Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

Early disturbances of gamma band dynamics in mild cognitive impairment.

Recent studies have indicated that gamma band oscillations participate in the temporal binding needed for the synchronization of cortical networks involved in short-term memory and attentional processes. To date, no study has explored the temporal dynamics of gamma band in the early stages of dementia. At baseline, gamma band analysis was performed in 29 cases with mild cognitive impairment (MCI) during the n-back task. Based on phase diagrams, multiple linear regression models were built to explore the relationship between the cognitive status and gamma oscillation changes over time. Individual measures of phase diagram complexity were made using fractal dimension values. After 1 year, all cases were assessed neuropsychologically using the same battery. A total of 16 MCI patients showed progressive cognitive decline (PMCI) and 13 remained stable (SMCI). When adjusted for gamma values at lag -2, and -3 ms, PMCI cases displayed significantly lower average changes in gamma values than SMCI cases both in detection and 2-back tasks. Gamma fractal dimension of PMCI cases displayed significantly higher gamma fractal dimension values compared to SMCI cases. This variable explained 11.8% of the cognitive variability in this series. Our data indicate that the progression of cognitive decline in MCI is associated with early deficits in temporal binding that occur during the activation of selective attention processes.

Expanding molecular modeling and design tools to non-natural sidechains.

Protein-protein interactions encode the wiring diagram of cellular signaling pathways and their deregulations underlie a variety of diseases, such as cancer. Inhibiting protein-protein interactions with peptide derivatives is a promising way to develop new biological and therapeutic tools. Here, we develop a general framework to computationally handle hundreds of non-natural amino acid sidechains and predict the effect of inserting them into peptides or proteins. We first generate all structural files (pdb and mol2), as well as parameters and topologies for standard molecular mechanics software (CHARMM and Gromacs). Accurate predictions of rotamer probabilities are provided using a novel combined knowledge and physics based strategy. Non-natural sidechains are useful to increase peptide ligand binding affinity. Our results obtained on non-natural mutants of a BCL9 peptide targeting beta-catenin show very good correlation between predicted and experimental binding free-energies, indicating that such predictions can be used to design new inhibitors. Data generated in this work, as well as PyMOL and UCSF Chimera plug-ins for user-friendly visualization of non-natural sidechains, are all available at http://www.swisssidechain.ch. Our results enable researchers to rapidly and efficiently work with hundreds of non-natural sidechains.

Causal assessment in finite extensive-form games

Two finite extensive-form games are empirically equivalent when theempirical distribution on action profiles generated by every behaviorstrategy in one can also be generated by an appropriately chosen behaviorstrategy in the other. This paper provides a characterization ofempirical equivalence. The central idea is to relate a game's informationstructure to the conditional independencies in the empirical distributionsit generates. We present a new analytical device, the influence opportunitydiagram of a game, describe how such a diagram is constructed for a givenextensive-form game, and demonstrate that it provides a complete summaryof the information needed to test empirical equivalence between two games.

Natural classification of knots

The principal objective of the knot theory is to provide a simple way of classifying and ordering all the knot types. Here, we propose a natural classification of knots based on their intrinsic position in the knot space that is defined by the set of knots to which a given knot can be converted by individual intersegmental passages. In addition, we characterize various knots using a set of simple quantum numbers that can be determined upon inspection of minimal crossing diagram of a knot. These numbers include: crossing number; average three-dimensional writhe; number of topological domains; and the average relaxation value

Acúmulo de N e P na parte aérea da soja após compactação subsuperficial e aplicação de gesso

