gebhart/patrepeval huggingface dataset:
Up-Regulation of miR-195 Expression Leads to Decreased Expression of Basic Fibroblast Growth Factor in CLL Patients Treated with DNA Methylation Inhibitors. (2007)

Abstract A higher than age-expected DNA methylation index is predictive for early disease progression in patients with CLL (Yu et al. Leukemia Research 2006). We hypothesized that miRNA expression can also be silenced by promoter hypermethylation in CLL. Thus, methyl pool or DNA methyltransferase inhibitors can upregulate microRNAs with tumor suppressor characteristics by restoring the “normal” pattern of methylation. Results of patients treated with cladribine, a methyl substrate inhibitor, or 5-azacitidine, a DNA methyltransferase inhibitor were compared in 2 separate clinical protocols. The global DNA methylation decreased after treatment with cladribine or 5-azacitidine in 60% of the patients. At the 2006 ASH meeting, we reported on the consistent upregulation of miR-17-3p, miR-21, miR-29a, miR-29b, miR-29c, miR-30e, miR-104, miR-126, miR-128a, miR-130a, miR-141, miR-142-3p, miR-148a, miR-151, miR-199a, miR-199a*, and miR-301 by real-time PCR using the Early Access Human Panel from Applied Biosystems. Data from two patients on the cladribine protocol and 10 patients on the 5-azacitidine protocol were used for statistical analyses. Non-parametric Wilcoxon tests as well as t-tests were performed. Comparisons were made of the responders versus non-responders, and of cladribine versus 5-azacytidine. Since many of the miRNAs showed differences in the cladribine versus 5-azacytidine comparison, a second responder vs non-responder analysis was performed in which the two cladribine subjects were removed. MiR-195 was statistically more upregulated in the cladribine treated responder whereas miR-29c was statistically most upregulated in the 5-azacitidine treated patients (p=0.02). In the patients with global demethylation after treatment, upregulation of microRNA-195 was observed and directly correlated with regional demethylation of the CpG island, confirmed by bisulfite sequencing. Some of the predicted targets of miR-195 include bcl-2, CNOT6L, USP15, PADAH1B1, and ESRRG. MiR-195 may also have tumor suppressor characteristics as it also targets basic fibroblast growth factor (FGF-2), a gene important in CLL angiogenesis. There has been some evidence suggesting FGF-2 is an oncogene. For example, overexpression of FGF-2 isoforms facilitates growth of NIH 3T3 cells in low serum media and also mediates radioresistance of HeLa cells. FGF-2 is also protective against irradiation activation of p53 in the leukemia cells derived from patients with CLL. Although cladribine has been reported to downregulate FGF-2 by inhibiting adenosine deaminase, downregulation of FGF-2 at the transcript and protein levels was also observed in before and after treatment samples from patients treated with 5-azacytidine. We propose an alternative mechanism by which the FGF-2 transcript is degraded after binding to excess miR-195. In patients responsive to treatment with DNA methylation inhibitors, a regional decrease in the methylation status of the CpG island 5′ to miR-195 may lead to increased expression.
Thin Films: Heteroepitaxial Systems (1999)

Atomic interactions and surface processes in heteroepitaxy ordering in III-V semiconductor alloys transition metal thin film epitaxy the growth and structure of epitaxial metal-oxide/metal interfaces heteroepitaxy of disparate materials - from chemisorption to epitaxy in CaF2/Si (111) recent progress in high Tc superconducting heteostructures strain accommodation and relief in GeSi/Si heteroepitaxy heteroepitaxial growth modes and morphologies on GaAs surfaces molecular beam epitaxy of Sb-based semiconductors P-based semiconductor multilayers MBE growth of wide-gap refractory nitride epitaxial films epitaxial growth, microstructural characterizations, and optical physics of wide bandgap II-VI heterostructures molecular beam epitaxy of narrowgap IV-VI semiconductors.
Rich interaction in the digital library (1995)

Effective information access involves rich interactions between users and information residing in diverse locations. Users seek and retrieve information from the sources—for example, file serves, databases, and digital libraries—and use various tools to browse, manipulate, reuse, and generally process the information. We have developed a number of techniques that support various aspects of the process of user/information interaction. These techniques can be considered attempts to increase the bandwidth and quality of the interactions between users and information in an information workspace —an environment designed to support information work (see Figure 1).
Efficacy of antibiotic‐impregnated cement in total hip replacement (2008)

