Proposed Framework for Official Document Sharing and Verification in E-government Environment Based on Blockchain Technology

Progression in Computer networks and emerging of new technologies in this field helps to find out new protocols and frameworks that provides new computer network-based services. E-government services, a modernized version of conventional government, are created through the steady evolution of technology in addition to the growing need of societies for numerous services. Government services are deeply related to citizens’ daily lives; therefore, it is important to evolve with technological developments—it is necessary to move from the traditional methods of managing government work to cutting-edge technical approaches that improve the effectiveness of government systems for providing services to citizens. Blockchain technology is among the modern technologies highly suitable for developing digital governance services, and its technological ability to sustain information stability is vital in digital governance systems since it improves integrity and transparency measures while preventing corruption. In this study, computer networking protocols are built to form a peer-to-peer network framework for managing official documents. using blockchain technology was built to illustrate how any element of government work may be developed using it. The suggested framework comprises the addition of a new official document, and the verification of an existing document. The system was created in socket programming using Java and tested the response times for many simultaneous requests. The system was tested using transactions per second (throughput) measurement. The result showed that the proposed system processed 200 document verification transactions within 50 seconds. In addition, the test of the proposed system presented the time required for document retrieval—about three seconds to answer 100 document retrieval transactions. Furthermore, the results of throughput were compared to the results of the same measurement of some popular applications such as bitcoin. And the result of the proposed system was within the average value of output throughput of the other compared applications

Role of p73 in Alzheimer disease: lack of association in mouse models or in human cohorts.

BACKGROUND: P73 belongs to the p53 family of cell survival regulators with the corresponding locus Trp73 producing the N-terminally distinct isoforms, TAp73 and DeltaNp73. Recently, two studies have implicated the murine Trp73 in the modulation in phospho-tau accumulation in aged wild type mice and in young mice modeling Alzheimer's disease (AD) suggesting that Trp73, particularly the DeltaNp73 isoform, links the accumulation of amyloid peptides to the creation of neurofibrillary tangles (NFTs). Here, we reevaluated tau pathologies in the same TgCRND8 mouse model as the previous studies. RESULTS: Despite the use of the same animal models, our in vivo studies failed to demonstrate biochemical or histological evidence for misprocessing of tau in young compound Trp73+/- + TgCRND8 mice or in aged Trp73+/- mice analyzed at the ages reported previously, or older. Secondly, we analyzed an additional mouse model where the DeltaNp73 was specifically deleted and confirmed a lack of impact of the DeltaNp73 allele, either in heterozygous or homozygous form, upon tau pathology in aged mice. Lastly, we also examined human TP73 for single nucleotide polymorphisms (SNPs) and/or copy number variants in a meta-analysis of 10 AD genome-wide association datasets. No SNPs reached significance after correction for multiple testing and no duplications/deletions in TP73 were found in 549 cases of AD and 544 non-demented controls. CONCLUSION: Our results fail to support P73 as a contributor to AD pathogenesis.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals

IMPORTANCE: Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. OBJECTIVE: To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer's Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES: The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. RESULTS: The African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer's Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. CONCLUSIONS AND RELEVANCE: To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Next-generation sequencing (NGS) is quickly revolutionizing how research into the genetic determinants of constitutional disease is performed. The technique is highly efficient with millions of sequencing reads being produced in a short time span and at relatively low cost. Specifically, targeted NGS is able to focus investigations to genomic regions of particular interest based on the disease of study. Not only does this further reduce costs and increase the speed of the process, but it lessens the computational burden that often accompanies NGS. Although targeted NGS is restricted to certain regions of the genome, preventing identification of potential novel loci of interest, it can be an excellent technique when faced with a phenotypically and genetically heterogeneous disease, for which there are previously known genetic associations. Because of the complex nature of the sequencing technique, it is important to closely adhere to protocols and methodologies in order to achieve sequencing reads of high coverage and quality. Further, once sequencing reads are obtained, a sophisticated bioinformatics workflow is utilized to accurately map reads to a reference genome, to call variants, and to ensure the variants pass quality metrics. Variants must also be annotated and curated based on their clinical significance, which can be standardized by applying the American College of Medical Genetics and Genomics Pathogenicity Guidelines. The methods presented herein will display the steps involved in generating and analyzing NGS data from a targeted sequencing panel, using the ONDRISeq neurodegenerative disease panel as a model, to identify variants that may be of clinical significance

