gebhart/patrepeval huggingface dataset:
Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance (2008)

The epidermal growth factor receptor (EGFR) secondary kinase domain T790M non-small cell lung cancer (NSCLC) mutation enhances receptor catalytic activity and confers resistance to the reversible tyrosine kinase inhibitors gefitinib and erlotinib. Currently, irreversible inhibitors represent the primary approach in clinical use to circumvent resistance. We show that higher concentrations of the irreversible EGFR inhibitor CL-387,785 are required to inhibit EGFR phosphorylation in T790M-expressing cells compared with EGFR mutant NSCLC cells without T790M. Additionally, CL-387,785 does not fully suppress phosphorylation of other activated receptor tyrosine kinases (RTK) in T790M-expressing cells. These deficiencies result in residual Akt and mammalian target of rapamycin (mTOR) activities. Full suppression of EGFR-mediated signaling in T790M-expressing cells requires the combination of CL-387,785 and rapamycin. In contrast, Hsp90 inhibition overcomes these limitations in vitro and depletes cells of EGFR, other RTKs, and phospho-Akt and inhibits mTOR signaling whether or not T790M is present. EGFR-T790M-expressing cells rendered resistant to CL-387,785 by a kinase switch mechanism retain sensitivity to Hsp90 inhibition. Finally, Hsp90 inhibition causes regression in murine lung adenocarcinomas driven by mutant EGFR (L858R) with or without T790M. However, efficacy in the L858R-T790M model requires a more intense treatment schedule and responses were transient. Nonetheless, these findings suggest that Hsp90 inhibitors may be effective in T790M-expressing cells and offer an alternative therapeutic strategy for this subset of lung cancers.
Image information and visual quality (2006)

Measurement of visual quality is of fundamental importance to numerous image and video processing applications. The goal of quality assessment (QA) research is to design algorithms that can automatically assess the quality of images or videos in a perceptually consistent manner. Image QA algorithms generally interpret image quality as fidelity or similarity with a "reference" or "perfect" image in some perceptual space. Such "full-reference" QA methods attempt to achieve consistency in quality prediction by modeling salient physiological and psychovisual features of the human visual system (HVS), or by signal fidelity measures. In this paper, we approach the image QA problem as an information fidelity problem. Specifically, we propose to quantify the loss of image information to the distortion process and explore the relationship between image information and visual quality. QA systems are invariably involved with judging the visual quality of "natural" images and videos that are meant for "human consumption." Researchers have developed sophisticated models to capture the statistics of such natural signals. Using these models, we previously presented an information fidelity criterion for image QA that related image quality with the amount of information shared between a reference and a distorted image. In this paper, we propose an image information measure that quantifies the information that is present in the reference image and how much of this reference information can be extracted from the distorted image. Combining these two quantities, we propose a visual information fidelity measure for image QA. We validate the performance of our algorithm with an extensive subjective study involving 779 images and show that our method outperforms recent state-of-the-art image QA algorithms by a sizeable margin in our simulations. The code and the data from the subjective study are available at the LIVE website.
Effects of Aromatase Inhibition in Elderly Men with Low or Borderline-Low Serum Testosterone Levels (2004)

