OH* Chemiluminescence: Pressure Dependence of O + H + M = OH* + M

The measure of chemiluminescence from the transition of the hydroxyl radical from its electronically excited state (A^2 Sigma^positive) to its ground state (X^2 Pi) is used in many combustion applications for diagnostic purposes due to the non-intrusive nature of the chemiluminescence measurement. The presence of the ultraviolet emission at 307nm is often used as an indicator of the flame zone in practical combustion systems, and its intensity may be correlated to the temperature distribution or other parameters of interest. To date, the measurement of the excited state OH, OH*, is mostly qualitative. With the use of an accurate chemical kinetics model, however, it is possible to obtain quantitative measurements. Shock-tube experiments have been performed in highly diluted mixtures of H2/O2/Ar at a wide range of pressures to evaluate the pressure-dependent rate coefficient of the title reaction. In such mixtures the main contributing reaction to the formation of OH* is, O H M = OH* M. R1 Previous work has determined the reaction rate of R1 at atmospheric conditions and accurately predicts the amount of OH* experimentally produced. At elevated pressures up to 15 atm, which are of interest to the gas turbine community, the currently used reaction rate of R1 (i.e., without any pressure dependence) significantly over predicts the amount of OH* formed. This work provides the pressure dependence of R1. The new reaction rate is able to reproduce the experimental data over the range of conditions studied and enables quantitative measurements applicable to practical combustion environments

Improving vaccine production with a serum-free medium for MRC-5 cells

MRC-5 cells are used for vaccine production, including varicella zoster virus, MMR, polio, rotavirus, rabies, hepatitis A, and dengue virus. As human diploid fibroblast cells, MRC-5 can be passaged for about 42-48 population doublings before they become senescent. Vaccine manufacturers generally culture diploid cells in classical medium with 10% serum. Due to the limited population doublings, there is a short window for adaptation to serum-free medium and successful scale-up for vaccine production. Here, we report the development of a serum-free medium for MRC-5 cells that allows for direct adaptation and reaches comparable doubling times and virus titers as serum-containing medium. Using metabolite analysis and a design of experiment rationale, we developed a serum-free medium for growth of MRC-5 cells that can support direct recovery from thaw and adaptation-free expansion, while resulting in performance that is comparable to serum-containing medium. Since requirements for production of viruses are different from cell growth, we optimized the production medium separately. With the animal-origin-free production medium, manufacturers can produce vaccines without concern about the bovine serum albumin limit of 50ng/dose as set by the WHO. We confirmed virus production with varicella zoster virus and vesicular stomatitis virus (as an analog to rabies virus) and demonstrate titers that are up to one log higher than classical medium control. Taken together, we have developed a serum-free medium for MRC-5 cells that supports growth and virus production. By switching to a serum-free process, vaccine manufacturers can reduce dependency on serum, production and purification costs, and increase product consistency and safety

C6orf10 low-frequency and rare variants in italian multiple sclerosis patients

In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (p-value <= 5 x 10(-6)). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) <= 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of C6orf10 rs 16870005 and IL2RA rs12722600 were significantly higher (i.e., controls gnomAD, p = 9.89 x 10(-7) and p < 1 x 10(-20)). TET2 rs61744960 and TRAF3 rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of C6orf10 rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the HLA-DRB1 locus. Sequencing in the MS cohort of the C6orf10 3' region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the C6orf10 rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The C6orf10 Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS.In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (p-value ≤ 5 × 10−6). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) ≤ 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of C6orf10 rs16870005 and IL2RA rs12722600 were significantly higher (i.e., controls gnomAD, p = 9.89 × 10−7 and p < 1 × 10−20). TET2 rs61744960 and TRAF3 rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of C6orf10 rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the HLA-DRB1 locus. Sequencing in the MS cohort of the C6orf10 3′ region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the C6orf10 rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The C6orf10 Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS

Human lunar lander system design, cost estimation and technology roadmaps

This paper describes the methodology developed at Politecnico di Torino to support the European Space Agency in the Human Lunar Landing System design activity and to complement the traditional conceptual design with a multidisciplinary set of analyses which includes a thorough assessment of the economic and technological viability of the solution. The paper briefly describes the logic laying behind each of these analyses and it shows the results of the validation of the integrated design methodology, called iDREAM, with an already existing case study, the Exploration Systems Architecture Study-Lunar Surface Access Module spacecraft (ESAS-LSAM). The results are satisfactory and reveals errors lower than 10% in average, perfectly in line with the expectations of a conceptual design phase

