Structures performance, benefit, cost-study

New technology concepts and structural analysis development needs which could lead to improved life cycle cost for future high-bypass turbofans were studied. The NASA-GE energy efficient engine technology is used as a base to assess the concept benefits. Recommended programs are identified for attaining these generic structural and other beneficial technologies

The identification of tyrosine as a common key residue in unrelated H-2Kd restricted antigenic peptides

we have compared the activity of several Kd-or Ld-restricted antigenic peptides as competitors in a functional competition assay using cytolytic T lymphocyte (CTL) clones. All of four unrelated Kd-restricted peptides tested could compete with each other but not with the Ld-restricted peptide P91A-.12-24 (P91A). Moreover, the P91A peptide falled to compete with the four Kd-restricted peptides. In contrast, another Ld-restricted peptide[mouse cytomegalovirus (MCMV) pp89 167-176] could clearly compete with both Kd- and Ld-restricted peptides. The comparison of a series of modified MCMV pp89 peptides suggested that distinct structural features allow the Interaction of the peptide with the two different MHC class I molecules. We showed previously that the competitor activity of two different Kd-restricted antigenic peptides was reduced substantially upon Ala substitution of the single Tyr residues present in these peptides. We now show a similar effect for two additional Kd-restricted peptides. Our results thus suggest that Tyr may function as an ‘anchor' residue for many antigentic peptides that bind to the Kdmolecule. Molecular modeling of the presumed antigen-binding site of the Kdmolecule revealed the presence of two deep cavities that may be involved in binding peptide amino acid side chains. A model Illustrating one possible interaction of a Tyr-containing peptide with the Kdmolecule is presente

Efectos de la genisteína en los niveles del Ca2+ citosólico en células musculares de arteria umbilical humana

Isoflavones are a group of natural phytoestrogens including the compound genistein. Health beneficial effects have been attributed to the consumption of this compound, but the fact that it has estrogen-like activity has raised doubts regarding its potential risk in infants, newborns, or in the fetus and placenta during pregnancy. This work is aimed at studying genistein effects on Ca2+ handling by smooth muscle cells of the human umbilical artery (HUA). Using fluorometric techniques, we found that in these cells genistein reduces the intracellular Ca2+ peak produced by serotonin. The same result could be demonstrated in absence of extracellular Ca2+, suggesting that the isoflavone reduces Ca2+ release from the sarcoplasmic reticulum. Force measurement experiments strengthen these results, since genistein reduced the peak force attained by intact HUA rings stimulated by serotonin in a Ca2+-free solution. Moreover, genistein induced the relaxation of HUA rings precontracted either with serotonin or a depolarizing high-extracellular K+ solution, hinting at a reduction of extracellular Ca2+ entry to the cell. This was confirmed by whole-cell patch-clamp experiments where it was shown that the isoflavone inhibits ionic currents through voltage-operated Ca2+ channels. In summary, we show that genistein inhibits two mechanisms that could increase intracellular Ca2+ in human umbilical smooth muscle cells, behaving in this way as a potential vasorelaxing substance of fetal vessels. Taking into account that genistein is able to cross the placental barrier, these data show that isoflavones may have important implications in the regulation of feto-maternal blood flow in pregnant women who consume soy-derived products as part of their meals.Facultad de Ciencias Exacta

The identification of tyrosine as a common key residue in unrelated H-2Kd restricted antigenic peptides

We have compared the activity of several Kd- or Ld-restricted antigenic peptides as competitors in a functional competition assay using cytolytic T lymphocyte (CTL) clones. All of four unrelated Kd-restricted peptides tested could compete with each other but not with the Ld-restricted peptide P91A-. 12-24 (P91A). Moreover, the P91A peptide failed to compete with the four Kd-restricted peptides. In contrast, another Ld-restricted peptide [mouse cytomegalovirus (MCMV) pp89 167-176] could clearly compete with both Kd- and Ld-restricted peptides. The comparison of a series of modified MCMV pp89 peptides suggested that distinct structural features allow the interaction of the peptide with the two different MHC class I molecules. We showed previously that the competitor activity of two different Kd-restricted antigenic peptides was reduced substantially upon Ala substitution of the single Tyr residues present in these peptides. We now show a similar effect for two additional Kd-restricted peptides. Our results thus suggest that Tyr may function as an 'anchor' residue for many antigenic peptides that bind to the Kd molecule. Molecular modeling of the presumed antigen-binding site of the Kd molecule revealed the presence of two deep cavities that may be involved in binding peptide amino acid side chains. A model illustrating one possible interaction of a Tyr-containing peptide with the Kd molecule is presented

Two-Dimensional Infrared Spectroscopy of Antiparallel β-Sheet Secondary Structure

