GEMPIC: Geometric ElectroMagnetic Particle-In-Cell Methods

We present a novel framework for Finite Element Particle-in-Cell methods based on the discretization of the underlying Hamiltonian structure of the Vlasov-Maxwell system. We derive a semi-discrete Poisson bracket, which retains the defining properties of a bracket, anti-symmetry and the Jacobi identity, as well as conservation of its Casimir invariants, implying that the semi-discrete system is still a Hamiltonian system. In order to obtain a fully discrete Poisson integrator, the semi-discrete bracket is used in conjunction with Hamiltonian splitting methods for integration in time. Techniques from Finite Element Exterior Calculus ensure conservation of the divergence of the magnetic field and Gauss' law as well as stability of the field solver. The resulting methods are gauge invariant, feature exact charge conservation and show excellent long-time energy and momentum behaviour. Due to the generality of our framework, these conservation properties are guaranteed independently of a particular choice of the Finite Element basis, as long as the corresponding Finite Element spaces satisfy certain compatibility conditions.Comment: 57 Page

In vivo Gene Correction of Cystic Fibrosis

The cystic fibrosis transmembrane conductance regulator (CFTR) gene was cloned over two decades ago and a vast number of pre-clinical and clinical studies have been performed since that time. Despite this progress, a true "cure" for the disease has not been achieved, partly because the lung is a major barrier for intruders, making it exceedingly difficult for new pharmaceutical formulations to penetrate target cells. Safety-engineered viral vectors, such as adeno-associated viral vectors (AAVs) or integrase-defective lentiviruses, have been used with moderate success in temporarily supplementing the expression of critical proteins. However, stability and safety concerns often dampen the effects of these approaches. With emerging technologies, such as modified messenger (mRNA) and new genome editing strategies, scientists are now exploring the possibility of not only supplementing defective proteins, but instead, correcting the genetic defects at their source. This chapter will highlight the theoretical possibilities and primary data in pre-clinical models supporting the efforts toward in vivo gene correction of cystic fibrosis (CF)

A Decision Support System for Photovoltaic Potential Estimation

With knowledge on the photovoltaic potential of individual residential buildings, solar companies, energy service providers and electric utilities can identify suitable customers for new PV installations and directly address them in renewable energy rollout and maintenance campaigns. However, many currently used solutions for the simulation of energy generation require detailed information about houses (roof tilt, shading, etc.) that is usually not available at scale. On the other hand, the methodologies enabling extraction of such details require costly remote-sensing data from three-dimensional (3D) laser scanners or aerial images. To bridge this gap, we present a decision support system (DSS) that estimates the potential amount of electric energy that could be generated at a given location if a photovoltaic system would be installed. The DSS automatically generates insights about photovoltaic yields of individual roofs by analyzing freely available data sources, including the crowdsourced volunteered geospatial information systems OpenStreetMap and climate databases. The resulting estimates pose a valuable foundation for selecting the most prospective households (e.g., for personal visit and screening by an expert) and targeted solar panel kit offerings, ultimately leading to significant reduction of manual human efforts, and to cost-effective personalized renewables adoption

CX3CR1 Polymorphisms are associated with atopy but not asthma in German children

Chemokines and their receptors are involved in many aspects of immunity. Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration and macrophage differentiation as well as T cell-dependent inflammation. Two common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk for asthma. Using matrix-assisted laser desorption/ionization time-of-flight technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross-sectional population of German children from Munich (n = 1,159) and Dresden ( n = 1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63-0.96; p = 0.017) and for 280Met an odds ratio of 0.71 ( 95% confidence interval 0.56-0.89; p = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. Potentially, other factors such as environmental effects may modify the role of CX3CR1 polymorphisms. Copyright (c) 2007 S. Karger AG, Basel

Exploratory Study of the X-Ray Properties of Quasars With Intrinsic Narrow Absorption Lines

