gebhart/patrepeval huggingface dataset:
Chelation-controlled facially selective cyclocondensation reactions of chiral alkoxy aldehydes: syntheses of a mouse androgen and of a carbon-linked disaccharide (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChelation-controlled facially selective cyclocondensation reactions of chiral alkoxy aldehydes: syntheses of a mouse androgen and of a carbon-linked disaccharideSamuel J. Danishefsky, William H. Pearson, Daniel F. Harvey, Clarence J. Maring, and James P. SpringerCite this: J. Am. Chem. Soc. 1985, 107, 5, 1256–1268Publication Date (Print):March 1, 1985Publication History Published online1 May 2002Published inissue 1 March 1985https://pubs.acs.org/doi/10.1021/ja00291a027https://doi.org/10.1021/ja00291a027research-articleACS PublicationsRequest reuse permissionsArticle Views1044Altmetric-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
Peroxisome proliferator‐activated receptor‐γ abrogates Smad‐dependent collagen stimulation by targeting the p300 transcriptional coactivator (2009)

Ligands of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) abrogate the stimulation of collagen gene transcription induced by transforming growth factor-beta (TGF-beta). Here, we delineate the mechanisms underlying this important novel physiological function for PPAR-gamma in connective tissue homeostasis. First, we demonstrated that antagonistic regulation of TGF-beta activity by PPAR-gamma ligands involves cellular PPAR-gamma, since 15-deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)) failed to block TGF-beta-induced responses in either primary cultures of PPAR-gamma-null murine embryonic fibroblasts, or in normal human skin fibroblasts with RNAi-mediated knockdown of PPAR-gamma. Next, we examined the molecular basis underlying the abrogation of TGF-beta signaling by PPAR-gamma in normal human fibroblasts in culture. The results demonstrated that Smad-dependent transcriptional responses were blocked by PPAR-gamma without preventing Smad2/3 activation. In contrast, the interaction between activated Smad2/3 and the transcriptional coactivator and histone acetyltransferase p300 induced by TGF-beta, and the accumulation of p300 on consensus Smad-binding DNA sequences and histone H4 hyperacetylation at the COL1A2 locus, were all prevented by PPAR-gamma. Wild-type p300, but not a mutant form of p300 lacking functional histone acetyltransferase, was able to restore TGF-beta-induced stimulation of COL1A2 in the presence of PPAR-gamma ligands. Collectively, these results indicate that PPAR-gamma blocked Smad-mediated transcriptional responses by preventing p300 recruitment and histone H4 hyperacetylation, resulting in the inhibition of TGF-beta-induced collagen gene expression. Pharmacological activation of PPAR-gamma thus may represent a novel therapeutic approach to target p300-dependent TGF-beta profibrotic responses such as stimulation of collagen gene expression.
The Ionization Behavior of Fatty Acids and Bile Acids in Micelles and Membranes (1984)

The ionization behavior of carboxylic acids including aliphatic chain fatty acids and bile acids in solutions, micelles, membranes and proteins is of considerable biological interest. The 13C nuclear magnetic resonance chemical shift of carboxyl carbon of a variety of acids has been shown to be a linear function of the state of ionization of the carboxyl group. Thus, by measuring the chemical shift as a function of the amount of acid or base added to a solution, the state of ionization and the apparent pKa of the carboxyl group may be determined. The method is illustrated in this paper using butyric acid, and results (given as apparent pKa values) are tabulated for a variety of fatty acids and cholic acid in different environments such as monomeric solutions, micelles, membranes and bound to albumin. The apparent pKa varies greatly depending upon the environment. For instance, the apparent pKa of oleic acid is about 4.2 when bound to albumin whereas it is about 7.5 when incorporated in the bilayer of a phospholipid vesicle. Cholic acid shows similar changes in the apparent pKa, being approximately 5.2 in sodium taurocholate micelles and at least 6.8 in phospholipid vesicles. The use of 13C nuclear magnetic resonance (NMR) and, in particular, 13C NMR of 13C-enriched carboxyl groups provides a method for direct observation of the state of ionization of the carboxyl group in biologically interesting acids. Such techniques may be adapted for use in biological systems, such as cells or tissues.
[Cardiac troponin I and T in unstable angina: incidence, correlation, kinetics of release and prognostic value]. (1996)

Our findings demonstrate that the incidence of altered cTnT and cTnI values in pts with unstable angina is low; there is close agreement between findings for the two proteins; in cases of angina, the cTnT and cTnI release kinetics are different from those in AMI. The finding of altered cTnT and cTnI values in the serum of our pts with unstable angina does not appear to be of prognostic value for future coronary events.
Central Sleep Apnea in Congestive Heart Failure: Prevalence, Mechanisms, Impact, and Therapeutic Options (2005)

