Predicting F2D(3) from the dipole cross-section

We employ a parameterisation of the proton dipole cross section previously extracted from electroproduction and photoproduction data to predict the diffractive structure function F2D(3)(Q^2, beta, xpom). Comparison with HERA H1 data yields good agreement.Comment: 5 pages,4 figures, Latex2e, uses espcrc1.sty. Presented at "Hadron 99" Beijing, August 1999. Reference added, erroneous citation correcte

The stability of microbially reduced U(IV); impact of residual electron donor and sediment ageing

AbstractThe stimulation of microbial U(VI) reduction to precipitate insoluble U(IV) has been proposed as a means of remediating mobile uranium groundwater contamination. Crucial to the success of such a remediation strategy is determining the longevity of U(IV) biominerals in the subsurface, particularly if the groundwater becomes oxidising. Here we describe experiments to assess the susceptibility of microbially-reduced U(IV) to oxidative remobilisation both via aeration and by the addition of nitrate at environmentally-relevant conditions. Additional factors examined include the possibility of biogenic U(IV) becoming more crystalline (and potentially more recalcitrant) during a period of ageing, and the role played by residual electron donor in controlling the long-term fate of the uranium. Biogenic U(IV) was precipitated as a non-crystalline U(IV) or “monomeric” phase, with a small but increasing contribution to the EXAFS spectra from nanocrystalline uraninite occurring during 15months of ageing. Despite this, no evidence was observed for an increase in recalcitrance to oxidative remobilisation. However, the presence of residual electron donor post-biostimulation was shown to exert a strong control on U(IV) reoxidation kinetics, highlighting the importance of maintaining the presence of electron donor in the subsurface, in order to protect biogenic U(IV) from oxidative remobilisation

On the absence of appreciable half-life changes in alpha emitters cooled in metals to 1 Kelvin and below

The recent suggestion that dramatic changes may occur in the lifetime of alpha and beta decay when the activity, in a pure metal host, is cooled to a few Kelvin, is examined in the light of published low temperature nuclear orientation (LTNO) experiments, with emphasis here on alpha decay. In LTNO observations are made of the anisotropy of radioactive emissions with respect to an axis of orientation. Correction of data for decay of metallic samples held at temperatures at and below 1 Kelvin for periods of days and longer has been a routine element of LTNO experiments for many years. No evidence for any change of half life on cooling, with an upper level of less than 1%, has been found, in striking contrast to the predicted changes, for alpha decay, of several orders of magnitude. The proposal that such dramatic changes might alleviate problems of disposal of long-lived radioactive waste is shown to be unrealistic.Comment: 27 pages, 12 figures, accepted for publication in Nucl.Phys.A. Revised version, including quantitative analysis of the sensitivity of nuclear orientation experiments, discussed in this work, to changes of alpha-decay lifetimes in metals at low temperatures. Conclusions remain unchange

TDP43 proteinopathy is associated with aberrant DNA methylation in human amyotrophic lateral sclerosis

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neurone (MN) degeneration and death. ALS can be sporadic (sALS) or familial, with a number of associated gene mutations, including C9orf72 (C9ALS). DNA methylation is an epigenetic mechanism whereby a methyl group is attached to a cytosine (5mC), resulting in gene expression repression. 5mC can be further oxidized to 5‐hydroxymethylcytosine (5hmC). DNA methylation has been studied in other neurodegenerative diseases, but little work has been conducted in ALS. Aims To assess differences in DNA methylation in individuals with ALS and the relationship between DNA methylation and TDP43 pathology. Methods Post mortem tissue from controls, sALS cases and C9ALS cases were assessed by immunohistochemistry for 5mC and 5hmC in spinal cord, motor cortex and prefrontal cortex. LMNs were extracted from a subset of cases using laser capture microdissection. DNA from these underwent analysis using the MethylationEPIC array to determine which molecular processes were most affected. Results There were higher levels of 5mC and 5hmC in sALS and C9ALS in the residual lower motor neurones (LMNs) of the spinal cord. Importantly, in LMNs with TDP43 pathology there was less nuclear 5mC and 5hmC compared to the majority of residual LMNs that lacked TDP43 pathology. Enrichment analysis of the array data suggested RNA metabolism was particularly affected. Conclusions DNA methylation is a contributory factor in ALS LMN pathology. This is not so for glia or neocortical neurones

Combined FUS+ basophilic inclusion body disease and atypical tauopathy presenting with an ALS/MND-plus phenotype

AIMS: Amyotrophic lateral sclerosis / motor neurone disease (ALS/MND) is characterised by the presence of inclusions containing TDP-43 within motor neurones. In rare cases, ALS/MND may be associated with inclusions containing other proteins, such as fused in sarcoma (FUS), whilst motor system pathology may rarely be a feature of other neurodegenerative disorders. We here have investigated the association of FUS and tau pathology. METHODS: We report a case with an ALS/MND-plus clinical syndrome which pathologically demonstrated both FUS pathology and an atypical tauopathy. RESULTS: Clinical motor involvement was predominantly upper motor neurone, and was accompanied by extrapyramidal features and sensory involvement, but with only minimal cognitive impairment. The presentation was sporadic and gene mutation screening was negative. Post-mortem study demonstrated inclusions positive for FUS, including basophilic inclusion bodies. This was associated with 4R-tauopathy, largely as non-fibrillary diffuse phospho-tau in neurones, with granulovacuolar degeneration in a more restricted distribution. Double-staining revealed that neurones contained both types of protein pathology. CONCLUSION: FUS-positive basophilic inclusion body disease is a rare cause of ALS/MND, but in this case was associated with an unusual atypical tauopathy. The coexistence of two such rare neuropathologies raises the question of a pathogenic interaction

