A Presynaptic Role for the Cytomatrix Protein GIT in Synaptic Vesicle Recycling

Neurotransmission involves the exo-endocytic cycling of synaptic vesicles (SVs) within nerve terminals. Exocytosis is facilitated by a cytomatrix assembled at the active zone (AZ). The precise spatial and functional relationship between exocytic fusion of SVs at AZ membranes and endocytic SV retrieval is unknown. Here, we identify the scaffold G protein coupled receptor kinase 2 interacting (GIT) protein as a component of the AZ- associated cytomatrix and as a regulator of SV endocytosis. GIT1 and its D. melanogaster ortholog, dGIT, are shown to directly associate with the endocytic adaptor stonin 2/stoned B. In Drosophila dgit mutants, stoned B and synaptotagmin levels are reduced and stoned B is partially mislocalized. Moreover, dgit mutants show morphological and functional defects in SV recycling. These data establish a presynaptic role for GIT in SV recycling and suggest a connection between the AZ cytomatrix and the endocytic machinery

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome. Am J Physiol Endocrinol Metab 315: E1087–E1097, 2018. First published August 21, 2018; doi:10.1152/ajpendo.00058.2018.—A 2-day workshop organized by the National Institutes of Health and U.S. Department of Agriculture included 16 presentations focused on the role of diet in alterations of the gastrointestinal microbiome, primarily that of the colon. Although thousands of research projects have been funded by U.S. federal agencies to study the intestinal microbiome of humans and a variety of animal models, only a minority addresses dietary effects, and a small subset is described in sufficient detail to allow reproduction of a study. Whereas there are standards being developed for many aspects of microbiome studies, such as sample collection, nucleic acid extraction, data handling, etc., none has been proposed for the dietary component; thus this workshop focused on the latter specific point. It is important to foster rigor in design and reproducibility of published studies to maintain high quality and enable designs that can be compared in systematic reviews. Speakers addressed the influence of the structure of the fermentable carbohydrate on the microbiota and the variables to consider in design of studies using animals, in vitro models, and human subjects. For all types of studies, strengths and weaknesses of various designs were highlighted, and for human studies, comparisons between controlled feeding and observational designs were discussed. Because of the lack of published, best-diet formulations for specific research questions, the main recommendation is to describe dietary ingredients and treatments in as much detail as possible to allow reproduction by other scientists

Scientific opportunies for bERLinPro 2020+, report with ideas and conclusions from bERLinProCamp 2019

The Energy Recovery Linac (ERL) paradigm offers the promise to generate intense electron beams of superior quality with extremely small six-dimensional phase space for many applications in the physical sciences, materials science, chemistry, health, information technology and security. Helmholtz-Zentrum Berlin started in 2010 an intensive R\&D programme to address the challenges related to the ERL as driver for future light sources by setting up the bERLinPro (Berlin ERL Project) ERL with 50 MeV beam energy and high average current. The project is close to reach its major milestone in 2020, acceleration and recovery of a high brightness electron beam. The goal of bERLinProCamp 2019 was to discuss scientific opportunities for bERLinPro 2020+. bERLinProCamp 2019 was held on Tue, 17.09.2019 at Helmholtz-Zentrum Berlin, Berlin, Germany. This paper summarizes the main themes and output of the workshop

A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ~4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ~60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.National Human Genome Research Institute (U.S.)National Institute of General Medical Sciences (U.S.) (Grant number GM82901)National Science Foundation (U.S.). Postdoctural Fellowship (Award 0905968)National Science Foundation (U.S.). Career (0644282)National Institutes of Health (U.S.) (R01-HG004037)Alfred P. Sloan Foundation.Austrian Science Fund. Erwin Schrodinger Fellowshi

