gebhart/patrepeval huggingface dataset:
Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery (2016)

KEAP1 is the key regulator of the NRF2-mediated cytoprotective response, and increasingly recognized as a target for diseases involving oxidative stress. Pharmacological intervention has focused on molecules that decrease NRF2-ubiquitination through covalent modification of KEAP1 cysteine residues, but such electrophilic compounds lack selectivity and may be associated with off-target toxicity. We report here the first use of a fragment-based approach to directly target the KEAP1 Kelch-NRF2 interaction. X-ray crystallographic screening identified three distinct "hot-spots" for fragment binding within the NRF2 binding pocket of KEAP1, allowing progression of a weak fragment hit to molecules with nanomolar affinity for KEAP1 while maintaining drug-like properties. This work resulted in a promising lead compound which exhibits tight and selective binding to KEAP1, and activates the NRF2 antioxidant response in cellular and in vivo models, thereby providing a high quality chemical probe to explore the therapeutic potential of disrupting the KEAP1-NRF2 interaction.
Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation (2006)

Ewing's family tumors (EFTs) are highly malignant tumors arising from bone and soft tissues that exhibit EWS-FLI1 or variant EWS-ETS gene fusions in more than 85% of the cases. Here we show that CIC, a human homolog of Drosophila capicua which encodes a high mobility group box transcription factor, is fused to a double homeodomain gene DUX4 as a result of a recurrent chromosomal translocation t(4;19)(q35;q13). This translocation was seen in two cases of soft tissue sarcoma diagnosed as Ewing-like sarcoma. CIC-DUX4 exhibits a transforming potential for NIH 3T3 fibroblasts, and as a consequence of fusion with a C-terminal fragment of DUX4, CIC acquires an enhanced transcriptional activity, suggesting that expression of its downstream targets might be deregulated. Gene expression analysis identified the ETS family genes, ERM/ETV5 and ETV1, as potential targets for the gene product of CIC-DUX4. Indeed, CIC-DUX4 directly binds the ERM promoter by recognizing a novel target sequence and significantly up-regulates its expression. This study clarifies the function of CIC and its role in tumorigenesis, as well as the importance of the PEA3 subclass of ETS family proteins in the development of EFTs arising through mechanisms different from those involving EWS-ETS chimeras. Moreover, the study identifies the role of DUX4 that is closely linked to facioscapulohumeral muscular dystrophy in transcriptional regulation.
RF MEMS impedance tuners for 6–24 GHz applications (2007)

RF MEMS tuners with wide impedance coverage have been developed for 6–24 GHz noise parameter and load-pull measurement systems. The tuners are based on triple-, double-, and single-stub topologies loaded with switched MEMS capacitors. Several designs are presented, and they use 10–13 switched MEMS capacitors to produce 1024–8192 (210–213) different impedances. The measured impedance coverage agrees well with simulations and it is the widest ever measured impedance coverage from any planar tuner to-date. © 2007 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2007.
Cost‐effectiveness analysis of sacral neuromodulation and botulinum toxin A treatment for patients with idiopathic overactive bladder (2010)

Starting with SNM, treatment is cost-effective after 5 years compared to BTX. However, in some scenarios, such as the use of local anaesthesia for BTX treatment and SNM peripheral nerve evaluation or bilateral test, SNM was not cost-effective.
Contributions of angiotensin II and tumor necrosis factor-α to the development of renal fibrosis (2001)

