2,471 research outputs found

    Digging Underneath the Reconciliation Paradigm in Northern Ireland: Survival, Temporal Resistance, Rebellious Mourning

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    This dissertation argues that the political and spatial control over time and temporality is a deeply under-studied aspect of transitional societies. Specifically, I examine the temporal assumptions and temporal demands of the “reconciliation paradigm” in Northern Ireland. In transitional societies supposedly emerging from war and interethnic conflict, dominant manifestations of political power seek to bracket, periodicise, or temporally discontinue the violent past from an allegedly reconciling present and the promise of a liberal democratic future. Justice-seeking victims, survivors, and bereaved of political violence, in these contexts, are widely presented as anachronisms, people out-of-step with the direction an allegedly reconciling society is going. In contrast to the impulses of the mainstream Transitional Justice, Trauma Studies, and Peace Studies, throughout this dissertation I argue that violent pasts are always in a state of “diabolical continuity” with an unjust present. I consider the reconciliation paradigm to be largely a mechanism of insulating the postconflict order from meaningful criticism and depoliticising survivors’ demands for justice. In this study, I examine the temporal and spatial practices of victims, survivors, and bereaved people in Northern Ireland, arguing that they are engaging in forms of “temporal resistance” that seek to prolong the past in the face of ubiquitous social and political pressure to “move on from” or “close the books on” Northern Ireland’s troubled past. But where this study departs from other excellent work critical of temporal power-formations in postconflict space is in its emphasis on geographical place as the crucial engine of temporal resistance. Specifically, I argue that temporal resistance is inseparable from the chronotopic, threshold places where the past can be re-emplotted in the present, places that still seethe and meddle with the lived realities and everyday mobilities of Northern Irish inhabitants

    Tracking TCRß sequence clonotype expansions during antiviral therapy using high-throughput sequencing of the hypervariable region

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    To maintain a persistent infection viruses such as hepatitis C virus (HCV) employ a range of mechanisms that subvert protective T cell responses. The suppression of antigen-specific T cell responses by HCV hinders efforts to profile T cell responses during chronic infection and antiviral therapy. Conventional methods of detecting antigen-specific T cells utilize either antigen stimulation (e.g., ELISpot, proliferation assays, cytokine production) or antigen-loaded tetramer staining. This limits the ability to profile T cell responses during chronic infection due to suppressed effector function and the requirement for prior knowledge of antigenic viral peptide sequences. Recently, high-throughput sequencing (HTS) technologies have been developed for the analysis of T cell repertoires. In the present study, we have assessed the feasibility of HTS of the TCRβ complementarity determining region (CDR)3 to track T cell expansions in an antigen-independent manner. Using sequential blood samples from HCV-infected individuals undergoing antiviral therapy, we were able to measure the population frequencies of >35,000 TCRβ sequence clonotypes in each individual over the course of 12 weeks. TRBV/TRBJ gene segment usage varied markedly between individuals but remained relatively constant within individuals across the course of therapy. Despite this stable TRBV/TRBJ gene segment usage, a number of TCRβ sequence clonotypes showed dramatic changes in read frequency. These changes could not be linked to therapy outcomes in the present study; however, the TCRβ CDR3 sequences with the largest fold changes did include sequences with identical TRBV/TRBJ gene segment usage and high junction region homology to previously published CDR3 sequences from HCV-specific T cells targeting the HLA-B*0801-restricted 1395HSKKKCDEL1403 and HLA-A*0101-restricted 1435ATDALMTGY1443 epitopes. The pipeline developed in this proof of concept study provides a platform for the design of future experiments to accurately address the question of whether T cell responses contribute to SVR upon antiviral therapy. This pipeline represents a novel technique to analyze T cell dynamics in situations where conventional antigen-dependent methods are limited due to suppression of T cell functions and highly diverse antigenic sequences

    Development of a low-maintenance measurement approach to continuously estimate methane emissions: a case study

