A decomposition-based uncertainty quantification approach for environmental impacts of aviation technology and operation

As a measure to manage the climate impact of aviation, significant enhancements to aviation technologies and operations are necessary. When assessing these enhancements and their respective impacts on the climate, it is important that we also quantify the associated uncertainties. This is important to support an effective decision and policymaking process. However, such quantification of uncertainty is challenging, especially in a complex system that comprises multiple interacting components. The uncertainty quantification task can quickly become computationally intractable and cumbersome for one individual or group to manage. Recognizing the challenge of quantifying uncertainty in multicomponent systems, we utilize a divide-and-conquer approach, inspired by the decomposition-based approaches used in multidisciplinary analysis and optimization. Specifically, we perform uncertainty analysis and global sensitivity analysis of our multicomponent aviation system in a decomposition-based manner. In this work, we demonstrate how to handle a high-dimensional multicomponent interface using sensitivity-based dimension reduction and a novel importance sampling method. Our results demonstrate that the decomposition-based uncertainty quantification approach can effectively quantify the uncertainty of a feed-forward multicomponent system for which the component models are housed in different locations and owned by different groups. Keywords: Aviation Environmental Impact; Decomposition; Global Sensitivity Analysis; Uncertainty Quantificatio

Targeted Inactivation of the mecB Gene, Encoding Cystathionine-γ-Lyase, Shows that the Reverse Transsulfuration Pathway Is Required for High-Level Cephalosporin Biosynthesis inAcremonium chrysogenum C10 but Not for Methionine Induction of the Cephalosporin Genes

[EN] Targeted gene disruption efficiency in Acremonium chrysogenum was increased 10-fold by applying the double-marker enrichment technique to this filamentous fungus. Disruption of themecB gene by the double-marker technique was achieved in 5% of the transformants screened. Mutants T6 and T24, obtained by gene replacement, showed an inactive mecB gene by Southern blot analysis and no cystathionine-γ-lyase activity. These mutants exhibited lower cephalosporin production than that of the control strain, A. chrysogenum C10, in MDFA medium supplemented with methionine. However, there was no difference in cephalosporin production between parental strain A. chrysogenum C10 and the mutants T6 and T24 in Shen's defined fermentation medium (MDFA) without methionine. These results indicate that the supply of cysteine through the transsulfuration pathway is required for high-level cephalosporin biosynthesis but not for low-level production of this antibiotic in methionine-unsupplemented medium. Therefore, cysteine for cephalosporin biosynthesis in A. chrysogenum derives from the autotrophic (SH2) and the reverse transsulfuration pathways. Levels of methionine induction of the cephalosporin biosynthesis gene pcbC were identical in the parental strain and the mecB mutants, indicating that the induction effect is not mediated by cystathionine-γ-lyase.SIThis work was supported by a grant of the CICYT (BIO97-0289-C02-01). We thank A. Paszewski for providing Aspergillus nidulansstrains M63 and C47 and M. Mediavilla, B. Martı́n, R. Barrientos, and M. Corrales for excellent technical assistance

Reseñas

Reseñas de las siguientes obras: Guía del lector; The role of national libraries: a reassesment por Maurice B. Une; Management by objectives por Ceorge S. Odióme; The moving finger "accesses" por Susan Spaeth Cherry; SCICON comes to San José por Richard E. Rendier; Library of Congress information bulletin, 1981; Zero-base budgeting and the management of library change por Lois Jennings.Departamento de Bibliotecologí

Reseñas

Reseñas de las siguientes obras: Guía del lector; The role of national libraries: a reassesment por Maurice B. Une; Management by objectives por Ceorge S. Odióme; The moving finger "accesses" por Susan Spaeth Cherry; SCICON comes to San José por Richard E. Rendier; Library of Congress information bulletin, 1981; Zero-base budgeting and the management of library change por Lois Jennings.Departamento de Bibliotecologí

Reseñas

Reseñas de las siguientes obras: Guía del lector; The role of national libraries: a reassesment por Maurice B. Une; Management by objectives por Ceorge S. Odióme; The moving finger "accesses" por Susan Spaeth Cherry; SCICON comes to San José por Richard E. Rendier; Library of Congress information bulletin, 1981; Zero-base budgeting and the management of library change por Lois Jennings.Departamento de Bibliotecologí

Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C.

