Promoter IV of the class II transactivator gene is essential for positive selection of CD4+ T cells.

Major histocompatibility complex class II (MHCII) expression is regulated by the transcriptional coactivator CIITA. Positive selection of CD4(+) T cells is abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is entirely due to the absence of MHCII expression in thymic epithelia, as demonstrated by bone marrow transfer experiments between wild-type and pIV(-/-) mice. Medullary thymic epithelial cells (mTECs) are also MHCII(-) in pIV(-/-) mice. Bone marrow-derived, professional antigen-presenting cells (APCs) retain normal MHCII expression in pIV(-/-) mice, including those believed to mediate negative selection in the thymic medulla. Endogenous retroviruses thus retain their ability to sustain negative selection of the residual CD4(+) thymocytes in pIV(-/-) mice. Interestingly, the passive acquisition of MHCII molecules by thymocytes is abrogated in pIV(-/-) mice. This identifies thymic epithelial cells as the source of this passive transfer. In peripheral lymphoid organs, the CD4(+) T-cell population of pIV(-/-) mice is quantitatively and qualitatively comparable to that of MHCII-deficient mice. It comprises a high proportion of CD1-restricted natural killer T cells, which results in a bias of the V beta repertoire of the residual CD4(+) T-cell population. We have also addressed the identity of the signal that sustains pIV expression in cortical epithelia. We found that the Jak/STAT pathways activated by the common gamma chain (CD132) or common beta chain (CDw131) cytokine receptors are not required for MHCII expression in thymic cortical epithelia.

Effects of erosion and deposition on particle size distribution of deposited farmland soils on the chinese loess plateau

Particle size distribution (PSD) in the soil profile is strongly related to erosion, deposition, and physical and chemical processes. Water cycling and plant growth are also affected by PSD. Material sedimented upstream of the dam constructions formed large areas of deposited farmland (DF) soils on the Chinese Loess Plateau (CLP), which has been the site of the most severe soil erosion in the world. Two DFs without tillage on the CLP were chosen to study the combined effect of erosion and check dams on PSD. Eighty-eight layers (each 10 cm thick) of filled deposited farmland (FDF) soils and 22 layers of silting deposited farmland (SDF) soils of each studied soil profile were collected and 932 soil samples were investigated using laser granulometry. The particle sizes were stratified in both DFs based on soil properties and erosion resistance. The obtained results of clay and silt fractions showed similar horizontal distribution, indicating parallel characteristics of erosion and deposition processes. Fine sand represented the largest fraction, suggesting the preferential detachment of this fraction. The most erodible range of particle sizes was 0.25-0.5 mm, followed by 0.2-0.25 mm in the studied soil profiles. The correlation between particle size and soil water contents tended to increase with increasing water contents in FDF. Due to the abundant shallow groundwater, the relationship between particle size and soil water content in SDF was lost. Further studies on PSD in the DF area are needed to enhance the conservation management of soil and water resources in this region.

The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: a meta-analysis

(from the journal abstract) Background: Despite the effectiveness of anti-psychotic pharmacotherapy, residual hallucinations and delusions do not completely resolve in some medicated patients. Additional cognitive behavioral therapy (CBT) seems to improve the management of positive symptoms. Despite promising results, the efficacy of CBT is still unclear. The present study addresses this issue taking into account a number of newly published controlled studies. Method: Fourteen studies including 1484 patients, published between 1990 and 2004 were identified and a meta-analysis of their results performed. Results: Compared to other adjunctive measures, CBT showed significant reduction in positive symptoms and there was a higher benefit of CBT for patients suffering an acute psychotic episode versus the chronic condition (effect size of 0.57 vs. 0.27). Discussion: CBT is a promising adjunctive treatment for positive symptoms in schizophrenia spectrum disorders. However, a number of potentially modifying variables have not yet been examined, such as therapeutic alliance and neuropsychological deficits. (PsycINFO Database Record (c) 2005 APA, all rights reserved)

A Confluence of Risks: Control and Compliance in the World of Unstructured Data, Big Data and the Cloud

The emergence of powerful new technologies, the existence of large quantities of data, and increasing demands for the extraction of added value from these technologies and data have created a number of significant challenges for those charged with both corporate and information technology management. The possibilities are great, the expectations high, and the risks significant. Organisations seeking to employ cloud technologies and exploit the value of the data to which they have access, be this in the form of "Big Data" available from different external sources or data held within the organisation, in structured or unstructured formats, need to understand the risks involved in such activities. Data owners have responsibilities towards the subjects of the data and must also, frequently, demonstrate that they are in compliance with current standards, laws and regulations. This thesis sets out to explore the nature of the technologies that organisations might utilise, identify the most pertinent constraints and risks, and propose a framework for the management of data from discovery to external hosting that will allow the most significant risks to be managed through the definition, implementation, and performance of appropriate internal control activities.