As men age, serum testosterone levels decrease, a factor that may contribute to some aspects of age-related physiological deterioration. Although androgen replacement has been shown to have beneficial effects in frankly hypogonadal men, its use in elderly men with borderline hypogonadism is controversial. Furthermore, current testosterone replacement methods have important limitations. We investigated the ability of the orally administered aromatase inhibitor, anastrozole, to increase endogenous testosterone production in 37 elderly men (aged 62-74 yr) with screening serum testosterone levels less than 350 ng/dl. Subjects were randomized in a double-blind fashion to the following 12-wk oral regimens: group 1: anastrozole 1 mg daily (n = 12); group 2: anastrozole 1 mg twice weekly (n = 11); and group 3: placebo daily (n = 14). Hormone levels, quality of life (MOS Short-Form Health Survey), sexual function (International Index of Erectile Function), benign prostate hyperplasia severity (American Urological Association Symptom Index Score), prostate-specific antigen, and measures of safety were compared among groups. Mean +/- SD bioavailable testosterone increased from 99 +/- 31 to 207 +/- 65 ng/dl in group 1 and from 115 +/- 37 to 178 +/- 55 ng/dl in group 2 (P < 0.001 vs. placebo for both groups and P = 0.054 group 1 vs. group 2). Total testosterone levels increased from 343 +/- 61 to 572 +/- 139 ng/dl in group 1 and from 397 +/- 106 to 520 +/- 91 ng/dl in group 2 (P < 0.001 vs. placebo for both groups and P = 0.012 group 1 vs. group 2). Serum estradiol levels decreased from 26 +/- 8 to 17 +/- 6 pg/ml in group 1 and from 27 +/- 8 to 17 +/- 5 pg/ml in group 2 (P < 0.001 vs. placebo for both groups and P = NS group 1 vs. group 2). Serum LH levels increased from 5.1 +/- 4.8 to 7.9 +/- 6.5 U/liter and from 4.1 +/- 1.6 to 7.2 +/- 2.8 U/liter in groups 1 and 2, respectively (P = 0.007 group 1 vs. placebo, P = 0.003 group 2 vs. placebo, and P = NS group 1 vs. group 2). Scores for hematocrit, MOS Short-Form Health Survey, International Index of Erectile Function, and American Urological Association Symptom Index Score did not change. Serum prostate-specific antigen levels increased in group 2 only (1.7 +/- 1.0 to 2.2 +/- 1.5 ng/ml, P = 0.031, compared with placebo). These data demonstrate that aromatase inhibition increases serum bioavailable and total testosterone levels to the youthful normal range in older men with mild hypogonadism. Serum estradiol levels decrease modestly but remain within the normal male range. The physiological consequences of these changes remain to be determined.
Edg-1, the G protein–coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation (2000)

Sphingolipid signaling pathways have been implicated in many critical cellular events. Sphingosine-1-phosphate (SPP), a sphingolipid metabolite found in high concentrations in platelets and blood, stimulates members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors and triggers diverse effects, including cell growth, survival, migration, and morphogenesis. To determine the in vivo functions of the SPP/Edg signaling pathway, we disrupted the Edg1 gene in mice. Edg1(-/-) mice exhibited embryonic hemorrhage leading to intrauterine death between E12.5 and E14.5. Vasculogenesis and angiogenesis appeared normal in the mutant embryos. However, vascular maturation was incomplete due to a deficiency of vascular smooth muscle cells/pericytes. We also show that Edg-1 mediates an SPP-induced migration response that is defective in mutant cells due to an inability to activate the small GTPase, Rac. Our data reveal Edg-1 to be the first G protein-coupled receptor required for blood vessel formation and show that sphingolipid signaling is essential during mammalian development.
1,3,4-Oxadiazole-Containing Polymers as Electron-Injection and Blue Electroluminescent Materials in Polymer Light-Emitting Diodes (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,3,4-Oxadiazole-Containing Polymers as Electron-Injection and Blue Electroluminescent Materials in Polymer Light-Emitting DiodesQ. Pei and Y. YangCite this: Chem. Mater. 1995, 7, 8, 1568–1575Publication Date (Print):August 1, 1995Publication History Published online1 May 2002Published inissue 1 August 1995https://pubs.acs.org/doi/10.1021/cm00056a025https://doi.org/10.1021/cm00056a025research-articleACS PublicationsRequest reuse permissionsArticle Views548Altmetric-Citations121LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Stereospecific Synthesis of Peptidyl .alpha.-Keto Amides as Inhibitors of Calpain (1994)

