Brain glucose sensing and neural regulation of insulin and glucagon secretion.

Glucose homeostasis requires the tight regulation of glucose utilization by liver, muscle and white or brown fat, and glucose production and release in the blood by liver. The major goal of maintaining glycemia at ∼ 5 mM is to ensure a sufficient flux of glucose to the brain, which depends mostly on this nutrient as a source of metabolic energy. This homeostatic process is controlled by hormones, mainly glucagon and insulin, and by autonomic nervous activities that control the metabolic state of liver, muscle and fat tissue but also the secretory activity of the endocrine pancreas. Activation or inhibition of the sympathetic or parasympathetic branches of the autonomic nervous systems are controlled by glucose-excited or glucose-inhibited neurons located at different anatomical sites, mainly in the brainstem and the hypothalamus. Activation of these neurons by hyper- or hypoglycemia represents a critical aspect of the control of glucose homeostasis, and loss of glucose sensing by these cells as well as by pancreatic β-cells is a hallmark of type 2 diabetes. In this article, aspects of the brain-endocrine pancreas axis are reviewed, highlighting the importance of central glucose sensing in the control of counterregulation to hypoglycemia but also mentioning the role of the neural control in β-cell mass and function. Overall, the conclusions of these studies is that impaired glucose homeostasis, such as associated with type 2 diabetes, but also defective counterregulation to hypoglycemia, may be caused by initial defects in glucose sensing.

Beyond EA Frameworks: Towards an Understanding of the Adoption of Enterprise Architecture Management

Enterprise architectures (EA) are considered promising approaches to reduce the complexities of growing information technology (IT) environments while keeping pace with an ever-changing business environment. However, the implementation of enterprise architecture management (EAM) has proven difficult in practice. Many EAM initiatives face severe challenges, as demonstrated by the low usage level of enterprise architecture documentation and enterprise architects' lack of authority regarding enforcing EAM standards and principles. These challenges motivate our research. Based on three field studies, we first analyze EAM implementation issues that arise when EAM is started as a dedicated and isolated initiative. Following a design-oriented paradigm, we then suggest a design theory for architecture-driven IT management (ADRIMA) that may guide organizations to successfully implement EAM. This theory summarizes prescriptive knowledge related to embedding EAM practices, artefacts and roles in the existing IT management processes and organization.

Re-usable ASIC integrationverification software architecture

Mikropiirien valmistus- ja suunnittelutekniikoiden kehittyminen mahdollistaa yhä monimutkaisempien mikropiirien valmistamisen. Piirien verifioinnista onkin tullut prosessin aikaa vievin osa,sillä kompleksisuuden kasvaessa kasvaa verifioinnin tarve eksponentiaalisesti. Vaikka erinäisiä strategioita piirien integroinnin verifiointiin on esitetty, mm. verifioinnin jakaminen koko suunnitteluprosessin ajalle, jopa yli puolet koko piirin suunnitteluun ja valmistukseen käytetystä työmäärästä kuluu verifiointiin. Uudelleenkäytettävät komponentit ovat pääosassa piirin suunnittelussa, mutta verifioinnissa uudelleenkäytettävyyttä ei ole otettu kunnolla käyttöön ainakaan verifiointiohjelmistojen osalta. Tämä diplomityö esittelee uudelleenkäytettävän mikropiirien verifiointiohjelmistoarkkitehtuurin, jolla saadaan verifiointitaakkaa vähennettyä poistamalla verifioinnissa käytettävien ohjelmistojen uudelleensuunnittelun ja toteuttamisen tarvetta.

