gebhart/patrepeval huggingface dataset:
SN2'-Reactions of Peptide Aziridines. A Cuprate-Based Approach to (E)-Alkene Isosteres (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSN2'-Reactions of Peptide Aziridines. A Cuprate-Based Approach to (E)-Alkene IsosteresPeter Wipf and Paul C. FritchCite this: J. Org. Chem. 1994, 59, 17, 4875–4886Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/jo00096a033https://doi.org/10.1021/jo00096a033research-articleACS PublicationsRequest reuse permissionsArticle Views1748Altmetric-Citations125LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Magneto-Optical Studies of Ferromagnetic Cr-Doped GaN Films Grown by Molecular Beam Epitaxy (2005)

Cr-doped GaN films were epitaxially grown on Si(111) substrates by molecular-beam epitaxy using NH 3 as a nitrogen source, and the magnetic and magneto-optical properties of the films were measured. Magnetic measurements using a superconducting quantum interference device (SQUID) magnetometer revealed that the Cr-doped GaN films showed ferromagnetic behavior at 5 K. However, magnetic circular dichroism (MCD) measurements revealed that the observed ferromagnetism could not be attributed to the Cr-doped GaN itself, but to unidentified ferromagnetic precipitates in the grown layers.
Efficacy, Safety and Mechanism of Cyclodextrins as Absorption Enhancers in Nasal Delivery of Peptide and Protein Drugs (1998)

Cyclodextrins are used in nasal drug delivery as absorption enhancing compounds to increase the intranasal bioavailability of peptide and protein drugs. The most effective cyclodextrins in animal experiments are the methylated derivatives, dimethyl-beta-cyclodextrin and randomly methylated beta-cyclodextrin, which are active at low concentrations ranging between 2% and 5%. However, large species differences between rats, rabbits and humans exist for the nasal absorption enhancement by cyclodextrins. Based on toxicological studies of the local effects of cyclodextrins on the nasal mucosa dimethyl-beta-cyclodextrin and randomly methylated beta-cyclodextrin are considered safe nasal absorption enhancers. Their effects were quite similar to controls (physiological saline), but smaller than those of the preservative benzalkonium chloride in histological and ciliary beat frequency studies. In these studies, and in a study of the release of marker compounds after nasal administration, methylated beta-cyclodextrins were less toxic than sodium glycocholate, sodium taurodihydrofusidate, laureth-9 and L-alpha-phosphatidylcholine. Systemic toxicity after nasal cyclodextrin administration is not expected, because very low doses of cyclodextrins are administered and only very small amounts are absorbed. The mechanism of action of cyclodextrins may be explained by their interaction with the nasal epithelial membranes and their ability to transiently open tight junctions.
A 32-bit PowerPC system-on-a-chip with support for dynamic voltage scaling and dynamic frequency scaling (2002)

A PowerPC system-on-a-chip processor which makes use of dynamic voltage scaling and on-the-fly frequency scaling to adapt to the dynamically changing performance demands and power consumption constraints of high-content, battery powered applications is described. The PowerPC core and caches achieve frequencies as high as 380 MHz at a supply of 1.8 V and active power consumption as low as 53 mW at a supply of 1.0 V. The system executes up to 500 MIPS and can achieve standby power as low as 54 /spl mu/W. Logic supply changes as fast as 10 mV//spl mu/s are supported. A low-voltage PLL supplied by an on-chip regulator, which isolates the clock generator from the variable logic supply, allows the SOC to operate continuously while the logic supply voltage is modified. Hardware accelerators for speech recognition, instruction-stream decompression and cryptography are included in the SOC. The SOC occupies 36 mm/sup 2/ in a 0.18 /spl mu/m, 1.8 V nominal supply, bulk CMOS process.
Down-regulation of Caveolin-1, an Inhibitor of Transforming Growth Factor-β Signaling, in Acute Allergen-induced Airway Remodeling (2007)