Heart failure due to left ventricular systolic dysfunction is a prevalent syndrome and associated with morbidity, mortality, and huge economic cost. According to reports from several laboratories, a large number of patients with heart failure have central sleep apnea. Central sleep apnea causes arousals and sleep disruption, alters blood gases, and increases sympathetic activity. The pathophysiological consequences of central sleep apnea could adversely affect left ventricular structure and functions and worsen prognosis of heart failure. Several treatment options, including use of nocturnal supplemental oxygen, positive airway pressure devices, and theophylline have been systematically studied and have been shown to improve central sleep apnea. Long-term studies, however, are necessary to determine the impact of therapy on natural history of left ventricular systolic dysfunction.
Discovery of a Novel Class of Diacylglycerol Acyltransferase 2 Inhibitors with a 1<i>H</i>-Pyrrolo[2,3-<i>b</i>]pyridine Core (2014)

Diacylglycerol acyltransferase 2 (DGAT2), which catalyzes the final step in triacylglycerol (TG) synthesis, is a key enzyme associated with hepatic steatosis and insulin resistance. Here, using an in vitro screen of 20000 molecules, we identified a class of compounds with a substituted 1H-pyrrolo[2,3-b]pyridine core which proved to be potent and selective inhibitors of human DGAT2. Of these compounds, H2-003 and -005 exhibited a considerable reduction in TG biosynthesis in HepG2 hepatic cells and 3T3-L1 preadipose cells. These compounds exert DGAT2-specific-inhibitory activity, which was further confirmed in DGAT2- or DGAT1-overexpressing HEK293 cells. In addition, these compounds almost completely abolished lipid droplet formation in 3T3-L1 cells when co-treated with a DGAT1 inhibitor, which was not attained using either a DGAT2 or DGAT1 inhibitor alone. Collectively, we identified two DGAT2 inhibitors, H2-003 and -005. These compounds will aid in DGAT2-related lipid metabolism research as well as in therapeutic development for the treatment of metabolic diseases associated with excessive TG.
Identification and characterization of vaccinia virus genes encoding proteins that are highly antigenic in animals and are immunodominant in vaccinated humans (1992)

Vaccinia virus (VV) is a potent immunogen, but the nature of VV proteins involved in the activation of the immune response of the host is not yet known. By screening a lambda gt11 expression library of rabbitpox virus DNA with serum from humans vaccinated against smallpox or with serum from VV-immunized animals, we identified several VV genes that encode highly antigenic viral proteins with molecular masses of 62, 39, 32, 25, 21, and 14 kDa. It was found that VV proteins of 62, 39, 25, and 21 kDa are part of the virus core, while proteins of 32 and 14 kDa are part of the virus envelope. All of these proteins were synthesized at late times postinfection. Proteins of 62 and 25 kDa were produced by cleavage of larger precursors of 95 kDa (p4a) and 28 kDa, respectively. The 21-kDa protein was the result of a cleavage of p4a, presumably at amino acid Gly-697. DNA sequence analysis, in comparison with the known nucleotide sequence of VV, provided identification of the corresponding open reading frames. Expression of the viral genes in Escherichia coli was used to monitor which of the viral antigens elicit immunodominant responses and the location of antigenic domains. Three viral antigens of 62, 39, and 32 kDa exhibited immunodominant characteristics. The most antigenic sites of 62 and 39 kDa were identified at the N terminus (amino acids 132 to 295) and C terminus (last 103 amino acids), respectively. Immunization of mice with the 62-, 39-, or 14-kDa antigenic proteins conferred different degrees of protection from VV challenge. Proteins of 32 and 14 kDa induced cellular proliferative responses in VV-infected mice. Our findings demonstrate the nature of VV proteins involved in the activation of host immune responses after vaccination, provide identification of the viral gene locus, and define structural and immunological properties of these antigenic VV proteins.
The planning of treatment for the tonsillar squamous cell carcinoma (2003)

