768 research outputs found

    Civil Procedure by Contract: A Convoluted Confluence of Private Contract and Public Procedure in Need of Congressional Control

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    There is great appeal to the notion that parties to a contract may provide in their agreement for how certain aspects of any dispute that may subsequently arise will be resolved. The appeal is so great, in fact, that both parties and courts have embraced the use and enforcement of pre-litigation agreements ( PLAs ). These agreements take a variety of forms. Parties may agree to the forum in which their dispute will be resolved. They may designate the law that will be applied to the resolution of the dispute. Parties may designate what evidence may or may not be presented as proof of their respective positions and what burden of proof should govern the weighing of the evidence presented. Parties may designate who will resolve their dispute, in terms of judge or jury. And they even may designate that the dispute will not be heard by a judicial tribunal at all, but rather will be re- solved outside the courts by means of some form of alternative dispute resolution ( ADR )

    Role for A-Type Lamins in Herpesviral DNA Targeting and Heterochromatin Modulation

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    Posttranslational modification of histones is known to regulate chromatin structure and transcriptional activity, and the nuclear lamina is thought to serve as a site for heterochromatin maintenance and transcriptional silencing. In this report, we show that the nuclear lamina can also play a role in the downregulation of heterochromatin and in gene activation. Herpes simplex virus DNA initiates replication in replication compartments near the inner edge of the nucleus, and histones are excluded from these structures. To define the role of nuclear lamins in HSV replication, we examined HSV infection in wild-type and A-type lamin–deficient (Lmna−/−) murine embryonic fibroblasts (MEFs). In Lmna−/− cells, viral replication compartments are reduced in size and fail to target to the nuclear periphery, as observed in WT cells. Chromatin immunoprecipitation and immunofluorescence studies demonstrate that HSV DNA is associated with increased heterochromatin in Lmna−/− MEFs. These results argue for a functional role for A-type lamins as viral gene expression, DNA replication, and growth are reduced in Lmna−/− MEFs, with the greatest effect on viral replication at low multiplicity of infection. Thus, lamin A/C is required for targeting of the viral genome and the reduction of heterochromatin on viral promoters during lytic infection. The nuclear lamina can serve as a molecular scaffold for DNA genomes and the protein complexes that regulate both euchromatin and heterochromatin histone modifications

    Harm minimisation for the management of self-harm: a mixed-methods analysis of electronic health records in secondary mental healthcare

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    BACKGROUND: Prevalence of self-harm in the UK was reported as 6.4% in 2014. Despite sparse evidence for effectiveness, guidelines recommend harm minimisation; a strategy in which people who self-harm are supported to do so safely. AIMS: To determine the prevalence, sociodemographic and clinical characteristics of those who self-harm and practise harm minimisation within a London mental health trust. METHOD: We included electronic health records for patients treated by South London and Maudsley NHS Trust. Using an iterative search strategy, we identified patients who practise harm minimisation, then classified the approaches using a content analysis. We compared the sociodemographic characteristics with that of a control group of patients who self-harm and do not use harm minimisation. RESULTS: In total 22 736 patients reported self-harm, of these 693 (3%) had records reporting the use of harm-minimisation techniques. We coded the approaches into categories: (a) ‘substitution’ (>50% of those using harm minimisation), such as using rubber bands or using ice; (b) ‘simulation’ (9%) such as using red pens; (c) ‘defer or avoid’ (7%) such as an alternative self-injury location; (d) ‘damage limitation’ (9%) such as using antiseptic techniques; the remainder were unclassifiable (24%). The majority of people using harm minimisation described it as helpful (>90%). Those practising harm minimisation were younger, female, of White ethnicity, had previous admissions and were less likely to have self-harmed with suicidal intent. CONCLUSIONS: A small minority of patients who self-harm report using harm minimisation, primarily substitution techniques, and the large majority find harm minimisation helpful. More research is required to determine the acceptability and effectiveness of harm-minimisation techniques and update national clinical guidelines

