gebhart/patrepeval huggingface dataset:
Bioactivity of Turmeric-derived Curcuminoids and Related Metabolites in Breast Cancer (2013)

While the chemotherapeutic effect of curcumin, one of three major curcuminoids derived from turmeric, has been reported, largely unexplored are the effects of complex turmeric extracts more analogous to traditional medicinal preparations, as well as the relative importance of the three curcuminoids and their metabolites as anti-cancer agents. These studies document the pharmacodynamic effects of chemically-complex turmeric extracts relative to curcuminoids on human breast cancer cell growth and tumor cell secretion of parathyroid hormone-related protein (PTHrP), an important driver of cancer bone metastasis. Finally, relative effects of structurallyrelated metabolites of curcuminoids were assessed on the same endpoints. We report that 3 curcuminoid-containing turmeric extracts differing with respect to the inclusion of additional naturally occurring chemicals (essential oils and/or polar compounds) were equipotent in inhibiting human breast cancer MDA-MB-231 cell growth (IC50=10-16µg/mL) and secretion of osteolytic PTHrP (IC50=2-3µg/mL) when concentrations were normalized to curcuminoid content. Moreover, these effects were curcuminoid-specific, as botanically-related gingerol containing extracts had no effect. While curcumin and bis-demethoxycurcumin were equipotent to each other and to the naturally occurring curcuminoid mixture (IC50=58µM), demethoxycurcumin did not have any effect on cell growth. However, each of the individual curcuminoids inhibited PTHrP secretion (IC50=22-31µM) to the same degree as the curcuminoid mixture (IC50=16µM). Degradative curcuminoid metabolites (vanillin and ferulic acid) did not inhibit cell growth or PTHrP, while reduced metabolites (tetrahydrocurcuminoids) had inhibitory effects on cell growth and PTHrP secretion but only at concentrations ≥10-fold higher than the curcuminoids. These studies emphasize the structural and biological importance of curcuminoids in the anti-breast cancer effects of turmeric and contradict recent assertions that certain of the curcuminoid metabolites studied here mediate these anti-cancer effects.
Synovial Tissue Response to Treatment with TNF Blockers in Peripheral Spondyloarthritis (2011)

This review describes the synovial response to treatment in peripheral spondyloarthritis (SpA). A series of recent studies demonstrates that the synovial histopathology is largely homogenous between different SpA subtypes and can be strongly modulated by effective treatment such as tumor necrosis factor (TNF) blockade. This includes a dramatic reduction of the infiltration with inflammatory cells (with the intriguing exception of B lymphocytes and plasma cells), a modulation of structural features such as vascularity, intimal lining layer hyperplasia, and ectopic lymphoid neogenesis, and a down-regulation of a variety of mediators involved in tissue damage. The analysis of tissue response to targeted therapies appears to be a novel and elegant approach to study the immunopathology of human peripheral SpA in vivo. Moreover, detailed cellular and molecular analysis of synovial features allows to identify synovial biomarkers of clinical response to therapeutic interventions which can be used in future early phase clinical trials in SpA.
Tyrphostins. II. Heterocyclic and .alpha.-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases (1991)

We have previously described a novel series of low molecular weight protein tyrosine kinase inhibitors which we named tyrphostins. The characteristic active pharmacophore of these compounds was the hydroxy-cis-benzylidenemalononitrile moiety. In this article we describe three novel groups of tyrphostins: (i) one group has the phenolic moiety of the cis-benzylidenemalononitrile replaced either with other substituted benzenes or with heteroaromatic rings, (ii) another is a series of conformationally constrained derivatives of hydroxy-cis-benzylidenemalononitriles in which the malononitrile moiety is fixed relative to the aromatic ring, and (iii) two groups of compounds in which the position trans to the benzenemalononitrile has been substituted by ketones and amides. Among the novel tyrphostins examined we found inhibitors which discriminate between the highly homologous EGF receptor kinase (HER1) and ErbB2/neu kinase (HER2). These findings may lead to selective tyrosine kinase blockers for the treatment of diseases in which ErbB2/neu is involved.
Browsing graphs using a fisheye view (abstract) (1993)

