gebhart/patrepeval huggingface dataset:
Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial (2005)

BACKGROUND: DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. PATIENTS AND METHODS: Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 x 1014 molecules) or peptides (10 versus 100 mug/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. RESULTS: The GMP process allowed to harvest about 5 x 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. CONCLUSION: The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration.
Increased protein nitrosylation in head and neck squamous cell carcinogenesis (2000)

Increasing amounts of nitrotyrosine staining were found in reactive/dysplastic and HNSCCa lesions compared to normal squamous mucosa. Inflammatory cell staining implicates NO. as a possible mediator of immunosuppression. Given these findings, the role of NO. in mutations leading to and the immunosuppression found in HNSCCa warrants further investigation.
Propaganda revolucionaria en Filipinas: el Resumen y la Liga Filipina. (1998)

Sin resumen
Improvement of nutritional value and functional properties of soybean glycinin by protein engineering (1990)

Glycinin is one of the predominant storage proteins of soybean. To improve its functional properties (heat-induced gelation and emulsification) and/or nutritional value, the A1aB1b proglycinin subunit was modified on the basis of genetically variable domains suggested from the comparison of amino acid sequences of glycinin-type globulins from various legumes and nonlegumes and the relationships between the structure and the functional properties of glycinin. Thus, nucleotide sequences corresponding to each of the variable domains were deleted from the cDNA encoding the A1aB1b proglycinin, and a synthetic DNA encoding four continuous methionines was inserted into the cDNA region corresponding to each of the variable domains. Expression plasmids carrying the modified cDNAs were constructed and expressed in Escherichia coli strain JM105. Some of the modified proteins were accumulated as soluble proteins in the cells at a high level and self-assembled. They exhibited functional properties superior to those of the native glycinin from soybean, which establishes the possibility of creating theoretically designed novel glycinins with high food qualities.
Effect of renal nerve stimulation on NaCl and H2O transport in Henle's loop of the rat (1982)

To assess the effect of renal nerve stimulation on sodium, chloride, and water transport in the loop of Henle, experiments were performed in anesthetized hydropenic and isotonic saline volume-expanded rats using renal clearance and Henle's loop microperfusion techniques (end-proximal convoluted tubule perfusion site, early distal convoluted tubule collection site). As compared with the control period values, low-frequency (less than 1.0 Hz) renal nerve stimulation decreased absolute and fractional urinary flow rate and sodium and chloride excretion without affecting mean arterial pressure, glomerular filtration rate, renal blood flow, or renal vascular resistance. In the loop of Henle, the absorptive transport of water was not affected, whereas the absorptive transport of sodium and chloride was increased in both hydropenic (Na 111 +/- 49 peq/min) and isotonic saline volume-expanded rats (Na 154 +/- 69 peq/min, Cl 180 +/- 52 peq/min) during low-frequency renal nerve stimulation. Low-frequency renal nerve stimulation decreases urinary sodium and chloride excretion via a direct effect of increasing renal tubular sodium and chloride reabsorption. In addition to the established effect of increasing proximal tubular sodium reabsorption, Henle's loop sodium and chloride absorption are also increased, supporting a physiological role for the adrenergic innervation of these structures.
DNA MISMATCH CORRECTION (1987)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Improved methodology for the evaluation of the velocity of clearance of indocyanine green in the rat. (1991)

Velocity of clearance of indocyanine green (ICG) is used for the measurement of liver function. Thirty-nine curves of ICG concentration vs. time, from 24 rats, were evaluated for the best method for the determination of the initial velocity of clearance of ICG. A bolus dose of ICG (0.66 +/- 0.10 mg/kg) was given, and [ICG] was recorded once per second for the 270 seconds from 30 seconds to 5 minutes after ICG administration with the aid of computer-assisted data acquisition. The 39 observed curves were then fit to six equations: a second- and third-order polynomial, the mathematical constant e raised to a first- (first-order kinetics), second-, and third-order polynomial, and an integrated form of the Michaelis-Menten equation. The residual errors of the fitted equation to the observed data were evaluated. First-order kinetics and an integrated form of the Michaelis-Menten equation were the least accurate methods of describing the [ICG]-time curve. The curve was better described by three equations: a third-order polynomial, e raised to a second-order polynomial, and e raised to a third-order polynomial. We recommend that one of the latter three equations be used in the determination of the initial velocity of clearance of ICG.
Metal–insulator–semiconductor structure on GaAs using a pseudomorphic Si/GaP interlayer (1997)