Trace elements in glucometabolic disorders: an update

Many trace elements, among which metals, are indispensable for proper functioning of a myriad of biochemical reactions, more particularly as enzyme cofactors. This is particularly true for the vast set of processes involved in regulation of glucose homeostasis, being it in glucose metabolism itself or in hormonal control, especially insulin. The role and importance of trace elements such as chromium, zinc, selenium, lithium and vanadium are much less evident and subjected to chronic debate. This review updates our actual knowledge concerning these five trace elements. A careful survey of the literature shows that while theoretical postulates from some key roles of these elements had led to real hopes for therapy of insulin resistance and diabetes, the limited experience based on available data indicates that beneficial effects and use of most of them are subjected to caution, given the narrow window between safe and unsafe doses. Clear therapeutic benefit in these pathologies is presently doubtful but some data indicate that these metals may have a clinical interest in patients presenting deficiencies in individual metal levels. The same holds true for an association of some trace elements such as chromium or zinc with oral antidiabetics. However, this area is essentially unexplored in adequate clinical trials, which are worth being performed

Molekular- und zytogenetische Analysen der autosomal rezessiven primären Mikrozephalie (MCPH) im Mausmodell

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopment disorder, arising from a failure in embryonic neurogenesis, leading to microcephaly at birth. All known genes implicated in this disorder are involved in the monitoring of centrosome integrity. Mutations in the human gene MCPH1, encoding microcephalin protein, cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC). Microcephalin contains highly conserved BRCT domains and has fundamental roles in cell cycle, chromosome condensation and DNA repair. The PhD project included generation of the first mouse model of impaired microcephalin function displaying the cellular phenotype of misregulated chromosome condensation, mapping a candidate MCPH locus on chromosome 10q11.23-21.3, reporting on a functionally notable MCPH1 missense mutation, p.Trp75Arg, with destabilizing effect on BRCT domain and identification of three mutations in the ASPM gene for MCPH disorder type five: p.Arg3096X, p.Arg1019X and the first reported missense variant p.Lys1862Gln. These results together provide further biological evidence for the MCPH proteins essential roles in brain development.Bei der autosomal rezessiven primären Mikrozephalie (MCPH) handelt es sich um eine fetale Entwicklungsstörung des Gehirns, die sich bereits zum Zeitpunkt der Geburt als Mikrozephalie manifestiert. Die bisher bekannten Gene sind in die Kontrolle des Centrosoms involviert. Mutationen in dem MCPH1 Gen des Menschen, das für das Protein Mikrozephalin kodiert, führen zu primärer Mikrozephalie in Verbindung mit einem singulären zellulären Phänotyp: der vorzeitigen Chromosomenkondensation (engl. premature chromosome condensation, PCC). Mikrozephalin weist zwei hoch konservierte BRCT Domänen auf und spielt eine wichtige Rolle in der Regulation des Zellzyklus, der Chromosomenkondensation und der DNA Reparatur. Im Rahmen dieser Promotion wurde das erste Mausmodell mit einem Defekt im Mcph1 Gen generiert, das mit einer fehlerhaften Chromosomenkondensation einhergeht. Zudem wurde ein neuer MCPH Lokus auf Chromosom 10q11.23-21.3 kartiert sowie eine funktionell bemerkenswerte missense Mutation im MCPH1 Gen, p.Trp75Arg, beschrieben, die die sich negativ auf die BRCT Domäne auswirkt. Ferner wurden drei Mutationen in dem MCPH5 (ASPM) Gen identifiziert, p.Arg3096X, p.Arg1019X und die erste missense Variante p.Lys1862Gln. Insgesamt haben die Ergebnisse weitere Belege für die grundlegende Rolle der MCPH Gene für die Gehirnentwicklung geliefert

User's verification to prevent malicious access in web-based forums

This paper aims to address the issue of malicious accounts that are created and used to imitate real users in web-based forums. In fact, form bots are used to create fake users on forums for several purposes. As a result hundreds of fake users start appearing in the forums and normally placing spam URLs. For forum administrators/managers/moderators, it is a frustrating job to keep members’ list clean. In order to overcome this issue, a novel approach is proposed that would be useful in order to prevent malicious users’ access and decrease rate of deception in web-based forums. We present a comparison between the proposed approach and IDology approach. The results illustrate that our proposed approach addresses the issue more efficiently as compared with IDology approach

The effect of using synthetic fibers on some properties of modified juss

This paper examines the mechanical properties of a composite material made of modified Iraqi gypsum (juss) reinforced with polypropylene fibers. The modified juss was prepared by adding two percentages of cement (5, 10) %. Two percentages of polypropylene fibers were used, to reinforce the modified juss (1, 2) %. The water/dry compound ratio used was equal to 0.53%. The composite was evaluated based on compressive strength, flexural strengths, absorption percentage, density, acoustic impedance, ultra - pulse velocity, longitudinal shrinkage and setting time tests. The results indicated that the inclusion of cement on to juss increases the compressive strength, absorption percentage, density, acoustic impedance, ultra - pulse velocity, longitudinal shrinkage and a reduction in flexural strength and setting time were observed by adding the cement. In addition, the inclusion of polypropylene fiber was significant in improving mechanical performance of the composite material, it shows a great improvement in longitudinal shrinkage, modulus of rupture and absorption percentages