Objective Radiotherapy alone, radiotherapy with salvage surgery, and planned combination of radiotherapy and surgery were treatment modalities for tonsillar squamous cell carcinoma This study is to discuss the treatment planning for this disease Methods Between 1984 and 2000, 108 patients with tonsillar squamous cell carcinoma were reviewed, including 82 males and 26 females, with ages ranging from 19 to 70 years old The treatment was radical radiotherapy in 83 cases and planned preoperative radiation plus surgery in 25 cases 83 cases of radical radiotherapy were further divided into radiotherapy alone (55 cases) and radiotherapy with salvage surgery (28 cases) For patients with lower differentiated squamous cell carcinoma or Ⅰ Ⅱ staged disease the treatment were radiotherapy alone For patients with moderately or well differentiated squamous cell carcinoma or Ⅲ Ⅳ staged disease the treatment were radiotherapy with salvage surgery or planned preoperative radiation plus surgery 83 2% (79/95) of patients were followed up 5 years after treatment or till the death of patient Survival curves were calculated using the life table method Results For radical radiotherapy, including radiotherapy alone and radiotherapy with salvage surgery, 5 years survival was 59 3% For planned preoperative radiation plus surgery, 5 years survival was 55 3% The difference between the two treatments was not significant in statistics ( P =0 705 6) For Ⅰ Ⅱ staged cases , 5 years survival was 84 2%, and it was 51 7% for Ⅲ Ⅳ staged cases The survival difference between Ⅰ Ⅱ staged and Ⅲ Ⅳ staged patients was significant in statistics ( P =0 005 7) The 5 years survival was 59 8% for 42 cases with lower differentiated, was 48 8% for 45 cases with moderately differentiated , and was 78 3% for 19 cases with well differentiated squamous cell carcinoma, which was not significant in statistics ( P =0 228 8). Conclusion Radiotherapy alone was recommended as the treatment of choice for Ⅰ Ⅱ staged or lower differentiated tonsillar squamous cell carcinoma The radical radiotherapy with salvage surgery or planned preoperative radiation plus surgery were the treatment of choice for Ⅲ Ⅳ staged or well differentiated tonsillar squamous cell carcinoma
The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment (2003)

The three mammalian receptors UNC5H1, UNC5H2, and UNC5H3 (also named UNC5A, UNC5B, and UNC5C in human) that belong to the family of the netrin-1 receptors, UNC5H, were initially proposed as mediators of the chemorepulsive effect of netrin-1 on specific axons. However, they were also recently shown to act as dependence receptors. Such receptors induce apoptosis when unbound to their ligand. We show here that the expression of the human UNC5A, UNC5B, or UNC5C is down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers. In colorectal tumors, this down-regulation is associated with loss of heterozygosity occurring within UNC5A, UNC5B, and UNC5C genes but may also be partially related to epigenetic processes because histone deacetylase inhibitor increased UNC5C expression in various cancer cell lines. Moreover, sequencing of UNC5C gene in patients with colorectal tumors revealed the presence of missense mutations. The lossreduction of expression may be a crucial mechanism for tumorigenicity because the expression of UNC5H1, UNC5H2, or UNC5H3 inhibits tumor cell anchorage-independent growth and invasion. Moreover, these hallmarks of malignant transformation can be restored by netrin-1 addition or apoptosis inhibition. Hence, UNC5H1, UNC5H2, and UNC5H3 receptors may represent tumor suppressors that inhibit tumor extension outside the region of netrin-1 availability by inducing apoptosis.
Comparison of the Immune Profile of Nonhealing Cutaneous Leishmaniasis Patients with Those with Active Lesions and Those Who Have Recovered from Infection (2000)

Th1-type cellular immune responses play a critical role in protection against infection with Leishmania parasites, whereas activation of Th2-type cells results in progressive disease. Cutaneous leishmaniasis caused by Leishmania major is often a self-healing disease; however, persistent nonhealing forms are also known. In the present study, we have described cell-mediated immune responses in nonhealing patients by measuring T-cell proliferation, cytokine production, and phenotypic characterization of these cells. The responses were compared with those of patients with active lesions, patients who had recovered from infection, and healthy controls. Peripheral blood mononuclear cells from patients with active lesions and recovered donors proliferated vigorously and produced Th1-type cytokine when stimulated with L. major antigens, whereas in nonhealing patients the proliferative responses were significantly lower and showed a Th2-type response to Leishmania antigens. Interleukin-10 (IL-10) production was not a feature of L. major stimulation. Flow cytometric analysis revealed that L. major antigen induced proliferation of the CD4-positive population and that these cells were the major source of gamma interferon and IL-4. These results show a distinct dichotomy in the cytokine response to L. major infection.
Carbon Nanotube Interaction with DNA (2005)

We investigate a system consisting of B-DNA and an array of (10,0) carbon nanotubes periodically arranged to fit into the major groove of the DNA. We obtain an accurate electronic structure of the combined system, which reveals that it is semiconducting and that the bands on either end of the gap are derived exclusively from one of the two components. We discuss in detail how this system can be used as either an electronic switch involving transport through both components, or as a device for ultrafast DNA sequencing.
Thrombospondin sequence motif (CSVTCG) is responsible for CD36 binding (1992)

To clarify the role of CD36 as a TSP receptor and to investigate the mechanisms of the TSP-CD36 interaction, transfection studies were performed using CD36-cDNA in a CDM8 plasmid. Jurkat cells transfected with CD36 cDNA express an 88kD membrane surface protein and acquire the ability to bind thrombospondin. The TSP amino acid sequence, CSVTCG, mediates the interaction of thrombospondin with CD36. CD36 transfectants but not control transfectants bind radiolabeled tyrosinated peptide (YCSVTCG). The hexapeptide inhibits thrombospondin expression on activated human platelets and results in diminished platelet aggregation. CSVTCG-albumin conjugates support CD36-dependent adhesion of tumor cells. We conclude that the CSVTCG repeat sequence is a crucial determinant of CD36 thrombospondin binding.
A Key Role of Dendritic Cells in Probiotic Functionality (2007)

