The Cost of Numerical Integration in Statistical Decision-theoretic Methods for Robust Design Optimization

The Bayes principle from statistical decision theory provides a conceptual framework for quantifying uncertainties that arise in robust design optimization. The difficulty with exploiting this framework is computational, as it leads to objective and constraint functions that must be evaluated by numerical integration. Using a prototypical robust design optimization problem, this study explores the computational cost of multidimensional integration (computing expectation) and its interplay with optimization algorithms. It concludes that straightforward application of standard off-the-shelf optimization software to robust design is prohibitively expensive, necessitating adaptive strategies and the use of surrogates

Arctic passages: liminality, Iñupiat Eskimo mothers and NW Alaska communities in transition

Background. While the primary goal of the NW Alaska Native maternal transport is safe deliveries for mothers from remote villages, little has been done to question the impact of transport on the mothers and communities involved. This study explores how presence of Iñupiat values influences the desire of indigenous women of differing eras and NW Alaska villages to participate in biomedical birth, largely made available by a tribal health-sponsored transport system. Objective. This paper portrays how important it is (and why) for Alaska Native families and women of different generations from various areas of Iñupiat villages of NW Alaska to get to the hospital to give birth. This research asks: How does a community’s presence of Iñupiat values influence women of different eras and locations to participate in a more biomedical mode of birth? Design. Theoretical frameworks of medical anthropology and maternal identity work are used to track the differences in regard to the maternal transport operation for Iñupiat mothers of the area. Presence of Iñupiat values in each of the communities is compared by birth era and location for each village. Content analysis is conducted to determine common themes in an inductive, recursive fashion. Results. A connection is shown between a community’s manifestation of Iñupiat cultural expression and mothers’ acceptance of maternal transport in this study. For this group of Iñupiat Eskimo mothers, there is interplay between community expression of Iñupiat values and desire and lengths gone to by women of different eras and locations. Conclusions. The more openly manifested the Iñupiat values of the community, the more likely alternative birthing practices sought, lessening the reliance on the existing transport policy. Conversely, the more openly western values are manifested in the village of origin, the less likely alternative measures are sought. For this study group, mothers from study villages with openly manifested western values are more likely to easily acquiesce to policy, and “make the best” of their prenatal travel

Multidimensional Scaling Reveals the Main Evolutionary Pathways of Class A G-Protein-Coupled Receptors

Class A G-protein-coupled receptors (GPCRs) constitute the largest family of transmembrane receptors in the human genome. Understanding the mechanisms which drove the evolution of such a large family would help understand the specificity of each GPCR sub-family with applications to drug design. To gain evolutionary information on class A GPCRs, we explored their sequence space by metric multidimensional scaling analysis (MDS). Three-dimensional mapping of human sequences shows a non-uniform distribution of GPCRs, organized in clusters that lay along four privileged directions. To interpret these directions, we projected supplementary sequences from different species onto the human space used as a reference. With this technique, we can easily monitor the evolutionary drift of several GPCR sub-families from cnidarians to humans. Results support a model of radiative evolution of class A GPCRs from a central node formed by peptide receptors. The privileged directions obtained from the MDS analysis are interpretable in terms of three main evolutionary pathways related to specific sequence determinants. The first pathway was initiated by a deletion in transmembrane helix 2 (TM2) and led to three sub-families by divergent evolution. The second pathway corresponds to the differentiation of the amine receptors. The third pathway corresponds to parallel evolution of several sub-families in relation with a covarion process involving proline residues in TM2 and TM5. As exemplified with GPCRs, the MDS projection technique is an important tool to compare orthologous sequence sets and to help decipher the mutational events that drove the evolution of protein families

Völkisch und sozial? : Neonazistische Agitation gegen die neue EU-Freizügigkeit für Arbeitnehmerinnen

Wnt/β-catenin signalling pathway is crucial for the formation of many tissues and organs during development. In recent years, this pathway has also been found to regulate the biology of stem cells in the intestine and probably in other organs in adult life. Abnormal activation of Wnt/β-catenin signalling, which controls the expression of a high number of genes, is critical for the initiation and progression of most colorectal cancers. In line with this, the gene expression signature induced by activation of the Wnt/β-catenin pathway defines the intestinal stem cells present at the bottom of the crypts and also colon cancer stem cells. This supports the importance of inhibitors of the Wnt/β-catenin pathway as potential agents in colorectal cancer therapy. However, the complexity, wide activity in the organism modulating the biology of several cell types, and characteristics of this pathway have delayed the identification of suitable targets and so, the development of such inhibitors that are only now reaching the clinic.Peer reviewe

Le blanchiment des horizons minéraux superficiels de sols forestiers à l'étage montagnard. Exemple d'une pessière dans les Alpes septentrionales humides (France)

In the northern Alps, the study of some soils developed under a mountainous Norway spruce forest has shown, within some profiles, the presence of a bleached superficial mineral layer, morphologically looking like an albic horizon such as defined in the usual classifications (USDA, 1994). However, one doesn't found in depth agilic, spodic (indeed placic) horizon thet are usually associated with. At the outset, it's not easy to link this superficial bleaching to one of the well-known pedological processes. In order to define its origin, a sequence of 6 profiles has some macro and micromorphological descriptions. the main results, especially these dealing with C rates and selective extractions of iron and aluminium, show the superficial bleaching of these mountainous soils is due to 2 main pedogenetical processes : hydromorphism ans pdzolisation. At the lowest altitude, hydromorphism is most dominant; uphill, a podzolic tendancy adds further to this still present hydromorphism. The both processes widely depend on the surrounding conditions under which these soils have developed. Thus, these alpine soils can be linked with the stagnosols yet described in mountainous environment.Dans les Alpes du Nord, l'étude des sols d'une pessière montagnarde a permis d'identifier, au sein de certains profils, la présence d'un horizon minéral superficiel blanchi, s'apparentant morphologiquement à un horizon albique tel que défini par les grandes classifications (USDA, 1994). Cependant, il est fréquent de ne pas trouver en profondeur un des horizons de diagnostic i.e. argillique, spodique (voire placique) auxquels il est classiquement associé. Il n'est donc pas évident de rattacher immédiatement ce phénomène de blanchiment de surface à l'un des grands processus pédogénétiques connus. Afin de définir l'origine de cette décoloration de surface, une séquence de 6 sols a été étudiée, par le biais d'analyses classiques (paramètres physico-chimiques, constituants organiques et minéraux), de descriptions macro et micromorphologiques. Les différents résultats, concernant notamment les taux de carbone ainsi que les extractions sélectives di fer et de l'aluminium, montrent que le blanchiment superficiel de ces sols de montagne apparaît lié à diverses causes dont les effets peuvent se cumuler. Dans les zones de plus faibles altitudes, les processus d'hydromorphie se révèlent être prédominants. Plus en amont, une tendance podzolique se surimpose à l'hydromorphie toujours présente. Ces processus sont largement conditionnés par les facteurs du milieu dans lequel ces sols sont développés, notamment climat, topographie et lithologie, rattachant ces sols alpins aux stagnosols, décrits par ailleurs dans les milieux montagnards

Hyperthermostable mutants of Bacillus licheniformis alpha-amylase : multiple amino acid replacements and molecular modelling

International audienc

Incremental Model-Based Clustering for Large Datasets with Small Clusters

Contains fulltext : 32627.pdf (publisher's version ) (Open Access