Forecasting tourism demand to Catalonia: neural networks vs. time series models

The increasing interest aroused by more advanced forecasting techniques, together with the requirement for more accurate forecasts of tourismdemand at the destination level due to the constant growth of world tourism, has lead us to evaluate the forecasting performance of neural modelling relative to that of time seriesmethods at a regional level. Seasonality and volatility are important features of tourism data, which makes it a particularly favourable context in which to compare the forecasting performance of linear models to that of nonlinear alternative approaches. Pre-processed official statistical data of overnight stays and tourist arrivals fromall the different countries of origin to Catalonia from 2001 to 2009 is used in the study. When comparing the forecasting accuracy of the different techniques for different time horizons, autoregressive integrated moving average models outperform self-exciting threshold autoregressions and artificial neural network models, especially for shorter horizons. These results suggest that the there is a trade-off between the degree of pre-processing and the accuracy of the forecasts obtained with neural networks, which are more suitable in the presence of nonlinearity in the data. In spite of the significant differences between countries, which can be explained by different patterns of consumer behaviour,we also find that forecasts of tourist arrivals aremore accurate than forecasts of overnight stays.

The neural basis for writing from dictation in the temporoparietal cortex.

Cortical electrical stimulation mapping was used to study neural substrates of the function of writing in the temporoparietal cortex. We identified the sites involved in oral language (sentence reading and naming) and writing from dictation, in order to spare these areas during removal of brain tumours in 30 patients (23 in the left, and 7 in the right hemisphere). Electrostimulation of the cortex impaired writing ability in 62 restricted cortical areas (.25 cm2). These were found in left temporoparietal lobes and were mostly located along the superior temporal gyrus (Brodmann's areas 22 and 42). Stimulation of right temporoparietal lobes in right-handed patients produced no writing impairments. However there was a high variability of location between individuals. Stimulation resulted in combined symptoms (affecting oral language and writing) in fourteen patients, whereas in eight other patients, stimulation-induced pure agraphia symptoms with no oral language disturbance in twelve of the identified areas. Each detected area affected writing in a different way. We detected the various different stages of the auditory-to-motor pathway of writing from dictation: either through comprehension of the dictated sentences (word deafness areas), lexico-semantic retrieval, or phonologic processing. In group analysis, barycentres of all different types of writing interferences reveal a hierarchical functional organization along the superior temporal gyrus from initial word recognition to lexico-semantic and phonologic processes along the ventral and the dorsal comprehension pathways, supporting the previously described auditory-to-motor process. The left posterior Sylvian region supports different aspects of writing function that are extremely specialized and localized, sometimes being segregated in a way that could account for the occurrence of pure agraphia that has long-been described in cases of damage to this region.

Destruction of lymphoid organ architecture and hepatitis caused by CD4 T cells.

Immune responses have the important function of host defense and protection against pathogens. However, the immune response also causes inflammation and host tissue injury, termed immunopathology. For example, hepatitis B and C virus infection in humans cause immunopathological sequel with destruction of liver cells by the host's own immune response. Similarly, after infection with lymphocytic choriomeningitis virus (LCMV) in mice, the adaptive immune response causes liver cell damage, choriomeningitis and destruction of lymphoid organ architecture. The immunopathological sequel during LCMV infection has been attributed to cytotoxic CD8(+) T cells. However, we now show that during LCMV infection CD4(+) T cells selectively induced the destruction of splenic marginal zone and caused liver cell damage with elevated serum alanin-transferase (ALT) levels. The destruction of the splenic marginal zone by CD4(+) T cells included the reduction of marginal zone B cells, marginal zone macrophages and marginal zone metallophilic macrophages. Functionally, this resulted in an impaired production of neutralizing antibodies against LCMV. Furthermore, CD4(+) T cells reduced B cells with an IgM(high)IgD(low) phenotype (transitional stage 1 and 2, marginal zone B cells), whereas other B cell subtypes such as follicular type 1 and 2 and germinal center/memory B cells were not affected. Adoptive transfer of CD4(+) T cells lacking different important effector cytokines and cytolytic pathways such as IFNγ, TNFα, perforin and Fas-FasL interaction did reveal that these cytolytic pathways are redundant in the induction of immunopathological sequel in spleen. In conclusion, our results define an important role of CD4(+) T cells in the induction of immunopathology in liver and spleen. This includes the CD4(+) T cell mediated destruction of the splenic marginal zone with consecutively impaired protective neutralizing antibody responses.