We investigate the sensitivity of femtosecond Fourier transform two-dimensional infrared spectroscopy to protein secondary structure with a study of antiparallel β-sheets. The results show that 2D IR spectroscopy is more sensitive to structural differences between proteins than traditional infrared spectroscopy, providing an observable that allows comparison to quantitative models of protein vibrational spectroscopy. 2D IR correlation spectra of the amide I region of poly-L-lysine, concanavalin A, ribonuclease A, and lysozyme show cross-peaks between the IR-active transitions that are characteristic of amide I couplings for polypeptides in antiparallel hydrogen-bonding registry. For poly-L-lysine, the 2D IR spectrum contains the eight-peak structure expected for two dominant vibrations of an extended, ordered antiparallel β-sheet. In the proteins with antiparallel β-sheets, interference effects between the diagonal and cross-peaks arising from the sheets, combined with diagonally elongated resonances from additional amide transitions, lead to a characteristic “Z”-shaped pattern for the amide I region in the 2D IR spectrum. We discuss in detail how the number of strands in the sheet, the local configurational disorder in the sheet, the delocalization of the vibrational excitation, and the angle between transition dipole moments affect the position, splitting, amplitude, and line shape of the cross-peaks and diagonal peaks.

Small bowel carcinomas in celiac or Crohn's disease: Distinctive histophenotypic, molecular and histogenetic patterns

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (β-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage- and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear β-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat β-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and/or pancreatobiliary-type) mucosa, often through dysplastic polypoid growths of metaplastic phenotype. In conclusion, despite their common origin in a chronically inflamed mucosa, celiac disease-associated and Crohn's disease-associated small bowel carcinomas differ substantially in histological structure, phenotype, microsatellite instability/tumor-infiltrating lymphocyte status, Wnt pathway activation, mucosal precursor lesions and prognosis

Homocysteinylated Albumin Promotes Increased Monocyte-Endothelial Cell Adhesion and Up-Regulation of MCP1, Hsp60 and ADAM17

RATIONALE:The cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties. OBJECTIVE:Aim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels. METHODS AND RESULTS:Treated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-α released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2. CONCLUSIONS:Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling

Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomised, double-blind, placebo-controlled, crossover study

Over the last decade, Asian ginseng (Panax ginseng) has been shown to improve aspects of human cognitive function. American ginseng (Panax quinquefolius) has a distinct ginsenoside profile from P. ginseng, promising cognitive enhancing properties in preclinical studies and benefits processes linked to human cognition. The availability of a highly standardised extract of P. quinquefolius (Cereboost (TM)) led us to evaluate its neurocognitive properties in humans for the first time. This randomised, double-blind, placebo-controlled, crossover trial (N = 32, healthy young adults) assessed the acute mood, neurocognitive and glycaemic effects of three doses (100, 200 400 mg) of Cereboost (TM) (P. quinquefolius standardised to 10.65% ginsenosides). Participants' mood, cognitive function and blood glucose were measured 1, 3 and 6 h following administration. There was a significant improvement of working memory (WM) performance associated with P. quinquefolius. Corsi block performance was improved by all doses at all testing times. There were differential effects of all doses on other WM tasks which were maintained across the testing day. Choice reaction time accuracy and 'calmness' were significantly improved by 100 mg. There were no changes in blood glucose levels. This preliminary study has identified robust working memory enhancement following administration of American ginseng. These effects are distinct from those of Asian ginseng and suggest that psychopharmacological properties depend critically on ginsenoside profiles. These results have ramifications for the psychopharmacology of herbal extracts and merit further study using different dosing regimens and in populations where cognition is fragile

Hunter–gatherer mobility and technological landscapes in southernmost South America: a statistical learning approach

The present work aims to quantitatively explore and understand the relationship between mobility types (nautical versus pedestrian), specific technological traits and shared technological knowledge in pedestrian hunter–gatherer and nautical hunter–fisher–gatherer societies from the southernmost portion of South America. To that end, advanced statistical learning techniques are used: state-of-the-art classification algorithms and variable importance analyses. Results show a strong relationship between technological knowledge, traits and mobility types. Occupations can be accurately classified into nautical and pedestrian due to the existence of a non-trivial pattern between mobility and a relatively small fraction of variables from some specific technological categories. Cases where the best-fitted classification algorithm fails to generalize are found significantly interesting. These instances can unveil lack of information, not enough entries in the training set, singular features or ambiguity, the latter case being a possible indicator of the interaction between nautical and pedestrian societies.HAR-2009-06996, CSD2010-00034, HAR2017- 90883-REDC, CULM-HAR2016-77672-P (Ministerio de Ciencia e Innovacio´n de Espan˜ a); PIP-0706, PIP-0348 (Consejo Nacional de Investigaciones Cientı´ficas y Tecnolo´gicas-Argentina) and PICT 2012-2148 (Ministerio de Ciencia, Tecnologı´a e Innovacio´n Productiva de la Repu´ blica Argentina); PROC/12-120610-A (SESAR WPE Long Term and Innovative Research-European Commission); and Project GR-7846 (Wenner-Gren Foundation for Anthropological Research