Um experimento com soja, utilizando amostra de Latossolo Vermelho-Escuro distrófico textura média, previamente corrigido com 2,5 t ha-1 de calcário dolomítico, foi desenvolvido em casa de vegetação da Escola Superior de Agricultura ''Luiz de Queiroz", Piracicaba (SP), no período de dezembro/1993 a julho/1994, visando avaliar o efeito da compactação subsuperficial e de doses de gesso nos teores de N e de P da parte aérea da soja. Utilizou-se o delineamento em blocos casualizados, com os tratamentos dispostos em fatorial 4 x 4, com quatro repetições, correspondendo à aplicação, na camada superficial, de quatro doses de gesso (zero; 3,25; 6,50 e 9,75 t ha-1) misturadas ao equivalente a 15 t ha-1 de matéria seca de crotalária (MSC) e 2,5 t ha-1 de calcário dolomítico, em quatro níveis de compactação (densidades: 1,32; 1,4 7; 1,62 e 1,77 kg dm-3). Utilizou-se prensa hidráulica no solo do anel central de uma coluna formada pela sobreposição de três anéis de PVC de 15 cm de diâmetro e altura de 5 cm para o anel central e inferior e 12,5 cm para o anel superior . Observou-se que as doses de gesso não tiveram influência no teor de N da parte aérea da soja, quando ocorreu o crescimento radicular em profundidade. Quando a compactação do solo restringiu o crescimento radicular somente à camada superficial, a concentração de N na parte aérea da soja foi maior, quando a dose de gesso estimada era de 5 t ha-1, reduzindo-se para doses maiores do que esta. De maneira geral, a aplicação dos níveis de compactação não alterou os teores de N na parte aérea na presença de gesso, mas levou à redução linear quando o gesso não foi aplicado. Com relação ao fósforo, observou-se que tanto as doses de gesso como os níveis de compactação elevados promoveram aumentos na quantidade de P absorvido pela soja.

Cartographier les géomorphosites : objectifs, publics et propositions méthodologiques

Related to the raise of the awareness of the importance of the Earth heritage, geomorphosites receive increasing attention from the scientific community. Assessment methods, classification and conservation strategies have been developed to safeguard the geomorphological heritage for present and future generations. On the other hand, Earth heritage offers opportunities to develop educational and recreational programs as well as tourism projects. Various interpretive supports and local development projects have been engendered in the past few years to promote geoheritage.¦Be it for the assessment, conservation or promotion of geomorphosites, maps are valuable from many standpoints. They can provide fundamental data for detailed geomorphosite description, serve as visual communication tools helping to guide the selection process in defining protection priority or supporting Earth heritage promotion and interpretàtion.¦This study reviews the main achievements and the objectives yet to be accomplished in the field of geomorphosite mapping and proposes a general framework for the mapping of geomorphosites that takes into account the different aims and publics. The main focus is on mapping geomorphosites for non-specialists in the field of Earth heritage promotion (Geotourism). In this context, maps are often employed to show itineraries or points of interest. Like a scheme or a diagram, a map can also be used as a method for visualising geoscientific information. This function is particularly important since some processes, which contributed to the formation of a geomorphosite or a geomorphological landscape are no longer or not always clearly visible in the landscape. In this case, maps become interpretive media that serve popularisation purposes.¦Mapping for non-specialists holds the challenging task to ensure the information transfer between the cartographer and the user. We therefore focus on both the implementation of the map by the cartographer (which information? which visualisation?) and the interpretation of the map by the user (effectiveness of the knowledge transfer). The research is based on empirical studies carried out in the Maderan valley (Canton of Uri) and in classes of the Cantons of Uri and Tessin that aim to gain knowledge about the familiarity and interests of non- specialists for geoheritage as well as about their map reading skills. The final objective is to formulate methodological proposals for geomorphosite mapping for interpretive purpose.

Bone regeneration and stem cells.

?  Introduction ?  Bone fracture healing and healing problems ?  Biomaterial scaffolds and tissue engineering in bone formation -  Bone tissue engineering -  Biomaterial scaffolds -  Synthetic scaffolds -  Micro- and nanostructural properties of scaffolds -  Conclusion ?  Mesenchymal stem cells and osteogenesis -  Bone tissue -  Origin of osteoblasts -  Isolation and characterization of bone marrow derived MSC -  In vitro differentiation of MSC into osteoblast lineage cells -  In vivo differentiation of MSC into bone -  Factors and pathways controlling osteoblast differentiation of hMSC -  Defining the relationship between osteoblast and adipocyte differentiation from MSC -  MSC and sex hormones -  Effect of aging on osteoblastogenesis -  Conclusion ?  Embryonic, foetal and adult stem cells in osteogenesis -  Cell-based therapies for bone -  Specific features of bone cells needed to be advantageous for clinical use -  Development of therapeutic biological agents -  Clinical application concerns -  Conclusion ?  Platelet-rich plasma (PRP), growth factors and osteogenesis -  PRP effects in vitro on the cells involved in bone repair -  PRP effects on osteoblasts -  PRP effects on osteoclasts -  PRP effects on endothelial cells -  PRP effects in vivo on experimental animals -  The clinical use of PRP for bone repair -  Non-union -  Distraction osteogenesis -  Spinal fusion -  Foot and ankle surgery -  Total knee arthroplasty -  Odontostomatology and maxillofacial surgery -  Conclusion ?  Molecular control of osteogenesis -  TGF-β signalling -  FGF signalling -  IGF signalling -  PDGF signalling -  MAPK signalling pathway -  Wnt signalling pathway -  Hedgehog signalling -  Notch signalling -  Ephrin signalling -  Transcription factors regulating osteoblast differentiation -  Conclusion ?  Summary This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.