Angiotensin II upregulates tumor necrosis factor-alpha (TNF-alpha) in the rat kidney with unilateral ureteral obstruction (UUO). In a mouse model of UUO, we found that tubulointerstitial fibrosis is blunted when the TNF-alpha receptor, TNFR1, is functionally knocked out. In this study, we used mutant mice with UUO in which the angiotensin II receptor AT(1a) or the TNF-alpha receptors TNFR1 and TNFR2 were knocked out to elucidate interactions between the two systems. The contribution of both systems to renal fibrosis was assessed by treating TNFR1/TNFR2-double knockout (KO) mice with an angiotensin-converting enzyme inhibitor, enalapril. The increased interstitial volume (Vv(int)) in the C57BI/6 wild-type mouse was decreased in the AT(1a) KO from 32.8 +/- 4.0 to 21.0 +/- 3.7% (P < 0.005) or in the TNFR1/TNFR2 KO to 22.3 +/- 2.1% (P < 0.005). The Vv(int) of the TNFR1/TNFR2 KO was further decreased to 15.2 +/- 3.7% (P < 0.01) by enalapril compared with no treatment. The induction of TNF-alpha mRNA and transforming growth factor-beta1 (TGF-beta1) mRNA in the kidney with UUO was significantly blunted in the AT(1a) or TNFR1/TNFR2 KO mice compared with the wild-type mice. Treatment of the TNFR1/TNFR2 KO mouse with enalapril reduced both TNF-alpha and TGF-beta1 mRNA and their proteins to near normal levels. Also, alpha-smooth muscle actin expression and myofibroblast proliferation were significantly inhibited in the AT(1a) or TNFR1/TNFR2 KO mice, and they were further inhibited in enalapril-treated TNFR1/TNFR2 KO mice. Incapacitating the angiotensin II or the TNF-alpha systems individually leads to partial blunting of fibrosis. Incapacitating both systems, by using a combination of genetic and pharmacological means, further inhibited interstitial fibrosis and tubule atrophy in obstructive nephropathy.
Self-assembled single-digit micro-display on plastic (2008)

We present the design and construction of a micro-display consisting of independently microfabricated light emitting diodes (LEDs) and silicon transistors on unconventional substrates such as flexible plastics. The fabrication process takes advantage of self-assembly to form the display. Silicon microcomponents and AlGaAs red LEDs were microfabricated and released to form a powder-like collection of parts. A plastic template containing binding sites was independently microfabricated. Each binding site on the template consisted of a well with a shape complementary to that of the released component. Self-assembly process was conducted in a fluidic medium to allow the microcomponents to assemble in proper receptor sites on the flexible template. We showed self-assembly of both LEDs and driving circuitry for display on plastic template. We got more than 90% yield for physically positioning the parts on template, with electrical connection yield of 62%.
Single-chain immunotoxins directed at the human transferrin receptor containing Pseudomonas exotoxin A or diphtheria toxin: anti-TFR(Fv)-PE40 and DT388-anti-TFR(Fv). (1991)

Two single-chain immunotoxins directed at the human transferrin receptor have been constructed by using polymerase chain reaction-based methods. Anti-TFR(Fv)-PE40 is encoded by a gene fusion between the DNA sequence encoding the antigen-binding portion (Fv) of a monoclonal antibody directed at the human transferrin receptor and that encoding a 40,000-molecular-weight fragment of Pseudomonas exotoxin (PE40). The other fusion protein, DT388-anti-TFR(Fv), is encoded by a gene fusion between the DNA encoding a truncated form of diphtheria toxin and that encoding the antigen-binding portion of antibody to human transferrin receptor. These gene fusions were expressed in Escherichia coli, and fusion proteins were purified by conventional chromatography techniques to near homogeneity. In anti-TFR(Fv)-PE40, the antigen-binding portion is placed at the amino terminus of the toxin, while in DT388-anti-TFR(Fv), it is at the carboxyl end of the toxin. Both these single-chain immunotoxins kill cells bearing the human transferrin receptors. However, anti-TFR(Fv)-PE40 was usually more active than DT388-anti-TFR(Fv), and in some cases it was several-hundred-fold more active. Anti-TFR(Fv)-PE40 was also more active on cell lines than a conjugate made by chemically coupling the native antibody to PE40, and in some cases it was more than 100-fold more active.
DIFFERENTIAL GENE EXPRESSION OF INTERLEUKIN-1 RECEPTOR ASSOCIATED KINASE-1 AND INTERLEUKIN-1 RECEPTOR ASSOCIATED KINASE-M IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF YOUNG AND AGED RATS FOLLOWING PRECONDITIONING WITH ENDOTOXIN (2008)

