The Tea4-PP1 landmark promotes local growth by dual Cdc42 GEF recruitment and GAP exclusion.

Cell polarization relies on small GTPases, such as Cdc42, which can break symmetry through self-organizing principles, and landmarks that define the axis of polarity. In fission yeast, microtubules deliver the Tea1-Tea4 complex to mark cell poles for growth, but how this complex activates Cdc42 is unknown. Here, we show that ectopic targeting of Tea4 to cell sides promotes the local activation of Cdc42 and cell growth. This activity requires that Tea4 binds the type I phosphatase (PP1) catalytic subunit Dis2 or Sds21, and ectopic targeting of either catalytic subunit is similarly instructive for growth. The Cdc42 guanine-nucleotide-exchange factor Gef1 and the GTPase-activating protein Rga4 are required for Tea4-PP1-dependent ectopic growth. Gef1 is recruited to ectopic Tea4 and Dis2 locations to promote Cdc42 activation. By contrast, Rga4 is locally excluded by Tea4, and its forced colocalization with Tea4 blocks ectopic growth, indicating that Rga4 must be present, but at sites distinct from Tea4. Thus, a Tea4-PP1 landmark promotes local Cdc42 activation and growth both through Cdc42 GEF recruitment and by creating a local trough in a Cdc42 GAP.

An investigation of the relationship between job characteristics and the gender wage gap

This paper re-examines gender wage differences, taking into account notonly worker characteristics but also job characteristics. Considerationof a wide set of job quality indicators can explain a fraction of thewage gap that would otherwise be attributed to pure wage discrimination.In any case, the fraction of the wage gap that remains associated todifferential rewards for identical factors across sexes is stillsubstantial. Our results suggest that in order to avoid overestimationof the fraction of the wage gap attributable to discrimination, it isnecessary to control for job characteristics.

Demand for private health insurance: Is there a quality gap?

Quality of care is qualified as a main determinant of the demand forvoluntary private health insurance (PHI) in National Health Systems(NHS). This paper provides new evidence on the influence of the qualitygap between public and private health insurance and other demanddeterminants in the demand for PHI in Catalonia. The demand for PHI ismodelled as a demand for health care quality. Unlike previous studies, the database employed allows for the development of a link between thetheoretical and the empirical model dealing with unobserved heterogeneityand endogeneity issues. Results suggest that a rise in PHI qualityenhances an equivalent influence in the demand for PHI as an equalreduction of NHS quality. Income and price elasticity estimates areconsistent with the observed feature that PHI appears to be a luxurygood and individuals tend to be relatively insensible to tax relief'sand monetary co-payments in insurance contracts.

How wide is the gap? An investigation of gender wage differences using quantile regression

In this paper we examine the determinants of wages and decompose theobserved differences across genders into the "explained by differentcharacteristics" and "explained by different returns components"using a sample of Spanish workers. Apart from the conditionalexpectation of wages, we estimate the conditional quantile functionsfor men and women and find that both the absolute wage gap and thepart attributed to different returns at each of the quantiles, farfrom being well represented by their counterparts at the mean, aregreater as we move up in the wage range.

Hypertension. L'enregistrement tensionnel en ambulatoire: indispensable pour diagnostiquer et traiter l'hypertension [Ambulatory blood pressure monitoring: essential for diagnosing and treating hypertension?].

According to recent international guidelines, 24-h ambulatory blood pressure monitoring plays an important role in the diagnostic and therapeutic approach of arterial hypertension. Indications of this technique are multiple, concerning both day- and night-time blood pressures. Blood pressures provided by ambulatory monitoring may be used to stratify cardiovascular risk.