Altogether, these results suggest that selected probiotics can stimulate DC regulatory functions by targeting specific pattern-recognition receptors and pathways. The results not only emphasize the role of DCs in probiotic immune interactions, but indicate a possible role in immune-intervention therapy for IBD.
Using Isotropic, Nematic, and Smectic Fluids for the Study of Self-Assembled Monolayers Formed from Alkanethiols on Gold (1996)

The use of isotropic and anisotropic fluids for the study of self-assembled monolayers (SAMs) formed from alkanethiols on gold is reported. A fluid with orientational ordera nematic liquid crystal (NLC)can be used to distinguish between surfaces that differ in molecular-level organization, mesoscale structure, or both, whereas isotropic fluids with the chemical functional groups of the NLC report these surfaces to be the same. A fluid with positional and orientational ordera smectic liquid crystalwas found to be a more sensitive probe of molecular-level “imperfection” in a SAM than a nematic fluid.
Facile and rapid synthesis of highly luminescent nanoparticles via pulsed laser ablation in liquid (2009)

This paper demonstrates the usefulness of pulsed laser ablation in liquids as a fast screening synthesis method able to prepare even complex compositions at the nanoscale. Nanoparticles of Y2O3:Eu3+, Lu2O2S:Eu3+, Gd2SiO5:Ce3+, Lu3TaO7:Gd3+ and Tb3+ are successfully synthesized by pulsed laser ablation in liquids. The phase and stoichiometries of the original materials are preserved while the sizes are reduced down to 5-10 nm. The optical properties of the materials are also preserved but show some small variations and some additional structures which are attributed to the specificities of the nanoscale (internal pressure, inhomogeneous broadening, surface states, etc).
PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis (2017)

In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell-mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking. PRMT5 is the main PRMT responsible for symmetric dimethylation of arginine residues of histones and other proteins. PRMT5 drives embryonic development and cancer, but its role in T cells, if any, has not been investigated. In this article, we show that PRMT5 is an important modulator of CD4<sup>+</sup> T cell expansion. PRMT5 was transiently upregulated during maximal proliferation of mouse and human memory Th cells. PRMT5 expression was regulated upstream by the NF-κB pathway, and it promoted IL-2 production and proliferation. Blocking PRMT5 with novel, highly selective small molecule PRMT5 inhibitors severely blunted memory Th expansion, with preferential suppression of Th1 cells over Th2 cells. In vivo, PRMT5 blockade efficiently suppressed recall T cell responses and reduced inflammation in delayed-type hypersensitivity and clinical disease in EAE mouse models. These data implicate PRMT5 in the regulation of adaptive memory Th cell responses and suggest that PRMT5 inhibitors may be a novel therapeutic approach for T cell-mediated inflammatory disease.
Power scalable mid-infrared supercontinuum generation in ZBLAN fluoride fibers with up to 1.3 watts time-averaged power (2007)

Mid-infrared supercontinuum (SC) extending to ~4.0 mum is generated with 1.3 W time-averaged power, the highest power to our knowledge, in ZBLAN (ZrF(4)-BaF(2)-LaF(3)-AlF(3)-NaF...) fluoride fiber by using cladding-pumped fiber amplifiers and modulated laser diode pulses. We demonstrate the scalability of the SC average power by varying the pump pulse repetition rate while maintaining the similar peak power. Simulation results obtained by solving the generalized nonlinear Schrödinger equation show that the long wavelength edge of the SC is primarily determined by the peak pump power in the ZBLAN fiber.
Characterization of perfluorosulfonic acid polymer coated enzyme electrodes and a miniaturized integrated potentiostat for glucose analysis in whole blood (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharacterization of perfluorosulfonic acid polymer coated enzyme electrodes and a miniaturized integrated potentiostat for glucose analysis in whole bloodD. Jed. Harrison, Robin F. B. Turner, and H. P. BaltesCite this: Anal. Chem. 1988, 60, 19, 2002–2007Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/ac00170a003https://doi.org/10.1021/ac00170a003research-articleACS PublicationsRequest reuse permissionsArticle Views1067Altmetric-Citations174LEARN 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
N-Substituted dibenzoxazepines as analgesic PGE2 antagonists (1993)

8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-acetylhydrazide (1, SC-19220) has been previously reported by us and others to be a PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activities. Analogs of SC-19220, in which the acetyl moiety has been replaced with pyridylpropionyl groups and their homologs, have been synthesized as illustrated by compounds 13 and 29. These and other members of this series have been shown to be efficacious analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure activity relationships within this series.