The IL-1 receptor-associated kinase 1 (IRAK-1) and IRAK-M are key signaling molecules in cellular responses to endotoxin initiated through the Toll-like receptors (TLRs). The aim of this study was to evaluate the effect of age on the modulation of TLRs and IRAK-1 and IRAK-M in peripheral blood mononuclear cells (PBMCs) exposed in vitro to endotoxin under conditions that could induce endotoxin tolerance. Peripheral blood mononuclear cells obtained from young (4- to 6-month-old) and aged (24- to 26-month-old) Brown Norway rats were treated with high-dose LPS, with or without priming with low-dose LPS. In comparison with younger rats, the intensity of TLR-4 expression was persistently high in monocytes from aged rats after stimulation with LPS and was not decreased by priming with low-dose LPS (P < 0.05). Messenger RNA (mRNA) for TLR-4 in PBMCs from aged rats did not show any decrease after priming with low-dose LPS as seen in PBMCs from young rats at 24 h (P = 0.01) after restimulation. In PBMCs from young rats, but not aged rats, preconditioning with low-dose LPS and subsequent stimulation with high-dose LPS resulted in markedly decreased IRAK-1 protein (P = 0.02) and decreased mRNA for IRAK-1 (P < 0.05). In contrast, PBMCs from aged rats treated in this manner continued to express measurable levels of IRAK-1 protein. Preconditioning with low-dose LPS caused an increase in both IRAK-M protein and mRNA (P = 0.05) after stimulation with high-dose LPS only in cells from young rats. These phenotypic characteristics of PBMCs from aged rats can interfere with their ability to develop tolerance to endotoxin.
High-Performance Nanowire Electronics and Photonics on Glass and Plastic Substrates (2003)

The merger of nanoscale building blocks with flexible and/or low cost substrates could enable the development of high-performance electronic and photonic devices with the potential to impact a broad spectrum of applications. Here we demonstrate that high-quality, single-crystal nanowires can be assembled onto inexpensive glass and flexible plastic substrates to create basic transistor and light-emitting diode devices. In our approach, the high-temperature synthesis of single-crystal nanowires is separated from ambient-temperature solution-based assembly to enable the fabrication of single-crystal-like devices on virtually any substrate. Silicon nanowire field-effect transistors were assembled on glass and plastic substrates and display device parameters rivaling those of single-crystal silicon and exceeding those of state-of-the-art amorphous silicon and organic transistors currently used for flexible electronics on plastic substrates. Nanowire transistor devices have been configured as low-threshold logic elements with gain; moreover, the high-performance characteristics are relatively unaffected by operation in a bent configuration or by repeated bending. The generality of this approach is further illustrated with the assembly of gallium nitride nanowire UV-light-emitting diodes on flexible plastic substrates. These results suggest that nanowires could serve as high-performance building blocks for the next of generation lightweight display, mobile computing, and information storage applications.
One-step inkjet printing of conductive silver tracks on polymer substrates (2009)

A one-step process to fabricate conductive features on flexible polymer substrates by inkjet printing an organometallic silver ink directly onto a substrate that is heated to 130 degrees C is presented. This process led to the immediate sintering of the printed features. The samples were left for 5 min at elevated temperature, which resulted in conductive silver features with a resistivity of eight times the bulk silver value. The combination of this ink and the simultaneous printing/sintering process opens up routes for the direct fabrication of conductive features on common polymer substrates that could be applied, for example, in roll-to-roll production of flexible microelectronic systems.
Atherosclerotic risk factors in female students of northwestern Greece. (1993)

