391 research outputs found

    SYMMETRIC BILINEAR CRYPTOGRAPHY ON ELLIPTIC CURVE AND LIE ALGEBRA

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    Elliptic Curve Cryptography (ECC) has gained widespread adoption in the field of cryptography due to its efficiency and security properties. Symmetric bilinear pairings on elliptic curves have emerged as a powerful tool in cryptographic protocols, enabling advanced constructions and functionalities. This paper explores the intersection of symmetric bilinear pairings, elliptic curves, and Lie algebras in the context of cryptography. We provide a comprehensive overview of the theoretical foundations, applications, and security considerations of this amalgamation

    Facility location via continuous optimization with discontinuous objective functions

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    Facility location problems are one of the most common applications of optimization methods. Continuous formulations are usually more accurate, but often result in complex problems that cannot be solved using traditional optimization methods. This paper examines the use of a global optimization method - AGOP - for solving location problems where the objective function is discontinuous. This approach is motivated by a real-world application in wireless networks design. © Australian Mathematical Society 2007

    Viral Apoptosis Evasion via the MAPK Pathway by Use of a Host Long Noncoding RNA

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    An emerging realization of infectious disease is that pathogens can cause a high incidence of genetic instability within the host as a result of infection-induced DNA lesions. These often lead to classical hallmarks of cancer, one of which is the ability to evade apoptosis despite the presence of numerous genetic mutations that should be otherwise lethal. The Human Immunodeficiency Virus type 1 (HIV-1) is one such pathogen as it induces apoptosis in CD4+ T cells but is largely non-cytopathic in macrophages. As a consequence there is long-term dissemination of the pathogen specifically by these infected yet surviving host cells. Apoptosis is triggered by double-strand breaks (DSBs), such as those induced by integrating retroviruses like HIV-1, and is coordinated by the p53-regulated long noncoding RNA lincRNA-p21. As is typical for a long noncoding RNA, lincRNA-p21 mediates its activities in a complex with one of its two protein binding partners, namely HuR and hnRNP-K. In this work, we monitor the cellular response to infection to determine how HIV-1 induces DSBs in macrophages yet evades apoptosis in these cells. We show that the virus does so by securing the pro-survival MAP2K1/ERK2 cascade early upon entry, in a gp120-dependent manner, to orchestrate a complex dysregulation of lincRNA-p21. By sequestering the lincRNA-p21 partner HuR in the nucleus, HIV-1 enables lincRNA-p21 degradation. Simultaneously, the virus permits transcription of pro-survival genes by sequestering lincRNA-p21's other protein partner hnRNP-K in the cytoplasm via the MAP2K1/ERK2 pathway. Of particular note, this MAP2K1/ERK2 pro-survival cascade is switched off during T cell maturation and is thus unavailable for similar viral manipulation in mature CD4+ T cells. We show that the introduction of MAP2K1, ERK2, or HDM2 inhibitors in HIV-infected macrophages results in apoptosis, providing strong evidence that the viral-mediated apoptotic block can be released, specifically by restoring the nuclear interaction of lincRNA-p21 and its apoptosis protein partner hnRNP-K. Together, these results reveal a unique example of pathogenic control over mammalian apoptosis and DNA damage via a host long noncoding RNA, and present MAP2K1/ERK2 inhibitors as a novel therapeutic intervention strategy for HIV-1 infection in macrophages

    New Insights Into the Anticonvulsant Effects of Essential Oil From Melissa officinalis L. (Lemon Balm)

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    Melissa officinalis L. is used in traditional European and Iranian folk medicines to treat a plethora of neurological diseases including epilepsy. We utilized the in vitro and in vivo models of epilepsy to probe the anticonvulsant potentials of essential oil from M. officinalis (MO) to gain insight into the scientific basis for its applications in traditional medicine for the management of convulsive disorders. MO was evaluated for effects on maximal electroshock (MES) and pentylenetetrazole (PTZ) -induced seizures in mice, on 4–aminopyridine (4-AP)-brain slice model of epilepsy and sustained repetitive firing of current clamped neurons; and its ameliorative effects were examined on seizure severity, anxiety, depression, cognitive dysfunction, oxidative stress and neuronal cell loss in PTZ-kindled rats. MO reversibly blocked spontaneous ictal-like discharges in the 4-AP-brain slice model of epilepsy and secondary spikes from sustained repetitive firing, suggesting anticonvulsant effects and voltage-gated sodium channel blockade. MO protected mice from PTZ– and MES–induced seizures and mortality, and ameliorated seizure severity, fear-avoidance, depressive-like behavior, cognitive deficits, oxidative stress and neuronal cell loss in PTZ–kindled rats. The findings warrant further study for the potential use of MO and/or its constituent(s) as adjunctive therapy for epileptic patients