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    The chemical breakdown of organic matter in landfills represents a significant source of methane gas (CH4). Current estimates suggest that landfills are responsible for between 3% and 19% of global anthropogenic emissions. The net CH4 emissions resulting from biogeochemical processes and their modulation by microbes in landfills are poorly constrained by imprecise knowledge of environmental constraints. The uncertainty in absolute CH4 emissions from landfills is therefore considerable. This study investigates a new method to estimate the temporal variability of CH4 emissions using meteorological and CH4 concentration measurements downwind of a landfill site in Suffolk, UK from July to September 2014, taking advantage of the statistics that such a measurement approach offers versus shorter-term, but more complex and instantaneously accurate, flux snapshots. Methane emissions were calculated from CH4 concentrations measured 700 m from the perimeter of the landfill with observed concentrations ranging from background to 46.4 ppm. Using an atmospheric dispersion model, we estimate a mean emission flux of 709 μg m−2 s−1 over this period, with a maximum value of 6.21 mg m−2 s−1, reflecting the wide natural variability in biogeochemical and other environmental controls on net site emission. The emissions calculated suggest that meteorological conditions have an influence on the magnitude of CH4 emissions. We also investigate the factors responsible for the large variability observed in the estimated CH4 emissions, and suggest that the largest component arises from uncertainty in the spatial distribution of CH4 emissions within the landfill area. The results determined using the low-maintenance approach discussed in this paper suggest that a network of cheaper, less precise CH4 sensors could be used to measure a continuous CH4 emission time series from a landfill site, something that is not practical using far-field approaches such as tracer release methods. Even though there are limitations to the approach described here, this easy, low-maintenance, low-cost method could be used by landfill operators to estimate time-averaged CH4 emissions and their impact downwind by simultaneously monitoring plume advection and CH4 concentrations

    Investigating the Behavior of Diffusion Models for Accelerating Electronic Structure Calculations

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    We present an investigation into diffusion models for molecular generation, with the aim of better understanding how their predictions compare to the results of physics-based calculations. The investigation into these models is driven by their potential to significantly accelerate electronic structure calculations using machine learning, without requiring expensive first-principles datasets for training interatomic potentials. We find that the inference process of a popular diffusion model for de novo molecular generation is divided into an exploration phase, where the model chooses the atomic species, and a relaxation phase, where it adjusts the atomic coordinates to find a low-energy geometry. As training proceeds, we show that the model initially learns about the first-order structure of the potential energy surface, and then later learns about higher-order structure. We also find that the relaxation phase of the diffusion model can be re-purposed to sample the Boltzmann distribution over conformations and to carry out structure relaxations. For structure relaxations, the model finds geometries with ~10x lower energy than those produced by a classical force field for small organic molecules. Initializing a density functional theory (DFT) relaxation at the diffusion-produced structures yields a >2x speedup to the DFT relaxation when compared to initializing at structures relaxed with a classical force field

    Circadian rhythm of oestradiol: Impact on the bone metabolism of adult males

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    Background: Few studies have examined the variation in oestradiol with respect to age and circadian rhythm and the subsequent effects on BMD. Aim: Demonstrate the presence or absence of a circadian rhythm for oestrodial in older men and the integral role of concerted circadian rhythms of several factors including parathyroid hormone (PTH) in regulating biochemical markers of bone resorption and formation. Examine whether concentrations of both circulating total and bioavailable oestrogen in men differ with age and BMD. Design: Males were recruited: young men with normal BMD, older men with normal BMD and older men with osteoporosis. Methods: Subjects were hospitalized for a 25-hour period. Blood samples were obtained every 30 minutes. Hormone analysis results were plotted and reviewed. Results: Both total and bioavailable oestradiol concentrations were significantly lower in the older men than the young men (Total oestradiol: 34.5±4.4 pmol/L vs. 49.0±6.5 pmol/L, p<0.0001; Bioavailable oestradiol 16.7±2.2 pmol/L vs. 26.3±3.6 pmol/L, p<0.0001). Bioavailable oestrogen rhythm mirrored that of total estrogen. Conclusion: Both age groups with normal BMD display circadian rhythmicity with respect to circulating and bioavailable oestradiol. Younger men have increased mean total and bioavailable oestrogen concentrations and later acrophase compared to older counterparts. In older men with low BMD, total circulating oestrogen was not significantly different compared to age-matched older men with normal BMD; bioavailable oestrogen was significantly lower. Total oestrogen demonstrated a concerted circadian rhythm in all 3 groups, but bioavailable oestrogen did not demonstrate circadian rhythmicity in older men with decreased BMD

    Comprehensive systematic review summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders

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    Objective To systematically evaluate the efficacy of treatments for tics and the risks associated with their use. Methods This project followed the methodologies outlined in the 2011 edition of the American Academy of Neurology\u27s guideline development process manual. We included systematic reviews and randomized controlled trials on the treatment of tics that included at least 20 participants (10 participants if a crossover trial), except for neurostimulation trials, for which no minimum sample size was required. To obtain additional information on drug safety, we included cohort studies or case series that specifically evaluated adverse drug effects in individuals with tics. Results There was high confidence that the Comprehensive Behavioral Intervention for Tics was more likely than psychoeducation and supportive therapy to reduce tics. There was moderate confidence that haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinumtoxinA injections, 5-ling granule, Ningdong granule, and deep brain stimulation of the globus pallidus were probably more likely than placebo to reduce tics. There was low confidence that pimozide, ziprasidone, metoclopramide, guanfacine, topiramate, and tetrahydrocannabinol were possibly more likely than placebo to reduce tics. Evidence of harm associated with various treatments was also demonstrated, including weight gain, drug-induced movement disorders, elevated prolactin levels, sedation, and effects on heart rate, blood pressure, and ECGs. Conclusions There is evidence to support the efficacy of various medical, behavioral, and neurostimulation interventions for the treatment of tics. Both the efficacy and harms associated with interventions must be considered in making treatment recommendations