    SquidLab—A user-friendly program for background subtraction and fitting of magnetization data

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    We present an open-source program free to download for academic use with a full user-friendly graphical interface for performing flexible and robust background subtraction and dipole fitting on magnetization data. For magnetic samples with small moment sizes or sample environments with large or asymmetric magnetic backgrounds, it can become necessary to separate background and sample contributions to each measured raw voltage measurement before fitting the dipole signal to extract magnetic moments. Originally designed for use with pressure cells on a Quantum Design MPMS3 SQUID magnetometer, SquidLab is a modular object-oriented platform implemented in Matlab with a range of importers for different widely available magnetometer systems (including MPMS, MPMS-XL, MPMS-IQuantum, MPMS3, and S700X models) and has been tested with a broad variety of background and signal types. The software allows background subtraction of baseline signals, signal preprocessing, and performing fits to dipole data using Levenberg–Marquardt non-linear least squares or a singular value decomposition linear algebra algorithm that excels at picking out noisy or weak dipole signals. A plugin system allows users to easily extend the built-in functionality with their own importers, processes, or fitting algorithms. SquidLab can be downloaded, under Academic License, from the University of Warwick depository (wrap.warwick.ac.uk/129665)

    Goal-oriented a posteriori error estimation for the travel time functional in porous media flows

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    In this article we consider the a posteriori error estimation and adaptive mesh refinement for the numerical approximation of the travel time functional arising in porous media flows. The key application of this work is in the safety assessment of radioactive waste facilities; in this setting, the travel time functional measures the time taken for a non-sorbing radioactive solute, transported by groundwater, to travel from a potential site deep underground to the biosphere. To ensure the computability of the travel time functional, we employ a mixed formulation of Darcy's law and conservation of mass, together with Raviart-Thomas H(div) conforming finite elements. The proposed a posteriori error bound is derived based on a variant of the standard Dual-Weighted-Residual approximation, which takes into account the lack of smoothness of the underlying functional of interest. The proposed adaptive refinement strategy is tested on both a simple academic test case and a problem based on the geological units found at the Sellafield site in the UK

    Reinforcement learning of normative monitoring intensities

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    Choosing actions within norm-regulated environments involves balancing achieving one’s goals and coping with any penalties for non-compliant behaviour. This choice becomes more complicated in environments where there is uncertainty. In this paper, we address the question of choosing actions in environments where there is uncertainty regarding both the outcomes of agent actions and the intensity of monitoring for norm violations. Our technique assumes no prior knowledge of probabilities over action outcomes or the likelihood of norm violations being detected by employing reinforcement learning to discover both the dynamics of the environment and the effectiveness of the enforcer. Results indicate agents become aware of greater rewards for violations when enforcement is lax, which gradually become less attractive as the enforcement is increased

    Direct imaging of correlated defect nanodomains in a metal-organic framework

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    Defect engineering can enhance key properties of metal-organic frameworks (MOFs). Tailoring the distribution of defects, for example in correlated nanodomains, requires characterization across length scales. However, a critical nanoscale characterization gap has emerged between the bulk diffraction techniques used to detect defect nanodomains and the sub-nanometer imaging used to observe individual defects. Here, we demonstrate that the emerging technique of scanning electron diffraction (SED) can bridge this gap uniquely enabling both nanoscale crystallographic analysis and the lowdose formation of multiple diffraction contrast images for defect analysis in MOFs. We directly image defect nanodomains in the MOF UiO-66(Hf) over an area of ca. 1 000 nm and with a spatial resolution ca. 5 nm to reveal domain morphology and distribution. Based on these observations, we suggest possible crystal growth processes underpinning synthetic control of defect nanodomains. We also identify likely dislocations and small angle grain boundaries, illustrating that SED could be a key technique in developing the potential for engineering the distribution of defects, or “microstructure”, in functional MOF design
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