The functions of sleep.

Here we report on The Satellite Symposium on Sleep Function that was held in Lausanne during 6(th) FENS forum and brought together neuroscientists from basic and clinical sleep research. We illustrate the principal questions that arose during this interdisciplinary gathering and introduce the contents of nine review articles on aspects of sleep that are contained in this Special Issue of the European Journal of Neuroscience.

Biased representation of homothetic preferences on homogeneous sets

In the homogeneous case of one-dimensional objects, we show that any preference relation that is positive and homothetic can be represented by a quantitative utility function and unique bias. This bias may favor or disfavor the preference for an object. In the first case, preferences are complete but not transitive and an object may be preferred even when its utility is lower. In the second case, preferences are asymmetric and transitive but not negatively transitive and it may not be sufficient for an object to have a greater utility for be preferred. In this manner, the bias reflects the extent to which preferences depart from the maximization of a utility function.

Functions of peroxisome proliferator-activated receptors (PPAR) in skin homeostasis.

The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that belong to the nuclear hormone receptor family. Three isotypes (PPAR alpha, PPAR beta or delta, and PPAR gamma) with distinct tissue distributions and cellular functions have been found in vertebrates. All three PPAR isotypes are expressed in rodent and human skin. They were initially investigated for a possible function in the establishment of the permeability barrier in skin because of their known function in lipid metabolism in other cell types. In vitro studies using specific PPAR agonists and in vivo gene disruption approaches in mice indeed suggest an important contribution of PPAR alpha in the formation of the epidermal barrier and in sebocyte differentiation. The PPAR gamma isotype plays a role in stimulating sebocyte development and lipogenesis, but does not appear to contribute to epidermal tissue differentiation. The third isotype, PPAR beta, regulates the late stages of sebaceous cell differentiation, and is the most effective isotype in stimulating lipid production in these cells, both in rodents and in humans. In addition, PPAR beta activation has pro-differentiating effects in keratinocytes under normal and inflammatory conditions. Finally, preliminary studies also point to a potential role of PPAR in hair follicle growth and in melanocyte differentiation. By their diverse biological effects on cell proliferation and differentiation in the skin, PPAR agonists or antagonists may offer interesting opportunities for the treatment of various skin disorders characterized by inflammation, cell hyperproliferation, and aberrant differentiation.

Riesz-Nágy singular functions revisited

In 1952 F. Riesz and Sz.Nágy published an example of a monotonic continuous function whose derivative is zero almost everywhere, that is to say, a singular function. Besides, the function was strictly increasing. Their example was built as the limit of a sequence of deformations of the identity function. As an easy consequence of the definition, the derivative, when it existed and was finite, was found to be zero. In this paper we revisit the Riesz-N´agy family of functions and we relate it to a system for real numberrepresentation which we call (t, t-1) expansions. With the help of these real number expansions we generalize the family. The singularity of the functions is proved through some metrical properties of the expansions used in their definition which also allows us to give a more precise way of determining when the derivative is 0 or infinity.

Unique and conserved functions of B cell-activating factor of the TNF family (BAFF) in the chicken.

The chicken represents the best-characterized animal model for B cell development in the so-called gut-associated lymphoid tissue (GALT) and the molecular processes leading to B cell receptor diversification in this species are well investigated. However, the mechanisms regulating B cell development and homeostasis in GALT species are largely unknown. Here we investigate the role played by the avian homologue of B cell-activating factor of the tumor necrosis factor family (BAFF). Flow cytometric analysis showed that the receptor for chicken B cell-activating factor of the tumor necrosis factor family (chBAFF) is expressed by mature and immature B cells. Unlike murine and human BAFF, chBAFF is primarily produced by B cells both in peripheral lymphoid organs and in the bursa of Fabricius, the chicken's unique primary lymphoid organ. In vitro and in vivo studies revealed that chBAFF is required for mature B cell survival. In addition, in vivo neutralization with a decoy receptor led to a reduction of the size and number of B cell follicles in the bursa, demonstrating that, in contrast to humans and mice, in chickens BAFF is also required for the development of immature B cells. Collectively, we show that chBAFF has phylogenetically conserved functions in mature B cell homeostasis but displays unique and thus far unknown properties in the regulation of B cell development in birds.