The use of antibiotic-impregnated cement lowered the infection rate by approximately 50% in primary hip arthroplasty. For revisions of previously infected hips, combinations or culture-dependent antibiotics lowered infection rates by approximately 40%.
In vivo properties of three human HER2/neu-expressing murine cell lines in immunocompetent mice. (1999)

Although an antibody response against the human HER2/neu antigen was observed, this response does not affect the growth rate of the HER2/neu-expressing cells. These murine models may be useful tools for evaluation of anti-cancer therapeutic approaches that target human HER2/neu.
Biochemical Characterization of a Glycoprotein Required for Rhinovirus Attachment (1989)

Human rhinoviruses attach to specific receptors located on the surfaces of host cells as a first step in viral infection. A 90-kDa cell surface protein was previously shown to be involved in the attachment of human rhinoviruses to susceptible cells (Tomassini, J. E., and Colonno, R.J. (1986) J. Virol. 58, 290-295). Digestion of purified receptor protein with various glycosidases revealed that 30% of its molecular mass was comprised of complex-type oligosaccharides, one-third being contributed by sialic acid. The presence of sialic acid was confirmed by demonstrating that wheat germ lectin can inhibit the attachment of rhinoviruses to host cell membranes, while lectins of other sugar specificities had no effect. The oligosaccharides were shown to be N-linked by tunicamycin treatment of host cells and by N-glycanase digestion. Seven N-linked glycosylation sites were detected by partial digestion of the receptor oligosaccharides with N-glycanase. Native receptor protein had an isoelectric focusing point of 4.2, compared to 5.3 for the deglycosylated protein. Studies of virus and antibody binding to neuraminidase-treated host cell membranes suggested that although carbohydrates may be involved in host-virus interaction, the receptor carbohydrate is not the predominant component of the cellular receptor site.
WHY MOZART IN THE NACHTWACHEN? (1987)

WHY MOZART IN THE NACHTWACHEN? Get access PAUL DAVIES PAUL DAVIES Kingston, Ontario Search for other works by this author on: Oxford Academic Google Scholar Forum for Modern Language Studies, Volume XXIII, Issue 3, July 1987, Pages 265–273, https://doi.org/10.1093/fmls/XXIII.3.265 Published: 01 July 1987
Phosphotyrosyl-protein phosphatases (1989)

Seven Tyr-protein phosphatase activities were isolated from bovine brain using phosphotyrosyl-casein as a model substrate. The activities were resolved from the cytosolic fraction by a three-step procedure employing successive DEAE-cellulose, phosphocellulose, and gel permeation chromatography steps. The seven activities accounted for 70% of the Tyr-protein phosphatase activity in bovine brain extracts and were distinct from type 1 and type 2 Ser/Thr-protein phosphatases and from the major alkaline phosphatase activities. Apparent molecular weights of the activities by gel permeation chromatography were: phosphotyrosyl-protein phosphatase (PTP)-1A (Mr 86,000), PTP-1B (Mr 24,000), PTP-2 (Mr 88,000), PTP-3 (Mr 90,000), PTP-4 (Mr 80,000), PTP-5 (Mr 48,000), and PTP-6 (Mr 104,000). PTP-5 was the major activity accounting for 26% of total while the remaining activity was divided rather evenly among the other six activities. PTP-5 was further purified to near homogeneity by additional chromatographies on Affi-Gel Blue, heparin-agarose, and Mono S giving an overall purification of 50,000-fold and a yield of 5.8%. One of two major polypeptides (Mr 46,000) in the preparation was identified as PTP-5 since it alone expressed protein phosphatase activity when protein-staining bands were eluted from sodium dodecyl sulfate-polyacrylamide gels and renatured. PTP-5 had a neutral pH optimum, and using phosphotyrosyl-casein as substrate it had a Km of 130 nM and a Vmax of 10 mumol Pi released.min-1.mg protein-1. These kinetic parameters are well within the range of values obtained for other pure protein phosphatases. PTP-5 also dephosphorylated pp60v-src (autophosphorylated at Tyr-416) at 10% of the rate observed with phosphotyrosyl-casein. Additionally the ratio of phosphotyrosyl-casein/pp60v-src phosphatase activity was relatively constant throughout the PTP-5 purification procedure. These results indicate that PTP-5 is able to bind and efficiently dephosphorylate phosphotyrosyl-proteins and suggest that it is a physiologically relevant Tyr-protein phosphatase.
WHEN DOES RACE MATTER? (2000)