    Practice Guideline Recommendations Summary: Treatment of Tics in People with Tourette Syndrome and Chronic Tic Disorders

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    Objective To make recommendations on the assessment and management of tics in people with Tourette syndrome and chronic tic disorders. Methods A multidisciplinary panel consisting of 9 physicians, 2 psychologists, and 2 patient representatives developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine–compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence. Results Forty-six recommendations were made regarding the assessment and management of tics in individuals with Tourette syndrome and chronic tic disorders. These include counseling recommendations on the natural history of tic disorders, psychoeducation for teachers and peers, assessment for comorbid disorders, and periodic reassessment of the need for ongoing therapy. Treatment options should be individualized, and the choice should be the result of a collaborative decision among patient, caregiver, and clinician, during which the benefits and harms of individual treatments as well as the presence of comorbid disorders are considered. Treatment options include watchful waiting, the Comprehensive Behavioral Intervention for Tics, and medication; recommendations are provided on how to offer and monitor these therapies. Recommendations on the assessment for and use of deep brain stimulation in adults with severe, treatment-refractory tics are provided as well as suggestions for future research

    HST ultraviolet spectral energy distributions for three ultraluminous infrared galaxies

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    We present HST Faint Object Camera ultraviolet (230 nm and 140 nm) images of three ultraluminous infrared galaxies (ULIG: L_ir > 10^12 L_sun) selected from the IRAS Revised Bright Galaxy Sample. The purpose is to estimate spectral energy distributions (SEDs) to facilitate the identification of similar objects at high redshift in deep optical, infrared, and submm surveys. All three galaxies (VII Zw031 = IRAS F12112+0305, and IRAS F22491-1808) were well detected at 230 nm. Two of the three were marginally detected at 140 nm. The fluxes, together with ground-based optical and infrared photometry, are used to compute SEDs over a wide wavelength range. The measured SEDs drop from the optical to the ultraviolet, but the magnitude of the drop ranges from a factor of ~3 in IRAS F22491-1808 to a factor of ~100 in VIIZw031. This is most likely due to different internal extinctions. Such an interpretation is also suggested by extrapolating to ultraviolet wavelengths the optical internal extinction measured in VIIZw031. K-corrections are calculated to determine the colors of the sample galaxies as seen at high redshifts. Galaxies like VIIZw031 have very low observed rest-frame UV fluxes which means that such galaxies at high redshift will be extremely red or even missing in optical surveys. On the other hand, galaxies like IRAS F12112+0305 and IRAS F22491-1808, if seen at high redshift, would be sufficiently blue that they would not easily be distinguished from normal field galaxies, and therefore, identified as ULIGs. The implication is then that submillimeter surveys may be the only means of properly identifying the majority of ULIGs at high redshift.Comment: AJ in press, TeX, 23 pages, 7 tab, 17 figs available also (at higher resolution) from http://www.ast.cam.ac.uk~trentham/ufigs.htm

    Biodegradable PLGA Based Nanoparticles for Sustained Regional Lymphatic Drug Delivery

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    The purpose of this work is to evaluate biodegradable drug carriers with defined size, hydrophobicity, and surface charge density for preferential lymphatic uptake and retention for sustained regional drug delivery. PLGA–PMA:PLA-PEG (PP) nanoparticles of defined size and relative hydrophobicity were prepared by nanoprecipitation method. These were compared with PS particles of similar sizes and higher hydrophobicity. PLGA–PMA:PLGA-COOH (PC) particles at 80:20, 50:50, and 20:80 ratios were prepared by nanoprecipitation for the charge study. Particle size and zeta potential were characterized by dynamic light scattering and laser doppler anemometry, respectively. Particles were administered in vivo to rats subcutaneously. Systemic and lymph node uptake was evaluated by marker recovery. Lymphatic uptake and node retention of PP nanoparticles was shown to be inversely related to size. Lymphatic uptake and node retention of PP particles, as compared to PS particles, was shown to be inversely related to hydrophobicity. Lastly, lymphatic uptake and node retention of PC nanoparticles were directly related to the anionic charge on the particles. In vivo lymphatic uptake and retention in a rat model indicates that the 50 nm PP particles are ideal for sustained regional delivery into the lymphatics for prevention/treatment of oligometastases
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