32,849 research outputs found

    Viral delivery of antioxidant genes as a therapeutic strategy in experimental models of amyotrophic lateral sclerosis.

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    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with no effective treatment to date. Despite its multi-factorial aetiology, oxidative stress is hypothesized to be one of the key pathogenic mechanisms. It is thus proposed that manipulation of the expression of antioxidant genes that are downregulated in the presence of mutant SOD1 may serve as a therapeutic strategy for motor neuronal protection. Lentiviral vectors expressing either PRDX3 or NRF2 genes were tested in the motor neuronal-like NSC34 cell line, and in the ALS tissue culture model, NSC34 cells expressing the human SOD1(G93A) mutation. The NSC34 SOD1(G93A) cells overexpressing either PRDX3 or NRF2 showed a significant decrease in endogenous oxidation stress levels by 40 and 50% respectively compared with controls, whereas cell survival was increased by 30% in both cases. The neuroprotective potential of those two genes was further investigated in vivo in the SOD1(G93A) ALS mouse model, by administering intramuscular injections of adenoassociated virus serotype 6 (AAV6) expressing either of the target genes at a presymptomatic stage. Despite the absence of a significant effect in survival, disease onset or progression, which can be explained by the inefficient viral delivery, the promising in vitro data suggest that a more widespread CNS delivery is needed

    Statistical analysis driven optimized deep learning system for intrusion detection

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    Attackers have developed ever more sophisticated and intelligent ways to hack information and communication technology systems. The extent of damage an individual hacker can carry out upon infiltrating a system is well understood. A potentially catastrophic scenario can be envisaged where a nation-state intercepting encrypted financial data gets hacked. Thus, intelligent cybersecurity systems have become inevitably important for improved protection against malicious threats. However, as malware attacks continue to dramatically increase in volume and complexity, it has become ever more challenging for traditional analytic tools to detect and mitigate threat. Furthermore, a huge amount of data produced by large networks has made the recognition task even more complicated and challenging. In this work, we propose an innovative statistical analysis driven optimized deep learning system for intrusion detection. The proposed intrusion detection system (IDS) extracts optimized and more correlated features using big data visualization and statistical analysis methods (human-in-the-loop), followed by a deep autoencoder for potential threat detection. Specifically, a pre-processing module eliminates the outliers and converts categorical variables into one-hot-encoded vectors. The feature extraction module discard features with null values and selects the most significant features as input to the deep autoencoder model (trained in a greedy-wise manner). The NSL-KDD dataset from the Canadian Institute for Cybersecurity is used as a benchmark to evaluate the feasibility and effectiveness of the proposed architecture. Simulation results demonstrate the potential of our proposed system and its outperformance as compared to existing state-of-the-art methods and recently published novel approaches. Ongoing work includes further optimization and real-time evaluation of our proposed IDS.Comment: To appear in the 9th International Conference on Brain Inspired Cognitive Systems (BICS 2018

    A Rapid Dynamical Monte Carlo Algorithm for Glassy Systems

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    In this paper we present a dynamical Monte Carlo algorithm which is applicable to systems satisfying a clustering condition: during the dynamical evolution the system is mostly trapped in deep local minima (as happens in glasses, pinning problems etc.). We compare the algorithm to the usual Monte Carlo algorithm, using as an example the Bernasconi model. In this model, a straightforward implementation of the algorithm gives an improvement of several orders of magnitude in computational speed with respect to a recent, already very efficient, implementation of the algorithm of Bortz, Kalos and Lebowitz.Comment: RevTex 7 pages + 4 figures (uuencoded) appended; LPS preprin

    The impact of body vigilance on help-seeking for cancer 'alarm' symptoms: a community-based survey.