The prevalence of predisposing atherosclerotic factors such as obesity, hypertension, hyperlipidaemia, smoking and consumption of animal fat in a cohort of all female students in the last class of high schools in Northwestern Greece was studied. A total of 590 students were included in the study. In all subjects body weight and height, SBP and DBP (in sitting position), total cholesterol and triglycerides (after 14 hours of fasting) were measured. Smoking and dietary habits were examined by a questionnaire. The results showed that 41.57% of the students were obese (Quetelet index > 22), 3.12% were considered as hypertensives (SBP > 140 mmHg and/or DBP > 90 mmHg), 14.19% had hypercholesterolaemia (total cholesterol > 5.439 mmol/l (210 mg/dl), 95th percentile in Greece), 4.7% had hypertriglyceridaemia (total triglycerides > 1.423 mmol/l (126 mg/dl) 95th percentile in Greece). Moreover, 22% consumed meat and 24% ate eggs at least four times per week. Only 13% of these students smoked habitually or occasionally. In conclusion, the prevalence of hyperlipidaemia and obesity in our cohort is significantly high and is correlated with nutritional factors. The detection of predisposing atherosclerotic factors in adolescents is of primary importance for early prevention of vascular damage.
Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+channel,IKCa1: A potential immunosuppressant (2000)

The antimycotic clotrimazole, a potent inhibitor of the intermediate-conductance calcium-activated K(+) channel, IKCa1, is in clinical trials for the treatment of sickle cell disease and diarrhea and is effective in ameliorating the symptoms of rheumatoid arthritis. However, inhibition of cytochrome P450 enzymes by clotrimazole limits its therapeutic value. We have used a rational design strategy to develop a clotrimazole analog that selectively inhibits IKCa1 without blocking cytochrome P450 enzymes. A screen of 83 triarylmethanes revealed the pharmacophore for channel block to be different from that required for cytochrome P450 inhibition. The "IKCa1-pharmacophore" consists of a (2-halogenophenyl)diphenylmethane moiety substituted by an unsubstituted polar pi-electron-rich heterocycle (pyrazole or tetrazole) or a -C≡N group, whereas cytochrome P450 inhibition absolutely requires the imidazole ring. A series of pyrazoles, acetonitriles, and tetrazoles were synthesized and found to selectively block IKCa1. TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole) inhibits the cloned and the native IKCa1 channel in human T lymphocytes with a K(d) of 20-25 nM and is 200- to 1,500-fold selective over other ion channels. Using TRAM-34, we show that blocking IKCa1 in human lymphocytes, in the absence of P450-inhibition, results in suppression of mitogen-stimulated [(3)H]thymidine incorporation of preactivated lymphocytes with EC(50)-values of 100 nM-1 microM depending on the donor. Combinations of TRAM-34 and cyclosporin A are more effective in suppressing lymphocyte mitogenesis than either compound alone. Our studies suggest that TRAM-34 and related compounds may hold therapeutic promise as immunosuppressants.
Evaluating the prospects for alternative electronic securities markets (1991)

Two alternative trading mechanisms for securities markets are compared using laboratory experimentation and computer simulation. One mechanism is the floor-based specialist auction in place in most U.S. stock exchanges today, and the other is an electronic alternative employing automatic order matching. We conclude that transition from the established floor-based exchanges to potentially superior electronic alternatives is possible, despite the inertia resulting from the experience of benefits investors trading in active markets, and that current proposals for electronic markets are not demonstrably superior on generally accepted criteria used to assess market quality. This has clear implications for established stock exchanges, market regulators, and vendors of electronic trading systems.
Cellular/Tissue Engineering (2008)

This article briefly reviews a few important technical challenges in the field of tissue engineering and describes current and potential strategies to advance the engineering of functional skeletal muscle toward potential clinical use in the repair of muscle damage.
Vasorelaxation by Red Blood Cells and Impairment in Diabetes (2004)