Location of multiple server common service centers or public facilities for minimizing general congestion and travel cost functions

We propose a model and solution methods, for locating a fixed number ofmultiple-server, congestible common service centers or congestible publicfacilities. Locations are chosen so to minimize consumers congestion (orqueuing) and travel costs, considering that all the demand must be served.Customers choose the facilities to which they travel in order to receiveservice at minimum travel and congestion cost. As a proxy for thiscriterion, total travel and waiting costs are minimized. The travel costis a general function of the origin and destination of the demand, whilethe congestion cost is a general function of the number of customers inqueue at the facilities.

The domain and interpretation of utility functions: An exploration

This paper proposes an exploration of the methodology of utilityfunctions that distinguishes interpretation from representation. Whilerepresentation univocally assigns numbers to the entities of the domainof utility functions, interpretation relates these entities withempirically observable objects of choice. This allows us to makeexplicit the standard interpretation of utility functions which assumesthat two objects have the same utility if and only if the individual isindifferent among them. We explore the underlying assumptions of suchan hypothesis and propose a non-standard interpretation according towhich objects of choice have a well-defined utility although individualsmay vary in the way they treat these objects in a specific context.We provide examples of such a methodological approach that may explainsome reversal of preferences and suggest possible mathematicalformulations for further research.

MACROPHAGES FROM CROHN'S DISEASE PATIENTS EXHIBIT DEFICIENT REPAIR FUNCTIONS

AbstractBackground: Mucosal healing is becoming a major goal in the treatment of Crohn's disease. It has been previously reported that myeloid cells induce mucosal healing in a mouse model of acute colitis. The aim in this study is to investigate the pro-repair function of myeloid cells in healthy donors (HD) and Crohn's disease patients (CD).Methods: Peripheral blood mononuclear cells (PBMC) from HD and CD patients were isolated from blood samples and tested either directly or after differentiation ex-vivo into macrophages (Μφ). Intestinal macrophages (IMACs) were isolated from the bowel mucosa of patients undergoing intestinal surgical resections. Through an in vitro wound healing assay the repairing ability of these various human myeloid cells and the mechanisms responsible of wound healing were evaluated.Results: PBMC and myeloid CD14+ cells from HD and CD were not able to repair at any tested cell concentration. Μφ from HD and ulcerative colitis (UC) patients were able to induce wound healing and this capacity was partially mediated by Hepatocyte Growth Factor (HGF). Remarkably, CD Μφ were unable to promote wound healing and produced lower levels of HGF as compared to Μφ from HD or UC patients. In particular, Μφ from CD in active phase (ACD) exhibited the weakest repair function, but this defect was rescued if rh- GM-CSF was added during the differentiation of PBMCs. Interestingly, IMACs from HD promoted wound healing and produced HGF.Conclusion: We demonstrated that CD Μφ, unlike HD or UC Μφ, were defective in promoting wound healing, in particular if coming from an ACD. This deficient pro-repair function was related to a lower production of HGF. IMACs from HD colonic mucosa induced wound healing, confirming the results obtained with Μφ. Our results are in keeping with the current theory of CD as an innate immunodeficiency. In this context, Μφ may be responsible for the mucosal repair defects observed in CD patients and for the subsequent chronic activation of the adaptive immune response.

Variability of apparently homogeneous soilscapes in São Paulo state, Brazil: I. spatial analysis

The spatial variability of strongly weathered soils under sugarcane and soybean/wheat rotation was quantitatively assessed on 33 fields in two regions in São Paulo State, Brazil: Araras (15 fields with sugarcane) and Assis (11 fields with sugarcane and seven fields with soybean/wheat rotation). Statistical methods used were: nested analysis of variance (for 11 fields), semivariance analysis and analysis of variance within and between fields. Spatial levels from 50 m to several km were analyzed. Results are discussed with reference to a previously published study carried out in the surroundings of Passo Fundo (RS). Similar variability patterns were found for clay content, organic C content and cation exchange capacity. The fields studied are quite homogeneous with respect to these relatively stable soil characteristics. Spatial variability of other characteristics (resin extractable P, pH, base- and Al-saturation and also soil colour), varies with region and, or land use management. Soil management for sugarcane seems to have induced modifications to greater depths than for soybean/wheat rotation. Surface layers of soils under soybean/wheat present relatively little variation, apparently as a result of very intensive soil management. The major part of within-field variation occurs at short distances (< 50 m) in all study areas. Hence, little extra information would be gained by increasing sampling density from, say, 1/km² to 1/50 m². For many purposes, the soils in the study regions can be mapped with the same observation density, but residual variance will not be the same in all areas. Bulk sampling may help to reveal spatial patterns between 50 and 1.000 m.