Análisis de Emisiones, Huella Hídrica y Balances Energéticos de la Producción de Bioetanol y co-Productos ACABIO Coop. Limitada 2016-2017

Análisis de la cadena productiva de bioetanol a partir de maíz de ACABIO desde la etapa agrícola hasta la etapa de industrialización en la planta de Villa María (Córdoba). A nivel nacional se ha acentuado un déficit crónico de energía provocado por el creciente agotamiento de las fuentes fósiles en explotación unido a un crecimiento sostenido de los consumos. Esto ha provocado una creciente dependencia de importaciones de combustibles líquidos y gaseosos con la consiguiente pérdida de divisas para el país impacto en la balanza de pagos etc. A nivel nacional, a partir del 2010 se acentuó un déficit crónico de energía provocado por el creciente agotamiento de las fuentes fósiles en explotación unido a un crecimiento sostenido de los consumos. Esto provocó una creciente dependencia de importaciones de combustibles líquidos y gaseosos con la consiguiente pérdida de divisas para el país y su impacto en la balanza de pagos (en 2013 se produce un record de importaciones por 13000 millones de dólares). Posteriormente debido al estancamiento económico y la explotación de yacimientos no convencionales la importación se reduce en volumen y posteriormente en monto por la baja del precio internacional del petróleo. A partir del 2016 se produce un cambio de política que incluye el fomento a las energías renovables para incorporar a la matriz energética 1000 MW año incorporando para el 2025 10000MW a la matriz. Esto junto a un incremento en la producción de shale gas y shale oil posibilitarían el autoabastecimiento en los próximos años.Instituto de Ingeniería RuralFil: Hilbert, Jorge Antonio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Ingeniería Rural; ArgentinaFil: Carballo, Stella Maris. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Clima y Agua; ArgentinaFil: Manosalva, Jonatan. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Ingeniería Rural; ArgentinaFil: Michard, Nicole Jacqueline. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Vitale, Juan Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Sistemas de Información Geográficos y Sensores Remotos; ArgentinaFil: Donato, Lidia Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Ingeniería Rural; ArgentinaFil: Galbusera, Sebastián. Ministerio de Ambiente y Desarrollo Sustentable de la Nación. Dirección de Cambio Climático; ArgentinaFil: Schein, Leila. Zoom Sustentable; Argentin

Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer

The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo

Brain dysfunction in tubular and tubulointerstitial kidney diseases

Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research

Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell of origin

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylation(low) tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylation(low)/IFNsign(high) and Methylation(high)/IFNsign(low) PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived Kras(G12D)/Trp53(−/−) mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylation(low)/IFNsign(high) subtype potentially targetable by agents blocking intrinsic IFN-signaling

Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated with First-Line Stavudine-Containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine

Background The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. Methods We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. Results Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. Conclusions Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therap

Global study of social odor awareness

Olfaction plays an important role in human social communication, including multiple domains in which people often rely on their sense of smell in the social context. The importance of the sense of smell and its role can however vary inter-individually and culturally. Despite the growing body of literature on differences in olfactory performance or hedonic preferences across the globe, the aspects of a given culture as well as culturally universal individual differences affecting odor awareness in human social life remain unknown. Here, we conducted a large-scale analysis of data collected from 10,794 participants from 52 study sites from 44 countries all over the world. The aim of our research was to explore the potential individual and country-level correlates of odor awareness in the social context. The results show that the individual characteristics were more strongly related than country-level factors to self-reported odor awareness in different social contexts. A model including individual-level predictors (gender, age, material situation, education and preferred social distance) provided a relatively good fit to the data, but adding country-level predictors (Human Development Index, population density and average temperature) did not improve model parameters. Although there were some cross-cultural differences in social odor awareness, the main differentiating role was played by the individual differences. This suggests that people living in different cultures and different climate conditions may still share some similar patterns of odor awareness if they share other individual-level characteristics