gebhart/patrepeval huggingface dataset:
1,5-Diaryl-2,3-pyrrolidinediones. XII. Enamines and the Pseudo-pyrrolidinediones1,2 (1960)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,5-Diaryl-2,3-pyrrolidinediones. XII. Enamines and the Pseudo-pyrrolidinediones1,2Wyman R. Vaughan and Robert C. TrippCite this: J. Am. Chem. Soc. 1960, 82, 16, 4370–4376Publication Date (Print):August 1, 1960Publication History Published online1 May 2002Published inissue 1 August 1960https://pubs.acs.org/doi/10.1021/ja01501a064https://doi.org/10.1021/ja01501a064research-articleACS PublicationsRequest reuse permissionsArticle Views170Altmetric-Citations18LEARN 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
Modifying Ligand-Induced and Constitutive Signaling of the Human 5-HT4 Receptor (2007)

G protein-coupled receptors (GPCRs) signal through a limited number of G-protein pathways and play crucial roles in many biological processes. Studies of their in vivo functions have been hampered by the molecular and functional diversity of GPCRs and the paucity of ligands with specific signaling effects. To better compare the effects of activating different G-protein signaling pathways through ligand-induced or constitutive signaling, we developed a new series of RASSLs (receptors activated solely by synthetic ligands) that activate different G-protein signaling pathways. These RASSLs are based on the human 5-HT(4b) receptor, a GPCR with high constitutive G(s) signaling and strong ligand-induced G-protein activation of the G(s) and G(s/q) pathways. The first receptor in this series, 5-HT(4)-D(100)A or Rs1 (RASSL serotonin 1), is not activated by its endogenous agonist, serotonin, but is selectively activated by the small synthetic molecules GR113808, GR125487, and RO110-0235. All agonists potently induced G(s) signaling, but only a few (e.g., zacopride) also induced signaling via the G(q) pathway. Zacopride-induced G(q) signaling was enhanced by replacing the C-terminus of Rs1 with the C-terminus of the human 5-HT(2C) receptor. Additional point mutations (D(66)A and D(66)N) blocked constitutive G(s) signaling and lowered ligand-induced G(q) signaling. Replacing the third intracellular loop of Rs1 with that of human 5-HT(1A) conferred ligand-mediated G(i) signaling. This G(i)-coupled RASSL, Rs1.3, exhibited no measurable signaling to the G(s) or G(q) pathway. These findings show that the signaling repertoire of Rs1 can be expanded and controlled by receptor engineering and drug selection.
The STE2 gene product is the ligand-binding component of the alpha-factor receptor of Saccharomyces cerevisiae. (1988)

The STE2 gene of Saccharomyces cerevisiae encodes a 431-residue protein containing seven hydrophobic segments that is thought to be an essential component of the cell-surface receptor for alpha-factor in MATa haploids. Methods were devised to prepare membrane fractions from MATa cells that retained high levels of alpha-factor binding activity, consistent with the view that the alpha-factor receptor resides in the plasma membrane. To demonstrate that the membrane constituent responsible for alpha-factor binding was the STE2 polypeptide, specific antibodies were generated and used to identify STE2-related polypeptides by radiolabeling, immunoprecipitation, and polyacrylamide gel electrophoresis. Under conditions of complete solubilization, the major form of the STE2 gene product detected was a glycoprotein with an apparent molecular weight of 49,000. Affinity labeling of yeast membrane preparations by chemical cross-linking to 35S-alpha-factor indicated that a molecule of 49,000 molecular weight was the major alpha-factor-binding species. This alpha-factor-binding species was shown to be the product of the STE2 gene in three ways. First, MATa haploids carrying the STE2 gene on a multicopy plasmid overproduced alpha-factor binding activity about 15-fold. Second, MATa cells completely lacking a STE2 gene showed only nonspecific binding of alpha-factor (equivalent to the level displayed by MAT alpha haploids) and possessed no species that could be cross-linked to 35S-alpha-factor. Third, MATa cells expressing a truncated but functional STE2 gene (in which the COOH-terminal 135-hydrophilic residues were deleted) produced a protein detected by cross-linking to 35S-alpha-factor of apparent molecular weight 33,000, close to the size expected for the predicted abbreviated STE2 polypeptide. These findings demonstrate unequivocally that the STE2 gene product is the membrane component responsible for the ligand recognition function of the yeast alpha-factor receptor.
Nibbling versus Gorging: Metabolic Advantages of Increased Meal Frequency (1989)