Positive impact of inhibitory Ly49 receptor-MHC class I interaction on NK cell development.

NK cells can kill MHC-different or MHC-deficient but not syngeneic MHC-expressing target cells. This MHC class I-specific tolerance is acquired during NK cell development. MHC recognition by murine NK cells largely depends on clonally distributed Ly49 family receptors, which inhibit NK cell function upon ligand engagement. We investigated whether these receptors play a role for the development of NK cells and provide evidence that the expression of a Ly49 receptor transgene on developing NK cells endowed these cells with a significant developmental advantage over NK cells lacking such a receptor, but only if the relevant MHC ligand was present in the environment. The data suggest that the transgenic Ly49 receptor accelerates and/or rescues the development of NK cells which would otherwise fail to acquire sufficient numbers of self-MHC-specific receptors. Interestingly, the positive effect on NK cell development is most prominent when the MHC ligand is simultaneously present on both hemopoietic and nonhemopoietic cells. These findings correlate with functional data showing that MHC class I ligand on all cells is required to generate functionally mature NK cells capable of reacting to cells lacking the respective MHC ligand. We conclude that the engagement of inhibitory MHC receptors during NK cell development provides signals that are important for further NK cell differentiation and/or maturation.

Self-selection and risk selection on the Swiss health insurance market

Abstract This thesis presents three empirical studies in the field of health insurance in Switzerland. First we investigate the link between health insurance coverage and health care expenditures. We use claims data for over 60 000 adult individuals covered by a major Swiss Health Insurance Fund, followed for four years; the data show a strong positive correlation between coverage and expenditures. Two methods are developed and estimated in order to separate selection effects (due to individual choice of coverage) and incentive effects ("ex post moral hazard"). The first method uses the comparison between inpatient and outpatient expenditures to identify both effects and we conclude that both selection and incentive effects are significantly present in our data. The second method is based on a structural model of joint demand of health care and health insurance and makes the most of the change in the marginal cost of health care to identify selection and incentive effects. We conclude that the correlation between insurance coverage and health care expenditures may be decomposed into the two effects: 75% may be attributed to selection, and 25 % to incentive effects. Moreover, we estimate that a decrease in the coinsurance rate from 100% to 10% increases the marginal demand for health care by about 90% and from 100% to 0% by about 150%. Secondly, having shown that selection and incentive effects exist in the Swiss health insurance market, we present the consequence of this result in the context of risk adjustment. We show that if individuals choose their insurance coverage in function of their health status (selection effect), the optimal compensations should be function of the se- lection and incentive effects. Therefore, a risk adjustment mechanism which ignores these effects, as it is the case presently in Switzerland, will miss his main goal to eliminate incentives for sickness funds to select risks. Using a simplified model, we show that the optimal compensations have to take into account the distribution of risks through the insurance plans in case of self-selection in order to avoid incentives to select risks.Then, we apply our propositions to Swiss data and propose a simple econometric procedure to control for self-selection in the estimation of the risk adjustment formula in order to compute the optimal compensations.

The distribution of the dinucleotide CpG and cytosine methylation in the vitellogenin gene family.

Sequence data from regions of five vertebrate vitellogenin genes were used to examine the frequency, distribution, and mutability of the dinucleotide CpG, the preferred modification site for eukaryotic DNA methyltransferases. The observed level of the CpG dinucleotide in all five genes was markedly lower than that expected from the known mononucleotide frequencies. CpG suppression was greater in introns than in exons. CpG-containing codons were found to be avoided in the vitellogenin genes, but not completely despite the redundancy of the genetic code. Frequency and distribution patterns of this dinucleotide varied dramatically among these otherwise closely related genes. Dense clusters of CpG dinucleotides tended to appear in regions of either functional or structural interest (e.g., in the transposon-like Vi-element of Xenopus) and these clusters contained 5-methylcytosine (5 mC). 5 mC is known to undergo deamination to form thymidine, but the extent to which this transition occurs in the heavily methylated genomes of vertebrates and its contribution to CpG suppression are still unclear. Sequence comparison of the methylated vitellogenin gene regions identified C----T and G----A substitutions that were found to occur at relatively high frequencies. The predicted products of CpG deamination, TpG and CpA, were elevated. These findings are consistent with the view that CpG distribution and methylation are interdependent and that deamination of 5 mC plays an important role in promoting evolutionary change at the nucleotide sequence level.