Niemann Pick Type-C disease (NPC) is an inherited lysosomal storage disease (LSD) caused by pathogenic variants in the Npc1 or Npc2 genes that lead to the accumulation of cholesterol and lipids in lysosomes. NPC1 deficiency causes neurodegeneration, dementia and early death. Cerebellar Purkinje cells (PCs) are particularly hypersensitive to NPC1 deficiency and degenerate earlier than other neurons in the brain. Activation of microglia is an important contributor to PCs degeneration in NPC. However, the mechanisms by which activated microglia promote PCs degeneration in NPC are not completely understood. Here, we are demonstrating that in the Npc1nmf164 mouse cerebellum, microglia in the molecular layer (ML) are activated and contacting dendrites at early stages of NPC, when no loss of PCs is detected. During the progression of PCs degeneration in Npc1nmf164 mice, accumulation of phagosomes and autofluorescent material in microglia at the ML coincided with the degeneration of dendrites and PCs. Feeding Npc1nmf164 mice a western diet (WD) increased microglia activation and corresponded with a more extensive degeneration of dendrites but not PC somata. Together our data suggest that microglia contribute to the degeneration of PCs by interacting, engulfing and phagocytosing their dendrites while the cell somata are still present

Trans-generational epigenetic regulation associated with the amelioration of Duchenne Muscular Dystrophy

Exon skipping is an effective strategy for the treatment of many Duchenne Muscular Dystrophy (DMD) mutations. Natural exon skipping observed in several DMD cases can help in identifying novel therapeutic tools. Here, we show a DMD study case where the lack of a splicing factor (Celf2a), which results in exon skipping and dystrophin rescue, is due to a maternally inherited trans-generational epigenetic silencing. We found that the study case and his mother express a repressive long non-coding RNA, DUXAP8, whose presence correlates with silencing of the Celf2a coding region. We also demonstrate that DUXAP8 expression is lost upon cell reprogramming and that, upon induction of iPSCs into myoblasts, Celf2a expression is recovered leading to the loss of exon skipping and loss of dystrophin synthesis. Finally, CRISPR/Cas9 inactivation of the splicing factor Celf2a was proven to ameliorate the pathological state in other DMD backgrounds establishing Celf2a ablation or inactivation as a novel therapeutic approach for the treatment of Duchenne Muscular Dystrophy

Transformación vía Agrobacterium tumefaciens para inducir tolerancia a la podredumbre blanca del aguacate

Comunicación presentada en el VII World Avocado Congress, celebrado en Cairns (Australia) del 5 al 9 de septiembre de 2011.[EN] One of the most important limiting factors for avocado production in Spain is the disease caused by the fungus Rosellinia necatrix . Genetic manipulation could be useful for the introduction of fungal resistance traits into this crop. A n efficient Agrobacterium - mediated transformation protocol for avocado using AGL1 Agrobacterium strain and somatic embryos as the target material has been established by our group, although embryo conversion rate into plants needs to be improved. For that reason, we are using the strawberry, another Rosellinia necatrix ́s host, as model species to test the effect of several transgenes (two of fungal origin, chit 42 chitinase and β - 1,3 - glucanase from Trichoderma harzianum , and one of plant origin, At NPR1), on inducing tolerance to this fungus. Strawberry transformation with the β - 1,3 - glucanase gene has allowed the selection of two lines, β6 and β10, with enhanced tolerance to R. necatrix while no positive results were obtained following transformation with the chit - 42 gene. In relation to the At NPR1 gene more than 30 independent transgenic lines have been obtained whose tolerance to R. necatrix is currently under evaluation. Concerning avocado transformation, more than 10 independent transgenic lines (derive d from an embryogenic line of an immature Duke7 zygotic embryo) have been obtained with At NPR1 gene. Plants have been recovered from one line and efforts are underway to recover plants from other lines following micrografting of the transgenic sprouted sho ots onto in vitro germinated seedlings.[ES] Uno de los factores limitantes de la producción de aguacate en España es la enfermedad causada por el hongo R. necatrix. La manipulación genética podría ser de utilidad para introducir caracteres de resistencia en este cultivo. Se ha establecido un sistema eficiente de transformación en aguacate usando la cepa de Agrobacterium AGL1 y células embriogénicas como diana, sin embargo, la conversión en plantas de los embriones transgénicos necesita ser mejorada. Por esta razón, estamos utilizando la fresa, otro huésped de R. necatrix, como especie modelo para testar el efecto de varios transgenes (2 de origen fúngico, la quitinasa chit-42 y la β-1,3-glucanasa de Trichoderma harzianum, y uno derivado de plantas, AtNPR1), en la inducción de tolerancia a este patógeno tras la transformación de esta especie. La transformación de fresa con el gen de β -1,3-glucanasa ha permitido la selección de dos líneas, β6 y β10, con mayor tolerancia a R. necatrix, mientras que no se han obtenido resultados positivos con el gen chit-42. En relación con el gen AtNPR1, se han obtenido más de 30 líneas transgénicas independientes, cuya tolerancia frente a R. necatrix se está evaluando en la actualidad. En relación con la transformación de aguacate, más de 10 líneas transgénicas independientes (derivadas de una línea embriogénica obtenida a partir de un embrión zigótico inmaduro del cv. Duke 7) se han obtenido con el gen AtNPR1. Se han recuperado plantas de una línea y actualmente se está intentando recuperar plantas de otras líneas mediante microinjerto de los embriones transgénicos germinados.Este trabajo se ha realizado en el marco del proyecto AGL2008 - 05453 - C02 - 01/AGR.Peer Reviewe

