307 research outputs found
United States Punitive Damage Awards in German Courts: The Evolving German Position on Service and Enforcement
This Article addresses the problems United States plaintiffs may face when seeking enforcement of United States court awards of punitive damages in German courts. The authors show the close relationship between service of process and subsequent enforcement procedures in Germany. The analysis focuses on two recent German court decisions that provide indications of how German courts might respond to requests to serve process and to enforce judgments in actions seeking punitive or multiple damages. The fundamentally different approaches to punitive damages taken by the German and the United States legal systems create the difficulties encountered when these two systems intersect.
The Article first addresses the potential for difficulty in the service of process. Punitive damage complaints, if viewed as criminal in nature, would fall outside the scope of the Hague Convention on Service Abroad of Judicial and Extrajudicial Documents in Civil or Commercial Matters (Hague Service Convention or Convention). A decision by the Oberlandesgericht Munchen (Court of Appeals at Munich), however, held that punitive damages would be characterized as civil in nature for the limited purpose of service of process under the Convention. Therefore, a United States plaintiff would be able to effect valid service under the Hague Service Convention via the German Central Authorities. Although the decision of the Oberlandesgericht Munchen is not binding on other German courts, the authors suggest that other German courts likely will adopt this characterization of punitive damages for service of process. The authors caution, however, that the question whether a German court would enforce a punitive damage judgment remains unresolved. According to the authors, a decision by the Landgericht Berlin (Trial Court at Berlin) indicates the manner in which a German court would analyze such a case. The Landgericht Berlin decision deals with excessive, rather than punitive, damages. Nevertheless, the authors cite the decision as suggesting that civil damages characterized as punitive or multiple may violate German public policy, and thus the judgments would not be enforced by German courts.
The authors criticize the reasoning of the Landgericht Berlin decision. They categorize the court\u27s reweighing of the evidence and its application of German substantive law to the facts as an impermissible revision au fond (a reexamination of the substantive basis of the foreign judgment). The authors speculate that if the Landgericht Berlin view prevails, this hostile approach could prompt United States courts to retaliate by refusing to enforce German court judgments.
The authors also question the blanket refusal of the Landgericht Berlin to enforce even the compensatory portion of the United States judgment. As a result of this refusal, the authors suggest that a litigant might have to forgo seeking punitive or multiple damages in the United States to ensure the enforceability of any compensatory award in Germany. The article concludes by emphasizing that the Landgericht Berlin decision, although not binding on subsequent courts, illustrates the skepticism United States plaintiffs may encounter when seeking enforcement of punitive damage awards in German courts
CAV-2 Vector Development and Gene Transfer in the Central and Peripheral Nervous Systems
The options available for genetic modification of cells of the central nervous system (CNS) have greatly increased in the last decade. The current panoply of viral and nonviral vectors provides multifunctional platforms to deliver expression cassettes to many structures and nuclei. These cassettes can replace defective genes, modify a given pathway perturbed by diseases, or express proteins that can be selectively activated by drugs or light to extinguish or excite neurons. This review focuses on the use of canine adenovirus type 2 (CAV-2) vectors for gene transfer to neurons in the brain, spinal cord, and peripheral nervous system. We discuss (1) recent advances in vector production, (2) why CAV-2 vectors preferentially transduce neurons, (3) the mechanism underlying their widespread distribution via retrograde axonal transport, (4) how CAV-2 vectors have been used to address structure/function, and (5) their therapeutic applications
A Replica Inference Approach to Unsupervised Multi-Scale Image Segmentation
We apply a replica inference based Potts model method to unsupervised image
segmentation on multiple scales. This approach was inspired by the statistical
mechanics problem of "community detection" and its phase diagram. Specifically,
the problem is cast as identifying tightly bound clusters ("communities" or
"solutes") against a background or "solvent". Within our multiresolution
approach, we compute information theory based correlations among multiple
solutions ("replicas") of the same graph over a range of resolutions.