Asthma can progress to subepithelial airway fibrosis, mediated in large part by transforming growth factor-beta (TGF-beta). The scaffolding protein caveolin-1 (cav1) can inhibit the activity of TGF-beta, perhaps by forming membrane invaginations that enfold TGF-beta receptors. The study goals were 1) to evaluate how allergen challenge affects lung expression of cav1 and the density of caveolae in vivo 2) to determine whether reduced cav1 expression is mediated by interleukin (IL)-4 and 3) to measure the effects of decreased expression of cav1 on TGF-beta signaling. C57BL/6J, IL-4-deficient mice, and cav1-deficient mice, sensitized by intraperitoneal injections of phosphate-buffered saline or ovalbumin (OVA) at days 0 and 12, received intranasal phosphate-buffered saline or OVA challenges at days 24, 26, and 28. Additionally, another group of C57BL/6J mice received IL-4 by intratracheal instillation for 7 days. We confirmed that the OVA-allergen challenge increased eosinophilia and T-helper type 2-related cytokine levels (IL-4, IL-5, and IL-13) in bronchoalveolar lavage. Allergen challenge reduced lung cav1 mRNA abundance by 40%, cav1 protein by 30%, and the number of lung fibroblast caveolae by 50%. Administration of IL-4 in vivo also substantially decreased cav1 expression. In contrast, the allergen challenge did not decrease cav1 expression in IL-4-deficient mice. The reduced expression of cav1 was associated with activation of TGF-beta signaling that was further enhanced in OVA-sensitized and challenged cav1-deficient mice. This study demonstrates a previously unknown modulation of TGF-beta signaling by IL-4, via cav1, suggesting novel therapeutic targets for controlling the effects of TGF-beta and thereby ameliorating pathological airway remodeling.
Canakinumab (2010)

Canakinumab (ACZ885, Ilaris) is a human anti-IL-1beta monoclonal antibody developed by Novartis. Its mode of action is based on the neutralization of IL-1beta signaling, resulting in suppression of inflammation in patients with disorders of autoimmune origin. In June 2009 the drug was approved by the US Food and Drug Administration for the treatment of familial cold auto-inflammatory syndrome and Muckle-Wells syndrome, which are inflammatory diseases related to cryopyrin-associated periodic syndromes. The drug is currently being evaluated for its potential in the treatment of rheumatoid arthritis, systemic-onset juvenile idiopathic arthritis, chronic obstructive pulmonary disease, type 1 and 2 diabetes and ocular diseases. Reports from clinical trials suggest that canakinumab is well-tolerated in most patients, and no serious adverse effects have been reported. The drug provides significant advantages over existing competitive therapies, including bimonthly administration and approved use in children.
Erythropoietin. Biology and clinical applications (1993)

Hemopoiesis is a complex process that underlies the production of highly specialized cells. The mechanisms involved in this process include positive and negative feedback by humoral activities, pluripotent stem cell self-renewal and differentiation, and local interactions between stromal components of the hemopoietic microenvironment and various stem and progenitor cells.
Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors (2005)

We developed a high-throughput HTRF (homogeneous time-resolved fluorescence) assay for Akt kinase activity and screened approx. 270000 compounds for their ability to inhibit the three isoforms of Akt. Two Akt inhibitors were identified that exhibited isoenzyme specificity. The first compound (Akt-I-1) inhibited only Akt1 (IC50 4.6 microM) while the second compound (Akt-I-1,2) inhibited both Akt1 and Akt2 with IC50 values of 2.7 and 21 microM respectively. Neither compound inhibited Akt3 nor mutants lacking the PH (pleckstrin homology) domain at concentrations up to 250 microM. These compounds were reversible inhibitors, and exhibited a linear mixed-type inhibition against ATP and peptide substrate. In addition to inhibiting kinase activity of individual Akt isoforms, both inhibitors blocked the phosphorylation and activation of the corresponding Akt isoforms by PDK1 (phosphoinositide-dependent kinase 1). A model is proposed in which these inhibitors bind to a site formed only in the presence of the PH domain. Binding of the inhibitor is postulated to promote the formation of an inactive conformation. In support of this model, antibodies to the Akt PH domain or hinge region blocked the inhibition of Akt by Akt-I-1 and Akt-I-1,2. These inhibitors were found to be cell-active and to block phosphorylation of Akt at Thr308 and Ser473, reduce the levels of active Akt in cells, block the phosphorylation of known Akt substrates and promote TRAIL (tumour-necrosis-factor-related apoptosis-inducing ligand)-induced apoptosis in LNCap prostate cancer cells.
Two-Dimensional Combinatorial Screening Identifies Specific Aminoglycoside−RNA Internal Loop Partners (2008)