We studied the effect of increasing the frequency of meals on serum lipid concentrations and carbohydrate tolerance in normal subjects. Seven men were assigned in random order to two metabolically identical diets. One diet consisted of 17 snacks per day (the nibbling diet), and the other of three meals per day (the three-meal diet); each diet was followed for two weeks. As compared with the three-meal diet, the nibbling diet reduced fasting serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B by a mean (+/- SE) of 8.5 +/- 2.5 percent (P less than 0.02), 13.5 +/- 3.4 percent (P less than 0.01), and 15.1 +/- 5.7 percent (P less than 0.05), respectively. Although the mean blood glucose level and serum concentrations of free fatty acids, 3-hydroxybutyrate, and triglyceride were similar during both diets, during the nibbling diet the mean serum insulin level decreased by 27.9 +/- 6.3 percent (P less than 0.01) and the mean 24-hour urinary C-peptide output decreased by 20.2 +/- 5.6 percent (P less than 0.02). In addition, the mean 24-hour urinary cortisol excretion was lower by 17.3 +/- 5.9 percent (P less than 0.05) at the end of the nibbling diet than at the end of the three-meal diet. The blood glucose, serum insulin, and C-peptide responses to a standardized breakfast and the results of an intravenous glucose-tolerance test conducted at the end of each diet were similar. We conclude that in addition to the amount and type of food eaten, the frequency of meals may be an important determinant of fasting serum lipid levels, possibly in relation to changes in insulin secretion.
Intermediate conductance Ca2+ activated K+ channels are expressed and functional in breast adenocarcinomas: correlation with tumour grade and metastasis status. (2010)

K+ channels are key molecules in the progression of several cancer types and are considered to be potential targets for cancer therapy. In this study, we investigated the intermediate- conductance Ca2+-activated K+ channels (hKCa3.1) expression in both breast carcinoma (BC) specimens and human breast cancer epithelial primary cell cultures (hBCE) using immuno-histochemistry (60 samples), quantitative Real-Time RT-PCR (30 samples) and Western blot assay (30 samples). We also looked at whether or not the expression of these channels is correlated with breast carcinomas grade tumours and metastasis status. Furthermore, we characterized the hKCa3.1 channel activity in hBCE cells by using the Whole Cell Patch Clamp Technique. We found that hKCa3.1 transcripts and proteins were expressed in both BC samples and hBCE cells. Clinicopathologic evaluation indicated a significant correlation between hKCa3.1-expression and tumour grade. hKCa3.1 mRNA and protein were more highly expressed in grade III tumours than in both grades I and II. However, the hKCa3.1 expression-increase according to grade was only observed in tumours with negative metastasis status. Moreover, the hKCa3.1 channels expressed in hBCE cells are functional. This was attested by patch-clamp recordings showing typical hKCa3.1-mediated currents in these cells. In conclusion, these data suggest that hKCa3.1 might contribute to breast tumour-progression and can serve as a useful prognostic marker for breast cancer.
Toward an aggregated understanding of enzymatic hydrolysis of cellulose: Noncomplexed cellulase systems (2004)