We have used archival Chandra and XMM-Newton observations of quasars hosting intrinsic narrow UV absorption lines (intrinsic NALs) to carry out an exploratory survey of their X-ray properties. Our sample consists of three intrinsic-NAL quasars and one "mini-BAL" quasar, plus four quasars without intrinsic absorption lines for comparison. These were drawn in a systematic manner from an optical/UV-selected sample. The X-ray properties of intrinsic-NAL quasars are indistinguishable from those of "normal" quasars. We do not find any excess absorption in quasars with intrinsic NALs, with upper limits of a few times 10^22 cm^-2. We compare the X-ray and UV properties of our sample quasars by plotting the equivalent width and blueshift velocity of the intrinsic NALs and the X-ray spectral index against the "optical-to-X-ray" slope, alpha-ox. When BAL quasars and other AGNs with intrinsic NALs are included, the plots suggest that intrinsic-NAL quasars form an extension of the BAL sequences and tend to bridge the gap between BAL and "normal" quasars. Observations of larger samples of intrinsic-NAL quasars are needed to verify these conclusions. We also test two competing scenarios for the location of the NAL gas in an accretion-disk wind. Our results strongly support a location of the NAL gas at high latitudes above the disk, closer to the disk axis than the dense BAL wind. We detect excess X-ray absorption only in Q0014+8118, which does not host intrinsic NALs. The absorbing medium very likely corresponds to an intervening system at z=1.1, which also produces strong absorption lines in the rest-frame UV spectrum of this quasar. In the appendix we discuss the connection between UV and X-ray attenuation and its effect on alpha-ox.Comment: Accepted by the Astrophysical Journa

Gravitational lensing magnification without multiple imaging

Gravitational lensing can amplify the apparent brightness of distant sources. Images that are highly magnified are often part of multiply-imaged systems, but we consider the possibility of having large magnifications without additional detectable images. In rare but non-negligible situations, lensing can produce a singly highly magnified image; this phenomenon is mainly associated with massive cluster-scale halos (>~1e13.5 Msun). Alternatively, lensing can produce multiply-imaged systems in which the extra images are either unresolved or too faint to be detectable. This phenomenon is dominated by galaxies and lower-mass halos (<~1e12 Msun), and is very sensitive to the inner density profile of the halos. Although we study the general problem, we customize our calculations to four quasars at redshift z~6 in the Sloan Digital Sky Survey (SDSS), for which Richards et al. (2004) have ruled out the presence of extra images down to an image splitting of 0.3" and a flux ratio of f=0.01. We predict that 9-29% of all z~6 quasars that are magnified by a factor of mu>10 would lack detectable extra images, with 5-10% being true singly-imaged systems. The maximum of 29% is reached only in the unlikely event that all low-mass (<~1e10 Msun) halos have highly concentrated (isothermal) profiles. In more realistic models where dwarf halos have flatter (NFW) inner profiles, the maximum probability is ~10%. We conclude that the probability that all four SDSS quasars are magnified by a factor of 10 is <~1e-4. The only escape from this conclusion is if there are many (>10) multiply-imaged z~6 quasars in the SDSS database that have not yet been identified, which seems unlikely. In other words, lensing cannot explain the brightnesses of the z~6 quasars, and models that invoke lensing to avoid having billion-Msun black holes in the young universe are not viable.Comment: accepted in ApJ; 15 emulateapj pages; small revisions to clarify the tex

Safety and feasibility of intranasal heroin-assisted treatment: 4-week preliminary findings from a Swiss multicentre observational study

Background: Heroin-assisted treatment (HAT) is effective for individuals with severe opioid use disorder (OUD) who do not respond sufficiently to other opioid agonist treatments. It is mostly offered with injectable diacetylmorphine (DAM) or DAM tablets creating a barrier for individuals who need the rapid onset of action but are either unable or unwilling to inject, or primarily snort opioids. To explore another route of administration, we evaluated the safety and feasibility of intranasal (IN) DAM. Methods: This is a multicentre observational cohort study among patients in Swiss HAT. All patients planning to receive IN DAM within the treatment centres were eligible to participate. Participants were either completely switched to IN DAM or received IN DAM in addition to other DAM formulations or opioid agonists. Patients were followed up for four weeks. Sociodemographic characteristics, current HAT regimen, reasons for starting IN DAM, IN DAM doses, number of injection events in the sample, IN DAM continuation rate, and appearance of adverse events and nose-related problems were evaluated. Results: Participants (n = 52) reported vein damage, preference for nasal route of administration, and desire of a stronger effect or for a less harmful route of administration as primary reasons for switching to IN DAM. After four weeks, 90.4% of participants (n = 47) still received IN DAM. Weekly average realised injection events decreased by 44.4% from the month before IN DAM initiation to the month following. No severe adverse events were reported. Conclusions: After four weeks, IN DAM was a feasible and safe alternative to other routes of administration for patients with severe OUD in HAT. It addressed the needs of individuals with OUD and reduced injection behaviour. More long-term research efforts are needed to systematically assess efficacy of and patient satisfaction with IN DAM

Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling

Objective The generation of acinar and ductal cells from human pluripotent stem cells (PSCs) is a poorly studied process, although various diseases arise from this compartment. Design We designed a straightforward approach to direct human PSCs towards pancreatic organoids resembling acinar and ductal progeny. Results Extensive phenotyping of the organoids not only shows the appropriate marker profile but also ultrastructural, global gene expression and functional hallmarks of the human pancreas in the dish. Upon orthotopic transplantation into immunodeficient mice, these organoids form normal pancreatic ducts and acinar tissue resembling fetal human pancreas without evidence of tumour formation or transformation. Finally, we implemented this unique phenotyping tool as a model to study the pancreatic facets of cystic fibrosis (CF). For the first time, we provide evidence that in vitro, but also in our xenograft transplantation assay, pancreatic commitment occurs generally unhindered in CF. Importantly, cystic fibrosis transmembrane conductance regulator (CFTR) activation in mutated pancreatic organoids not only mirrors the CF phenotype in functional assays but also at a global expression level. We also conducted a scalable proof-of-concept screen in CF pancreatic organoids using a set of CFTR correctors and activators, and established an mRNA-mediated gene therapy approach in CF organoids. Conclusions Taken together, our platform provides novel opportunities to model pancreatic disease and development, screen for disease-rescuing agents and to test therapeutic procedures.This study was funded by the Deutsche Forschungsgemeinschaft (DFG, K.L. 2544/1-1 and 1-2), the Forschungskern SyStaR to AK, BIU (Böhringer Ingelheim Ulm to AK), the Fritz-Thyssen Foundation (Az. 10.15.2.040), the German Cancer Aid (111879) and the Else-Kröner-Fresenius-Stiftung (2011_A200). AK is indebted to the Baden-Württemberg Stiftung for the financial support of this research project by the Eliteprogramme for Postdocs. AK is also an Else-Kröner-Fresenius Memorial Fellow. LP is supported by a research fellowship of the Else-Kröner-Fresenius-Stiftung. MH was supported by the International Graduate School in Molecular Medicine and the Bausteinprogramme (L.SBN. 110), Ulm University. MM is supported by a grant of Ulm University (Baustein for Senior Clinician Scientists). IGC is funded by the Interdisciplinary Center for Clinical Research (IZKF Aachen) and Start Program, RWTH Aachen University Medical School, Aachen, German

BIOFRAG: A new database for analysing BIOdiversity responses to forest FRAGmentation

