2 protein. Pharmacological studies and siRNA knockdown experiments showed that NaB-mediated AMPK activation induced the phosphorylation and nuclear translocation of Sirtuin 1, leading to the increased assembly of mammalian TOR complex 2 and phosphorylation of AKT at Ser473 and subsequent induction of Nrf2 expression and activation. These favorable changes caused an obvious decrease in hepatic fibrous deposition, GST-P-positive foci development, and hepatocarcinogenesis. Our data clearly established that the probiotic MIYAIRI 588 has beneficial effects in the prevention of NAFLD progression.
Mismatch Repair Deficiency, Apoptosis, and Drug Resistance (1999)

The most clearly understood function of mismatch repair (MMR) is its role in the correction of mismatches occurring during DNA replication or DNA recombination. However, expression of MMR proteins is also now associated with sensitivity of mammalian cells to an ever-increasing range of DNA-damaging agents, and loss of MMR has been correlated with reduced ability of cells to undergo apoptosis, induced by a wide variety of clinically important chemotherapeutic drugs. The mechanisms by which MMR affects DNA damage-induced apoptosis are unclear. It has been proposed that certain types of DNA damage induce futile MMR activity and/or MMR-dependent replication stalling, which could lead to cell death. Alternatively, MMR may modulate the probability of bypassing DNA lesions by recombination-dependent mechanisms. Experimental models have implicated MMR as being necessary to activate (c-Jun NH2-terminal kinase), c-Abl nonreceptor tyrosine kinase, p53-dependent apoptosis, and G2 arrest in response to DNA damage. Thus, loss of MMR in cells may affect many signaling pathways, leading to important cellular responses to DNA damage, including apoptosis, although the relative contribution of any given pathway will depend on the cell type being examined. Correlation of MMR status with prognosis and response of tumors to treatment are beginning to emerge; however, larger prospective studies need to be done. If reduced apoptosis of patients’ tumors is mediated by loss of MMR, this will provide new challenges for how to overcome drug resistance.
Interleukin 1 beta induces the formation of nitric oxide by beta-cells purified from rodent islets of Langerhans. Evidence for the beta-cell as a source and site of action of nitric oxide. (1992)

Nitric oxide has recently been implicated as the effector molecule that mediates IL-1 beta-induced inhibition of glucose-stimulated insulin secretion and beta-cell specific destruction. The pancreatic islet represents a heterogeneous cell population containing both endocrine cells (beta-[insulin], alpha-]glucagon], gamma[somatostatin], and PP-[polypeptide] secreting cells) and non-endocrine cells (fibroblast, macrophage, endothelial, and dendritic cells). The purpose of this investigation was to determine if the beta-cell, which is selectively destroyed during insulin-dependent diabetes mellitus, is both a source of IL-1 beta-induced nitric oxide production and also a site of action of this free radical. Pretreatment of beta-cells, purified by FACS with IL-1 beta results in a 40% inhibition of glucose-stimulated insulin secretion that is prevented by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (NMMA). IL-1 beta induces the formation of nitric oxide by purified beta-cells as evidenced by the accumulation of cGMP, which is blocked by NMMA. IL-1 beta also induces the accumulation of cGMP by the insulinoma cell line Rin-m5F, and both NMMA as well as the protein synthesis inhibitor cycloheximide prevent this cGMP accumulation. Iron-sulfur proteins appear to be intracellular targets of nitric oxide. IL-1 beta induces the formation of an iron-dinitrosyl complex by Rin-m5F cells indicating that nitric oxide mediates the destruction of iron-sulfur clusters of iron containing enzymes. This is further demonstrated by IL-1 beta-induced inhibition of glucose oxidation by purified beta-cells, mitochondrial aconitase activity of dispersed islet cells, and mitochondrial aconitase activity of Rin-m5F cells, all of which are prevented by NMMA. IL-1 beta does not appear to affect FACS-purified alpha-cell metabolic activity or intracellular cGMP levels, suggesting that IL-1 beta does not exert any effect on alpha-cells. These results demonstrate that the islet beta-cell is a source of IL-1 beta-induced nitric oxide production, and that beta-cell mitochondrial iron-sulfur containing enzymes are one site of action of nitric oxide.
Drug glycosides: potential prodrugs for colon-specific drug delivery (1985)