Information pertaining to enzymatic hydrolysis of cellulose by noncomplexed cellulase enzyme systems is reviewed with a particular emphasis on development of aggregated understanding incorporating substrate features in addition to concentration and multiple cellulase components. Topics considered include properties of cellulose, adsorption, cellulose hydrolysis, and quantitative models. A classification scheme is proposed for quantitative models for enzymatic hydrolysis of cellulose based on the number of solubilizing activities and substrate state variables included. We suggest that it is timely to revisit and reinvigorate functional modeling of cellulose hydrolysis, and that this would be highly beneficial if not necessary in order to bring to bear the large volume of information available on cellulase components on the primary applications that motivate interest in the subject.
Fabrication and domain imaging of iron magnetic nanowire arrays (1998)

Arrays of magnetic nanowires are fabricated by using a corrugated surface, produced by chromium atoms laser-focused in a one-dimensional standing wave, as a shadow mask for an iron evaporator. The deposited iron forms a periodic array consisting of thousands of 20–40 nm high ferromagnetic lines with width of ∼100 nm, spaced every 213 nm, and having aspect ratios (width:length) of 1:1500. Images of the magnetic domain structures of these nanowires are obtained by scanning electron microscopy with polarization analysis. Elongated domains ∼100 nm wide and ∼16 μm long are observed.
Genetic dissection reveals two separate pathways for rod and cone regeneration in the teleost retina (2008)

Development of therapies to treat visual system dystrophies resulting from the degeneration of rod and cone photoreceptors may directly benefit from studies of animal models, such as the zebrafish, that display continuous retinal neurogenesis and the capacity for injury-induced regeneration. Previous studies of retinal regeneration in fish have been conducted on adult animals and have relied on methods that cause acute damage to both rods and cones, as well as other retinal cell types. We report here the use of a genetic approach to study progenitor cell responses to photoreceptor degeneration in the larval and adult zebrafish retina. We have compared the responses to selective rod or cone degeneration using, respectively, the XOPS-mCFP transgenic line and zebrafish with a null mutation in the pde6c gene. Notably, rod degeneration induces increased proliferation of progenitors in the outer nuclear layer (ONL) and is not associated with proliferation or reactive gliosis in the inner nuclear layer (INL). Molecular characterization of the rod progenitor cells demonstrated that they are committed to the rod photoreceptor fate while they are still mitotic. In contrast, cone degeneration induces both Müller cell proliferation and reactive gliosis, with little change in proliferation in the ONL. We found that in both lines, proliferative responses to photoreceptor degeneration can be observed as 7 days post fertilization (dpf). These two genetic models therefore offer new opportunities for investigating the molecular mechanisms of selective degeneration and regeneration of rods and cones.
17β-Estradiol abrogates apoptosis in murine skeletal muscle cells through estrogen receptors: role of the phosphatidylinositol 3-kinase/Akt pathway (2007)

Estrogens can regulate apoptosis in various cellular systems. The present study shows that 17beta-estradiol (E2), at physiological concentrations, abrogates DNA damage, poly (ADP-ribose) polymerase cleavage, and mitochondrial cytochrome c release induced by H2O2 or etoposide in mouse skeletal muscle C2C12 cells. This protective action, which involved PI3K/Akt activation and Bcl-2 associated death agonist (BAD) phosphorylation, was inhibited by antibodies against the estrogen receptor (ER) alpha or beta isoforms, or transfecting siRNA specific for each isoform. The inhibition of the antiapoptotic action of E2 at the mitochondrial level was more pronounced when ER-beta was immunoneutralized or suppressed by mRNA silencing, whereas transfection of C2C12 cells with either ER-alpha siRNA or ER-beta siRNA blocked the activation of Akt by E2, suggesting differential involvement of ER isoforms depending on the step of the apoptotic/survival pathway evaluated. These results indicate that E2 exerts antiapoptotic effects in skeletal muscle cells which are mediated by ER-beta and ER-alpha and involve the PI3K/Akt pathway.
The Development of a High-Performance Snowmobile Variable Speed Belt (1996)