Significant multiresolution structures are identified by replica correlations
as manifest in information theory overlaps. With the aid of these correlations
as well as thermodynamic measures, the phase diagram of the corresponding Potts
model is analyzed both at zero and finite temperatures. Optimal parameters
corresponding to a sensible unsupervised segmentation correspond to the "easy
phase" of the Potts model. Our algorithm is fast and shown to be at least as
accurate as the best algorithms to date and to be especially suited to the
detection of camouflaged images.Comment: 26 pages, 22 figure
The chronology and tectonic style of landscape evolution along the elevated Atlantic continental margin of South Africa resolved by joint apatite fission track and (U-Th-Sm)/He thermochronology
Atlantic-type continental margins have long been considered âpassiveâ tectonic settings throughout the entire postrift phase. Recent studies question the long-term stability of these margins and have shown that postrift uplift and reactivation of preexisting structures may be a common feature of a continental marginâs evolution. The Namaqualand sector of the western continental margin of South Africa is characterized by a ubiquitously faulted basement but lacks preservation of younger geological strata to constrain postrift tectonic fault activity. Here we present the first systematic study using joint apatite fission track and apatite (U-Th-Sm)/He thermochronology to achieve a better understanding on the chronology and tectonic style of landscape evolution across this region. Apatite fission track ages range from 58.3 ± 2.6 to 132.2 ± 3.6Ma, with mean track lengths between 10.9 ± 0.19 and 14.35 ± 0.22 ÎŒm, and mean (U-Th-Sm)/He sample ages range from 55.8 ± 31.3 to 120.6 ± 31.4Ma. Joint inverse modeling of these data reveals two distinct episodes of cooling at approximately 150â130Ma and 110â90Ma with limited cooling during the Cenozoic. Estimates of denudation based on these
thermal histories predict approximately 1â3 km of denudation coinciding with two major tectonic events. The first event, during the Early Cretaceous, was driven by continental rifting and the development and removal of synrift topography. The second event, during the Late Cretaceous, includes localized reactivation of basement structures as well as regional mantle-driven uplift. Relative tectonic stability prevailed during the Cenozoic, and regional denudation over this time is constrained to be less than 1 km
Genetic regulation of RNA splicing in human pancreatic islets
Background
Non-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown.
Results
We examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform in ERO1B, a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such as DCLRE1B, a senescence regulator, and lncRNA MEG3.
Conclusions
These data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.This research was supported by Ministerio de Ciencia e InnovaciĂłn (BFU2014-54284-R, RTI2018-095666-B-I00), Medical Research Council (MR/L02036X/1), a Wellcome Trust Senior Investigator Award (WT101033), European Research Council Advanced Grant (789055), EU Horizon 2020 TDSystems (667191), ESPACE (874710), and Marie Sklodowska-Curie (643062, ZENCODE). S.B.G was supported by a Juan de la Cierva postdoctoral fellowship (MINECO; FJCI-2017-32090). M.C.A was supported by a Boehringer Ingelheim Fonds PhD fellowship. Work in CRG was supported by the CERCA Programme, Generalitat de Catalunya, Centro de Excelencia Severo Ochoa (CEX2020-001049), and support of the Spanish Ministry of Science and Innovation to the EMBL partnership. Work in Imperial College was supported by NIHR Imperial Biomedical Research Centre. M.I. was supported by a European Research Council consolidator award (101002275). D.J.M.C. and J.A.T. were supported by JDRF grants 9-2011-253, 5-SRA-2015-130-A-N, 4- SRA-2017-473-A-N, and Wellcome grants 091157/Z/10/Z and 107212/Z/15/Z, to the Diabetes and Inflammation Laboratory, Oxford, as well as the Oxford Biomedical Research Computing (BMRC) facility, a joint development between the Wellcome Centre for Human Genetics and the Big Data Institute supported by Health Data Research UK and NIHR Oxford Biomedical Research Centre, and Wellcome Trust Core Award grant 203141/Z/16/Z. D.M.J.C analysis with the UK Biobank Resource was conducted under Application 31295. A.L.G. is a Wellcome Senior Fellow in Basic Biomedical Science and was supported by the Wellcome Trust (095101, 200837, 106130, 203141), the NIDDK (U01DK105535 and UM1 DK126185), and the Oxford NIHR Biomedical Research Centre.Peer Reviewed"Article signat per 20 autors/es: Goutham Atla, Silvia BonĂ s-Guarch, Mirabai Cuenca-Ardura, Anthony Beucher, Daniel J. M. Crouch, Javier Garcia-Hurtado, Ignasi Moran, the T2DSystems Consortium, Manuel Irimia, Rashmi B. Prasad, Anna L. Gloyn, Lorella Marselli, Mara Suleiman, Thierry Berney, Eelco J. P. de Koning, Julie Kerr-Conte, Francois Pattou, John A. Todd, Lorenzo Piemonti & Jorge Ferrer"Postprint (published version