Research investigating the relationship between offender race/ethnicity and sentence severity suggests the existence of contextual discrimination. That is, minority offenders are sentenced more harshly than white offenders in some jurisdictions, for some types of offenses, and under some circumstances. The findings of our study confirm this. We compare the sentences imposed on black, Hispanic and white felony offenders in three jurisdictions: Cook County (Chicago), Illinois; Dade County (Miami), Florida; and Jackson County (Kansas City), Missouri. Our results reveal that offender race/ethnicity has both overt and subtle effects on the decision to incarcerate or not. Although race had no effect on the likelihood of incarceration in Kansas City, both blacks and Hispanics were more likely than whites to be sentenced to prison in Chicago, and Hispanics (but not blacks) were more likely than whites to be incarcerated in Miami. Further analysis revealed that offender race interacted * This manuscript is based on work supported by the National Science Foundation under Grant SBR–93321852. Points of view are those of the authors and do not necessarily represent the position of the National Science Foundation. Sociology of Crime, Law and Deviance, Volume 2, pages 3–37. Copyright © 2000 by Elsevier Science Inc. All rights of reproduction in any form reserved. ISBN: 0-7623-0680-7
Optimized Large Scale Synthesis of Phosphorothioate Oligonucleotides on PS-PEG Supports (1997)

Sulphurization is a crucial step during synthesis of phosphorothioate oligonucleotides. Insufficient reaction leads to inhomogeneous products with phosphodiester defects and subsequently to destabilization of the oligomers in biological media. To achieve a maximum extent of sulphur incorporation, various sulphurizing agents have been investigated. Solely, the use of Beaucage reagent provided satisfactory results on PS-PEG supports. Based on our investigations in small scale synthesis (1 μmol) with continuous-flow technique, upscaling to the 0.1-0.25 mmolar range has been achieved using a peptide synthesizer. The syntheses were performed in batch mode with standard phosphoramidite chemistry. Additionally, large scale synthesis of a phosphodiester oligonucleotide has been carried out on PS-PEG with optimized protocols and compared to small scale synthesis on different supports. Products were analysed by 31 P NMR, capillary gel electrophoresis and electrospray mass spectrometry. An extent of sulphurization of 99% and coupling effiencies of more than 99% were obtained and the products proved to have similar purity compared to small scale syntheses on CPG
Stable Principal Component Pursuit (2010)

In this paper, we study the problem of recovering a low-rank matrix (the principal components) from a high-dimensional data matrix despite both small entry-wise noise and gross sparse errors. Recently, it has been shown that a convex program, named Principal Component Pursuit (PCP), can recover the low-rank matrix when the data matrix is corrupted by gross sparse errors. We further prove that the solution to a related convex program (a relaxed PCP) gives an estimate of the low-rank matrix that is simultaneously stable to small entry-wise noise and robust to gross sparse errors. More precisely, our result shows that the proposed convex program recovers the low-rank matrix even though a positive fraction of its entries are arbitrarily corrupted, with an error bound proportional to the noise level. We present simulation results to support our result and demonstrate that the new convex program accurately recovers the principal components (the low-rank matrix) under quite broad conditions. To our knowledge, this is the first result that shows the classical Principal Component Analysis (PCA), optimal for small i.i.d. noise, can be made robust to gross sparse errors; or the first that shows the newly proposed PCP can be made stable to small entry-wise perturbations.
Three Distinct Epitopes on the Extracellular Face of the Glucagon Receptor Determine Specificity for the Glucagon Amino Terminus (2003)

The glucagon and glucagon-like peptide-1 (GLP-1) receptors are homologous family B seven-transmembrane (7TM) G protein-coupled receptors, and they selectively recognize the homologous peptide hormones glucagon (29 amino acids) and GLP-1 (30-31 amino acids), respectively. The amino-terminal extracellular domain of the glucagon and GLP-1 receptors (140-150 amino acids) determines specificity for the carboxyl terminus of glucagon and GLP-1, respectively. In addition, the glucagon receptor core domain (7TM helices and connecting loops) strongly determines specificity for the glucagon amino terminus. Only 4 of 15 residues are divergent in the glucagon and GLP-1 amino termini; Ser2, Gln3, Tyr10, and Lys12 in glucagon and the corresponding Ala8, Glu9, Val16, and Ser18 in GLP-1. In this study, individual substitution of these four residues of glucagon with the corresponding residues of GLP-1 decreased the affinity and potency at the glucagon receptor relative to glucagon. Substitution of distinct segments of the glucagon receptor core domain with the corresponding segments of the GLP-1 receptor rescued the affinity and potency of specific glucagon analogs. Site-directed mutagenesis identified the Asp385 --> Glu glucagon receptor mutant that specifically rescued Ala2-glucagon. The results show that three distinct epitopes of the glucagon receptor core domain determine specificity for the N terminus of glucagon. We suggest a glucagon receptor binding model in which the extracellular ends of TM2 and TM7 are close to and determine specificity for Gln3 and Ser2 of glucagon, respectively. Furthermore, the second extracellular loop and/or proximal segments of TM4 and/or TM5 are close to and determine specificity for Lys12 of glucagon.
Paclitaxel Partitioning into Lipid Bilayers (1996)