Herein is described the identification of RNA internal loops that bind to derivatives of neomycin B, neamine, tobramycin, and kanamycin A. RNA loop-ligand partners were identified by a two-dimensional combinatorial screening (2DCS) platform that probes RNA and chemical spaces simultaneously. In 2DCS, an aminoglycoside library immobilized onto an agarose microarray was probed for binding to a 3 x 3 nucleotide RNA internal loop library (81,920 interactions probed in duplicate in a single experiment). RNAs that bound aminoglycosides were harvested from the array via gel excision. RNA internal loop preferences for three aminoglycosides were identified from statistical analysis of selected structures. This provides consensus RNA internal loops that bind these structures and include: loops with potential GA pairs for the neomycin derivative, loops with potential GG pairs for the tobramycin derivative, and pyrimidine-rich loops for the kanamycin A derivative. Results with the neamine derivative show that it binds a variety of loops, including loops that contain potential GA pairs that also recognize the neomycin B derivative. All studied selected internal loops are specific for the aminoglycoside that they were selected to bind. Specificity was quantified for 16 selected internal loops by studying their binding to each of the arrayed aminoglycosides. Specificities ranged from 2- to 80-fold with an average specificity of 20-fold. These studies show that 2DCS is a unique platform to probe RNA and chemical space simultaneously to identify specific RNA motif-ligand interactions.
Brain proline-directed protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer's paired helical filaments. (1993)

Brain proline-directed protein kinase (BPDK), which contains a catalytic subunit homologous to and displaying site-specific phosphorylation similar to p34cdc2 kinase (Lew, J., Winkfein, R. J., Paudel, H. K., and Wang, J. H. (1992) J. Biol. Chem. 267, 25922-25926), has been examined for possible involvement in tau phosphorylation. Immunoblot analyses using peptide antibodies specific for BPDK have revealed the presence of the kinase in bovine brain microtubules purified extensively by repeated polymerization and depolymerization cycles. When the microtubule proteins are separated into the tubulin and microtubule-associated protein fractions, BPDK is found exclusively in the latter fraction. BPDK phosphorylates both tau and MAP2, the former protein being phosphorylated to a stoichiometry of 3.8 mol of phosphate/mol of tau. Analysis of the phosphopeptides isolated from the tryptic digest of the phosphorylated bovine tau has revealed seven phosphorylation sites. Based on the sequence alignment between bovine and human tau proteins, these sites correspond to Ser-195, Ser-202, Thr-205, Thr-231, Ser-235, Ser-396, and Ser-404 of human tau. Mass spectrometric analysis of the tau protein isolated from Alzheimer's paired helical filaments (PHFs) has determined three abnormal phosphorylation sites and two phosphopeptides containing a total of five abnormal phosphates (Hasegawa, M., Morishima-Kawashima, M., Takio, K., Suzuki, M., Titani, K., and Ihara, Y. (1992) J. Biol. Chem. 267, 17047-17054). Two of the sites in tau phosphorylated by BPDK, Thr-231 and Ser-235, are among the abnormal phosphorylation sites, and the other sites phosphorylated by BPDK are within phosphopeptides from PHF-tau. These results suggest that BPDK may be one of the kinases responsible for the abnormal phosphorylation-associated PHF-tau.
Impaired Heart Contractility in Apelin Gene–Deficient Mice Associated With Aging and Pressure Overload (2007)