Modelling the influence of change in fire regime on the local distribution of a Mediterranean pyrophytic plant species (Cistus salviifolius) at its northern range limit

Aims: To assess the potential distribution of an obligate seeder and active pyrophyte, Cistus salviifolius, a vulnerable species in the Swiss Red List; to derive scenarios by changing the fire return interval; and to discuss the results from a conservation perspective. A more general aim is to assess the impact of fire as a natural factor influencing the vegetation of the southern slopes of the Alps. Locations: Alps, southern Switzerland. Methods: Presence-absence data to fit the model were obtained from the most recent field mapping of C. salviifolius. The quantitative environmental predictors used in this study include topographic, climatic and disturbance (fire) predictors. Models were fitted by logistic regression and evaluated by jackknife and bootstrap approaches. Changes in fire regime were simulated by increasing the time-return interval of fire (simulating longer periods without fire). Two scenarios were considered: no fire in the past 15 years; or in the past 35 years. Results: Rock cover, slope, topographic position, potential evapotranspiration and time elapsed since the last fire were selected in the final model. The Nagelkerke R-2 of the model for C. salviifolius was 0.57 and the Jackknife area under the curve evaluation was 0.89. The bootstrap evaluation revealed model robustness. By increasing the return interval of fire by either up to 15 years, or 35 years, the modelled C. salviifolius population declined by 30-40%, respectively. Main conclusions: Although fire plays a significant role, topography and rock cover appear to be the most important predictors, suggesting that the distribution of C. salviifolius in the southern Swiss Alps is closely related to the availability of supposedly competition-free sites, such as emerging bedrock, ridge locations or steep slopes. Fire is more likely to play a secondary role in allowing C. salviifolius to extend its occurrence temporarily, by increasing germination rates and reducing the competition from surrounding vegetation. To maintain a viable dormant seed bank for C. salviifolius, conservation managers should consider carrying out vegetation clearing and managing wild fire propagation to reduce competition and ensure sufficient recruitment for this species.

DISTRIBUTION OF ORGANIC CARBON IN DIFFERENT SOIL FRACTIONS IN ECOSYSTEMS OF CENTRAL AMAZONIA

Organic matter plays an important role in many soil properties, and for that reason it is necessary to identify management systems which maintain or increase its concentrations. The aim of the present study was to determine the quality and quantity of organic C in different compartments of the soil fraction in different Amazonian ecosystems. The soil organic matter (FSOM) was fractionated and soil C stocks were estimated in primary forest (PF), pasture (P), secondary succession (SS) and an agroforestry system (AFS). Samples were collected at the depths 0-5, 5-10, 10-20, 20-40, 40-60, 60-80, 80-100, 100-160, and 160-200 cm. Densimetric and particle size analysis methods were used for FSOM, obtaining the following fractions: FLF (free light fraction), IALF (intra-aggregate light fraction), F-sand (sand fraction), F-clay (clay fraction) and F-silt (silt fraction). The 0-5 cm layer contains 60 % of soil C, which is associated with the FLF. The F-clay was responsible for 70 % of C retained in the 0-200 cm depth. There was a 12.7 g kg-1 C gain in the FLF from PF to SS, and a 4.4 g kg-1 C gain from PF to AFS, showing that SS and AFS areas recover soil organic C, constituting feasible C-recovery alternatives for degraded and intensively farmed soils in Amazonia. The greatest total stocks of carbon in soil fractions were, in decreasing order: (101.3 Mg ha-1 of C - AFS) > (98.4 Mg ha-1 of C - FP) > (92.9 Mg ha-1 of C - SS) > (64.0 Mg ha-1 of C - P). The forms of land use in the Amazon influence C distribution in soil fractions, resulting in short- or long-term changes.