We report on a novel GaAs metal–insulator–semiconductor (MIS) structure exhibiting the interface state densities in the 9.2×1010 eV−1 cm−2 with a Si (10 Å)/GaP (12 Å) layer on GaAs. The structure was grown by a combination of molecular beam epitaxy and chemical vapor deposition. The hysteresis and frequency dispersion of the MIS capacitor were lower than 100 mV, some of them as low as 70 mV under a field swing of about ±1.4 MV/cm. Ex situ solid phase annealing around 500–550 °C in N2 using rapid thermal annealing was high enough to recrystallize the as-deposited Si interlayer at low temperature (∼300 °C). The 100 kHz frequency response at 77 K suggests that the interface pinning levels are close to the conduction band edge of GaAs. This article reports the first application of a pseudomorphic Si/GaP interlayer to ideal GaAs MIS diodes and exhibits a favorable interface stability with high temperature annealing.
The VIVA Trial (2003)

rhVEGF seems to be safe and well tolerated. rhVEGF offered no improvement beyond placebo in all measurements by day 60. By day 120, high-dose rhVEGF resulted in significant improvement in angina and favorable trends in ETT time and angina frequency.
Gallstone Formation and Weight Loss (1993)

Obesity is associated with increased bile stasis and cholesterol saturation, and an increased risk of gallstone development. Conversely, bile composition is normalized following reduction in body weight. It would appear advantageous to promote weight loss in obesity, which would reduce the predisposition to gallstone formation. Despite the potential health benefits of weight reduction, very-low-calorie diets appear to increase the risk for cholesterol crystal and gallstone formation. The incidence of gallstone formation seems to be dependent on the degree of caloric restriction, the rate of weight loss, and the duration of the dietary intervention. Thus, faster rates of weight loss for longer periods of time are associated with increased risk. Available data obtained from prospective studies of subjects during active weight loss suggest that newly formed gallstones occur within 4 weeks and with incidence rates 15 to 25-fold higher than in the general obese population. The stones produce symptoms in approximately one-third of the subjects, of whom approximately one-half will undergo surgery. Proposed mechanisms underlying gallstone formation during weight reduction include bile stasis due to reduced caloric intake, increased biliary cholesterol saturation secondary to increased cholesterol mobilization, and increased nucleation due to changes in bile arachidonate and glycoprotein concentrations. Data are lacking on the effects of gradual rates of weight loss and risk of gallstone formation.
In Vitro Systems for Tissue Engineering (2002)

Tissue engineering, by necessity, encompasses a wide array of experimental directions and scientific disciplines. In vitro tissue engineering involves the manipulation of cells in vitro, prior to implantation into the in vivo environment. In contrast, in vivo tissue engineering relies on the body's natural ability to regenerate over non-cell-seeded biomaterials. Cells, biomaterials, and controlled incubation conditions all play important roles in the construction and use of modern in vitro systems for tissue engineering. Gene delivery is also an important factor for controlling or supporting the function of engineered cells both in vitro and post implantation, where appropriate. In this review, systems involved in the context of in vitro tissue engineering are addressed, including bioreactors, cell-seeded constructs, cell encapsulation, and gene delivery. Emphasis is placed upon investigations that are more directly linked to the treatment of clinical conditions.
α-Lithiation of N-(tert-Butoxycarbonyl)-N-(p- methoxyphenyl)allylamines Mediated by (−)-Sparteine:  Enantioselective Syntheses of Either Enantiomer of 3-Substituted Enecarbamates (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTα-Lithiation of N-(tert-Butoxycarbonyl)-N-(p- methoxyphenyl)allylamines Mediated by (−)-Sparteine: Enantioselective Syntheses of Either Enantiomer of 3-Substituted EnecarbamatesGerald A. Weisenburger and Peter BeakView Author Information Department of Chemistry University of Illinois at Urbana−Champaign Urbana, Illinois 61801 Cite this: J. Am. Chem. Soc. 1996, 118, 48, 12218–12219Publication Date (Web):December 4, 1996Publication History Received12 August 1996Published online4 December 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja962793ohttps://doi.org/10.1021/ja962793orapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views687Altmetric-Citations85LEARN 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 SUBJECTS:Absolute configuration,Chemical reactions,Electrophiles,Molecular structure,Substitution reactions Get e-Alerts
Efficacy and safety of dendrimer nanoparticles with coexpression of tumor necrosis factor-&alpha; and herpes simplex virus thymidine kinase in gene radiotherapy of the human uveal melanoma OCM-1 cell line (2013)

