gebhart/patrepeval huggingface dataset:
Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: A critical review of non-selective COX-2 blockade (Review) (2005)

We comprehensively reviewed the published scientific literature on non-steroidal anti-inflammatory drugs (NSAIDs) and cancer and evaluated results based upon epidemiologic criteria of judgment: consistency of results, strength of association, dose response, molecular specificity, and biological plausibility. Sufficient data from 91 epidemiologic studies were available to examine the dose response of relative risk and level of NSAID intake for ten human malignancies. Dose response curves were fitted by exponential regression. Results showed a significant exponential decline in the risk with increasing intake of NSAIDs (primarily aspirin or ibuprofen) for 7-10 malignancies including the four major types: colon, breast, lung, and prostate cancer. Daily intake of NSAIDs, primarily aspirin, produced risk reductions of 63% for colon, 39% for breast, 36% for lung, and 39% for prostate cancer. Significant risk reductions were also observed for esophageal (73%), stomach (62%), and ovarian cancer (47%). NSAID effects became apparent after five or more years of use and were stronger with longer duration. Observed protective effects were also consistently stronger for gastrointestinal malignancies (esophagus, stomach, and colon). Results for pancreatic, urinary bladder, and renal cancer were inconsistent. Initial epidemiologic studies of malignant melanoma, Hodgkin's disease, and adult leukemia also found that NSAIDs are protective. A few studies suggest that ibuprofen has stronger anticancer effects than aspirin, particularly against breast and lung cancer. Overexpression of cyclooxygenase-2 (COX-2) and increased prostaglandin biosynthesis correlates with carcinogenesis and metastasis at most anatomic sites. Preclinical investigations provide consistent evidence that both selective and non-selective NSAIDs effectively inhibit chemically-induced carcinogenesis of epithelial tumors. This review provides compelling and converging evidence that regular intake of NSAIDs that non-selectively block COX-2 protects against the development of many types of cancer.
Transforming Growth Factor β: Tumor Suppressor or Promoter? Are Host Immune Cells the Answer? (2008)

Therapies targeting transforming growth factor beta (TGFbeta) signaling using neutralizing antibodies and small molecular inhibitors are in multiple clinical trails. However, TGFbeta is known to work as both a tumor suppressor and a tumor promoter, and current knowledge does not provide sufficient information on what factors mediate this switch in function and when this switch occurs. Recent advances in multiple disciplines suggest that immune cells from the tumor host may provide the answer.
The role of human bromodomains in chromatin biology and gene transcription. (2009)

The acetylation of histone lysine is central to providing the dynamic regulation of chromatin-based gene transcription. The bromodomain (BRD), which is the conserved structural module in chromatin-associated proteins and histone acetyltranferases, is the sole protein domain known to recognize acetyl-lysine residues on proteins. Structural analyses of the recognition of lysine-acetylated peptides derived from histones and cellular proteins by BRDs have provided new insights into the differences between and unifying features of the selectivity that BRDs exhibit in binding biological ligands. Recent research has highlighted the importance of BRD/acetyl-lysine binding in orchestrating molecular interactions in chromatin biology and regulating gene transcription. These studies suggest that modulating BRD/acetyl-lysine interactions with small molecules may provide new opportunities for the control of gene expression in human health and disease.
Involvement of the Golgi Apparatus in the Synthesis and Secretion of Hydroxyproline-rich Cell Wall Glycoproteins (1975)

Pulse labeling of carrot root phloem parenchyma (Daucus carota L. cv. Nantes) tissue with (14)C-proline followed by fractionation of the cytoplasmic organelles on sucrose gradients was used to determine the identity of the membranous organelles involved in the secretion of the hydroxyproline-rich glycoproteins of the cell wall. Identification of the organelles was done through electron-microscopical observations and through the localization of marker enzymes on the sucrose gradients. Enrichment of the organelles involved in secretion was determined by measuring the percentage of the incorporated radioactivity present as (14)C-hydroxyproline. The Golgi apparatus (dictyosome) was found to be a major site of glycoprotein transport. This identification was based on the observed enrichment of dictyosomes paralleling the purification of newly synthesized cell-wall glycoproteins. A marker enzyme for the Golgi apparatus, inosinediphosphatase, banded with the newly synthesized cell wall glycoproteins on sequential isopycnic and rate zonal sucrose gradients. Marker enzymes for the endoplasmic reticulum and the plasma membrane were clearly separated from the dictyosome-rich fraction. UDP-arabinose arabinosyl transferase, an enzyme involved in the glycosylation of the peptide moiety of this glycoprotein, also banded with the dictyosomes on both kinds of gradients. The results suggest an important role of the Golgi apparatus in the biosynthesis and the secretion of the cell wall glycoproteins of higher plants.
Solid phase microextraction of pesticide residues from strawberries (1999)