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Quantifying the evolution of soil fabric during shearing using directional parameters
Over the past 50 years, experimental studies have repeatedly demonstrated that the mechanical behaviour of sand is sensitive to the material fabric, that is, the arrangement of the grains. Up until now there have been relatively few attempts to describe this fabric quantitatively. Much of our understanding of the link between the particle movements and interactions and the macro-scale response of granular materials, including sand, comes from discrete-element modelling and experiments on âanalogueâ sands with simple, idealised shapes. This paper investigates methods of quantifying the directional fabric of a real sand and its evolution under loading. Statistical analyses of the distribution of fabric directional data in terms of particle, contact normal, branch vector and void orientations were carried out at different stages of shearing deformation. The data show that the initial particle orientation fabric that develops during the deposition of the material tends to persist during shearing, while in the post-peak regime the contact normals seem to be reoriented along the direction of the major principal stress. Different patterns were observed within the shear
band, as both the particles and the contact normal vectors appeared to rotate along the shear plane
Long non-coding RNAs as local regulators of pancreatic islet transcription factor genes
The transcriptional programs of differentiated cells are tightly regulated by interactions between cell type-specific transcription factors and cis-regulatory elements. Long non-coding RNAs (lncRNAs) have emerged as additional regulators of gene transcription. Current evidence indicates that lncRNAs are a very heterogeneous group of molecules. For example, selected lncRNAs have been shown to regulate gene expression in cis or trans, although in most cases the precise underlying molecular mechanisms is unknown. Recent studies have uncovered a large number of lncRNAs that are selectively expressed in pancreatic islet cells, some of which were shown to regulate ÎČ cell transcriptional programs. A subset of such islet lncRNAs appears to control the expression of ÎČ cell-specific transcription factor (TF) genes by local cis-regulation. In this review, we discuss current knowledge of molecular mechanisms underlying cis-regulatory lncRNAs and discuss challenges involved in using genetic perturbations to define their function. We then discuss known examples of pancreatic islet lncRNAs that appear to exert cis-regulation of TF genes. We propose that cis-regulatory lncRNAs could represent a molecular target for modulation of diabetes-relevant genes
AFTER, the front end ASIC of the T2K Time Projection Chambers
The T2K (Tokai-to-Kamioka) experiment is a long baseline neutrino oscillation experiment in Japan. A near detector, located at 280m of the production target, is used to characterize the beam. One of its key elements is a tracker, made of three Time Projection Chambers (TPC) read by Micromegas endplates. A new readout system has been developed to collect, amplify, condition and acquire the data produced by the 124,000 detector channels of these detectors. The front-end element of this system is a a new 72-channel application specific integrated circuit. Each channel includes a low noise charge preamplifier, a pole zero compensation stage, a second order Sallen-Key low pass filter and a 511-cell Switched Capacitor Array. This electronics offers a large flexibility in sampling frequency, shaping time, gain, while taking advantage of the low physics events rate of 0.3 Hz. We detail the design and the performance of this ASIC and report on the deployment of the frond-end electronics on-site
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