Peptidyl alpha-keto amides have been synthesized and tested as inhibitors of the cysteine protease calpain. A stereospecific synthesis was devised in which Cbz-dipeptidyl-alpha-hydroxy amides were oxidized with TEMPO/hypochlorite to the corresponding alpha-keto amides. This oxidation was accomplished in good yields and without epimerization of the chiral center adjacent to the ketone. The potent inhibition of porcine calpain I by the L,L diastereomers, combined with the poor inhibition by the L,D diastereomers, established the requirement for the all-L stereochemistry of the active inhibitor. The early lead inhibitors were very hydrophobic and, therefore, poorly soluble in aqueous solutions. Using the stereospecific route, new compounds were prepared with polar groups at the C- and N-termini. These modifications resulted in more soluble inhibitors that were still potent inhibitors of calpain. Studies of the stability of these alpha-keto amides showed that absolute stereochemistry can be maintained in acidic and unbuffered environments but general base-catalyzed epimerization of the chiral center adjacent to the ketone occurred rapidly. The alpha-hydroxy precursors were inactive as inhibitors of calpain, which supports the hypothesis that the alpha-keto compounds reversibly form an enzyme-bound tetrahedral species that results from the nucleophilic addition of the catalytic thiol of calpain to the electrophilic ketone of the inhibitor.
Identification and Characterisation of C1q-Binding Phage Displayed Peptides (1997)

Five phage displayed peptide libraries were screened for binders to C1q, the recognition subunit of the classical complement pathway. Two rounds of panning resulted in the isolation and characterisation of several different phage displayed C1q-binding peptides from all five libraries. Two groups of the characterised peptides show sequence similarity with part of the metal ion dependent adhesion site (MIDAS) of integrin A-domains, and the site 187LRNPCPNKEKECQPPF of CD18 (integrin beta2), respectively. These results support binding of complement receptor 3 (CR3, CD11b/CD18, Mac1) to C1q and further suggest C1q binding sites in CR3. We also discuss sequence matches between the characterised peptides and proteins known to interact with C1q, as well as other proteins listed in the SwissProt databank. These findings are of interest for the study of the complement system and may lead to the development of peptides, fusion products or peptido-mimetics with C1q modulating potential.
Inhibition of S‐(1,2‐dichlorovinyl)‐L‐cysteine‐induced lipid peroxidation by antioxidants in rabbit renal cortical slices: Dissociation of lipid peroxidation and toxicity (1994)

Precision-cut, rabbit renal slices were used to examine the effects of three novel antioxidants (U-74006, U-74500, and U-78517) on S-(1,2-dichlorovinyl)-L-cysteine (DCVC)-induced lipid peroxidation and toxicity. Slices exposed to DCVC showed a dose- and time-dependent increase in lipid peroxidation (TBARS) and a decrease in cellular viability, as evidenced by the loss of intracellular potassium, during the course of a 3 hour incubation. Subsequent studies employed DCVC concentrations of 100 microM. Microemulsion formulations of U-78517, U-74500, and U-74006 (100 microM) inhibited DCVC-induced lipid peroxidation by 100 +/-, 50 +/-, and < 5% (not significant), respectively. However, none of these antioxidants had a significant effect on DCVC-dependent cytotoxicity, as indicated by intracellular potassium release. The effects of U-78517, the most potent of the three antioxidants, were similar to those observed with two model antioxidants, diphenyl-p-phenylenediamine (DPPD) and the iron chelator, deferoxamine. Aminooxyacetic (AOAA), an inhibitor of renal cysteine conjugate beta-lyase, had only a minimal effect on DCVC-induced lipid peroxidation, and no effect on toxicity. These data represent the first report of DCVC-induced lipid peroxidation in rabbit renal cortical slices, a system which has been widely used to investigate mechanisms of nephrotoxicity, including that induced by DCVC. Our results demonstrate that DCVC-induced lipid peroxidation in renal slices can be inhibited by a variety of antioxidant compounds operating by different mechanisms. Because inhibition of lipid peroxidation had minimal effect on DCVC-dependent cytotoxicity, the data suggest that DCVC-induced lipid peroxidation is not a major mechanism in the cytotoxicity induced by this compound.
Iron Status and Analysis of Efficacy and Safety of Ferric Carboxymaltose Treatment in Patients with Inflammatory Bowel Disease (2011)

Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients.
Thiolactomycin, a new antibiotic. I. Taxonomy of the producing organism, fermentation and biological properties. (1982)

A strain of actinomycetes, isolated from a soil sample, has produced a novel antibiotic (C11H14O2S) containing a unique thiolactone moiety in its molecule. On the basis of taxonomic studies the producing organism was identified as belonging to the genus Nocardia. The antibiotic, named thiolactomycin, exhibits a broad antibacterial spectrum and particularly potent activity against Salmonella, Serratia and Bacteroides. Furthermore, the acute toxicity is weak in experimental animals. These results indicate that thiolactomycin is distinct from other known antibiotics and represents a new type of antibiotic.
Where Light Silently Falls (2017)