A new solid phase microextraction method for the determination of pesticide residues in strawberries for 16 commonly used compounds was described. The strawberries were crushed and centrifuged. An aliquot of the well agitated aqueous supernatant (4 ml) was extracted with a fibre coated with polydimethylsiloxane (PDMS, 100 microns) for 45 min at room temperature. Identification and quantification were achieved using a gas chromatography-mass spectrometry (GC-MS) system and selective ion monitoring (SIM). The method was tested for the following pesticides: carbofuran, diethofencarb, penconazole, hexaconazole, metalaxyl, folpet, bromopropylate, dichlofluanid, alpha-endosulfan, beta-endosulfan, parathion ethyl, procymidone, iprodione, vinclozolin, myclobutanil and chlorothalonil. Limits of detection, repeatability and linearity for standard calibration in strawberries were obtained. Positive and negative effects of the matrix between the extracting solution of strawberries and water were observed. Stabilities of these compounds in the extracting solution of strawberries were determined. The solvent-free SPME procedure was found to be quicker and more cost effective than the solvent extraction methods commonly used.
Cloning and expression of the recombinant FAb fragment of monoclonal antibody K1 that reacts with mesothelin present on mesotheliomas and ovarian cancers (1997)

The monoclonal antibody (MAb) K1 recognizes an approximate 40 kDa glycoprotein, mesothelin, that is present on the surface of human mesothelial cells, mesotheliomas and ovarian cancers. We have cloned the cDNAs encoding the variable regions of MAb K1 and constructed plasmids for expression of recombinant K1(FAb). Recombinant FAb was produced in Escherichia coli in inclusion bodies that were solubilized and refolded to active protein. Binding of K1 MAb and FAb was compared by radioactive binding and competition assays and by surface plasmon resonance (BIAcore). Recombinant K1(FAb) binds to cells expressing K1-antigen with a similar affinity as papain derived FAb from K1(IgG) and with a 4- to 10-fold reduced affinity compared with bivalent IgG. The cloned FAb can be used to make higher affinity antibodies and immunoconjugates that could be useful for various types of immunotherapies.
ALK Fusion Partners Impact Response to ALK Inhibition: Differential Effects on Sensitivity, Cellular Phenotypes, and Biochemical Properties (2018)

Oncogenic tyrosine kinase fusions involving the anaplastic lymphoma kinase (ALK) are detected in numerous tumor types. Although more than 30 distinct 5' fusion partner genes have been reported, treatment of <i>ALK</i>-rearranged cancers is decided without regard to which 5' partner is present. There is little data addressing how the 5' partner affects the biology of the fusion or responsiveness to ALK tyrosine kinase inhibitors (TKI). On the basis of the hypothesis that the 5' partner influences the intrinsic properties of the fusion protein, cellular functions that impact oncogenic potential, and sensitivity to ALK TKIs, clonal 3T3 cell lines stably expressing seven different ALK fusion variants were generated. Biochemical and cellular assays were used to assess the efficacy of various ALK TKIs in clinical use, transformative phenotypes, and biochemical properties of each fusion. All seven ALK fusions induced focus formation and colonies in soft agar, albeit to varying degrees. IC<sub>50</sub>s were calculated for different ALK TKIs (crizotinib, ensartinib, alectinib, lorlatinib) and consistent differences (5-10 fold) in drug sensitivity were noted across the seven ALK fusions tested. Finally, biochemical analyses revealed negative correlations between kinase activity and protein stability. These results demonstrate that the 5' fusion partner plays an important biological role that affects sensitivity to ALK TKIs.<b>Implications:</b> This study shows that the 5' ALK fusion partner influences ALK TKI drug sensitivity. As many other kinase fusions are found in numerous cancers, often with overlapping fusion partners, these studies have ramifications for other kinase-driven malignancies. <i>Mol Cancer Res; 16(11); 1724-36. ©2018 AACR</i>.
A locality preserving routing overlay using geographic coordinates (2009)