Paclitaxel (taxol) is diterpenoid anticancer drug with a new mechanism of cytostatic action. It is under investigation in clinical trials for treatment of various types of human cancer. A major difficulty in developing paclitaxel as a chemotherapeutic agent in its poor water solubility. In order to improve the bioavailability of paclitaxel, novel vehicle systems such as mixed micelles or liposome-based formulations are being developed. In this study we determined the partition coefficient of paclitaxel partitioning into small unilamellar lipid vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine using two different methods, namely high-sensitivity titration calorimetry and fluorescence spectrometry. We measured a partition coefficient of Kp approximately equal to 9,500 M-1, a partition enthalpy of Delta H = -25 +/- 3 kcal mol-1 and a free energy of binding of Delta G = -7.9 kcal mol-1. The binding reaction is enthalpy-driven, which can be explained by van der Waals interactions between the hydrophobic drug and the strong temperature dependence of the partition equilibrium. A temperature increase of 10 degrees C reduces the paclitaxel solubility in the lipid phase by a factor of 4.
Dependence based prefetching for linked data structures (1998)

We introduce a dynamic scheme that captures the accesspat-terns of linked data structures and can be used to predict future accesses with high accuracy. Our technique exploits the dependence relationships that exist between loads that produce addresses and loads that consume these addresses. By identzj+ing producer-consumer pairs, we construct a compact internal representation for the associated structure and its traversal. To achieve a prefetching eflect, a small prefetch engine speculatively traverses this representation ahead of the executing program. Dependence-based prefetching achieves speedups of up to 25% on a suite of pointer-intensive programs.
Influence of theCCR2-V64IPolymorphism on Human Immunodeficiency Virus Type 1 Coreceptor Activity and on Chemokine Receptor Function of CCR2b, CCR3, CCR5, and CXCR4 (1998)

The chemokine receptors CCR5 and CXCR4 are used by human immunodeficiency virus type 1 (HIV-1) in conjunction with CD4 to infect cells. In addition, some virus strains can use alternative chemokine receptors, including CCR2b and CCR3, for infection. A polymorphism in CCR2 (CCR2-V64I) is associated with a 2- to 4-year delay in the progression to AIDS. To investigate the mechanism of this protective effect, we studied the expression of CCR2b and CCR2b-V64I, their chemokine and HIV-1 coreceptor activities, and their effects on the expression and receptor activities of the major HIV-1 coreceptors. CCR2b and CCR2b-V64I were expressed at similar levels, and neither molecule affected the expression or coreceptor activity of CCR3, CCR5, or CXCR4 in cotransfected cell lines. Peripheral blood mononuclear cells (PBMCs) from CCR2-V64I heterozygotes had normal levels of CCR2b and CCR5 but slightly reduced levels of CXCR4. CCR2b and CCR2b-V64I functioned equally well as HIV-1 coreceptors, and CCR2-V64I PBMCs were permissive for HIV-1 infection regardless of viral tropism. The MCP-1-induced calcium mobilization mediated by CCR2b signaling was unaffected by the polymorphism, but MCP-1 signaling mediated by either CCR2b- or CCR2-V64I-encoded receptors resulted in heterologous desensitization (i.e., limiting the signal response of other receptors) of both CCR5 and CXCR4. The heterologous desensitization of CCR5 and CXCR4 signaling by both CCR2 allele receptor types provides a mechanistic link that might help explain the in vivo effects of CCR2 gene variants on progression to AIDS as well as the reported antiviral activity of natural CCR2 ligands.
WHERE DID THE ANGER GO? THE ROLE OF CONTEXT IN INTERPRETING EMOTION IN SPEECH (2000)