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    BACKGROUND: The act of detecting bodily changes is a pre-requisite for subsequent responses to symptoms, such as seeking medical help. This is the first study to explore associations between self-reported body vigilance and help-seeking in a community sample currently experiencing cancer 'alarm' symptoms. METHODS: Using a cross-sectional study design, a 'health survey' was mailed through primary care practices to 4913 UK adults (age ≥50 years, no cancer diagnosis), asking about symptom experiences and medical help-seeking over the previous three months. Body vigilance, cancer worry and current illness were assessed with a small number of self-report items derived from existing measures. RESULTS: The response rate was 42% (N = 2042). Almost half the respondents (936/2042; 46%) experienced at least one cancer alarm symptom. Results from logistic regression analysis revealed that paying more attention to bodily changes was significantly associated with help-seeking for cancer symptoms (OR = 1.44; 1.06-1.97), after controlling for socio-demographics, current illness and cancer worry. Being more sensitive to bodily changes was not significantly associated with help-seeking. CONCLUSIONS: Respondents who paid attention to their bodily changes were more likely to seek help for their symptoms. Although the use of a cross-sectional study design and the limited assessment of key variables preclude any firm conclusions, encouraging people to be body vigilant may contribute towards earlier cancer diagnosis. More needs to be understood about the impact this might have on cancer-related anxiety

    Oral feeding of minocycline attenuates glial activation and reductions of tau and drebrin in response to systemically injected cytokines

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    Next-to-leading order QCD predictions for W+W+jj production at the LHC

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    Because the LHC is a proton-proton collider, sizable production of two positively charged W-bosons in association with two jets is possible. This process leads to a distinct signature of same sign high-pt leptons, missing energy and jets. We compute the NLO QCD corrections to the QCD-mediated part of pp -> W+W+jj. These corrections reduce the dependence of the production cross-section on the renormalization and factorization scale to about +- 10 percent. We find that a large number of W+W+jj events contain a relatively hard third jet. The presence of this jet should help to either pick up the W+W+jj signal or to reject it as an unwanted background.Comment: 15 pages, 5 (lovely) figures, v3 accepted for publication in JHEP, corrects tables in appendi

    Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

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    Copyright @ 2012 Nature Publishing GroupThis article has been made available through the Brunel Open Access Publishing Fund.Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund

    Fundamental Aspects of the ISM Fractality

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    The ubiquitous clumpy state of the ISM raises a fundamental and open problem of physics, which is the correct statistical treatment of systems dominated by long range interactions. A simple solvable hierarchical model is presented which explains why systems dominated by gravity prefer to adopt a fractal dimension around 2 or less, like the cold ISM and large scale structures. This has direct relation with the general transparency, or blackness, of the Universe.Comment: 6 pages, LaTeX2e, crckapb macro, no figure, uuencoded compressed tar file. To be published in the proceeedings of the "Dust-Morphology" conference, Johannesburg, 22-26 January, 1996, D. Block (ed.), (Kluwer Dordrecht

    Stratification of persons with diabetes into risk categories for foot ulceration

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    Background: Patients with diabetes mellitus are at a higher risk of lower extremity complications as compared to their non-diabetic counterparts.Objective: To study risk factors for diabetic foot ulcer disease and stratify patients with diabetes into risk categories for foot ulceration.Design: Cross-sectional descriptive study over five months period.Setting: Diabetic outpatient clinic, at the Kenyatta National Hospital.Subjects: Two hundred and eighteen ambulatory subjects with diabetes mellitus without active foot lesions.Results: The prevalence of previous foot ulceration was 16% while that of previous amputation was 8%. Neuropathy was present in 42% of the study subjects and was significantly associated with age, male gender, duration of diabetes, random blood sugar, systolic blood pressure and the presence of foot deformity. Peripheral arterial disease was present in 12% and showed significant association with male gender. Foot deformities were observed in 46% of study subjects and were significantly associated with age, male gender, and presence of neuropathy. Subsequently 57% were categorised into IWGDF group 0 - no neuropathy, 10% were placed in group 1- neuropathy alone, 16% were put in group 2 - neuropathy plus either peripheral arterial disease or foot deformity and 17% were placed in risk group 3 - previous foot ulceration/amputation.Conclusion: More than one third (33%) of diabetic patients were found to be at high risk for future foot ulceration (lWGDF groups 2 and 3). Published evidence exists that shows improved outcomes with interventions targeting individual patients with diabetes at high-risk of foot ulceration. Long term prospective studies to determine outcomes for the different risk categories should be carried out locally
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