Human uveal melanoma is the most common primary intraocular tumor, and brachytherapy is one of the most common and effective treatment strategies. In order to find a safer and more effective way to increase the radio sensitivity of the tumor, we tried to use the dendrimer nanoparticle performing coexpression gene radiotherapy. In this study, we constructed recombinant DNA plasmids (early growth response-1 tumor necrosis factor-α [pEgr1-TNFα], pEgr1 thymidine kinase [TK], and pEgr1-TNFα-TK) according to the Egr1 promoter sequence. The sequences of human TNFα and herpes simplex virus (HSV) TK that were published by GenBank. Agarose gel electrophoresis and DNA sequencing had proven that we constructed the double-gene recombined plasmids pEgr1-TNF-TK correctly, as well as the plasmids pEgr1-TNFα and pEgr1-TK. The dendrimer nanoparticles combined with plasmid DNA as dendriplexes were verified with agarose gel electrophoresis and observed by transmission electron microscopy (TEM) and scanning electron microscopy to define size and shape. Zeta potential was measured using a Zetasizer analyzer. Optimal size and neutral zeta-potential characteristics of dendriplexes were achieved for the transfection studies. DNase I examination proved that the dendriplexes could protect plasmid DNA for at least 6 hours. The recombinant plasmids were transfected with dendrimer nanoparticles into the human choroidal melanoma OCM-1 cell line, followed by exposure to iodine-125 ((125)I) after transfection. After transfection with dendrimer nanoparticles and the irradiation of (125)I, the gene expressions of TNFα and HSV1-TK were significantly increased at the protein level by enzyme-linked immunosorbent assay and Western blot analysis in OCM-1 cells. The cellular morphology of OCM-1 cells altering was observed by TEM, and a decrease in cell proliferation was revealed in cell-growth curves. Flow cytometry of annexin V/propidium iodide double-dyeing apoptosis and caspase-3 fluorescence staining showed that this treatment method could turn transfected OCM-1 cells into apoptosis and necrosis by the effects of the gene expression. This study indicated that the dendrimer nanoparticles with coexpression of TNF-α and HSV1-TK gene therapy are effective and safe and can provide us with a novel strategy to treat human uveal melanoma in the future.
Analysing Argumentative Strategies: A Reply to a Complaint. (1995)

An analysis of discourse focuses on argumentative strategies used in reply to a complaint. The complaint was in the form of a letter, in English, written to a breakfast cereal company, expressing concern about a stone found in the product. The response, also in letter form, is examined for its text strategy. These elements are discussed: the letter's interactive framework using firstand second-person references, which signals involvement; increasing text complexity within the main body of the letter; expository text suggesting careful thought; use of text patterns signaling concession; a conclusion with a false suggestion of coherence; and patterns corresponding to rhetorical structure theory. It is noted that when the text was presented to 6 national speakers of English and 18 students of English as a Second Language, who were then asked to point out the portion they thought represented the essence of the text as a whole, the two groups selected different paragraphs. Contains 20 references. (MSE) *********************************************************************** * Reproductions supplied by EDRS are the best that can be made * * from the original document. * ************************************************************k********** Analyzing Argumentive Strategies: A Reply to a Complaint
DNA methylation controls Foxp3 gene expression (2008)

Compelling evidence suggests that Foxp3-expressing CD25(+)CD4(+) regulatory T cells (Treg) are generated within the thymus as a separate lineage. However, Foxp3(+)CD4(+) Treg can also be generated de novo in a TGF-beta-dependent process from naive T cells by TCR triggering. Recently, we have shown that naturally occurring, but not in vitro TGF-beta-induced Foxp3(+) Treg display stable Foxp3 expression that was associated with selective demethylation of an evolutionarily conserved element within the Foxp3 locus named TSDR (Treg-specific demethylated region). Here, we report that inhibition of DNA methylation by azacytidine, even in absence of exogenous TGF-beta, not only promoted de novo induction of Foxp3 expression during priming, but also conferred stability of Foxp3 expression upon restimulation. Most notably, such stable Foxp3 expression was found only for cells displaying enhanced TSDR demethylation. In contrast, in vitro TSDR methylation diminished its transcriptional activity. Foxp3(+) Treg generated in vivo by DEC-205-mediated targeting of agonist ligands to dendritic cells showed long-term survival in the absence of the inducing antigen and exhibited efficient TSDR demethylation. Together, our data suggest that TSDR is an important methylation-sensitive element regulating Foxp3 expression and demonstrate that epigenetic imprinting in this region is critical for establishment of a stable Treg lineage.
Sunlight and Breast Cancer Incidence in the USSR (1990)