Growing up on the south coast of England, artist Martin Richman found himself fascinated by light. How the light interacted with the water at the beach or became muted by clouds and mist. The lighting in the synagogue as rays of sun entered through colored glass. And the lamps that illuminated the promenade along the beach and led to the frenetic lighting of the “fun fair,” a kind of carnival.
Nucleocapsid protein N of Lelystad virus: expression by recombinant baculovirus, immunological properties, and suitability for detection of serum antibodies (1995)

The ORF7 gene, encoding the nucleocapsid protein N of Lelystad virus (LV), was inserted downstream of the P10 promoter into Autographa californica nuclear polyhedrosis virus (baculovirus). The resulting recombinant baculovirus, designated bac-ORF7, expressed a 15-kDa protein in insect cells. This protein was similar in size to the N protein expressed by LV in CL2621 cells when it was analyzed on sodium dodecyl sulfate-polyacrylamide gels. The N protein expressed by bac-ORF7 was immunoprecipitated with anti-ORF7 was immunoprecipitated with anti-ORF7 peptide serum, porcine convalescent-phase anti-LV serum, and N protein-specific monoclonal antibodies, indicating that this N protein had retained its native antigenic structure. The recombinant N protein was immunogenic in pigs, and the porcine antibodies raised against this protein recognized LV in an immunoperoxidase monolayer assay. However, pigs vaccinated twice with approximately 20 micrograms of N protein were not protected against a challenge with 10(5) 50% tissue culture infective doses of LV. Experimental and field sera directed against various European and North American isolates reacted with the N protein expressed by bac-ORF7 in a blocking enzyme-linked immunosorbent assay. Therefore, the recombinant N protein may be useful for developing diagnostic assays for the detection of serum antibodies directed against different isolates of LV.
Endothelin-1-induced modulation of contractile responses elicited by an alpha 1-adrenergic agonist on human corpus cavernosum smooth muscle. (1996)

The goal of these studies was to examine endothelin-1 (ET-1)-induced modulation of contractile responses elicited by the selective alpha 1-adrenergic agonist, phenylephrine (PE), on isolated human corporal tissue strips. Pharmacological studies were conducted on human corporal tissue strips obtained from 22 patients undergoing implantation of penile prostheses for erectile dysfunction. For the purposes of statistical analysis, the patients were stratified into two age groups: A, age < or = 59 y (n = 10) and B, age > or = 60 y (n = 12). The patients were further sub-divided into two diagnostic categories, diabetics (DM, n = 9) and nondiabetics (ND, n = 13). Cumulative concentration-response curves (CRCs) were constructed to the alpha 1-adrenergic agonist, PE, prior to constructing a CRC to a single mixture of PE and ET-1 on the same tissue. A previously described fixed molar ratio (FMR) protocol was used to generate CRCs to mixtures of PE and ET-1. In all cases, for the PE:ET-1 FMRs of 90:10, 80:20 and 70:30, the partial substitution of PE with ET-1 resulted in an approx 3-fold leftward shift in the EC50 of the PE alone CRC with an approx 4% concomitant increase in Emax and a decrease in the slope factor value. There were no significant age- or disease-related differences in any of the logistic parameter estimates that describe the FMR CRC, indicating that there are no detectable age- or disease-related alterations in ET-1-induced amplification of alpha 1-adrenergic-mediated contractions in these studies. In addition, the location of the FMR CRC was precisely predicted by the theoretical CRC for simple additivity of agonist effects. In conclusion, since relatively small increases in ET-1 concentrations were associated with significant increases in alpha 1-adrenergic-mediated contractile responses, these data provide further testimony to the importance of ET-1 in modulating corporal smooth muscle tone, and moreover, establish a conceptual framework for understanding the mechanism of its action(s).
Improving the End-of-Life for Electronic Materials via Sustainable Recycling Methods (2012)