This paper presents a design for a general locality preserving routing overlay network based on geographic coordinates of nodes. For efficient use of network resources, it is important to follow some locality principles while routing bulk multimedia content. The proposed overlay network creates the interconnection among large number of highly dynamic nodes in a completely decentralized manner, based on adaptive hierarchical partitioning of the geographical space. A major benefit of using coarse grain geographic coordinates is that they are available at off-the-shelf databases and thus do not incur additional measurement overhead. The performance of the proposed geography based routing overlay, in terms of two locality properties - stretch and route-convergence, is evaluated by simulation studies. Real topology data of 65 ISPs with presence in 534 cities across the world, collected by the RocketFuel project, is used as the basis of the simulated network. The performance results are compared with corresponding results obtained from a simulated Pastry overlay constructed on the same underlying network. The performance results show that proposed overlay has significantly better stretch and route-convergence characteristics compared to a regular Pastry network. The locality properties of the proposed routing overlay are almost equivalent to those of an optimal Pastry network where all nodes use the most proximal neighbor for each routing table row. Thus the proposed geographical routing network provides good locality properties without the overhead of proximity neighbor selection. Moreover, the proposed scheme facilitates certain geographical search applications that are difficult to realize in a Pastry overlay.
Coronary blood flow in left ventricular hypertrophy: a review of experimental data (1982)

Journal Article Coronary blood flow in left ventricular hypertrophy: a review of experimental data Get access P. Wicker, P. Wicker Cleveland Clinic Foundation, Research DivisionCleveland, Ohio, U.S.A. Requests for reprints to: Pierre Wicker, Hopital Cardiologique, Avenue de Magellan, 33604 Pessac, France. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. C. Tarazi R. C. Tarazi Cleveland Clinic Foundation, Research DivisionCleveland, Ohio, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, Volume 3, Issue suppl_A, January 1982, Pages 111–118, https://doi.org/10.1093/eurheartj/3.suppl_A.111 Published: 01 June 1982
Secondary Lymphoid-tissue Chemokine Is a Functional Ligand for the CC Chemokine Receptor CCR7 (1998)

Secondary Lymphoid-tissue Chemokine (SLC) is a recently identified CC chemokine that is constitutively expressed in various lymphoid tissues and is a potent and specific chemoattractant for lymphocytes. The SLC gene and the gene encoding another lymphocyte-specific CC chemokine, EBI1-ligand chemokine (ELC), form a mini-cluster at human chromosome 9p13. Here, we show that SLC is a high affinity functional ligand for chemokine receptor 7 (CCR7) that is expressed on T and B lymphocytes and a known receptor for ELC. SLC induced a vigorous calcium mobilization in murine L1.2 cells stably expressing human CCR7. SLC tagged with the secreted form of alkaline phosphatase (SLC-SEAP) showed specific binding to CCR7 that was fully competed by SLC with an IC50 of 0.5 nM. SLC also induced a vigorous chemotactic response in CCR7-expressing L1.2 cells with a typical bell-shaped dose-response curve and a maximal migration at 10 nM. When assessed using CCR7-transfected L1.2 cells, SLC and ELC were essentially equivalent in terms of cross desensitization in calcium mobilization via CCR7, cross-competition in binding to CCR7, and induction of chemotaxis via CCR7. SLC and ELC were also shown to fully share receptors expressed on cultured normal T cells known to express CCR7. Notably, however, SLC was somehow less efficient in cross-desensitization against ELC in calcium mobilization and in cross-competition with ELC for binding when assessed using cultured normal T cells. Thus, SLC and ELC, even though sharing only 32% amino acid identity, constitute a genetically and functionally highly related subgroup of CC chemokines.
Detecting objects in image sequences using rule-based control in an active contour model (2003)

