356 research outputs found
A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale
In this era of complete genomes, our knowledge of neuroanatomical circuitry
remains surprisingly sparse. Such knowledge is however critical both for basic
and clinical research into brain function. Here we advocate for a concerted
effort to fill this gap, through systematic, experimental mapping of neural
circuits at a mesoscopic scale of resolution suitable for comprehensive,
brain-wide coverage, using injections of tracers or viral vectors. We detail
the scientific and medical rationale and briefly review existing knowledge and
experimental techniques. We define a set of desiderata, including brain-wide
coverage; validated and extensible experimental techniques suitable for
standardization and automation; centralized, open access data repository;
compatibility with existing resources, and tractability with current
informatics technology. We discuss a hypothetical but tractable plan for mouse,
additional efforts for the macaque, and technique development for human. We
estimate that the mouse connectivity project could be completed within five
years with a comparatively modest budget.Comment: 41 page
Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates
Non-Alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant
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Report on the Depth Requirements for a Massive Detector at Homestake
This report provides the technical justification for locating a large detector underground in a US based Deep Underground Science and Engineering Laboratory. A large detector with a fiducial mass greater than 100 kTon will most likely be a multipurpose facility. The main physics justification for such a device is detection of accelerator generated neutrinos, nucleon decay, and natural sources of neutrinos such as solar, atmospheric and supernova neutrinos. The requirement on the depth of this detector will be guided by the rate of signals from these sources and the rate of backgrounds from cosmic rays over a very wide range of energies (from solar neutrino energies of 5 MeV to high energies in the range of hundreds of GeV). For the present report, we have examined the depth requirement for a large water Cherenkov detector and a liquid argon time projection chamber. There has been extensive previous experience with underground water Cherenkov detectors such as IMB, Kamioka, and most recently, Super-Kamiokande which has a fiducial mass of 22 kTon and a total mass of 50 kTon at a depth of 2700 meters-water-equivalent in a mountain. Projections for signal and background capability for a larger and deeper(or shallower) detectors of this type can be scaled from these previous detectors. The liquid argon time projection chamber has the advantage of being a very fine-grained tracking detector, which should provide enhanced capability for background rejection. We have based background rejection on reasonable estimates of track and energy resolution, and in some cases scaled background rates from measurements in water. In the current work we have taken the approach that the depth should be sufficient to suppress the cosmogenic background below predicted signal rates for either of the above two technologies. Nevertheless, it is also clear that the underground facility that we are examining must have a long life and will most likely be used either for future novel uses of the currently planned detectors or new technologies. Therefore the depth requirement also needs to be made on the basis of sound judgment regarding possible future use. In particular, the depth should be sufficient for any possible future use of these cavities or the level which will be developed for these large structures.Along with these physics justifications there are practical issues regarding the existing infrastructure at Homestake and also the stress characteristics of the Homestake rock formations. In this report we will examine the various depth choices at Homestake from the point of view of the particle and nuclear physics signatures of interest. We also have sufficient information about the existing infrastructure and the rock characteristics to narrow the choice of levels for the development of large cavities with long lifetimes. We make general remarks on desirable ground conditions for such large cavities and then make recommendations on how to start examining these levels to make a final choice. In the appendix we have outlined the initial requirements for the detectors. These requirements will undergo refinement during the course of the design. Finally, we strongly recommend that the geotechnical studies be commenced at the 4850 ft level, which we find to be the most suitable, in a timely manner
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
The reductive glycine pathway allows autotrophic growth of Desulfovibrio desulfuricans