Context has greater explanatory force regarding the perception of emotions in speech than any causative association we may attempt to make between phonetic features and psychological labels. Informants, when asked to judge whether a speaker sounds angry or not, make different decisions according to whether they hear utterances in-isolation or in-context. There was a strong tendency for ‘anger’ to be heard in the isolated extracts, but not in the ‘in-context’ forms.
Regulation of mouse CYP1A1 gene expression by dioxin: requirement of two cis-acting elements during induction. (1989)

The mouse cytochrome P1450 (CYP1A1) gene is responsible for the metabolism of numerous carcinogens and toxic chemicals. Induction by the environmental contaminant tetrachlorodibenzo-p-dioxin (TCDD) requires a functional aromatic hydrocarbon (Ah) receptor. We examined the 5'-flanking region of the CYP1A1 gene in mouse hepatoma Hepa-1 wild-type cells and a mutant line having a defect in chromatin binding of the TCDD-receptor complex. We identified two cis-acting elements (distal, -1071 to -901 region; proximal, -245 to -50 region) required for constitutive and TCDD-inducible CYP1A1 gene expression. Three classes of DNA-protein complexes binding to the distal element were identified: class I, found only in the presence of TCDD and a functional Ah receptor, that was heat labile and not competed against by simian virus 40 (SV40) early promoter DNA; class II, consisting of at least three constitutive complexes that were heat stable and bound to SV40 DNA; and class III, composed of at least three constitutive complexes that were thermolabile and were not competed against by SV40 DNA. Essential contacts for these proteins were centered at -993 to -990 for the class I complex, -987, -986, or both for the class II complexes, and -938 to -927 for the class III complexes. The proximal element was absolutely essential for both constitutive and TCDD-inducible CYP1A1 gene expression, and at least two constitutive complexes bound to this region. These data are consistent with the proximal element that binds proteins being necessary but not sufficient for inducible gene expression; interaction of these proteins with those at the distal element was found to be required for full CYP1A1 induction by TCDD.
Photochemistry of a 1,1-diazene, N-(2,2,5,5-tetramethylpyrrolidinyl)nitrene (1981)

The photochemistry of the 1,1-diazene has never been examined due to its transient nature. Several theoretical groups have calculated the order of the electronic states of the 1,1-diazene (aminonitrene, N-nitrene) during the past decade. Goddard's GVB-CI calculations of the parent H2N-N suggest a ground-state singlet with low-lying n,π* singlet (50.7 kcal) and triplet states (13.8 kcal) (Figure 1). The 1,1-diazene is isoelectronic with the carbonyl, a functional group whose photochemistry is well documented. The recent synthesis and characterization of persistent 1,1-diazenes allows an investigation of the photochemical reactivity of this species. We report the direct and sensitized irradiation of N-(2,2,5,5-tetramethylpyrrolidinyl)nitrene 1 in the visible region (n,π* transition) which reveal both unimolecular and bimolecular photoreactivity. In addition, the fluorescence spectrum of a 1,1-diazene has been obtained.
Identification of a novel antigenic structure of the human receptor for interleukin‐6 involved in the interaction with the glycoprotein 130 chain (1996)

The receptor for interleukin-6 (IL-6) is characterized by a ligand-binding glycoprotein 80 (gp80) transmembrane chain (IL-6R) which associates with a signal-transducer gp130 chain. We previously raised a series of monoclonal antibodies (mAb) recognizing different epitopes of the human IL-6R and interfering with the function of the receptor. One of them, M182, was able to diminish the proliferation of IL-6-dependent plasmacytoma cell lines although it was found unable to inhibit the binding of IL-6 to its receptor. Using an enzyme-linked immunosorbent assay for measuring the binding of IL-6 IL-6R to the gp130 chain, we showed that M182 was directed against a structure directly involved in the IL-6R gp130 interaction. M182 was able to potentiate the inhibitor effect of anti-IL-6R mAB which interfere with the binding of IL-6, leading to complete inhibition of the proliferation of IL-6-dependent cell lines. M182 was also found to synergize with inhibitory anti-IL-6 mAb. Therefore this structure appears to be an important regulatory domain of the IL-6R and a valuable target for inhibiting IL-6 signalling.
Allocation of Airline Seats between Stochastically Dependent Demands (1990)

This paper examines the problem of allocating airline seats between two nested fare classes when the demands for the classes are stochastically dependent. The well known simple seat allotment formula of Littlewood which requires the assumption of statistical independence between demands is generalized to a formula which requires only a much weaker monotonic association assumption. The model employed here is also used to examine the problems of full fare passenger spillage and passenger upgrades from the discount class.