UBVRI-CCD photometry of Cepheus OB3 association

Johnson CCD photometry was performed in the two subgroups of the association Cepheus OB3, for selected fields each containing at least one star with previous UBV photoelectric photometry. Photometry for about 1000 stars down to visual magnitude 21 is provided, although the completeness tests show that the sample is complete down to V=19mag. Individual errors were assigned to the magnitude and colours for each star. Colour-colour and colour-magnitude diagrams are shown. Astrometric positions of the stars are also given. Description of the reduction procedure is fully detailed.

An analysis of the currently available calibrations inStromgren photometry by using open clusters

In recent years, several authors have revised the calibrations used to compute physical parameters (tex2html_wrap_inline498, tex2html_wrap_inline500, log g, [Fe/H]) from intrinsic colours in the tex2html_wrap_inline504 photometric system. For reddened stars, these intrinsic colours can be computed through the standard relations among colour indices for each of the regions defined by Strömgren (1966) on the HR diagram. We present a discussion of the coherence of these calibrations for main-sequence stars. Stars from open clusters are used to carry out this analysis. Assuming that individual reddening values and distances should be similar for all the members of a given open cluster, systematic differences among the calibrations used in each of the photometric regions might arise when comparing mean reddening values and distances for the members of each region. To classify the stars into Strömgren's regions we extended the algorithm presented by Figueras et al. (1991) to a wider range of spectral types and luminosity classes. The observational ZAMS are compared with the theoretical ZAMS from stellar evolutionary models, in the range tex2html_wrap_inline506 K. The discrepancies are also discussed.

Period-Luminosity-Colour distribution and classification of Galactic oxygen-rich LPVs I. Luminosity calibrations

The absolute K magnitudes and kinematic parameters of about 350 oxygen-rich Long-Period Variable stars are calibrated, by means of an up-to-date maximum-likelihood method, using HIPPARCOS parallaxes and proper motions together with radial velocities and, as additional data, periods and V-K colour indices. Four groups, differing by their kinematics and mean magnitudes, are found. For each of them, we also obtain the distributions of magnitude, period and de-reddened colour of the base population, as well as de-biased period-luminosity-colour relations and their two-dimensional projections. The SRa semiregulars do not seem to constitute a separate class of LPVs. The SRb appear to belong to two populations of different ages. In a PL diagram, they constitute two evolutionary sequences towards the Mira stage. The Miras of the disk appear to pulsate on a lower-order mode. The slopes of their de-biased PL and PC relations are found to be very different from the ones of the Oxygen Miras of the LMC. This suggests that a significant number of so-called Miras of the LMC are misclassified. This also suggests that the Miras of the LMC do not constitute a homogeneous group, but include a significant proportion of metal-deficient stars, suggesting a relatively smooth star formation history. As a consequence, one may not trivially transpose the LMC period-luminosity relation from one galaxy to the other.

Stem cell populations derived from heart and pancreas show a with a unique phenotype and give rise to functional cardiomyocytes and insulin-producing cells, respectively