No abstract available.
Atomic-Scale Imaging and Spectroscopy for In Situ Liquid Scanning Transmission Electron Microscopy (2012)

Observation of growth, synthesis, dynamics, and electrochemical reactions in the liquid state is an important yet largely unstudied aspect of nanotechnology. The only techniques that can potentially provide the insights necessary to advance our understanding of these mechanisms is simultaneous atomic-scale imaging and quantitative chemical analysis (through spectroscopy) under environmental conditions in the transmission electron microscope. In this study we describe the experimental and technical conditions necessary to obtain electron energy loss (EEL) spectra from a nanoparticle in colloidal suspension using aberration-corrected scanning transmission electron microscopy (STEM) combined with the environmental liquid stage. At a fluid path length below 400 nm, atomic resolution images can be obtained and simultaneous compositional analysis can be achieved. We show that EEL spectroscopy can be used to quantify the total fluid path length around the nanoparticle and demonstrate that characteristic core-loss signals from the suspended nanoparticles can be resolved and analyzed to provide information on the local interfacial chemistry with the surrounding environment. The combined approach using aberration-corrected STEM and EEL spectra with the in situ fluid stage demonstrates a plenary platform for detailed investigations of solution-based catalysis.
Strategies for the Use of Mixture-Based Synthetic Combinatorial Libraries: Scaffold Ranking, Direct Testing In Vivo, and Enhanced Deconvolution by Computational Methods (2007)

ADVERTISEMENT RETURN TO ISSUEPREVAccountsNEXTStrategies for the Use of Mixture-Based Synthetic Combinatorial Libraries: Scaffold Ranking, Direct Testing In Vivo, and Enhanced Deconvolution by Computational MethodsRichard A. Houghten*†, Clemencia Pinilla†, Marc A. Giulianotti†, Jon R. Appel†, Colette T. Dooley†, Adel Nefzi†, John M. Ostresh†, Yongping Yu⊥†, Gerald M. Maggiora‡, Jose L. Medina-Franco‡, Daniela Brunner§, and Jeff Schneider§∥View Author Information Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California 92121, BIO5 Institute and College of Pharmacy, University of Arizona, Tucson, Arizona 85721, PsychoGenics, Inc., 765 Old Saw Mill River Road, Tarrytown, New York 10591, and School of Computer Science, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213* To whom correspondence should be addressed. Phone: 858-455-3805 . Fax: 858-455-3804. E-mail: [email protected]†Torrey Pines Institute for Molecular Studies.‡University of Arizona.§PsychoGenics, Inc.∥Carnegie Mellon University.⊥Current address: College of Pharmaceutical Science, Zijin Campus, Zhejiang University, Hangzhou 310058, P. R. China.Cite this: J. Comb. Chem. 2008, 10, 1, 3–19Publication Date (Web):December 8, 2007Publication History Received19 July 2007Published online8 December 2007Published inissue 1 January 2008https://pubs.acs.org/doi/10.1021/cc7001205https://doi.org/10.1021/cc7001205review-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views1161Altmetric-Citations100LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Assays,Drug discovery,Mixtures,Peptides and proteins,Scaffolds Get e-Alerts
Evaluation of new x-ray stepper, the XRA (2001)

The exposure performance has been evaluated for the new x-ray stepper, the XRA, which is equipped with global alignment and magnification correction systems. Dose uniformity in the exposure field of 3.9%, stage accuracy of less than 20 nm, and good linearity and stability between the magnification change and applied force were obtained. For the 100 nm node, both critical dimension (CD) control of 10 nm and overlay accuracy of less than 30 nm were obtained using two 4 Gbit masks of the gate and contact hole by the double exposure method. Possible improvements of the dose uniformity and mask pattern CD will result in more accurate CD control. By compensating for the alignment offset, overlay accuracy of 23 nm for the 70 nm node is also expected.
An optimality test for semi-infinite linear programming (1992)