&lt;div class="htmlview paragraph"&gt;This paper will cover the development of a high-performance snowmobile variable speed belt from concept to successful implementation. The paper includes the definition of the extraordinary demands of this extremely high-performance application, formation and membership of the development team (including the dynamic membership of the team as the development phases were achieved), modeling of the drive geometry and discussion of the vast number of design variables which had to be balanced to achieve both superior drive functionality and belt durability. The end product is described in detail to illustrate the technology employed to address the severe conditions to which the belt is exposed. Finally, the paper details the test methods (both field and laboratory) and development of a unique, application specific, test dynamometer to evaluate the various belt attributes.&lt;/div&gt;
Michael Acceptors as Cysteine Protease Inhibitors (2007)

Cysteine proteases selectively catalyze the hydrolysis of peptide bonds. Uncontrolled, unregulated, or undesired proteolysis can lead to many disease states including emphysema, stroke, viral infections, cancer, Alzheimer's disease, inflammation, and arthritis. Cysteine proteases inhibitors thus have considerable potential utility for therapeutic intervention in a variety of disease states. This review emphasizes on the new developments from literature reports on Michael acceptors as potential cysteine protease inhibitors, namely vinyl sulfones, alpha,beta-unsaturated carbonyl derivatives and aza-peptides. These compounds irreversibly alkylate the active site cysteine residue via conjugate addition. Examples of Michael acceptors inhibitors that have already progressed to clinical testing are also presented.
Gene therapy following subretinal AAV5 vector delivery is not affected by a previous intravitreal AAV5 vector administration in the partner eye. (2009)

These results show that an initial intravitreal injection of AAV vectors to one eye of a mouse does not influence AAV-mediated gene expression or related therapeutic effects in the other eye when vectors are administered to the subretinal space. This suggests that the subretinal space possesses a unique immune privilege relative to the vitreous cavity.
Improved sensitivity to cerebral hemodynamics during brain activation with a time-gated optical system: analytical model and experimental validation (2005)

Time domain (TD) diffuse optical measurement systems are being applied to neuroimaging, where they can detect hemodynamics changes associated with cerebral activity. We show that TD systems can provide better depth sensitivity than the more traditional continuous wave (CW) systems by gating late photons, which carry information about deep layers of the brain, and rejecting early light, which is sensitive to the superficial physiological signal clutter. We use an analytical model to estimate the contrast due to an activated region of the brain, the instrumental noise of the systems, and the background signal resulting from superficial physiological signal clutter. We study the contrast-to-noise ratio and the contrast-to-background ratio as a function of the activation depth and of the source-detector separation. We then present experimental results obtained with a time-gated instrument on the motor cortex during finger-tapping exercises. Both the model and the experimental results show a similar contrast-to-noise ratio for CW and TD, but that estimation of the contrast is experimentally limited by background fluctuations and that a better contrast-to-background ratio is obtained in the TD case. Finally, we use the time-gated measurements to resolve in depth the brain activation during the motor stimulus.
Analysis of Bcl-2, Bax and Survivin genes in uterine cancer. (1999)

To investigate the role of the apoptosis-related genes, Bcl-2, Bax and Survivin genes were analyzed. For the Bax gene, abnormality was detected in 1 of 7 cervical and 1 of 6 endometrial cancer cell lines, 1 of 25 cervical cancer tissues and none of 17 endometrial cancer tissues using PCR-SSCP. In 4 cervical and 2 endometrial cancer cell lines, the ratio of Bcl-2 to Bax expression was higher than the control ratio using Western blotting. Survivin mRNA was detectable in all cell lines and all cancer tissues. The data suggested that these apoptosis-related genes may play important roles in the pathway of carcinogenesis of human uterine cancer.
Enhancement of bone formation by drawn poly(L-lactide) (1996)