The Expression of Fibroblast Activation Protein in Clear Cell Renal Cell Carcinomas Is Associated with Synchronous Lymph Node Metastases

Clear cell renal cell carcinoma (CCRCC) is a heterogeneous and complex disease that frequently develops distant metastases. Fibroblast activation protein (FAP) is a serine peptidase the expression of which in cancer-associated fibroblasts has been associated with higher risk of metastases and poor survival. The objective of this study was to evaluate the role of FAP in metastatic CCRCC (mCCRCC). A series of 59 mCCRCC retrospectively collected was included in the study. Metastases developed either synchronous (n = 14) or metachronous to renal disease (n = 45). Tumor specimens were obtained from both primary lesion (n = 59) and metastases (n = 54) and FAP expression was immunohistochemically analyzed. FAP expression in fibroblasts from primary tumors correlated with FAP expression in the corresponding metastatic lesions. Also, primary and metastatic FAP expression was correlated with large tumor diameter (>7cm), high grade (G3/4), high stage (pT3/4), tumor necrosis and sarcomatoid transformation. The expression of FAP in primary tumors and in their metastases was associated both with synchronous metastases and also with metastases to the lymph nodes. FAP expression in the primary tumor was correlated with worse 10-year overall survival. Immunohistochemical detection of FAP in the stromal tumor fibroblasts could be a biomarker of early lymph node metastatic status and therefore could account for the poor prognosis of FAP positive CCRCC.This work was partially funded by Grant SAF2013-48812-R from Ministerio de Economia y Competitividad (Spain), IT 8-11/13 from de Basque Government and EHUA14/25 from de University of the Basque Country (UPV/EHU). The current work has been developed as PhD project of PE and MB, who are recipients of a Predoctoral Fellowship from the Basque Government (Exp no PRE_2013_1_762 and PRE_2015_2_0148). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Developmental and metabolic plasticity of white-skinned grape berries in response to <i>Botrytis cinerea</i> during noble rot

Noble rot results from exceptional infections of ripe grape (Vitis vinifera) berries by Botrytis cinerea. Unlike bunch rot, noble rot promotes favorable changes in grape berries and the accumulation of secondary metabolites that enhance wine grape composition. Noble rot-infected berries of cv Sémillon, a white-skinned variety, were collected over 3 years from a commercial vineyard at the same time that fruit were harvested for botrytized wine production. Using an integrated transcriptomics and metabolomics approach, we demonstrate that noble rot alters the metabolism of cv Sémillon berries by inducing biotic and abiotic stress responses as well as ripening processes. During noble rot, B. cinerea induced the expression of key regulators of ripening-associated pathways, some of which are distinctive to the normal ripening of red-skinned cultivars. Enhancement of phenylpropanoid metabolism, characterized by a restricted flux in white-skinned berries, was a common outcome of noble rot and red-skinned berry ripening. Transcript and metabolite analyses together with enzymatic assays determined that the biosynthesis of anthocyanins is a consistent hallmark of noble rot in cv Sémillon berries. The biosynthesis of terpenes and fatty acid aroma precursors also increased during noble rot. We finally characterized the impact of noble rot in botrytized wines. Altogether, the results of this work demonstrated that noble rot causes a major reprogramming of berry development and metabolism. This desirable interaction between a fruit and a fungus stimulates pathways otherwise inactive in white-skinned berries, leading to a greater accumulation of compounds involved in the unique flavor and aroma of botrytized wines.Facultad de Ciencias Agrarias y Forestale