In this paper we present a test to characterize the optimal solutions for the continuous semi-infinite linear programming problem. This optimality characterization is a condition of Kuhn–Tucker type. The resolution of a linear program permits to check the optimality of a feasible point,to detect the unboundedness of the problem and to find descent directions. We give some illustrative examples. We show that the local Mangasarian–Fromovitz constraint qualification is almost equivalent to Slater qualification for this problem. Furthermore, it follows from our study that this optimality condition is always necessary for a wide class of semi-infinite linear programming problems
Severity and Mortality of Experimental Pancreatitis Are Dependent on Interleukin-1 Converting Enzyme (ICE) (1997)

Interleukin-1 beta (IL-1 beta) is produced in large amounts during acute pancreatitis and is believed to play a role in disease progression. Because secretion of IL-1 beta is dependent on intracellular processing of pro-IL-1 beta by IL-1 converting enzyme (ICE), we aimed to determine the efficacy of a novel ICE inactivator (VE-13045) in inhibiting secretion of active IL-1 beta in vivo and if the loss of ICE activity would affect the severity and mortality of experimental pancreatitis. Severe hemorrhagic pancreatitis was induced in adult rats by infusion of bile acid into the pancreatic duct. Animals were randomized to receive VE-13045 or vehicle before induction of pancreatitis. To confirm our findings and to ensure that the results were not model dependent, a second series of experiments was conducted using mice possessing a homozygous knockout of the ICE gene in which lethal pancreatitis was induced by feeding a choline-deficient, ethionine-supplemented diet. The severity of pancreatitis was assessed for both experiments by standard surrogate markers, blind histologic grading, and serum IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) levels. Pancreatic IL-1 beta mRNA induction was assessed by differential RT-PCR. Acute pancreatitis was associated with a 120-fold increase in IL-1 beta mRNA, which was not affected by ICE inhibition or gene deletion. Cytokine processing and secretion were affected, as evidenced by decreased serum levels of IL-1 beta and TNF-alpha (p < 0.001) in all animals with an inactive ICE enzyme. This lack of cytokine production increased survival from 32% to 78% following bile salt pancreatitis (p < 0.01) and from 24% to 80% following diet-induced pancreatitis (p < 0.005). Both ICE-defective groups demonstrated decreased pancreatic necrosis, edema, inflammation, wet weight (all p < 0.05), and amylase and lipase (p < 0.01). In vivo blockade or genetic deletion of ICE inhibits pancreatitis-induced secretion of proinflammatory cytokines without altering IL-1 mRNA production and is associated with decreased pancreatitis severity and dramatic survival benefits.
Novel oxime derivatives of radicicol induce erythroid differentiation associated with preferential G1 phase accumulation against chronic myelogenous leukemia cells through destabilization of Bcr-Abl with Hsp90 complex (2000)

Chronic myelogenous leukemia (CML) is a clonal disorder of a pluripotent hematopoietic stem cells characterized by a chimeric bcr-abl gene giving rise to a p210(Bcr-Abl) protein with dysregulated tyrosine kinase activity. Radicicol, a macrocyclic antifungal antibiotic, binds to the N-terminal of heat shock protein 90 (Hsp90) and destabilizes Hsp90-associated proteins such as Raf-1. This study investigated the effect of radicicol, novel oxime derivatives of radicicol (KF25706 and KF58333), and herbimycin A (HA), a benzoquinoid ansamycin antibiotic, on the growth and differentiation of human K562 CML cells. Although KF25706 and KF58333 induced the expression of glycophorin A in K562 cells, radicicol and HA caused erythroid differentiation transiently. Cell cycle analysis showed that G(1) phase accumulation was observed in K562 cells treated with KF58333. KF58333 treatment depleted p210(Bcr-Abl), Raf-1, and cellular tyrosine phosphorylated proteins in K562 cells, whereas radicicol and HA showed transient depletion of these proteins. KF58333 also down-regulated the level of cell cycle-dependent kinases 4 and 6 and up-regulated cell cycle-dependent kinase inhibitor p27(Kip1) protein without an effect on the level of Erk and Hsp90 proteins. Immunoprecipitation analysis showed that p210(Bcr-Abl) formed multiple complexes with Hsp90, some containing p23 and others Hsp70; KF58333 treatment dissociated p210(Bcr-Abl) from Hsp90/p23 chaperone complexes. Furthermore, KF58333 induced apoptosis in K562 cells and administration of KF58333 prolonged the survival time of SCID mice inoculated with K562 cells. These results suggest that KF58333 may have therapeutic potential for the treatment of CML that involves abnormal cellular proliferation induced by p210(Bcr-Abl).
Insulin-like growth factor (IGF)-I and -II and IGF binding proteins in serum and mammary secretions during the dry period and early lactation in dairy cows. (1991)