The influence of prodrug structure on specificity of glycoside/glycosidase based colon-specific drug delivery was studied by preparing nine steroid glycosides, measuring their relative lipophilicities, and hydrolyzing them with bacterial glycosidases from rat intestines. The 21-yl beta-D-glucosides and galactosides of dexamethasone, prednisolone, hydrocortisone, and fludrocortisone and the 21-yl beta-D-cellobioside of prednisolone were prepared by a modified Koenigs-Knorr reaction. The deacetylated glycoside prodrugs, along with the P-nitrophenyl derivatives of beta-D-glucoside, galactoside, and cellobioside, were subjected to hydrolysis by the contents of the rat stomach, proximal small intestine (PSI), distal small intestine (DSI), and cecum. All the prodrugs were hydrolyzed slowly by PSI and stomach contents, more rapidly by contents of the DSI, and most rapidly by cecal contents. This is the basis of the site-specific drug delivery reported earlier (Friend, D. R.; Chang, G. W. J. Med. Chem. 1984, 27, 261). Furthermore, the prodrugs themselves had very different susceptibilities to hydrolysis. Hydrolysis rates catalyzed by DSI contents decreased in the following order: prednisolon-21-yl beta-D-galactoside (10) greater than prednisolon-21-yl beta-D-glucoside (2) greater than prednisolon-21-yl beta-D-cellobioside (13) greater than dexamethason-21-yl beta-D-galactoside (9) greater than dexamethason-21-yl beta-D-glucoside (1). Hydrolysis of cellobioside 13 was only half that of glucoside 2 and one-fourth that of galactoside 10. Hydrolysis of all the prodrugs in cecal contents was rapid, with the exceptions of hydrocortison-21-yl beta-D-glucoside (5) and fludrocortison-21-yl beta-D-glucoside (7), which were hydrolyzed more slowly than the other glucoside prodrugs. Eadie-Hofstee plots for hydrolysis of the glucoside compounds suggested that bacterial beta-D-glucosidase activity in the colon may be more heterogeneous in nature than beta-D-galactosidase activity. Relative lipophilicities of the prodrugs and free steroids were compared by measuring their octanol-buffer partition coefficients (P). The logarithm of the P of cellobioside 13 (-0.56) was considerably lower than that of the other prodrugs, which ranged from 0.11 to 0.84. Log P of the free steroids ranged from 1.54 to 1.73. These relative rates of hydrolysis and relative lipophilicities, along with previously reported animal experiments, enable one to estimate the site specificity of glycoside prodrugs prior to extensive animal studies.
Sugar‐Derived Ras Inhibitors: Group Epitope Mapping by NMR Spectroscopy and Biological Evaluation (2006)

Abstract Novel inhibitors of Ras protein activation have been found, containing a bicyclic core derived from D ‐arabinose and benzyl and phenylhydroxylamine moieties. NMR studies (trNOE, saturation‐transfer difference, STD) of the binding between these molecules and human p21 h‐Ras are reported. A pharmacophore mapping indicates that both the benzyl and the phenylhydroxylamine moieties are essential for protein binding. Molecules lacking one of these groups were synthesized and tested to confirm this hypothesis, and no interaction with Ras in vitro, nor biological activity in mammalian cells was observed. Our studies led to the development of molecules that selectively inhibit Ras‐dependent cellular growth in mammalian cells. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)
Tuning the Electronic Structure of Graphene by an Organic Molecule (2008)

The electronic structure of an electron-acceptor molecule, tetracyanoethylene (TCNE), on graphene was investigated using the first-principles method based on density functional theory. It was theoretically demonstrated that a p-type graphene can be obtained via charge transfer between an organic molecule and graphene. Both the carrier concentration and band gap at the Dirac point can be controlled by coverage of organic molecules. The spin split and partially filled pi* orbitals of the TCNE anion radical induce spin density in the graphene layer. Surface modification of graphene by organic molecules could be a simple and effective method to control the electronic structure of graphene over a wide range.
Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients (2002)

The role of maintenance therapy in multiple myeloma is controversial. Recent studies have shown an improvement in both progression-free and overall survival for patients receiving maintenance treatment with a combination of interferon and glucocorticoids, compared with interferon alone. The role of glucocorticoids alone as maintenance therapy has not been previously addressed. We compared alternate-day, oral prednisone at 2 different dose levels (10 mg versus 50 mg) for remission maintenance among previously untreated myeloma patients following a response to induction with standard-dose vincristine, doxorubicin, and dexamethasone with prednisone (VAD-P) or VAD-P plus quinine (VAD-P/Q). There were 250 eligible patients registered on Southwest Oncology Group study 9210 and randomized to receive VAD-P or VAD-P/Q. There were 125 patients achieving at least a 25% tumor reduction following induction therapy who were randomized to either physiologic (10 mg) or pharmacologic (50 mg) doses of alternate-day, oral prednisone until disease progression. At the time of study entry, patient characteristics were similar in VAD-P and VAD-P/Q patients and in the 2 arms randomized to maintenance therapy. After a median follow-up of 53 months, there was no difference in either progression-free or overall survival between the 2 induction regimens. However, from the time of maintenance randomization, both progression-free (14 versus 5 months; P =.003) and overall survival (37 versus 26 months; P =.05) were significantly improved in patients receiving 50 mg as compared with 10 mg alternate-day prednisone. There was no difference in treatment-related adverse events between the groups. Thus, 50 mg, oral, alternate-day prednisone is effective maintenance treatment for multiple myeloma patients who achieve a response to induction chemotherapy. (Blood. 2002;99:3163-3168)
Quantum repeater with encoding (2009)

We propose an approach to implement quantum repeaters for long-distance quantum communication. Our protocol generates a backbone of encoded Bell pairs and uses the procedure of classical error correction during simultaneous entanglement connection. We illustrate that the repeater protocol with simple Calderbank-Shor-Steane encoding can significantly extend the communication distance, while still maintaining a fast key generation rate.