A method is presented for tracking object boundaries in sequential images using an active contour model, based on fuzzy reasoning rule-based control. Evolution of contour segments is controlled by separate processes based on whether the segment is judged to be inside, outside, or near the boundary of the object, leading to robust boundary detection.
Dynamic Developmental Elaboration of N-Linked Glycan Complexity in the Drosophila melanogaster Embryo (2007)

The structural diversity of glycoprotein N-linked oligosaccharides is determined by the expression and regulation of glycosyltransferase activities and by the availability of the appropriate acceptor/donor substrates. Cells in different tissues and in different developmental stages utilize these control points to manifest unique glycan expression patterns in response to their surroundings. The activity of a Toll-like receptor, called Tollo/Toll-8, induces a pattern of incompletely defined, but neural specific, glycan expression in the Drosophila embryo. Understanding the full extent of the changes in glycan expression that result from altered Tollo/Toll-8 signaling requires characterization of the complete N-linked glycan profile of both wild-type and mutant embryos. N-Linked glycans harvested from wild-type or mutant embryos were subjected to direct structural analysis by analytic and preparative high pressure liquid chromatography, by multidimensional mass spectrometry, and by exoglycosidase digestion, revealing a predominance of high mannose and paucimannose glycans. Di-, mono-, and nonfucosylated forms of hybrid, complex biantennary, and triantennary glycans account for 12% of the total wild-type glycan profile. Two sialylated glycans bearing N-acetylneuraminic acid were detected, the first direct demonstration of this modification in Drosophila. Glycan profiles change during normal development consistent with increasing alpha-mannosidase II and core fucosyl-transferase enzyme activities, and with decreasing activity of the Fused lobes processing hexosaminidase. In tollo/toll-8 mutants, a dramatic, expected loss of difucosylated glycans is accompanied by unexpected decreases in monofucosylated and nonfucosylated hybrid glycans and increases in some nonfucosylated paucimannose and biantennary glycans. Therefore, tollo/toll-8 signaling influences flux through several processing steps that affect the maturation of N-linked glycans.
Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney. (1995)

Natriuretic peptide receptor B (ANP-RGC(B)) has been previously identified in the kidney. It binds C-type natriuretic peptide (CNP) with high affinity and the two other natriuretic peptides (atrial natriuretic peptide and brain natriuretic peptide) with low affinity, and mediates the biological effects of CNP. The purpose of this investigation was to identify sites of ANP-RGC(B) mRNA in the rat renal tubule and to confirm that CNP itself is synthesized in the rat kidney. Kidneys from male Sprague-Dawley rats were removed and divided into cortex, outer medulla, and inner medulla. Using reverse transcriptase and polymerase chain reaction techniques, ANP-RGC(B) mRNA was identified in the three principal regions of the kidney. Individual glomeruli and segments of the renal tubule were microdissected and subjected to reverse transcriptase-polymerase chain reaction. ANP-RGC(B) mRNA was regularly found (>60% of animals) in glomeruli, distal convoluted tubule, and cortical, outer medullary, and inner medullary tubules but not in the proximal convoluted tubule, proximal straight tubule, thin or medullary thick ascending limb. ANP-RGC(B) mRNA was also identified in outer medullary descending vasa recta. Glyceraldehyde-3-phosphate-dehydrogenase and natriuretic peptide A receptor mRNA were present in all segments. In a separate study, CNP mRNA was identified in whole kidney, cortex, and medulla. These findings confirm that CNP and its receptor are present in the rat kidney. The proximity of the ligand and receptor suggests that CNP may have paracrine or autocrine regulatory functions in the rat kidney.
A 30-MHz hybrid analog/digital clock recovery circuit in 2- mu m CMOS (1990)