Habitat fragmentation studies are producing inconsistent and complex results across which it is nearly impossible to synthesise. Consistent analytical techniques can be applied to primary datasets, if stored in a flexible database that allows simple data retrieval for subsequent analyses. Method: We developed a relational database linking data collected in the field to taxonomic nomenclature, spatial and temporal plot attributes and further environmental variables (e.g. information on biogeographic region. Typical field assessments include measures of biological variables (e.g. presence, abundance, ground cover) of one species or a set of species linked to a set of plots in fragments of a forested landscape. Conclusion: The database currently holds records of 5792 unique species sampled in 52 landscapes in six of eight biogeographic regions: mammals 173, birds 1101, herpetofauna 284, insects 2317, other arthropods: 48, plants 1804, snails 65. Most species are found in one or two landscapes, but some are found in four. Using the huge amount of primary data on biodiversity response to fragmentation becomes increasingly important as anthropogenic pressures from high population growth and land demands are increasing. This database can be queried to extract data for subsequent analyses of the biological response to forest fragmentation with new metrics that can integrate across the components of fragmented landscapes. Meta-analyses of findings based on consistent methods and metrics will be able to generalise over studies allowing inter-comparisons for unified answers. The database can thus help researchers in providing findings for analyses of trade-offs between land use benefits and impacts on biodiversity and to track performance of management for biodiversity conservation in human-modified landscapes.Fil: Pfeifer, Marion. Imperial College London; Reino UnidoFil: Lefebvre, Veronique. Imperial College London; Reino UnidoFil: Gardner, Toby A.. Stockholm Environment Institute; SueciaFil: Arroyo Rodríguez, Víctor. Universidad Nacional Autónoma de México; MéxicoFil: Baeten, Lander. University of Ghent; BélgicaFil: Banks Leite, Cristina. Imperial College London; Reino UnidoFil: Barlow, Jos. Lancaster University; Reino UnidoFil: Betts, Matthew G.. State University of Oregon; Estados UnidosFil: Brunet, Joerg. Swedish University of Agricultural Sciences; SueciaFil: Cerezo Blandón, Alexis Mauricio. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; ArgentinaFil: Cisneros, Laura M.. University of Connecticut; Estados UnidosFil: Collard, Stuart. Nature Conservation Society of South Australia; AustraliaFil: D´Cruze, Neil. The World Society for the Protection of Animals; Reino UnidoFil: Da Silva Motta, Catarina. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Duguay, Stephanie. Carleton University; CanadáFil: Eggermont, Hilde. University of Ghent; BélgicaFil: Eigenbrod, Félix. University of Southampton; Reino UnidoFil: Hadley, Adam S.. State University of Oregon; Estados UnidosFil: Hanson, Thor R.. No especifíca;Fil: Hawes, Joseph E.. University of East Anglia; Reino UnidoFil: Heartsill Scalley, Tamara. United State Department of Agriculture. Forestry Service; Puerto RicoFil: Klingbeil, Brian T.. University of Connecticut; Estados UnidosFil: Kolb, Annette. Universitat Bremen; AlemaniaFil: Kormann, Urs. Universität Göttingen; AlemaniaFil: Kumar, Sunil. State University of Colorado - Fort Collins; Estados UnidosFil: Lachat, Thibault. Swiss Federal Institute for Forest; SuizaFil: Lakeman Fraser, Poppy. Imperial College London; Reino UnidoFil: Lantschner, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Laurance, William F.. James Cook University; AustraliaFil: Leal, Inara R.. Universidade Federal de Pernambuco; BrasilFil: Lens, Luc. University of Ghent; BélgicaFil: Marsh, Charles J.. University of Leeds; Reino UnidoFil: Medina Rangel, Guido F.. Universidad Nacional de Colombia; ColombiaFil: Melles, Stephanie. University of Toronto; CanadáFil: Mezger, Dirk. Field Museum of Natural History; Estados UnidosFil: Oldekop, Johan A.. University of Sheffield; Reino UnidoFil: Overal , Williams L.. Museu Paraense Emílio Goeldi. Departamento de Entomologia; BrasilFil: Owen, Charlotte. Imperial College London; Reino UnidoFil: Peres, Carlos A.. University of East Anglia; Reino UnidoFil: Phalan, Ben. University of Southampton; Reino UnidoFil: Pidgeon, Anna Michle. University of Wisconsin; Estados UnidosFil: Pilia, Oriana. Imperial College London; Reino UnidoFil: Possingham, Hugh P.. Imperial College London; Reino Unido. The University Of Queensland; AustraliaFil: Possingham, Max L.. No especifíca;Fil: Raheem, Dinarzarde C.. Royal Belgian Institute of Natural Sciences; Bélgica. Natural History Museum; Reino UnidoFil: Ribeiro, Danilo B.. Universidade Federal do Mato Grosso do Sul; BrasilFil: Ribeiro Neto, Jose D.. Universidade Federal de Pernambuco; BrasilFil: Robinson, Douglas W.. State University of Oregon; Estados UnidosFil: Robinson, Richard. Manjimup Research Centre; AustraliaFil: Rytwinski, Trina. Carleton University; CanadáFil: Scherber, Christoph. Universität Göttingen; AlemaniaFil: Slade, Eleanor M.. University of Oxford; Reino UnidoFil: Somarriba, Eduardo. Centro Agronómico Tropical de Investigación y Enseñanza; Costa RicaFil: Stouffer, Philip C.. State University of Louisiana; Estados UnidosFil: Struebig, Matthew J.. University of Kent; Reino UnidoFil: Tylianakis, Jason M.. University College London; Estados Unidos. Imperial College London; Reino UnidoFil: Teja, Tscharntke. Universität Göttingen; AlemaniaFil: Tyre, Andrew J.. Universidad de Nebraska - Lincoln; Estados UnidosFil: Urbina Cardona, Jose N.. Pontificia Universidad Javeriana; ColombiaFil: Vasconcelos, Heraldo L.. Universidade Federal de Uberlandia; BrasilFil: Wearn, Oliver. Imperial College London; Reino Unido. The Zoological Society of London; Reino UnidoFil: Wells, Konstans. University of Adelaide; AustraliaFil: Willig, Michael R.. University of Connecticut; Estados UnidosFil: Wood, Eric. University of Wisconsin; Estados UnidosFil: Young, Richard P.. Durrell Wildlife Conservation Trust; Reino UnidoFil: Bradley, Andrew V.. Imperial College London; Reino UnidoFil: Ewers, Robert M.. Imperial College London; Reino Unid