Introduction: Recently, mesenchymal stem cells (MSC) of perivascular origin have been identified in several organs not including the heart. Using a novel cell isolation protocol, we have isolated cells sharing common characteristics from mouse hearts and pancreas. The aim of the present study was to characterize these cells in vitro.Methods: Cells were isolated from neonatal and adult mouse hearts and pancreas and cultured for more than 6 months. Surface marker expression was analyzed by flow cytometry and immunocytochemistry. Cell differentiation was tested using multiple differentiation media. Insulin production by pancreas-derived cells was tested by dithizone staining.Results: Cells showing a similar, distinctive morphology were obtained from the heart and pancreas after 4-8 weeks of culture. Cells from the two organs also showed a very similar immunophenotype, characterized by expression of c-kit (stem cell factor receptor), CD44, the common leukocyte marker CD45, and the monocytic markers CD11b and CD14. A significant proportion of cardiac and pancreatic cells expressed NG2, a marker for pericytes and other vascular cells. A significant proportion of cardiac, but not of pancreatic cells expressed stem cell antigen-1 (Sca-1). However, cells did not express T, B or dendritic cell markers. Cells of both cardiac and pancreatic origin spontaneously formed "spheres" (spherical cell aggregates similar to "neurospheres" formed by neural stem cells) in vitro. Cardiosphere formation was enhanced by TNF-alpha. Several cardiospheres (but no "pancreatospheres") derived from neonatal (but not adult) cells showed spontaneous rhythmic contractions, thus demonstrating cardiac differentiation (this was confirmed by immunostaining for alpha-sarcomeric actinin). Beating activity was enhanced by low serum conditions. Cells from both organs formed adipocytes, osteocytes and osteocytes under appropriate conditions, the typical differentiation pattern of MSCs. Pancreas-derived cells also formed dithizonepositive insulin-producing cells.Conclusions: We have defined cardiac and pancreatic cell populations that share a common morphology, growth characteristics, and a unique immunophenotype. Expression of perivascular and monocytic markers, along with stem/priogenitor cell markers by these cells suggests a relationship with pericytes-mesoangioblasts and so-called multipotent monocytes. Cells show MSC-typical growth and differentiation patterns, together with tissue-specific differentiation potential: cardiomyocytes for cardiac-derived cells and insulinproducing cells for pancreas-derived cells.

Influence of the (111) twinning on the formation of diamond cubic/diamond hexagonal heterostructures in Cu-catalyzed Si nanowires

The occurrence of heterostructures of cubic silicon/hexagonal silicon as disks defined along the nanowire (111) growth direction is reviewed in detail for Si nanowires obtained using Cu as catalyst. Detailed measurements on the structural properties of both semiconductor phases and their interface are presented. We observe that during growth, lamellar twinning on the cubic phase along the (111) direction is generated. Consecutive presence of twins along the (111) growth direction was found to be correlated with the origin of the local formation of the hexagonal Si segments along the nanowires, which define quantum wells of hexagonal Si diamond. Finally, we evaluate and comment on the consequences of the twins and wurtzite in the final electronic properties of the wires with the help of the predicted energy band diagram.

Semiclassical theory of shot noise in ballistic n+in+ semiconductor structures: relevance of Pauli and long range Coulomb interactions

We work out a semiclassical theory of shot noise in ballistic n+-i-n+ semiconductor structures aiming at studying two fundamental physical correlations coming from Pauli exclusion principle and long-range Coulomb interaction. The theory provides a unifying scheme which, in addition to the current-voltage characteristics, describes the suppression of shot noise due to Pauli and Coulomb correlations in the whole range of system parameters and applied bias. The whole scenario is summarized by a phase diagram in the plane of two dimensionless variables related to the sample length and contact chemical potential. Here different regions of physical interest can be identified where only Coulomb or only Pauli correlations are active, or where both are present with different relevance. The predictions of the theory are proven to be fully corroborated by Monte Carlo simulations.

Diffusionless first-order phase transitions in systems with frozen configurational degrees of freedom

We consider systems that can be described in terms of two kinds of degree of freedom. The corresponding ordering modes may, under certain conditions, be coupled to each other. We may thus assume that the primary ordering mode gives rise to a diffusionless first-order phase transition. The change of its thermodynamic properties as a function of the secondary-ordering-mode state is then analyzed. Two specific examples are discussed. First, we study a three-state Potts model in a binary system. Using mean-field techniques, we obtain the phase diagram and different properties of the system as a function of the distribution of atoms on the different lattice sites. In the second case, the properties of a displacive structural phase transition of martensitic type in a binary alloy are studied as a function of atomic order. Because of the directional character of the martensitic-transition mechanism, we find only a very weak dependence of the entropy on atomic order. Experimental results are found to be in quite good agreement with theoretical predictions.