Apelin constitutes a novel endogenous peptide system suggested to be involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, and obesity. Apelin is also a catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The in vivo physiological role of Apelin is still elusive. Here we report the generation of Apelin gene-targeted mice. Apelin mutant mice are viable and fertile, appear healthy, and exhibit normal body weight, water and food intake, heart rates, and heart morphology. Intriguingly, aged Apelin knockout mice developed progressive impairment of cardiac contractility associated with systolic dysfunction in the absence of histological abnormalities. We also report that pressure overload induces upregulation of Apelin expression in the heart. Importantly, in pressure overload-induced heart failure, loss of Apelin did not significantly affect the hypertrophy response, but Apelin mutant mice developed progressive heart failure. Global gene expression arrays and hierarchical clustering of differentially expressed genes in hearts of banded Apelin(-/y) and Apelin(+/y) mice showed concerted upregulation of genes involved in extracellular matrix remodeling and muscle contraction. These genetic data show that the endogenous peptide Apelin is crucial to maintain cardiac contractility in pressure overload and aging.
One-pot synthesis of tetrasubstituted pyrazoles—proof of regiochemistry (1996)

1-Alkyl-5-amino-3-aryl-4-cyanopyrazoles, useful intermediates for fused heterocyclic systems, are synthesised by a one-pot three-step procedure from acid chlorides, malononitrile and alkylhydrazines. The regiochemistry of the hydrazine incorporation was proved in each case by X-ray crystallography and NMR spectroscopy.
Enhanced experimental metastatic capacity of a human tumor line following treatment with 5-azacytidine. (1986)

We have studied the effect of the nucleoside analogue 5-azacytidine (5-azaC) a known activator of gene expression, on the metastatic behavior of the human melanoma cell line DX3. After exposure to 3 microM 5-azaC for 24 h cells were carried through five subcultures before being tested for their metastatic capacity. Following i.v. injection in BALB/c nude mice, cells treated with 5-azaC showed a 40-fold increase in the number of lung tumor nodules as compared to that obtained with control cells. Tumors resulting from 5-azaC-treated cells exhibited a 5-fold increase in mitotic figures, considerable cellular pleomorphism, and variation in the histological character of the individual nodules. These in vivo differences were not reflected in vitro where treated and untreated cells showed no significant differences in morphology, karyotypes, growth rates, saturation densities, or plating efficiencies. Cells populating the lung tumor nodules retained their increased metastatic capacity through successive cycles of growth in vitro followed by reinjection into nude mice and indeed the ability of the cell lines to form lung tumors was increased with the succeeding cycles in vivo. These cell lines, each established from individual tumor nodules, maintained a human karyotype and reacted positively with human-specific antiserum. Characterization of these lines showed that while there were no alterations in in vitro growth behavior the selected lines exhibited a decreased latency period for s.c. tumor formation, increased retention in the lungs following i.v. injection, and enhanced lung nodule formation (60- to 80-fold compared to control cells). Examination of genomic DNA showed that treatment with 5-azaC brought about a significant decrease (50%) in the percentage of methylated cytosine residues but this extensive hypomethylation was not maintained in the lung tumor nodule-derived cell lines.
Software Components with ADA: Structures, Tools, and Subsystems (1987)

Software components with Ada: structures, tools, and subsystems , Software components with Ada: structures, tools, and subsystems , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Efficient coding scheme for super high definition video based on extending H.264 high profile (2006)

H.264 High Profile, one of the standard video coding schemes, can be utilized for super high definition video since target image resolution is up to 4096×2304. However, in the case of encoding super high definition video such as the 4Kx2K system whose resolution corresponds to 4096×2160, the coding syntax might be redundant since available macroblock size become quite small compared to the image resolution. The problem is caused by the limitation of the macroblock size by which motion compensated prediction is conducted. To overcome the problem within the framework of the H.264 High Profile encoder, extending the limitation of macroblock size is required. From this perspective, this paper describes an efficient coding scheme applicable to super high definition video based on extending the H.264 High Profile. As the key technology of the proposed coding scheme, an approach for extending the limitation of available macroblock size is introduced. From experimental results, it was confirmed that the outstanding coding gain was achieved by the proposed scheme especially for the low bit-rate condition.
R-spondins can potentiate WNT signaling without LGRs (2018)

