Intestinal barrier tightening by a cell-penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis.

Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lowe

Quantitative Effects of Fiscal Foresight

Changes in fiscal policy typically entail two kinds of lags: the legislative lag—between when legislation is proposed and when it is signed into law—and the implementation lag—from when a new fiscal law is enacted and when it takes effect. These lags imply that substantial time evolves between when news arrives about fiscal changes and when the changes actually take place—time when households and firms can adjust their behavior. We identify two types of fiscal news—government spending and changes in tax policy—and map the news processes into standard DSGE models. We identify news concerning taxes through the municipal bond market. If asset markets are efficient, the yield spread between tax-exempt municipal bonds and treasuries should be a function of the news concerning changes in tax policy. We identify news concerning government spending through the Survey of Professional Forecasters. We conclude that news concerning fiscal variables is a time-varying process that can have important qualitative and quantitative effects.

Choosing between an apple and a chocolate bar: the impact of health and taste labels.

Increasing the consumption of fruit and vegetables is a central component of improving population health. Reasons people give for choosing one food over another suggest health is of lower importance than taste. This study assesses the impact of using a simple descriptive label to highlight the taste as opposed to the health value of fruit on the likelihood of its selection. Participants (N=439) were randomly allocated to one of five groups that varied in the label added to an apple: apple; healthy apple; succulent apple; healthy and succulent apple; succulent and healthy apple. The primary outcome measure was selection of either an apple or a chocolate bar as a dessert. Measures of the perceived qualities of the apple (taste, health, value, quality, satiety) and of participant characteristics (restraint, belief that tasty foods are unhealthy, BMI) were also taken. When compared with apple selection without any descriptor (50%), the labels combining both health and taste descriptors significantly increased selection of the apple ('healthy & succulent' 65.9% and 'succulent & healthy' 62.4%), while the use of a single descriptor had no impact on the rate of apple selection ('healthy' 50.5% and 'succulent' 52%). The strongest predictors of individual dessert choice were the taste score given to the apple, and the lack of belief that healthy foods are not tasty. Interventions that emphasize the taste attributes of healthier foods are likely to be more effective at achieving healthier diets than those emphasizing health alone

Assessing sampling of the fossil record in a geographically and stratigraphically constrained dataset: the Chalk Group of Hampshire, southern UK

Taphonomic, geological and sampling processes have been cited as biasing richness measurements in the fossil record, and sampling proxies have been widely used to assess this. However, the link between sampling and taxonomic richness is poorly understood, and there has been much debate on the equivalence and relevance of proxies. We approach this question by combining both historical and novel data: a historical fossil occurrence dataset with uniquely high spatial resolution from the Upper Cretaceous Chalk Group of Hampshire, UK, and a newly compiled 3D geological model that maps subsurface extent. The geological model provides rock volumes, and these are compared with exposure and outcrop area, sampling proxies that have often been conflated in previous studies. The extent to which exposure area (true rock availability) has changed over research time is also tested. We find a trend of low Cenomanian to high Turonian to Campanian raw richness, which correlates with, and is possibly driven by, the number of specimens found. After sampling standardization, an unexpected mid-Turonian peak diversity is recovered, and sampling-standardized genus richness is best predicted by rock volume, suggesting a species–area (or ‘genus–area’) effect. Additionally, total exposure area has changed over time, but relative exposure remains the same. Supplementary materials: A locality list, abundance matrix and all correlation and modelling results are available at https://doi.org/10.6084/m9.figshare.c.3592208

Assessing sampling of the fossil record in a geographically and stratigraphically constrained dataset: the Chalk Group of Hampshire, southern UK

