A New View of Coastal Oceans From the Space Station

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Environmental assessment of mountain grassland farms with mixed cattle systems: use of bioeconomic simulations

Management practices of cattle farming systems must be improved, particularly to increase the systems’ feed self-sufficiency, food production and environmental performances. In mountain areas of the Massif Central (central France), mixed dairy/suckler cattle systems enable farmers to use grassland resources better and cope with economic fluctuations. Our objective was to estimate levels of ecosystem services provided by mixed dairy/suckler cattle systems as a function of the degree of mixing, along with their greenhouse gas emissions and energy use when their operation is optimized on an economic basis. The hypothesis was that mixed dairy/suckler cattle systems allow for controlled use of biomass, with better environmental performances than specialized systems (pure dairy or suckler herd) by maintaining grassland ecosystem services. Five herd-distribution scenarios were simulated using the Orfee bioeconomic optimization model. Environmental performances of the five systems were assessed according to three functional units (i.e., per farm, ha and kg protein produced). Mixed dairy/suckler cattle systems, which enabled larger herds, had higher greenhouse gas emissions per ha than specialized systems. However, because dairy cows produce more protein (milk and beef) than suckler cows, specialized dairy systems had the lowest greenhouse gas emissions and energy use per kg of protein. Specialized dairy systems had less advantage when dairy cows had less access to grassland. For the production of both milk and beef, mixed dairy/suckler cattle systems favour more sustainable use of biomass and tend to maintain a better combination of levels of ecosystem services for livestock production than specialized cattle farming systems

Small-Molecule Hydrophobic Tagging Induced Degradation of HaloTag Fusion Proteins

The ability to regulate any protein of interest in living systems with small molecules remains a challenge. We hypothesized that appending a hydrophobic moiety to the surface of a protein would mimic the partially denatured state of the protein, thus engaging the cellular quality control machinery to induce its proteasomal degradation. We designed and synthesized bifunctional small molecules to bind a bacterial dehalogenase (the HaloTag protein) and present a hydrophobic group on its surface. Hydrophobic tagging of the HaloTag protein with an adamantyl moiety induced the degradation of cytosolic, isoprenylated and transmembrane HaloTag fusion proteins in cell culture. We demonstrated the in vivo utility of hydrophobic tagging by degrading proteins expressed in zebrafish embryos and by inhibiting Hras1G12V-driven tumor progression in mice. Therefore, hydrophobic tagging of HaloTag fusion proteins affords small-molecule control over any protein of interest, making it an ideal system for validating potential drug targets in disease models

Continuous selections of multivalued mappings

This survey covers in our opinion the most important results in the theory of continuous selections of multivalued mappings (approximately) from 2002 through 2012. It extends and continues our previous such survey which appeared in Recent Progress in General Topology, II, which was published in 2002. In comparison, our present survey considers more restricted and specific areas of mathematics. Note that we do not consider the theory of selectors (i.e. continuous choices of elements from subsets of topological spaces) since this topics is covered by another survey in this volume

Increased ventral striatal volume in college-aged binge drinkers

BACKGROUND Binge drinking is a serious public health issue associated with cognitive, physiological, and anatomical differences from healthy individuals. No studies, however, have reported subcortical grey matter differences in this population. To address this, we compared the grey matter volumes of college-age binge drinkers and healthy controls, focusing on the ventral striatum, hippocampus and amygdala. METHOD T1-weighted images of 19 binge drinkers and 19 healthy volunteers were analyzed using voxel-based morphometry. Structural data were also covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Cluster-extent threshold and small volume corrections were both used to analyze imaging data. RESULTS Binge drinkers had significantly larger ventral striatal grey matter volumes compared to controls. There were no between group differences in hippocampal or amygdalar volume. Ventral striatal, amygdalar, and hippocampal volumes were also negatively related to AUDIT scores across groups. CONCLUSIONS Our findings stand in contrast to the lower ventral striatal volume previously observed in more severe forms of alcohol use disorders, suggesting that college-age binge drinkers may represent a distinct population from those groups. These findings may instead represent early sequelae, compensatory effects of repeated binge and withdrawal, or an endophenotypic risk factor

Hyperspectral Imager for the Coastal Ocean: instrument description and first images

The Hyperspectral Imager for the Coastal Ocean (HICO) is the first spaceborne hyperspectral sensor designed specifically for the coastal ocean and estuarial, riverine, or other shallow-water areas. The HICO generates hyperspectral images, primarily over the 400–900nm spectral range, with a ground sample distance of ≈90m (at nadir) and a high signal-to-noise ratio. The HICO is now operating on the International Space Station (ISS). Its cross-track and along-track fields of view are 42km (at nadir) and 192 km, respectively, for a total scene area of 8000km². The HICO is an innovative prototype sensor that builds on extensive experience with airborne sensors and makes extensive use of commercial off-theshelf components to build a space sensor at a small fraction of the usual cost and time. Here we describe the instrument’s design and characterization and present early images from the ISS.This paper was published in Applied Optics and is made available as an electronic reprint with the permission of OSA. The paper can be found atthe following URL on the OSA website: http://www.opticsinfobase.org/ao/home.cfm. Systematic ormultiple reproduction or distribution to multiple locations viaelectronic or other means is prohibited and is subject to penaltiesunder law

Limited Urban Growth: London's Street Network Dynamics since the 18th Century

We investigate the growth dynamics of Greater London defined by the administrative boundary of the Greater London Authority, based on the evolution of its street network during the last two centuries. This is done by employing a unique dataset, consisting of the planar graph representation of nine time slices of Greater London's road network spanning 224 years, from 1786 to 2010. Within this time-frame, we address the concept of the metropolitan area or city in physical terms, in that urban evolution reveals observable transitions in the distribution of relevant geometrical properties. Given that London has a hard boundary enforced by its long-standing green belt, we show that its street network dynamics can be described as a fractal space-filling phenomena up to a capacitated limit, whence its growth can be predicted with a striking level of accuracy. This observation is confirmed by the analytical calculation of key topological properties of the planar graph, such as the topological growth of the network and its average connectivity. This study thus represents an example of a strong violation of Gibrat's law. In particular, we are able to show analytically how London evolves from a more loop-like structure, typical of planned cities, toward a more tree-like structure, typical of self-organized cities. These observations are relevant to the discourse on sustainable urban planning with respect to the control of urban sprawl in many large cities, which have developed under the conditions of spatial constraints imposed by green belts and hard urban boundaries.Comment: PlosOne, in publicatio

Manipulating the alpha level cannot cure significance testing

We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable

Selective small molecule induced degradation of the BET bromodomain protein BRD4

The Bromo- and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 play important roles in transcriptional regulation, epigenetics, and cancer and are the targets of pan-BET selective bromodomain inhibitor JQ1. However, the lack of intra-BET selectivity limits the scope of current inhibitors as probes for target validation and could lead to unwanted side effects or toxicity in a therapeutic setting. We designed Proteolysis Targeted Chimeras (PROTACs) that tether JQ1 to a ligand for the E3 ubiquitin ligase VHL, aimed at triggering the intracellular destruction of BET proteins. Compound MZ1 potently and rapidly induces reversible, long-lasting, and unexpectedly selective removal of BRD4 over BRD2 and BRD3. The activity of MZ1 is dependent on binding to VHL but is achieved at a sufficiently low concentration not to induce stabilization of HIF-1α. Gene expression profiles of selected cancer-related genes responsive to JQ1 reveal distinct and more limited transcriptional responses induced by MZ1, consistent with selective suppression of BRD4. Our discovery opens up new opportunities to elucidate the cellular phenotypes and therapeutic implications associated with selective targeting of BRD4