The WNT signaling pathway regulates patterning and morphogenesis during development and promotes tissue renewal and regeneration in adults. The R-spondin (RSPO) family of four secreted proteins, RSPO1-4, amplifies target cell sensitivity to WNT ligands by increasing WNT receptor levels. Leucine-rich repeat-containing G-protein coupled receptors (LGRs) 4-6 are considered obligate high-affinity receptors for RSPOs. We discovered that RSPO2 and RSPO3, but not RSPO1 or RSPO4, can potentiate WNT/β-catenin signaling in the absence of all three LGRs. By mapping the domains on RSPO3 that are necessary and sufficient for this activity, we show that the requirement for LGRs is dictated by the interaction between RSPOs and the ZNRF3/RNF43 E3 ubiquitin ligases and that LGR-independent signaling depends on heparan sulfate proteoglycans (HSPGs). We propose that RSPOs can potentiate WNT signals through distinct mechanisms that differ in their use of either LGRs or HSPGs, with implications for understanding their biological functions.
Review article: new treatments in non‐alcoholic fatty liver disease (2017)

Rising demand and an improved understanding of NASH pathophysiology has led to a surge in development of new therapies. Tailoring pharmacotherapy to the dominant pathogenic pathway in a given patient along with use of combination therapy is likely to represent the future direction in treatment of patients with NASH.
Polyunsaturated Fatty Acids Ameliorate Hepatic Steatosis in Obese Mice by Srebp–1 Suppression (2003)

Leptin-deficient ob/ob mice show many characteristics of obesity, including excess peripheral adiposity as well as severe hepatic steatosis, at least in part, due to increased hepatic lipogenesis. Polyunsaturated fatty acids (PUFAs) are not only ligands for peroxisome proliferator-activated receptor (PPAR) alpha but are also negative regulators of hepatic lipogenesis, which is thought to be mediated by the repression of sterol regulatory element-binding protein (SREBP)-1. We have previously shown that the disruption of SREBP-1 in ob/ob mice decreased their liver triglyceride storage. To examine whether PUFAs could reduce hepatic triglyceride deposition, we challenged ob/ob mice with dietary PUFA. It is demonstrated that PUFA markedly decreased the mature form of SREBP-1 protein and thereby reduced the expression of lipogenic genes such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1) in the livers of ob/ob mice. Consequently, the liver triglyceride content and plasma alanine aminotransferase (ALT) levels were decreased. Furthermore, both hyperglycemia and hyperinsulinemia in ob/ob mice were improved by PUFA administration, similar to the effect of PPARalpha activators. In conclusion, PUFAs ameliorate obesity-associated symptoms, such as hepatic steatosis and insulin resistance, presumably through both down-regulation of SREBP-1 and activation of PPARalpha.
Isolation and characterization of the GFA1 gene encoding the glutamine:fructose-6-phosphate amidotransferase of Candida albicans (1996)

Glutamine:fructose-6-phosphate amidotransferase (glucosamine-6-phosphate synthase) catalyzes the first step of the hexosamine pathway required for the biosynthesis of cell wall precursors. The Candida albicans GFA1 gene was cloned by complementing a gfa1 mutation of Saccharomyces cerevisiae (previously known as gcn1-1; W. L. Whelan and C. E. Ballou, J. Bacteriol. 124:1545-1557, 1975). GFA1 encodes a predicted protein of 713 amino acids and is homologous to the corresponding gene from S. cerevisiae (72% identity at the nucleotide sequence level) as well as to the genes encoding glucosamine-6-phosphate synthases in bacteria and vertebrates. In cell extracts, the C. albicans enzyme was 4-fold more sensitive than the S. cerevisiae enzyme to UDP-N-acetylglucosamine (an inhibitor of the mammalian enzyme) and 2.5-fold more sensitive to N3-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (a glutamine analog and specific inhibitor of glucosamine-6-phosphate synthase). Cell extracts from the S. cerevisiae gfa1 strain transformed with the C. albicans GFA1 gene exhibited sensitivities to glucosamine-6-phosphate synthase inhibitors that were similar to those shown by the C. albicans enzyme. Southern hybridization indicated that a single GFA1 locus exists in the C. albicans genome. Quantitative Northern (RNA) analysis showed that the expression of GFA1 in C. albicans is regulated during growth: maximum mRNA levels were detected during early log phase. GFA1 mRNA levels increased following induction of the yeast-to-hyphal-form transition, but this was a response to fresh medium rather than to the morphological change.