496 research outputs found
An assessment of blockchain consensus protocols for the Internet of Things
In a few short years the Internet of Things has become an intrinsic part of everyday life, with connected devices included in products created for homes, cars and even medical equipment. But its rapid growth has created several security problems, with respect to the transmission and storage of vast amounts of customers data, across an insecure heterogeneous collection of networks. The Internet of Things is therefore creating a unique set of risk and problems that will affect most households. From breaches in confidentiality, which could allow users to be snooped on, through to failures in integrity, which could lead to consumer data being compromised; devices are presenting many security challenges to which consumers are ill equipped to protect themselves from. Moreover, when this is coupled with the heterogeneous nature of the industry, and the interoperable and scalability problems it becomes apparent that the Internet of Things has created an increased attack surface from which security vulnerabilities may be easily exploited. However, it has been conjectured that blockchain may provide a solution to the Internet of Things security and scalability problems. Because of blockchain’s immutability, integrity and scalability, it is possible that its architecture could be used for the storage and transfer of Internet of Things data. Within this paper a cross section of blockchain consensus protocols have been assessed against a requirement framework, to establish each consensus protocols strengths and weaknesses with respect to their potential implementation in an Internet of Things blockchain environment
A new subtype of frontotemporal lobar degeneration with FUS pathology
Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. The neuropathology associated with most FTD is characterized by abnormal cellular aggregates of either transactive response DNA-binding protein with Mr 43 kDa (TDP-43) or tau protein. However, we recently described a subgroup of FTD patients, representing around 10%, with an unusual clinical phenotype and pathology characterized by frontotemporal lobar degeneration with neuronal inclusions composed of an unidentified ubiquitinated protein (atypical FTLD-U; aFTLD-U). All cases were sporadic and had early-onset FTD with severe progressive behavioural and personality changes in the absence of aphasia or significant motor features. Mutations in the fused in sarcoma (FUS) gene have recently been identified as a cause of familial amyotrophic lateral sclerosis, with these cases reported to have abnormal cellular accumulations of FUS protein. Because of the recognized clinical, genetic and pathological overlap between FTD and amyotrophic lateral sclerosis, we investigated whether FUS might also be the pathological protein in aFTLD-U. In all our aFTLD-U cases (n = 15), FUS immunohistochemistry labelled all the neuronal inclusions and also demonstrated previously unrecognized glial pathology. Immunoblot analysis of protein extracted from post-mortem aFTLD-U brain tissue demonstrated increased levels of insoluble FUS. No mutations in the FUS gene were identified in any of our patients. These findings suggest that FUS is the pathological protein in a significant subgroup of sporadic FTD and reinforce the concept that FTD and amyotrophic lateral sclerosis are closely related condition
Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes
Funded by •ERC. Grant Number: 284167 •NIH. Grant Number: 1RO1DK0921127-01 •NWO. Grant Numbers: 463-06-001, 451-04-034Peer reviewedPublisher PD
Larval Trophodynamics, Turbulence, and Drift on Georges Bank : A Sensitivity Analysis of Cod and Haddock
Using an individual-based model approach we consider trophodynamic effects on the growth and survival of larval cod (Gadus morhua) and haddock (Melanogrammus aeglefinus) on Georges Bank during late winter/early spring. These studies represent an extension of results described in Werner et al. (1996; Deep-Sea Res. II), wherein the effect of turbulence-enhanced larval-prey contact rates increased the effective prey concentration resulting in growth of cod larvae consistent with observed rates in the field. We reformulated the feeding of the larvae to include existing relationships between maximum prey-length and larval-length and we examined: (i) larval search behaviour and its effect on encounter with prey, (ii) the ability of larvae to pursue and capture prey in a turbulent environment, and (iii) the effect of turbulence on the dispersion of larvae in the vertical. We find that search behaviour, the effect of turbulence on pursuit and capture, and vertical dispersion decrease the predicted larval growth rates compared to those observed in the earlier study. These results suggest that larval feeding behaviour, and especially the ability of larvae to pursue encountered prey, could be an important input to larval growth and survival models. The inclusion of turbulence in determining the position of passive larvae in the water column allows the larvae to sample the entire water column, contributing to a decrease in the variance of the size of the larvae over time. The ability of larvae to swim and aggregate in the vertical will be necessary to reproduce distributions observed in the field
Neuropathological background of phenotypical variability in frontotemporal dementia
Frontotemporal lobar degeneration (FTLD) is the umbrella term encompassing a heterogeneous group of pathological disorders. With recent discoveries, the FTLDs have been show to classify nicely into three main groups based on the major protein deposited in the brain: FTLD-tau, FTLD-TDP and FTLD-FUS. These pathological groups, and their specific pathologies, underlie a number of well-defined clinical syndromes, including three frontotemporal dementia (FTD) variants [behavioral variant frontotemporal dementia (bvFTD), progressive non-fluent aphasia, and semantic dementia (SD)], progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS). Understanding the neuropathological background of the phenotypic variability in FTD, PSPS and CBS requires large clinicopathological studies. We review current knowledge on the relationship between the FTLD pathologies and clinical syndromes, and pool data from a number of large clinicopathological studies that collectively provide data on 544 cases. Strong relationships were identified as follows: FTD with motor neuron disease and FTLD-TDP; SD and FTLD-TDP; PSPS and FTLD-tau; and CBS and FTLD-tau. However, the relationship between some of these clinical diagnoses and specific pathologies is not so clear cut. In addition, the clinical diagnosis of bvFTD does not have a strong relationship to any FTLD subtype or specific pathology and therefore remains a diagnostic challenge. Some evidence suggests improved clinicopathological association of bvFTD by further refining clinical characteristics. Unlike FTLD-tau and FTLD-TDP, FTLD-FUS has been less well characterized, with only 69 cases reported. However, there appears to be some associations between clinical phenotypes and FTLD-FUS pathologies. Clinical diagnosis is therefore promising in predicting molecular pathology
Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.
The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis
TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1
Risk Adjustment and Outcome Measures for Out-of-hospital Respiratory Distress
: The purpose of the Emergency Medical Services Outcomes Project (EMSOP) is to develop a foundation and framework for out-of-hospital outcomes research. In prior work, this group delineated the priority conditions, described conceptual models, suggested core and risk adjustment measures potentially useful to emergency medical services research, and summarized out-of-hospital pain measurement. In this fifth article in the EMSOP series, the authors recommend specific risk-adjustment measures and outcome measures for use in out-of-hospital research on patients presenting with respiratory distress. The methodology included systematic literature searches and a structured review by an expert panel. The EMSOP group recommends use of pulse oximetry, peak expiratory flow rate, and the visual analog dyspnea scale as potential risk-adjustment measures and outcome measures for out-of-hospital research in patients with respiratory distress. Furthermore, using mortality as an outcome measure is also recommended. Future research is needed to alleviate the paucity of validated tools for out-of-hospital outcomes research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73779/1/j.aem.2004.03.010.pd
Establishing the Scope and Methodological Approach to Out-of-hospital Outcomes and Effectiveness Research
: Outcomes research offers out-of-hospital medicine a valuable methodology for studying the effectiveness of services provided in the out-of hospital setting. A clear understanding of the history and constructs of outcomes research is necessary for its integration into emergency medical services research. This report describes the conceptual framework of outcomes research and key methodological considerations for the successful implementation of out-of-hospital outcomes research. Illustrations of the specific applications of outcomes research and implications to existing methodologies are given, as well as suggestions for improved interdisciplinary research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75033/1/j.aem.2004.04.014.pd
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