Advanced Technology Materials, Inc. (ATMI) has developed a novel process based on green chemistry and green engineering methodologies for reclaiming valuable materials from waste electronics. We have demonstrated that we can recover metals and valuable components from end-of-life products using cost-effective, sustainable, and scalable methods (e.g., systems that are closed-loop, energy efficient and environmentally benign). This includes both chemical desoldering and precious metal reclaim from printed wiring boards (PWBs) and integrated circuits (ICs) near room temperature with all metals recovered and resold. Our current system is processing approximately 400 lbs. per hour of high value printed wiring boards.
Statin-Sensitive Dysregulated AT1 Receptor Function and Density in Hypercholesterolemic Men (1999)

Hypercholesterolemia induces AT1 receptor overexpression and enhances biological effects of angiotensin II in men. These findings provide novel insights into the pathogenesis of hypertension and atherosclerosis and may initiate rational and new therapeutic concepts.
The interaction between caveolin-1 and Rho-GTPases promotes metastasis by controlling the expression of alpha5-integrin and the activation of Src, Ras and Erk (2011)

Proteins containing a caveolin-binding domain (CBD), such as the Rho-GTPases, can interact with caveolin-1 (Cav1) through its caveolin scaffold domain. Rho-GTPases are important regulators of p130(Cas), which is crucial for both normal cell migration and Src kinase-mediated metastasis of cancer cells. However, although Rho-GTPases (particularly RhoC) and Cav1 have been linked to cancer progression and metastasis, the underlying molecular mechanisms are largely unknown. To investigate the function of Cav1-Rho-GTPase interaction in metastasis, we disrupted Cav1-Rho-GTPase binding in melanoma and mammary epithelial tumor cells by overexpressing CBD, and examined the loss-of-function of RhoC in metastatic cancer cells. Cancer cells overexpressing CBD or lacking RhoC had reduced p130(Cas) phosphorylation and Rac1 activation, resulting in an inhibition of migration and invasion in vitro. The activity of Src and the activation of its downstream targets FAK, Pyk2, Ras and extracellular signal-regulated kinase (Erk)1/2 were also impaired. A reduction in α5-integrin expression, which is required for binding to fibronectin and thus cell migration and survival, was observed in CBD-expressing cells and cells lacking RhoC. As a result of these defects, CBD-expressing melanoma cells had a reduced ability to metastasize in recipient mice, and impaired extravasation and survival in secondary sites in chicken embryos. Our data indicate that interaction between Cav1 and Rho-GTPases (most likely RhoC but not RhoA) promotes metastasis by stimulating α5-integrin expression and regulating the Src-dependent activation of p130(Cas)/Rac1, FAK/Pyk2 and Ras/Erk1/2 signaling cascades.
CCR3, CCR5, interleukin 4, and interferon-gamma expression on synovial and peripheral T cells and monocytes in patients with rheumatoid arthritis. (2003)

T cells and monocytes infiltrating joints in RA and in other arthritides showed increased activation of both type 1 and type 2 immune markers. More pronounced type 1 immune response in joints, shown as an increased CCR5/CCR3 ratio, was found in the patients with RA versus those with other arthritides. Monocytes but not T cells in PB showed increased activation in RA.
Optimized recipe for sol-gel-based SERS substrates (2000)

The aim of this study was to develop further surface-enhanced Raman scattering (SERS) substrates appropriate for the in situ environmental determination of chemicals in sea-water important for global environmental problems. By encapsulating silver colloids in a sol–gel-derived xerogel, SERS-active coatings were produced with the high mechanical and chemical stability required for underwater field measurements. A flow-through system was used which simulates measurements under real flow conditions. Substrates were optimized regarding sensitivity to different analytes and long-term stability by varying solvent type, pH and sol–gel precursors. The substrates were characterized by their SERS activity and calibration functions of the Langmuir isotherm type were found for a variety of aromatic hydrocarbons. Limits of detection as low as 9 ppb for phenylacetylene and 135 ppb for biphenyl were achieved. Detailed tests on long-term stability in sea-water yielded a substrate half-life of 13 days, which resulted in a substrate lifetime of at least 5 weeks. Copyright © 2000 John Wiley & Sons, Ltd.