Concentrations of IGF-I and IGF-II, and IGF binding proteins (IGFBP) in serum and mammary gland secretions were surveyed during the dry period and early lactation of 30 Holstein cows. Although there was a threefold drop in the concentration of IGF-I in serum from the last week of the dry period to parturition (81 +/- 7 to 24 +/- 3 ng/ml, P less than .01), there was no significant change in serum IGF-II concentration during this period (150 +/- 17 vs 173 +/- 13 ng/ml, P greater than .05). Furthermore, a 57% increase in serum IGF-I was observed from the last week of lactation to the second week of drying off (100 +/- 5 to 157 +/- 8 ng/ml, P less than .05). Changes in serum IGF-II were not observed (126 +/- 11 vs 150 +/- 10 ng/ml, respectively; P greater than .05). Although IGF-I, IGF-II, and IGFBP concentrations in mammary secretions peaked 2 wk before parturition (2.95 +/- 1.1, 1.83 +/- .6, and 7.27 +/- .76 micrograms/ml, respectively), total output/quarter was highest in colostrum (394 +/- 119, 295 +/- 132, and 2,680 +/- 1,967 micrograms/quarter, respectively). Weekly milking of two individual quarters during the dry period did not affect (P greater than .05) IGF-I or IGF-II concentration (ng/ml) or total output (microgram/quarter) and milk yield in colostrum and milk (2 wk and 7 wk) compared with the ipsilateral quarter. The data support the hypothesis that IGF-I may be transported by the mammary gland epithelium. Furthermore, the secretion mechanisms of IGF-I, IGF-II, and IGFBP by the gland may be related to each other.
Efficiency of High-Sensitivity Gear Trains, Such as Cycloid Drives (2013)

Compact, high torque ratio, high efficiency transmissions are required in many applications, such as robotics. However, compact size and high torque ratios often come at the expense of surprisingly low efficiency. Here we apply Del Castillo's sensitivity framework (Del Castillo, J. M., 2002, “The Analytical Expression of the Efficiency of Planetary Gear Trains,” Mech. Mach. Theory, 37(2), pp. 197–214) to explain the low efficiency of a subset of transmissions that exploit small differences in tooth number between gears to generate high torque ratios. We add adjustment factors for several transmissions within this category, such as cycloids and harmonic drives; demonstrate that the models match empirical results for the case of cycloids across a range of torque ratios, topologies, and roller conditions; and compare and optimize the topologies of the various mechanisms. We demonstrate that for this subset of transmissions, the efficiency approaches a function of the torque ratio.
Pyridines and pyridinium salts from cyanoacetamides (1976)

Self-condensation of cyanoacetamides under the influence of phosphorus oxychloride leads to pyridines and pyridinium salts in high yield. The mechanism of the reaction is discussed and evidence for the structure of the products is described. The chemical activity of the new pyridine derivatives has been briefly explored.
Treatment response with transurethral microwave hyperthermia in different forms of benign prostatic hyperplasia: A preliminary report (1991)