Collider aspects of flavour physics at high Q

This review presents flavour related issues in the production and decays of heavy states at LHC, both from the experimental side and from the theoretical side. We review top quark physics and discuss flavour aspects of several extensions of the Standard Model, such as supersymmetry, little Higgs model or models with extra dimensions. This includes discovery aspects as well as measurement of several properties of these heavy states. We also present public available computational tools related to this topic.Comment: Report of Working Group 1 of the CERN Workshop ``Flavour in the era of the LHC'', Geneva, Switzerland, November 2005 -- March 200

Avkastningsmål i norsk næringseiendom : en komparativ studie

I denne masteroppgaven ønsker vi å utrede i hvor stor grad et representativt utvalg av norsk næringseiendom samsvarer med gjeldende referanseindeks innen næringseiendom, IPDindeksen. Oppgaven tar utgangspunkt i våre egne beregnede avkastningstall, basert på investorrapporter fra 299 eiendomssyndikater i Norge i tidsperioden 1998-2016. Analysen er i all hovedsak en komparativ studie hvor vi sammenligner våre resultater med gjeldende referanseindeks, og analyserer avvikene. I forlengelsen av disse analysene, har vi også kommentert empiriske funn knyttet til aktivaklassen, samt problemstillinger knyttet til rapportering av avkastning på næringseiendom i dag. Vi finner en verdivektet annualisert avkastning på 10,49 % i perioden, med et tilhørende standardavvik på 4,26 %. Den likevektede avkastningen er marginalt lavere på 10,31 %, med et tilhørende standardavvik på 4,33 %. Ved bruk av 5-års norsk statsobligasjon som risikofri rente, viser vi at eiendom som aktivaklasse i perioden 1998 til 2016 har en Sharpe-ratio på 2,27, noe som anses som svært høyt. Videre beviser vi i oppgaven at det eksisterer en diversifiseringseffekt ved å inkludere næringseiendom i en markedsportefølje, ettersom aktivaklassen har lav korrelasjon med aksjer, og negativ korrelasjon med obligasjoner. Oppgaven viser også at en eiendomsinvestor i større grad enn investorer på Oslo Børs kompenseres for å påta seg usystematisk risiko, noe som er i strid med Malkiel’s teori om effisiente markeder. Vi finner også at investorrapportene og IPD-indeksen gir to avkastningsserier som er signifikant ulike. Gjennom analyser beviser vi at avvikene i hovedsak er på to områder: volatilitet og annualisert avkastning. Vi finner at volatiliteten rapporteres lavere, mens avkastningen rapporteres høyere. Oppgaven finner dermed at et representativt utvalg av norsk næringseiendom i liten grad samsvarer med gjeldende referanseindeks innen aktivaklassen.nhhma

Toward the integrated design of organic rankine cycle power plants: A method for the simultaneous optimization of working fluid, thermodynamic cycle, and turbine

The conventional design of organic Rankine cycle (ORC) power systems starts with the selection of the working fluid and the subsequent optimization of the corresponding thermodynamic cycle. More recently, systematic methods have been proposed integrating the selection of the working fluid into the optimization of the thermodynamic cycle. However, in both cases, the turbine is designed subsequently. This procedure can lead to a suboptimal design, especially in the case of mini- and small-scale ORC systems, since the preselected combination of working fluid and operating conditions may lead to infeasible turbine designs. The resulting iterative design procedure may end in conservative solutions after multiple trial-and-error attempts due to the strong interdependence of the many design variables and constraints involved. In this work, we therefore present a new design and optimization method integrating working fluid selection, thermodynamic cycle design, and preliminary turbine design. To this purpose, our recent 1-stage continuous-molecular targeting (CoMT)-computer-aided molecular design (CAMD) method for the integrated design of the ORC process and working fluid is expanded by a turbine meanline design procedure. Thereby, the search space of the optimization is bounded to regions where the design of the turbine is feasible. The resulting method has been tested for the design of a small-scale high-temperature ORC unit adopting a radial-inflow turbo-expander. The results confirm the potential of the proposed method over the conventional iterative design practice for the design of small-scale ORC turbogenerators.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Flight Performance and Propulsio