Taphonomic, geological and sampling processes have been cited as biasing richness measurements in the fossil record, and sampling proxies have been widely used to assess this. However, the link between sampling and taxonomic richness is poorly understood, and there has been much debate on the equivalence and relevance of proxies. We approach this question by combining both historical and novel data: a historical fossil occurrence dataset with uniquely high spatial resolution from the Upper Cretaceous Chalk Group of Hampshire, UK, and a newly compiled 3D geological model that maps subsurface extent. The geological model provides rock volumes, and these are compared with exposure and outcrop area, sampling proxies that have often been conflated in previous studies. The extent to which exposure area (true rock availability) has changed over research time is also tested. We find a trend of low Cenomanian to high Turonian to Campanian raw richness, which correlates with, and is possibly driven by, the number of specimens found. After sampling standardization, an unexpected mid-Turonian peak diversity is recovered, and sampling-standardized genus richness is best predicted by rock volume, suggesting a species–area (or ‘genus–area’) effect. Additionally, total exposure area has changed over time, but relative exposure remains the same. Supplementary materials: A locality list, abundance matrix and all correlation and modelling results are available at https://doi.org/10.6084/m9.figshare.c.3592208

Multilevel modelling of the incidence of visceral leishmaniasis in Teresina, Brazil

Epidemics of visceral leishmaniasis (VL) in major Brazilian cities are new phenomena since 1980. As determinants of transmission in urban settings probably operate at different geographic scales, and information is not available for each scale, a multilevel approach was used to examine the effect of canine infection and environmental and socio-economic factors on the spatial variability of incidence rates of VL in the city of Teresina. Details on an outbreak of greater than 1200 cases of VL in Teresina during 1993-1996 were available at two hierarchical levels: census tracts (socio-economic characteristics, incidence rates of human VL) and districts, which encompass census tracts (prevalence of canine infection). Remotely sensed data obtained by satellite generated environmental information at both levels. Data from census tracts and districts were analysed simultaneously by multilevel modelling. Poor socio-economic conditions and increased vegetation were associated with a high incidence of human VL. Increasing prevalence of canine infection also predicted a high incidence of human VL, as did high prevalence of canine infection before and during the epidemic. Poor socio-economic conditions had an amplifying effect on the association between canine infection and the incidence of human VL. Focusing interventions on areas with characteristics identified by multilevel analysis could be a cost-effective strategy for controlling VL. Because risk factors for infectious diseases operate simultaneously at several levels and ecological data usually are available at different geographical scales, multilevel modelling is a valuable tool for epidemiological investigation of disease transmission

Interpretation of photocurrent transients at semiconductor electrodes:Effects of band-edge unpinning

The transient photocurrent response of semiconductor electrodes to chopped illumination often shows spikes and overshoots that are usually interpreted as evidence that surface recombination is occurring. In the case of the high intensities used for light-driven water splitting, the interpretation is less straightforward since the electron transfer reactions are so slow that the minority carrier concentration at or near the surface increases to high values that modify the potential drop across the Helmholtz layer in the electrolyte, leading to ‘band edge unpinning’. In addition, changes in chemical composition of the surface or local changes in pH may also alter the potential distribution across the semiconductor/electrolyte junction. A quantitative theory of band edge unpinning due to minority carrier build up is presented, and numerical calculations of transient photocurrent responses are compared with experimental examples for n-type Fe2O3 and p-type lithium-doped CuO electrodes. It is shown that the apparently high reaction orders (up to third order) with respect to hole concentration reported for hematite photoanodes can be explained as arising from an acceleration of hole transfer by the increased voltage drop across the Helmholtz layer associated with band edge unpinning. The limitations of the band edge unpinning model are discussed considering additional effects associated with modification of the potential distribution brought about by light-induced changes in surface composition, surface dipoles and surface ionic charge.</p

The Ti environment in natural hibonite: XANES spectroscopy and computer modelling

The local atomic structure around Ti in Ti-bearing hibonite (CaAl12O19) was studied using X-ray absorption near-edge structure (XANES) spectroscopy and computer modelling. Structural models of the direct substitution of Al by Ti3+, Al by Ti4+ charge balanced by the coupled substitution of Mg2+ for Al, and small Ti clusters were considered. The Ti K-XANES spectra of natural hibonite with different Ti concentration were recorded. Theoretical Ti K- XANES spectra for structural models of hibonite were calculated. It was shown that the theoretical Ti K-XANES spectra for a model with Ti at the five-coordinated M2 site are in agreement with the experimental XANES spectra of hibonite with low concentrations of Ti, while the theoretical spectra for a structural model of clustered Ti are in agreement with the experimental spectra of hibonite with higher Ti contents