Highly Available Enterprise-level Application Server Architecture

Korkeasaatavuus on olennainen osa nykyaikaisissa, integroiduissa yritysjärjestelmissä. Yritysten kansainvälistyessä tiedon on oltava saatavissa ympärivuorokautisesti, mikä asettaa yhä kovempia vaatimuksia järjestelmän yksittäisten osien saatavuudelle. Kasvava tietojärjestelmäintegraatio puolestaan tekee järjestelmän solmukohdista kriittisiä liiketoiminnan kannalta. Tässä työssä perehdytään hajautettujen järjestelmien ominaisuuksiin ja niiden asettamiin haasteisiin. Esiteltyjä teknologioita ovat muun muassa väliohjelmistot, klusterit ja kuormantasaus. Yrityssovellusten pohjana käytetty Java 2 Enterprise Edition (J2EE) -teknologia käsitellään olennaisilta osiltaan. Työssä käytetään sovelluspalvelinalustana BEA WebLogic Server -ohjelmistoa, jonka ominaisuudet käydään läpi hajautuksen kannalta. Työn käytännön osuudessa toteutetaan kahdelle erilaiselle olemassa olevalle yrityssovellukselle korkean saatavuuden sovelluspalvelinympäristö, joissa sovellusten asettamat rajoitukset on otettu huomioon.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Ochratoxin A at nanomolar concentration perturbs the homeostasis of neural stem cells in highly differentiated but not in immature three-dimensional brain cell cultures.

Ochratoxin A (OTA), a fungal contaminant of basic food commodities, is known to be highly cytotoxic, but the pathways underlying adverse effects at subcytotoxic concentrations remain to be elucidated. Recent reports indicate that OTA affects cell cycle regulation. Therefore, 3D brain cell cultures were used to study OTA effects on mitotically active neural stem/progenitor cells, comparing highly differentiated cultures with their immature counterparts. Changes in the rate of DNA synthesis were related to early changes in the mRNA expression of neural stem/progenitor cell markers. OTA at 10nM, a concentration below the cytotoxic level, was ineffective in immature cultures, whereas in mature cultures it significantly decreased the rate of DNA synthesis together with the mRNA expression of key transcriptional regulators such as Sox2, Mash1, Hes5, and Gli1; the cell cycle activator cyclin D2; the phenotypic markers nestin, doublecortin, and PDGFRα. These effects were largely prevented by Sonic hedgehog (Shh) peptide (500ngml(-1)) administration, indicating that OTA impaired the Shh pathway and the Sox2 regulatory transcription factor critical for stem cell self-renewal. Similar adverse effects of OTA in vivo might perturb the regulation of stem cell proliferation in the adult brain and in other organs exhibiting homeostatic and/or regenerative cell proliferation.

Domestic architecture and social differences in North-Eastern Iberia during the iron age (c.525-200 BC)

This paper is concerned with the organization of societies in north-eastern Iberia (present-day Catalonia) during the Iron Age, using data provided by domestic architecture and settlement organization. I offer an analysis of the social differences detected in the dwellings based on a sample of houses excavated at different types of settlement. Although many Iberian houses had simple layouts and small surface areas, some larger dwellings at the main sites are distinguished by the shape of their ground plans, their surface areas, architectural features, and central locations; these houses are believed to be the residences of the Iberian elite. Such dwellings are not found at all sites and the data suggest that there was a relationship between the category of the settlement (or its function) and the types of dwelling in it.

Dictionnaire d'architecture civile et hydraulique et des arts qui en dépendent : comme la maçonnerie, la charpenterie, la menuiserie... ([Reprod.]) / par Augustin Charles d'Aviler...

Collection : Archives de la linguistique française ; 18

Des principes de l'architecture, de la sculpture, de la peinture, et des autres arts qui en dépendent : avec un Dictionnaire des termes propres à chacun de ces arts (Ed. sur microfiche) / [Félibien]

Collection : Archives de la linguistique française ; 151