Highly Regioselective Copper-Catalyzed Transfer Hydrodeuteration of Unactivated Terminal Alkenes

Catalytic transfer hydrodeuteration of unactivated alkenes is challenging because of the requirement that similar hydrogen and deuterium undergo selective insertion across a π-bond. We now report a highly regioselective catalytic transfer hydrodeuteration of unactivated terminal alkenes across a variety of heteroatom- or heterocycle-containing substrates. The base-metal-catalyzed reaction is also demonstrated on two complex natural products. Reaction studies indicate modular conditions that can also be extended to perform either an alkene transfer hydrogenation or transfer deuteration

Effect of the acrylic acid content on the permeability and water uptake of latex films

Acrylic acid (AA) is a monomer commonly employed in emulsion polymerization to provide electrostatic colloidal stability and improve specific film performance. The addition of AA not only modifies the kinetics of the polymerization, but also it takes part in the interaction between colloidal particles, which has a strong influence on their packing and consequent latex film properties. In this contribution a theoretical modeling of the latex film formation is presented and compared to experimental results: water vapor permeability and latex film capacitance are studied as a function of AA content. It has been shown that water uptake is mainly affected by film morphology which in turn is defined by intercolloidal interaction and drying rate.Comment: 16 pages, 7 figure

Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.

Stressors motivate an array of adaptive responses ranging from \u27fight or flight\u27 to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF\u27s capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders

Bias adjustment and ensemble recalibration methods for seasonal forecasting: a comprehensive intercomparison using the C3S dataset

This work presents a comprehensive intercomparison of diferent alternatives for the calibration of seasonal forecasts, ranging from simple bias adjustment (BA)-e.g. quantile mapping-to more sophisticated ensemble recalibration (RC) methods- e.g. non-homogeneous Gaussian regression, which build on the temporal correspondence between the climate model and the corresponding observations to generate reliable predictions. To be as critical as possible, we validate the raw model and the calibrated forecasts in terms of a number of metrics which take into account diferent aspects of forecast quality (association, accuracy, discrimination and reliability). We focus on one-month lead forecasts of precipitation and temperature from four state-of-the-art seasonal forecasting systems, three of them included in the Copernicus Climate Change Service dataset (ECMWF-SEAS5, UK Met Ofce-GloSea5 and Météo France-System5) for boreal winter and summer over two illustrative regions with diferent skill characteristics (Europe and Southeast Asia). Our results indicate that both BA and RC methods efectively correct the large raw model biases, which is of paramount importance for users, particularly when directly using the climate model outputs to run impact models, or when computing climate indices depending on absolute values/thresholds. However, except for particular regions and/or seasons (typically with high skill), there is only marginal added value-with respect to the raw model outputs-beyond this bias removal. For those cases, RC methods can outperform BA ones, mostly due to an improvement in reliability. Finally, we also show that whereas an increase in the number of members only modestly afects the results obtained from calibration, longer hindcast periods lead to improved forecast quality, particularly for RC methods.This work has been funded by the C3S activity on Evaluation and Quality Control for seasonal forecasts. JMG was partially supported by the project MULTI-SDM (CGL2015-66583-R, MINECO/FEDER). FJDR was partially funded by the H2020 EUCP project (GA 776613)

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

An integrated silicon sensor with microfluidic chip for monitoring potassium and pH

We present ion-sensitive field effect transistor-based sensors, integrated with a microfluidic chip, for monitoring pH and potassium cations. The sensor is strategically located at the base of a well so that the response time of the device depends both on the mean flow through the device and the diffusion coefficient of the analyte being monitored. This would enable monitoring of ions in the presence of larger molecules. The dependence of the device response time on diffusive transport of analytes was examined through a numerical study of the flow field and the passive diffusion of a chemical species. The predicted device response time was compared with the experimental measurements and reasonable agreement found. The general dependence of device response time on geometry, flow rate, and analyte diffusion coefficient was derived. These devices can be used with biological fluids where monitoring of pH and cations provide vital information about the well-being of patients. © 2010 Springer-Verlag

Operationalizing local ecological knowledge in climate change research : challenges and opportunities of citizen science

Current research on the local impacts of climate change is based on contrasting results from the simulation of historical trends in climatic variables produced with global models against climate data from independent observations. To date, these observations have mostly consisted of weather data from standardized meteorological stations. Given that the spatial distribution of weather stations is patchy, climate scientists have called for the exploration of new data sources. Knowledge developed by Indigenous Peoples and local communities with a long history of interaction with their environment has been proposed as a data source with untapped potential to contribute to our understanding of the local impacts of climate change. In this chapter, we discuss an approach that aims to bring insights from local knowledge systems to climate change research. First, we present a number of theoretical arguments that give support to the idea that local knowledge systems can contribute in original ways to the endeavors of climate change research. Then, we explore the potential of using information and communication technologies to gather and share local knowledge of climate change impacts. We do so through the examination of a citizen science initiative aiming to collect local indicators of climate change impacts: the LICCI project (www.licci.eu). Our findings illustrate that citizen science can inspire new approaches to articulate the inclusion of local knowledge systems in climate change research. However, this requires outlining careful approaches, with high ethical standards, toward knowledge validation and recognizing that there are aspects of local ecological knowledge that are incommensurable with scientific knowledge