    Prevalence of Trachoma in Bauchi State, Nigeria: Results of 20 Local Government Area-Level Surveys.

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    PURPOSE: To determine the prevalence of trachomatous inflammation - follicular (TF) and trichiasis in each of the 20 local government areas (LGAs) of Bauchi State, Nigeria. METHODS: We undertook a population-based prevalence survey in each LGA in Bauchi State, employing the Global Trachoma Mapping Project methodology. We used a 2-stage, systematic and quasi-random sampling strategy. Using probability proportional to size, we selected 25 clusters, in each of which 25 households were selected by random walk. All residents of selected households 1 year and older were examined for TF, trachomatous inflammation - intense, and trichiasis, using the World Health Organization simplified grading scheme. RESULTS: Only two LGAs in Bauchi State had TF prevalences in 1-9-year-olds over 5%, with none having TF prevalences of 10% or greater. Only one LGA had a trichiasis prevalence in adults below the elimination threshold; all the others had trichiasis at levels suggestive of public health significance. In all 20 LGAs, more than 60% of households were within 1 km of an improved source of water for hygiene. CONCLUSION: Efforts need to be made in Bauchi State to provide trichiasis surgery in order to avert trachomatous blindness. Water supplies needs to be sustained and good personal hygiene practices assured so that elimination of trachoma as a public health problem will be achieved and sustained

    The barriers and facilitators to young people's engagement with bidirectional digital sexual health interventions: A mixed methods systematic review

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    Background: Sexual health is fundamental to the overall health and wellbeing of individuals and to the social and economic development of communities and countries. However, internationally young people endure a disproportionate burden of sexually transmitted infections and unintended pregnancies which can be associated with poor psycho-social outcomes. Digital sexual health interventions have been developed to increase young people’s access to sexual health services, but are currently underutilised. Aim: This systematic review sought to identify the barriers and facilitators to young people’s engagement with bidirectional digital sexual health interventions, which are standalone two-way tailored interventions between a young person and healthcare professional. Methods: The review was conducted in accordance with the JBI methodology for mixed methods systematic reviews, following a convergent integrated approach to synthesis and integration of qualitative and quantitative evidence. Searches of ten electronic databases were conducted, spanning database inception to January 2022. No restrictions were imposed on language, geographical location or community setting. All included studies were critically appraised with JBI Critical Appraisal tools. Data extraction was performed using standardised tools, followed by data transformation. Data synthesis followed the convergent integrated approach. Each stage was conducted by two independent reviewers. Results: Eight thousand four hundred thirty-nine titles and abstracts and, subsequently, 255 full-texts underwent review. Nine studies were selected for inclusion with no studies added following forward and backward citation tracking. The included studies comprised three qualitative and six quantitative designs. Three meta synthesised findings were identified: (1) The design of a digital intervention for adolescent sexual health needs to reflect the end users’ specific needs (2) Young people need to feel comfortable when using a digital sexual health intervention (3) Potential barriers to engagement need to be addressed. The review identified that although barriers and facilitators to promoting young people’s engagement with bidirectional digital sexual health interventions are nuanced, young people’s privacy and security need to be prioritised for them to engage with digital interventions, regardless of the platform of choice. Conclusions: Co-production of digital sexual health services, in partnership with young people, has shaped many of the insights reported in this systematic review. Further international research which places an emphasis on young people’s perspectives is vital to unleash the full potential of digital technology in this domain

    Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

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    Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

    The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

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    Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

    The Human Cell Atlas.

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    The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community
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