Epidemiological and laboratory evidence suggest that vitamin D may play a role in reducing risk of breast cancer. Lack of exposure to ultraviolet sunlight can increase the prevalence of vitamin D deficiency, and may place some populations at higher risk of breast cancer. The association between total average annual sunlight energy striking the ground and age-adjusted breast cancer incidence rates in the USSR was evaluated. Breast cancer had a threefold range of incidence. Sunlight levels varied from 210 to 400 calories per cm2 per day. A statistically significant negative association was found between breast cancer incidence rates and total sunlight levels (R = -0.75, p = 0.001). The slope of the regression line corresponded to two additional cases per 100,000 per year for each reduction of 35 calories per cm2 of sunlight. The pattern of increased breast cancer incidence in regions of low solar radiation in the USSR is consistent with the geographical pattern seen for breast cancer mortality in the US and worldwide. A positive relationship between socioeconomic status and breast cancer incidence was also present in the Soviet Union, based on an approximate socioeconomic measure, the number of doctors per 1000 population (R = +0.89, p = 0.0001). The possibility that correlates of socioeconomic status, such as dietary, ethnic, or behavioural factors, could account for the association is discussed.
Alternate mRNA Splicing in Multiple Human Tryptase Genes Is Predicted to Regulate Tetramer Formation (2008)

Tryptases are serine proteases that are thought to be uniquely and proteolytically active as tetramers. Crystallographic studies reveal that the active tetramer is a flat ring structure composed of four monomers, with their active sites arranged around a narrow central pore. This model explains why many of the preferred substrates of tryptase are short peptides; however, it does not explain how tryptase cleaves large protein substrates such as fibronectin, although a number of studies have reported in vitro mechanisms for generating active monomers that could digest larger substrates. Here we suggest that alternate mRNA splicing of human tryptase genes generates active tryptase monomers (or dimers). We have identified a conserved pattern of alternate splicing in four tryptase alleles (alphaII, betaI, betaIII, and deltaI), representing three distinct tryptase gene loci. When compared with their full-length counterparts, the splice variants use an alternate acceptor site within exon 4. This results in the deletion of 27 nucleotides within the central coding sequence and 9 amino acids from the translated protein product. Although modeling suggests that the deletion can be easily accommodated by the enzymes structurally, it is predicted to alter the specificity by enlarging the S1' or S2' binding pocket and results in the complete loss of the "47 loop," reported to be critical for the formation of tetramers. Although active monomers can be generated in vitro using a range of artificial conditions, we suggest that alternate splicing is the in vivo mechanism used to generate active tryptase that can cleave large protein substrates.
THE FRIES ISOMERIZATION OF ACETYL AND BENZOYL ESTERS OF UMBELLIFERONES (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE FRIES ISOMERIZATION OF ACETYL AND BENZOYL ESTERS OF UMBELLIFERONESD. N. SHAH and N. M. SHAHCite this: J. Org. Chem. 1954, 19, 10, 1681–1685Publication Date (Print):October 1, 1954Publication History Published online1 May 2002Published inissue 1 October 1954https://pubs.acs.org/doi/10.1021/jo01375a018https://doi.org/10.1021/jo01375a018research-articleACS PublicationsRequest reuse permissionsArticle Views309Altmetric-Citations13LEARN 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
High-sensitivity molecular sensing using hollow-core photonic crystal fiber and surface-enhanced Raman scattering (2010)

A high-sensitivity molecular sensor using a hollow-core photonic crystal fiber (HCPCF) based on surface-enhanced Raman scattering (SERS) has been experimentally demonstrated and theoretically analyzed. A factor of 100 in sensitivity enhancement is shown in comparison to direct sampling under the same conditions. With a silver nanoparticle colloid as the SERS substrate and Rhodamine 6G as a test molecule, the lowest detectable concentration is 10(-10) M with a liquid-core photonic crystal fiber (LCPCF) probe, and 10(-8) M for direct sampling. The high sensitivity provided by the LCPCF SERS probe is promising for molecular detection in various sensing applications.