Supplementary informationis available for this paper athttps://doi.org/10.1038/s41467-020-18906-7Six CO2 fixation pathways are known to operate in photoautotrophic and chemoautotrophic microorganisms. Here, we describe chemolithoautotrophic growth of the sulphate-reducing bacterium Desulfovibrio desulfuricans (strain G11) with hydrogen and sulphate as energy substrates. Genomic, transcriptomic, proteomic and metabolomic analyses reveal that D. desulfuricans assimilates CO2 via the reductive glycine pathway, a seventh CO2 fixation pathway. In this pathway, CO2 is first reduced to formate, which is reduced and condensed with a second CO2 to generate glycine. Glycine is further reduced in D. desulfuricans by glycine reductase to acetyl-P, and then to acetyl-CoA, which is condensed with another CO2 to form pyruvate. Ammonia is involved in the operation of the pathway, which is reflected in the dependence of the autotrophic growth rate on the ammonia concentration. Our study demonstrates microbial autotrophic growth fully supported by this highly ATP-efficient CO2 fixation pathway.We acknowledge Änne-Michaelis and William Newell for assistance with the LC-MS forthe metabolomics experiments and Daniel Amador-Noguez for access to the LC-MS usedfor13C intracellular metabolomic analysis. We thank Ines Cardoso Pereira and John vander Oost for critically reading the manuscript. This research was funded by the Neth-erlands Organisation for Scientific Research (NWO) through SIAM Gravitation Grant024.002.002 and the Innovation Program Microbiology (WUR), NJC acknowledgesfunding from NWO through a Rubicon Grant (019.163LW.035) and a Veni Grant(VI.Veni.192.156).info:eu-repo/semantics/publishedVersio
GABA Expression and Regulation by Sensory Experience in the Developing Visual System
The developing retinotectal system of the Xenopus laevis tadpole is a model of choice for studying visual experience-dependent circuit maturation in the intact animal. The neurotransmitter gamma-aminobutyric acid (GABA) has been shown to play a critical role in the formation of sensory circuits in this preparation, however a comprehensive neuroanatomical study of GABAergic cell distribution in the developing tadpole has not been conducted. We report a detailed description of the spatial expression of GABA immunoreactivity in the Xenopus laevis tadpole brain at two key developmental stages: stage 40/42 around the onset of retinotectal innervation and stage 47 when the retinotectal circuit supports visually-guided behavior. During this period, GABAergic neurons within specific brain structures appeared to redistribute from clusters of neuronal somata to a sparser, more uniform distribution. Furthermore, we found that GABA levels were regulated by recent sensory experience. Both ELISA measurements of GABA concentration and quantitative analysis of GABA immunoreactivity in tissue sections from the optic tectum show that GABA increased in response to a 4 hr period of enhanced visual stimulation in stage 47 tadpoles. These observations reveal a remarkable degree of adaptability of GABAergic neurons in the developing brain, consistent with their key contributions to circuit development and function
Accounting for Extreme Events in the Economic Assessment of Climate Change
Extreme events are one of the main channels through which climate and socio- economic systems interact. It is likely that climate change will modify their probability distributions and their consequences. The long-term growth models used in climate change assessments, however, cannot capture the effects of short-term shocks; they thus model extreme events in a very crude manner. To assess the importance of this limitation, a non-equilibrium dynamic model (NEDyM) is used to model the macroeconomic consequences of extreme events. Its conclusions are the following: (i) Dynamic processes multiply the extreme event direct costs by a factor 20; half of this increase comes from short-term processes; (ii) A possible modication of the extreme event distribution due to climate change can be responsible for significant GDP losses; (iii) The production losses caused by extreme events depend, with strong non-linearity, both on the changes in the extreme distribution and on the ability to fund the rehabilitation after each disaster. These conclusions illustrate that the economic assessment of climate change does not only depend on beliefs on climate change but also on beliefs on the economy. Moreover, they suggest that averaging short-term processes like extreme events over the five- or ten-year time step of a classical long-term growth model can lead to inaccurately low assessments of the climate change damages
Search for exotic resonances decaying into WZ/ZZ in pp collisions at √s=7 TeV
Journal of High Energy Physics 2013.2 (2013): 036 reproduced by permission of Scuola Internazionale Superiore di Studi Avanzati (SISSA)Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMA search for new exotic particles decaying to the VZ final state is performed, where V is either a W or a Z boson decaying into two overlapping jets and the Z decays into a pair of electrons, muons or neutrinos. The analysis uses a data sample of pp collisions corresponding to an integrated luminosity of 5 fb-1 collected by the CMS experiment at the LHC at √s=7 TeV in 2011. No significant excess is observed in the mass distribution of the VZ candidates compared with the background expectation from standard model processes. Model-dependent upper limits at the 95% confidence level are set on the product of the cross section times the branching fraction of hypothetical particles decaying to the VZ final state as a function of mass. Sequential standard model W′ bosons with masses between 700 and 940 GeV are excluded. In the Randall-Sundrum model for graviton resonances with a coupling parameter of 0.05, masses between 750 and 880 GeV are also exclude
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