Integration of high-resolution geophysical data for the characterization of alluvial aquifers : new approaches and implications for hydrological predictions

Abstract Accurate characterization of the spatial distribution of hydrological properties in heterogeneous aquifers at a range of scales is a key prerequisite for reliable modeling of subsurface contaminant transport, and is essential for designing effective and cost-efficient groundwater management and remediation strategies. To this end, high-resolution geophysical methods have shown significant potential to bridge a critical gap in subsurface resolution and coverage between traditional hydrological measurement techniques such as borehole log/core analyses and tracer or pumping tests. An important and still largely unresolved issue, however, is how to best quantitatively integrate geophysical data into a characterization study in order to estimate the spatial distribution of one or more pertinent hydrological parameters, thus improving hydrological predictions. Recognizing the importance of this issue, the aim of the research presented in this thesis was to first develop a strategy for the assimilation of several types of hydrogeophysical data having varying degrees of resolution, subsurface coverage, and sensitivity to the hydrologic parameter of interest. In this regard a novel simulated annealing (SA)-based conditional simulation approach was developed and then tested in its ability to generate realizations of porosity given crosshole ground-penetrating radar (GPR) and neutron porosity log data. This was done successfully for both synthetic and field data sets. A subsequent issue that needed to be addressed involved assessing the potential benefits and implications of the resulting porosity realizations in terms of groundwater flow and contaminant transport. This was investigated synthetically assuming first that the relationship between porosity and hydraulic conductivity was well-defined. Then, the relationship was itself investigated in the context of a calibration procedure using hypothetical tracer test data. Essentially, the relationship best predicting the observed tracer test measurements was determined given the geophysically derived porosity structure. Both of these investigations showed that the SA-based approach, in general, allows much more reliable hydrological predictions than other more elementary techniques considered. Further, the developed calibration procedure was seen to be very effective, even at the scale of tomographic resolution, for predictions of transport. This also held true at locations within the aquifer where only geophysical data were available. This is significant because the acquisition of hydrological tracer test measurements is clearly more complicated and expensive than the acquisition of geophysical measurements. Although the above methodologies were tested using porosity logs and GPR data, the findings are expected to remain valid for a large number of pertinent combinations of geophysical and borehole log data of comparable resolution and sensitivity to the hydrological target parameter. Moreover, the obtained results allow us to have confidence for future developments in integration methodologies for geophysical and hydrological data to improve the 3-D estimation of hydrological properties.

Identifying the gap between need and intervention for alcohol use disorders in Europe.

AIMS: A literature review of existing research on the prevalence of alcohol use disorders (AUDs) and availability of alcohol interventions in Europe was conducted. The review also explored what is known about the gap between need and provision of alcohol interventions in Europe. METHODS: The review search strategy included: (i) descriptive studies of alcohol intervention systems in Europe; (ii) studies of alcohol service provision in Europe; and (iii) studies of prevalence of AUD and alcohol needs assessment in Europe. RESULTS: Europe has a relatively high level of alcohol consumption and the resulting disabilities are the highest in the world. Most research on implementation of alcohol interventions in Europe has been restricted to screening and brief interventions. Alcohol needs assessment methodology has been developed but has not been applied in comparative studies across countries in Europe. CONCLUSIONS: This review points to key gaps in knowledge related to alcohol interventions in Europe. There is a lack of comparative data on variations in alcohol treatment systems across European countries and there is also a lack of comparative data on the prevalence of alcohol use disorders across European countries and the relative gap between need and access to treatment. The forthcoming Alcohol Measures for Public Health Research Alliance (AMPHORA) research project work package on 'Early identification and treatment' aims to address these gaps.

Effects of a treatment gap during adjuvant chemotherapy in node-positive breast cancer: results of International Breast Cancer Study Group (IBCSG) Trials 13-93 and 14-93.