Negative and positive effects of trade on health.

Comment on: Blouin C, Chopra M, van der Hoeven R.Trade and social determinants of health. Lancet. 2009;373(9662):502-7. PMID: 19167058.

Distribution of the transposable elements bilbo and gypsy in original and colonizing populations of Drosophila subobscura

Background: Transposable elements (TEs) constitute a substantial amount of all eukaryotic genomes. They induce an important proportion of deleterious mutations by insertion into genes or gene regulatory regions. However, their mutational capabilities are not always adverse but can contribute to the genetic diversity and evolution of organisms. Knowledge of their distribution and activity in the genomes of populations under different environmental and demographic regimes, is important to understand their role in species evolution. In this work we study the chromosomaldistribution of two TEs, gypsy and bilbo, in original and colonizing populations of Drosophilasubobscura to reveal the putative effect of colonization on their insertion profile.Results: Chromosomal frequency distribution of two TEs in one original and three colonizingpopulations of D. subobscura, is different. Whereas the original population shows a low insertionfrequency in most TE sites, colonizing populations have a mixture of high (frequency ¿ 10%) andlow insertion sites for both TEs. Most highly occupied sites are coincident among colonizingpopulations and some of them are correlated to chromosomal arrangements. Comparisons of TEcopy number between the X chromosome and autosomes show that gypsy occupancy seems to becontrolled by negative selection, but bilbo one does not. Conclusion: These results are in accordance that TEs in Drosophila subobscura colonizing populations are submitted to a founder effect followed by genetic drift as a consequence of colonization. This would explain the high insertion frequencies of bilbo and gypsy in coincident sites of colonizing populations. High occupancy sites would represent insertion events prior to colonization. Sites of low frequency would be insertions that occurred after colonization and/orcopies from the original population whose frequency is decreasing in colonizing populations. Thiswork is a pioneer attempt to explain the chromosomal distribution of TEs in a colonizing specieswith high inversion polymorphism to reveal the putative effect of arrangements in TE insertionprofiles. In general no associations between arrangements and TE have been found, except in a fewcases where the association is very strong. Alternatively, founder drift effects, seem to play aleading role in TE genome distribution in colonizing populations.

Predicting potential distribution of the jaguar (Panthera onca) in Mexico: identification of priority areas for conservation

Aim The jaguar, Panthera onca, is a species of global conservation concern. In Mexico, the northernmost part of its distribution range, its conservation status, is particularly critical, while its potential and actual distribution is poorly known. We propose an ensemble model (EM) of the potential distribution for the jaguar in Mexico and identify the priority areas for conservation.Location Mexico.Methods We generated our EM based on three presence-only methods (Ecological Niche Factor Analysis, Mahalanobis distance, Maxent) and considering environmental, biological and anthropogenic factors. We used this model to evaluate the efficacy of the existing Mexican protected areas (PAs), to evaluate the adequacy of the jaguar conservation units (JCUs) and to propose new areas that should be considered for conservation and management of the species in Mexico.Results Our results outline that 16% of Mexico (c. 312,000 km2) can be considered as suitable for the presence of the jaguar. Furthermore, 13% of the suitable areas are included in existing PAs and 14% are included in JCUs (Sanderson et al., 2002).Main conclusions Clearly much more should be carried out to establish a proactive conservation strategy. Based on our results, we propose here new jaguar conservation and management areas that are important for a nationwide conservation blueprint.

Testing the bivariate distribution of daily equity returns using copulas: an application to the Spanish stock market

In this paper we deal with the identification of dependencies between time series of equity returns. Marginal distribution functions are assumed to be known, and a bivariate chi-square test of fit is applied in a fully parametric copula approach. Several families of copulas are fitted and compared with Spanish stock market data. The results show that the t-copula generally outperforms other dependence structures, and highlight the difficulty in adjusting a significant number of bivariate data series

Formation and distribution of point defects on a disclination line near a free nematic interface

Point defects of opposite signs can alternately nucleate on the -1/2 disclination line that forms near the free surface of a confined nematic liquid crystal. We show the existence of metastable configurations consisting of periodic repetitions of such defects. These configurations are characterized by a minimal interdefect spacing that is seen to depend on sample thickness and on an applied electric field. The time evolution of the defect distribution suggests that the defects attract at small distances and repel at large distances.