Visions in monochrome: Families, marriage and the individualisation thesis

This paper takes issue with the way in which the individualisation thesis – in which it is assumed that close relationships have become tenuous and fragile - has become so dominant in ‘new’ sociological theorising about family life. Although others have criticised this thesis, in this paper the main criticism derives from empirical research findings carried out with members of transnational families living in Britain whose values and practices do not fit easily with ideas of individualisation. It is argued that we need a much more complex and less linear notion of how families change across generations and in time

Proteinopathies as hallmarks of impaired gene expression, proteostasis and mitochondrial function in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. As with the majority of neurodegenerative diseases, the pathological hallmarks of ALS involve proteinopathies which lead to the formation of various polyubiquitylated protein aggregates in neurons and glia. ALS is a highly heterogeneous disease, with both familial and sporadic forms arising from the convergence of multiple disease mechanisms, many of which remain elusive. There has been considerable research effort invested into exploring these disease mechanisms and in recent years dysregulation of RNA metabolism and mitochondrial function have emerged as of crucial importance to the onset and development of ALS proteinopathies. Widespread alterations of the RNA metabolism and post-translational processing of proteins lead to the disruption of multiple biological pathways. Abnormal mitochondrial structure, impaired ATP production, dysregulation of energy metabolism and calcium homeostasis as well as apoptosis have been implicated in the neurodegenerative process. Dysfunctional mitochondria further accumulate in ALS motor neurons and reflect a wider failure of cellular quality control systems, including mitophagy and other autophagic processes. Here, we review the evidence for RNA and mitochondrial dysfunction as some of the earliest critical pathophysiological events leading to the development of ALS proteinopathies, explore their relative pathological contributions and their points of convergence with other key disease mechanisms. This review will focus primarily on mutations in genes causing four major types of ALS (C9ORF72, SOD1, TARDBP/TDP-43, and FUS) and in protein homeostasis genes (SQSTM1, OPTN, VCP, and UBQLN2) as well as sporadic forms of the disease. Finally, we will look to the future of ALS research and how an improved understanding of central mechanisms underpinning proteinopathies might inform research directions and have implications for the development of novel therapeutic approaches

National geological screening : the Hampshire Basin and adjoining areas

This report is the published product of one of a series of studies covering England, Wales and Northern Ireland commissioned by Radioactive Waste Management (RWM) Ltd. The report provides geological information about the Hampshire Basin and adjoining areas region to underpin the process of national geological screening set out in the UK’s government White Paper Implementing geological disposal: a framework for the long-term management of higher activity radioactive waste (DECC, 2014). The report describes geological features relevant to the safety requirements of a geological disposal facility (GDF) for radioactive waste emplaced onshore and up to 20 km offshore at depths between 200 and 1000 m from surface. It is written for a technical audience but is intended to inform RWM in its discussions with communities interested in finding out about the potential for their area to host a GDF

Patient-Powered Research Networks of the Autoimmune Research Collaborative: Rationale, Capacity, and Future Directions

Patient-Powered Research Networks (PPRNs) are US-based registry infrastructures co-created by advocacy groups, patient research partners, academic investigators, and other healthcare stakeholders. Patient-Powered Research Networks collect information directly from patients to conduct and disseminate the results of patient-centered/powered research that helps patients make more informed decisions about their healthcare. Patient-Powered Research Networks gather and utilize real-world data and patient-reported outcomes to conduct comparative effectiveness, safety, and other research, and leverage the Internet to accomplish this effectively and efficiently. Four PPRNs focused on autoimmune and immune-mediated conditions formed the Autoimmune Research Collaborative: ArthritisPower (rheumatoid arthritis, spondyloarthritis, and other rheumatic and musculoskeletal diseases), IBD Partners (inflammatory bowel disease), iConquerMS (multiple sclerosis), and the Vasculitis PPRN (vasculitis). The Autoimmune Research Collaborative aims to inform the healthcare decision making of patients, care partners, and other stakeholders, such as clinicians, regulators, and payers. Illustrated by practical applications from the Autoimmune Research Collaborative and its constituent PPRNs, this article discusses the shared capacities and challenges of the PPRN model, and the opportunities presented by collaborating across autoimmune conditions to design, conduct, and disseminate patient-centered outcomes research

National geological screening : East Anglia region

This report is the published product of one of a series of studies covering England, Wales and Northern Ireland commissioned by Radioactive Waste Management (RWM) Ltd. The report provides geological information about the East Anglia region to underpin the process of national geological screening set out in the UK’s government White Paper Implementing geological disposal: a framework for the long-term management of higher activity radioactive waste (DECC, 2014). The report describes geological features relevant to the safety requirements of a geological disposal facility (GDF) for radioactive waste emplaced onshore and up to 20 km offshore at depths between 200 and 1000 m from surface. It is written for a technical audience but is intended to inform RWM in its discussions with communities interested in finding out about the potential for their area to host a GDF