During a 7-month period, 79 patients with benign prostatic hyperplasia (BPH) were treated with 915 MHz transurethral hyperthermia (TUHT). All patients had obstructive and irritative signs and symptoms which warranted surgical treatment considerations. Of the 79 patients treated, 31 had follow-ups of 12 months or longer and seven additional patients experienced treatment failure requiring surgical management. These 38 patients were studied to evaluate the relationship of treatment response to the pretreatment prostatic morphology assessed during cystoscopy. There was a well-balanced distribution of patients regarding the important pretreatment characteristics in different morphological types of prostatic hypertrophy. These important characteristics included: prostate volume, postvoiding residual volume, mean peak flow rate, and mean symptom score on the FDA scale. The study patients were scheduled to receive five 60-min TUHT sessions with temperature controlled on the urethral surface at 45.5 degrees C. The treatment were well tolerated and administered on an outpatient basis without sedation or anesthesia. There was a significant difference in the incidence of major improvement in patients with lateral lobe hyperplasia and those with median lobe enlargement, 73 vs. 30%, P = 0.018. From this study, it appears that BPH patients who are found at cystoscopy to have a predominance of median lobe hypertrophy should, perhaps, be selected for treatment other than TUHT. A Phase I study utilizing a modified transurethral applicator to accommodate the specific problem of patients with median lobe hyperplasia is currently being planned.
Cdc42 - the centre of polarity (2004)

All cell types polarize, at least transiently, during division or to generate specialized shapes and functions. This capacity extends from yeast to mammals, and it is now clear that many features of the molecular mechanisms controlling polarization are conserved in all eukaryotic cells. At the centre of the action is Cdc42, a small GTPase of the Rho family. Its activity is precisely controlled both temporally and spatially, and this can be achieved by a wide variety of extracellular cues in multicellular organisms. Moreover, although the functional characteristics of cell polarity are extremely variable (depending on the cell type and the biological context), Cdc42 has an amazing capacity to co-ordinate the control of multiple signal transduction pathways.
Natural killer cells in human autoimmune diseases (2010)

Natural killer (NK) cells have been implicated in tumour surveillance and in the early control of several microbial infections. In autoimmune disease their involvement in these processes has been evaluated in animal models, with conflicting results. Both a disease-controlling and a disease-promoting role have been suggested. In human autoimmune disease only a few studies, mainly descriptive, have demonstrated qualitative and quantitative modification of NK cells. These changes were observed on blood- or tissue-infiltrating NK cells. Taken together with our expanding knowledge of the genetical variability of NK cell receptors and NK cell physiology, these findings pave the way for the dissection of the role of NK cells in human autoimmune diseases. NK cells may be directly involved in these diseases through their potential autoreactivity or through their interaction with dendritic cells, macrophages or T lymphocytes, thereby inducing excessive inflammation or favouring the adaptive autoimmune response. Thus, NK cells may be implicated in the onset, the maintenance or the progression of autoimmune diseases. Some reports also suggest the involvement of NK cells in the treatment of human autoimmune disease by biotherapies. All these observations suggest that NK cells are involved in the complex processes of autoimmune diseases. Nevertheless, further careful analysis of NK cells at different steps of these diseases, in different tissues and through combined genetical and functional studies will contribute to a better understanding of their role in autoimmune diseases. This knowledge might allow the development of new therapeutic strategies based on NK cells for the treatment of some autoimmune diseases.
Testosterone Treatment and Mortality in Men with Low Testosterone Levels (2012)

In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment. These results should be interpreted cautiously because residual confounding may still be a source of bias. Large, randomized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels.
Fuzzy control for wind response of guyed mast by MR damper (2005)

The strategy of two-input and single-output fuzzy control is adopted in vibrant control for wind response of guyed mast, and the simulated analysis of fuzzy control is done. The results indicate that fuzzy control strategy is effective in the vibrant control for wind response of guyed mast, and the effect of fuzzy control is better than that of Semi-active control which is based upon displacement.