BACKGROUND: The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials to assess whether a treatment-free gap during adjuvant chemotherapy influenced outcome. PATIENTS AND METHODS: From 1993 to 1999, IBCSG Trials 13-93 and 14-93 enrolled 2215 premenopausal and postmenopausal women with axillary node-positive, operable breast cancer. All patients received cyclophosphamide (Cytoxan, C) plus either doxorubicin (Adriamycin, A) or epirubicin (E) for four courses followed immediately (No Gap) or after a 16-week delay (Gap) by classical cyclophosphamide, methotrexate, and fluorouracil (CMF) for three courses. The median follow-up was 7.7 years. RESULTS: The Gap and No-Gap groups had similar disease-free survival (DFS) and overall survival (OS). No identified subgroup showed a statistically significant difference, but exploratory subgroup analysis noted a trend towards decreased DFS for Gap compared with No Gap for women with estrogen receptor (ER)-negative tumors not receiving tamoxifen, especially evident during the first 2 years. CONCLUSIONS: A 16-week gap between adjuvant AC/EC and CMF provided no benefit and may have increased early recurrence rates in patients with ER-negative tumors.

Toxic effects of essential plant oils in adult Sitophilus oryzae (Linnaeus) (Coleoptera, Curculionidae)

Toxic effects of essential plant oils in adult Sitophilus oryzae (Linnaeus) (Coleoptera, Curculionidae). Stored grains are subject to losses in quality nutritional value and in sanitation from the time they are stored to the time they are consumed. Botanical insecticides may offer an alternative solution for pest control. The objective was to test the insecticidal properties of the essential oils of Cymbopogon citratus (leaf), Zingiber officinale (root) and Mentha sp. (leaf). The efficacy of these oils was tested to control the rice weevil, S. oryzae, using hydrodistillation. Chemical analysis of the essential oils was carried out by gas chromatography. Major components of C. citratus were geranial (48%) and neral (31%), of Z. officinale were α-zingibereno (13%), geranial (16%), neral (10%) and α-farneseno (5%) and of Mentha sp. was menthol (92%). Bioassays were carried out by fumigation and topical application. In topical application assays, the essential oil of C. citratus had greater toxicity (LC50 0.027 µL mL-1) and shorter exposure time than the oils of the other two plants. After 24 h and 48 h, 70% and 100% mortality of S. oryzae occurred, respectively. In fumigation assays, essential oil of Z. officinale had a lower LC50 (1.18 µL cm-2) and 70% mortality after 24 h exposure. Therefore, we recommend the use of essential oils of C. citratus and Z. officinale to control the rice weevil S. oryzae.

Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.

Bridging the Accountability Gap: Rights for New Entities in the Information Society?

Technological developments in the information society bring new challenges, both to the applicability and to the enforceability of the law. One major challenge is posed by new entities such as pseudonyms, avatars, and software agents that operate at an increasing distance from the physical persons "behind" them (the "principal"). In case of accidents or misbehavior, current laws require that the physical or legal principal behind the entity be found so that she can be held to account. This may be problematic if the linkability of the principal and the operating entity is questionable. In light of the ongoing developments in electronic agents, there is sufficient reason to conduct a review of the literature in order to more closely examine arguments for and against legal personhood for some nonhuman acting entities. This article also includes a discussion of alternative approaches to solving the "accountability gap."

Globalization and culture shaping the gender gap: A comparative analysis of urban Latin America and East Asia (1970 - 2000)

In this paper we present: 1. The available data on comparative gender inequality at themacroeconomic level and 2. Gender inequality measures at the microeconomic and case studylevel. We see that market openness has a significant effect on the narrowing of the human capitalgender gap. Globalization and market openness stand as factors that improve both the humancapital endowments of women and their economic position. But we also see that the effects ofculture and religious beliefs are very different. While Catholicism has a statistically significantinfluence on the improvement of the human capital gender gap, Muslim and Buddhist religiousbeliefs have the opposite effect and increase human capital gender differences.In the second global era, some Catholic Latin American countries benefited from market opennessin terms of the human capital and income gender gap, whereas we find the opposite impact inBuddhist and Muslim countries like China and South Korea where women s economic positionhas worsened in terms of human capital and wage inequality.

Renal tissue oxygenation in essential hypertension and chronic kidney disease.

Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD). In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system) or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.