A high-speed hybrid clock recovery circuit composed of an analog phase-locked loop (PLL) and a digital PLL (DPLL) for disk drive applications is described. The chip operates at a maximum data rate of 33 MHz from a single 5-V power supply and achieves fast acquisition, a decode window of 95% of full window width, effective sampling jitter of 100-ps rms, and an effective input sampling rate of 1 GHz. The ring oscillator in the analog PLL shows a 62 p.p.m./ degrees C temperature coefficient (TC) and 4.5%/V supply sensitivity of free-running frequency. The total power dissipation is about 600 mW, and the active area is 30000 mil/sup 2/ in a 2- mu m single-poly double-metal n-well CMOS process.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Product Metrics for Automatic Identification of "Bad Smell" Design Problems in Java Source-Code (2005)

Refactoring can have a direct influence on reducing the cost of software maintenance through changing the internal structure of the source-code to improve the overall design that helps the present and future programmers evolve and understand a system. Bad smells are a set of design problems with refactoring identified as a solution. Locating these bad smells has been described as more a human intuition than an exact science. This paper addresses the issue of identifying the characteristics of a bad smell through the use of a set of software metrics. Then by using a pre-defined set of interpretation rules to interpret the software metric results applied to Java source-code, the software engineer can be provided with significant guidance as to the location of bad smells. These issues are addressed in a number of ways. Firstly, a precise definition of bad smells is given from the informal descriptions given by the originators Fowler and Beck. The characteristics of the bad smells have been used to define a set of measurements and interpretation rules for a subset of the bad smells. A prototype tool has been implemented to enable the evaluation of the interpretation rules in two case studies.
A phase I clinical trial of immunotherapy with interferon-? gene-modified autologous melanoma cells (1997)

These data suggest that gene therapy with IFN-gamma-transduced melanoma cells is safe and worthy of further investigation in patients with less advanced stage malignant melanoma. The ability to monitor changes in the humoral responses of the immunized patients has been demonstrated.
Effect of dietary n-6-to-n-3 fatty acid ratio on complete blood and total white blood cell counts, and T-cell subpopulations in aged dogs (1999)

Feeding a diet with n-6-to-n-3 FA ratio of 1.4:1 had significant effects on CD4+ T lymphocytes in healthy, aged Beagles after vaccination.
Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice (2009)

Increasing interest in the use of phytochemicals to reduce prostate cancer led us to investigate 2 potential agents, curcumin and resveratrol as preventive agents. However, there is concern about the bioavailability of these agents pertinent to the poor absorption and thereby limiting its clinical use. With the view to improve their bioavailability, we used the liposome encapsulated curcumin, and resveratrol individually and in combination in male B6C3F1/J mice. Further, we examined the chemopreventive effect of liposome encapsulated curcumin and resveratrol in combination in prostate-specific PTEN knockout mice. In vitro assays using PTEN-CaP8 cancer cells were performed to investigate the combined effects curcumin with resveratrol on (i) cell growth, apoptosis and cell cycle (ii) impact on activated p-Akt, cyclin D1, m-TOR and androgen receptor (AR) proteins involved in tumor progression. HPLC analysis of serum and prostate tissues showed a significant increase in curcumin level when liposome encapsulated curcumin coadministered with liposomal resveratrol (p < 0.001). Combination of liposomal forms of curcumin and resveratrol significantly decreased prostatic adenocarcinoma in vivo (p < 0.001). In vitro studies revealed that curcumin plus resveratrol effectively inhibit cell growth and induced apoptosis. Molecular targets activated due to the loss of phosphatase and tensin homolog (PTEN) including p-Akt, cyclin D1, mammalian target of rapamycin and AR were downregulated by these agents in combination. Findings from this study for the first time provide evidence on phytochemicals in combination to enhance chemopreventive efficacy in prostate cancer. These findings clearly suggest that phytochemicals in combination may reduce prostate cancer incidence due to the loss of the tumor suppressor gene PTEN.
Optical properties near the band gap on hexagonal and cubic GaN (1994)

We have measured the photoluminescence and optical reflection spectra of cubic and hexagonal GaN films epitaxially grown on GaAs and 3C-SiC substrates by gas-source molecular beam epitaxy using microwave-activated NH3 source. The crystalline quality of the epilayers was improved by using an activated NH3 beam and 3C-SiC substrates, which enabled us to obtain intense optical signals. The measured spectra suggest that the band gap of cubic GaN is around 190 meV smaller than that of hexagonal GaN.