Poly(L-lactide) (PLLA) was molded into films and rods, and drawn in the longitudinal direction to endow them with piezoelectricity. The piezoelectric constants of PLLA films increased with the draw ratio and, after passing a maximum at a draw ratio around 5, decreased. PLLA samples with a draw ratio 5 underwent fibrilization. The PLLA rods were intramedullarily implanted in the cut tibiae of cats for internal fixation up to 8 weeks. Fracture healing was clearly promoted with increased callus formation as the draw ratio of the PLLA rod increased, whereas the undrawn PLLA as well as a polyethylene control rod had no effect on callus formation, or rather, retarded it. This finding strongly suggests that the promotion of fracture healing by fixation with drawn PLLA can be ascribed to the piezoelectric current generated by the strains accompanying leg movement.
Dacron arterial grafts: the influence of porosity, velour, and maturity on thrombogenicity. (1982)

It has been claimed that the neointimal healing of Dacron arterial prostheses can be enhanced by increasing porosity and including both an internal and an external velour layer. To test this, 24 patients received at random either woven (USCI, DeBakey, C. R. Bard, Inc.) or more porous, double-velour, knitted (Microvel, Meadox Medicals, Inc.) Dacron aortobifemoral prostheses. Graft thrombogenicity was measured using autogenous 111In-labeled platelets shortly following surgery and 6 to 9 months later. The thrombogenicity index was defined as the mean daily rise in the ratio of emissions over the graft to emissions over a reference area (aortic arch) and is a measure of platelet deposition. At early study the mean (+/- SE) thrombogenicity index was similar in woven and knitted graft patients at 0.19 +/- 0.4 and 0.14 +/- 0.2, respectively. In both groups it was lower (P less than 0.05) 6 to 9 months later at 0.06 +/- 0.2 (woven( and 0.08 +/- 0.1 (knitted), with again no difference between materials. Although platelet survival was restored to near normal values in both groups by 6 to 9 months, only one woven graft failed to demonstrate continued platelet accumulation by gamma-imaging. Thrombogenicity in Dacron grafts diminishes in the early months of maturation but is not affected by porosity and velour. Moreover, this thrombogenicity persists beyond the period of altered platelet survival.
Synthesis and properties of poly(acrylamide)s containing both long chain alkyl groups and phosphatidylcholine analogues in the side chains (1996)

A series of new phospholipid analogous acrylamide monomers (4a–e) containing long alkyl chains as hydrophobic groups and containing phosphatidylcholine analogues as hydrophilic group were synthesized in high yields. The homopolymerizations and copolymerization (4b with 4e) were carried out in the presence of a radical initiator. The structures and thermal properties of these polymers were investigated by x-ray diffraction analysis, DSC, and polarizing microscopy measurements. It has been revealed that these homopolymers (5b, 5c, and 5d) which bear saturated long-hydrocarbon chains in the side chains exhibited not only orderly stacked bilayer structures at room temperature but also clear liquid crystalline behavior within a wide temperature range. The viscosity behavior of all polymers was found similar to usual polyelectrolytes in porlar solvent. The polymers obtained were also characterized by 1H-NMR, IR, and melting point, respectively. © 1996 John Wiley & Sons, Inc.
NEUROPROTECTION AND ENHANCED RECOVERY WITH HYPERICUM PERFORATUM EXTRACT AFTER EXPERIMENTAL SPINAL CORD INJURY IN MICE (2006)

Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants, and/or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidative stress and exaggerated production of reactive oxygen species play a major role in several aspects of inflammation. Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely, flavonoids and phenolic acids. Because polyphenolic compounds have high antioxidant potential, in this study, we evaluated the effect of H. perforatum (given at 30 mg . kg (-1)) in an experimental animal model of spinal cord injury, which was induced by the application of vascular clips to the dura via a four-level T5 through T8 laminectomy. The degree of (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine, (c) poly(adenosine diphosphate-ribose), (d) neutrophils infiltration, and (e) the activation of signal transducer and activator transcription 3 was markedly reduced in spinal cord tissue obtained from H. perforatum extract-treated mice. We have also demonstrated that H. perforatum extract significantly ameliorated the recovery of limb function.