Variability of apparently homogeneous soilscapes in São Paulo state, Brazil: II. quality of soil maps

The quality of semi-detailed (scale 1:100.000) soil maps and the utility of a taxonomically based legend were assessed by studying 33 apparently homogeneous fields with strongly weathered soils in two regions in São Paulo State: Araras and Assis. An independent data set of 395 auger sites was used to determine purity of soil mapping units and analysis of variance within and between mapping units and soil classification units. Twenty three soil profiles were studied in detail. The studied soil maps have a high purity for some legend criteria, such as B horizon type (> 90%) and soil texture class (> 80%). The purity for the "trophic character" (eutrophic, dystrophic, allic) was only 55% in Assis. It was 88% in Araras, where many soil units had been mapped as associations. In both regions, the base status of clay-textured soils was generally better than suggested by the maps. Analysis of variance showed that mapping was successful for "durable" soil characteristics such as clay content (> 80% of variance explained) and cation exchange capacity (≥ 50% of variance explained) of 0-20 and 60-80 cm layers. For soil characteristics that are easily modified by management, such as base saturation of the 0-20 cm layer, the maps had explained very little (< 15%) of the total variance in the study areas. Intermediate results were obtained for base saturation of the 60-80 cm layer (56% in Assis; 42% in Araras). Variance explained by taxonomic groupings that formed the basis for the legend of the soil maps was similar to, often even smaller than, variance explained by mapping units. The conclusion is that map boundaries have been very carefully located, but descriptions of mapping units could be improved. In future mappings, this could possibly be done at low cost by (a) bulk sampling to remove short range variation and enhance visualization of spatial patterns at distances > 100 m; (b) taking advantage of correlations between easily measured soil characteristics and chemical soil properties and, (c) unbending the link between legend criteria and a taxonomic system. The maps are well suited to obtain an impression of land suitability for high-input farming. Additional field work and data on former land use/management are necessary for the evaluation of chemical properties of surface horizons.

Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor beta/delta.

Mutation of the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) severely affects placenta development, leading to embryonic death at embryonic day 9.5 (E9.5) to E10.5 of most, but not all, PPARbeta/delta-null mutant embryos. While very little is known at present about the pathway governed by PPARbeta/delta in the developing placenta, this paper demonstrates that the main alteration of the placenta of PPARbeta/delta-null embryos is found in the giant cell layer. PPARbeta/delta activity is in fact essential for the differentiation of the Rcho-1 cells in giant cells, as shown by the severe inhibition of differentiation once PPARbeta/delta is silenced. Conversely, exposure of Rcho-1 cells to a PPARbeta/delta agonist triggers a massive differentiation via increased expression of 3-phosphoinositide-dependent kinase 1 and integrin-linked kinase and subsequent phosphorylation of Akt. The links between PPARbeta/delta activity in giant cells and its role on Akt activity are further strengthened by the remarkable pattern of phospho-Akt expression in vivo at E9.5, specifically in the nucleus of the giant cells. In addition to this phosphatidylinositol 3-kinase/Akt main pathway, PPARbeta/delta also induced giant cell differentiation via increased expression of I-mfa, an inhibitor of Mash-2 activity. Finally, giant cell differentiation at E9.5 is accompanied by a PPARbeta/delta-dependent accumulation of lipid droplets and an increased expression of the adipose differentiation-related protein (also called adipophilin), which may participate to lipid metabolism and/or steroidogenesis. Altogether, this important role of PPARbeta/delta in placenta development and giant cell differentiation should be considered when contemplating the potency of PPARbeta/delta agonist as therapeutic agents of broad application.

Predicting stroke through genetic risk functions: the CHARGE Risk Score Project.

BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke.

Generating functions for the numbers of Abelian extensions of a local field

The aim of this paper is to give an explicit formula for the num- bers of abelian extensions of a p-adic number field and to study the generating function of these numbers. More precisely, we give the number of abelian ex- tensions with given degree and ramification index, and the number of abelian extensions with given degree of any local field of characteristic zero. Moreover, we give a concrete expression of a generating function for these last numbers

Genetic parameters for growth traits in pigs estimated using third degree polynomial functions

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