Vascular dysfunction in diabetes is attributed to lack of bioavailable nitric oxide (NO) and is postulated as a primary cause of small vessel complications as a result of poor glycemic control. Although it has been proposed that NO is bound by red blood cells (RBCs) and can induce relaxation of blood vessels distal to its site of production in the normal circulation, the effect of RBC glycation on NO binding and relaxation of hypoxic vessels is unknown. We confirm RBC-induced vessel relaxation is inversely related to tissue oxygenation and is proportional to RBC S-nitrosohemoglobin (HbSNO) content (but not nitrosylhemoglobin content). We show more total NO bound inside highly glycated RBCs (0.0134 versus 0.0119 NO/Hb, respectively; P<0.05) although proportionally less HbSNO (0.0053 versus 0.0088 NO/Hb, respectively; P<0.05). We also show glycosylation impairs the vasodilator function of RBCs within a physiological range of tissue oxygenation. These findings may represent an important contribution to reduced NO bioavailability in the microvasculature in diabetes.
II. Biogeographical charts (2004)

The following CPR Atlas contains the biogeographical distribution of 240 common pelagic plankton taxa of the North Sea and North Atlantic Ocean. The biogeographical charts were produced using data collected by the Continuous Plankton Recorder (CPR) survey from 1958 to 1999, incorporating over 155 000 plankton samples. The methodology on spatial interpretation of CPR data and protocols of the CPR survey are fully described in Beaugrand (2004, this volume). The charts are printed in alphabetical order of the genera within each major taxon. Nomenclature for diatoms is based on Details on selected taxa (indicated by * on the charts) are given following the index of the charts.
Transformation of Chlorobium limicola by a plasmid that confers the ability to utilize thiosulfate (1994)

A modified transformation method for Chlorobium limicola confirms the role of an endogenous plasmid in thiosulfate metabolism. The plasmid was present in two forma specialis thiosulfatophilum (Tio+) strains and absent in one non-thiosulfate-utilizing (Tio-) strain. The plasmid (size, 14 kb) was transferred by transformation from Tio- to Tio+. The chromosomal restriction patterns, analyzed by pulsed-field gel electrophoresis, were used to distinguish between the different strains.
Dimerization of a 3-Substituted Oxindole at C-3 and Its Application to the Synthesis of (.+-.)-Folicanthine (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDimerization of a 3-Substituted Oxindole at C-3 and Its Application to the Synthesis of (.+-.)-FolicanthineCheng-Lin Fang, Stephen Horne, Nicholas Taylor, and Russell RodrigoCite this: J. Am. Chem. Soc. 1994, 116, 21, 9480–9486Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/ja00100a010https://doi.org/10.1021/ja00100a010research-articleACS PublicationsRequest reuse permissionsArticle Views1382Altmetric-Citations99LEARN 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-AlertscloseSupporting Info (5)»Supporting Information Supporting Information Get e-Alerts
Glassy State and Thermal Inactivation of Invertase and Lactase in Dried Amorphous Matrices (1997)

The thermal stability of enzymes lactase and invertase in dried, amorphous matrices of sugars (trehalose, maltose, lactose, sucrose, raffinose) and some other selected systems (casein, PVP, milk) was studied. The glass transition temperature (Tg) was limited as a threshold parameter for predicting enzyme inactivation because (a) enzyme inactivation was observed in glassy matrices, (b) a specific effect of enzyme stabilization by certain matrices particularly trehalose was observed, and (c) enzyme stability appeared to depend on heating temperature (T) "per se" rather than (T-Tg). For these reasons, a protective mechanism by sugars related to the maintenance of the tertiary structure of the enzyme was favored. A rapid loss of enzyme (lactase) activity was observed in heated sucrose systems at T > Tg, and this was attributed to sucrose crystallization since it is known that upon crystallization the protective effect of sugars is lost. Thus, the stabilizing effect could be indirectly affected by the Tg of the matrix, since crystallization of sugars only occurs above Tg. Trehalose model systems (with added invertase) showed an exceptional stability toward "darkening" (e.g., non-enzymatic browning) when heated in the dried state to elevated temperatures and for long periods of time.
Dietary modification of human macular pigment density. (1997)

Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.