Search results for: gene regulatory network

Authors: Alisa Kazarina, Guntis Gerhards, Elina Petersone-Gordina, Ilva Pole, Viktorija Igumnova, Janis Kimsis, Valentina Capligina, Renate Ranka

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Human body is inhabited by a vast number of microorganisms, collectively known as the human microbiome, and there is a tremendous interest in evolutionary changes in human microbial ecology, diversity and function. The field of paleomicrobiology, study of ancient human microbiome, is powered by modern techniques of Next Generation Sequencing (NGS), which allows extracting microbial genomic data directly from archaeological sample of interest. One of the major techniques is 16S rRNA gene sequencing, by which certain 16S rRNA gene hypervariable regions are being amplified and sequenced. However, some limitations of this method exist including the taxonomic precision and efficacy of different regions used. The aim of this study was to evaluate the phylogenetic sensitivity of different 16S rRNA gene hypervariable regions for microbiome studies in the archaeological samples. Towards this aim, archaeological bone samples and corresponding soil samples from each burial environment were collected in Medieval cemeteries in Latvia. The Ion 16S™ Metagenomics Kit targeting different 16S rRNA gene hypervariable regions was used for library construction (Ion Torrent technologies). Sequenced data were analysed by using appropriate bioinformatic techniques; alignment and taxonomic representation was done using Mothur program. Sequences of most abundant genus were further aligned to E. coli 16S rRNA gene reference sequence using MEGA7 in order to identify the hypervariable region of the segment of interest. Our results showed that different hypervariable regions had different discriminatory power depending on the groups of microbes, as well as the nature of samples. On the basis of our results, we suggest that wider range of primers used can provide more accurate recapitulation of microbial communities in archaeological samples. Acknowledgements. This work was supported by the ERAF grant Nr. 1.1.1.1/16/A/101.

Keywords: 16S rRNA gene, ancient human microbiome, archaeology, bioinformatics, genomics, microbiome, molecular biology, next-generation sequencing

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Authors: Y. I. Tretyakova, S. G. Shulkina, T. Y. Kravtsova, A. A. Antipova, N. Y. Kolomeets

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The research aimed to assess the functional significance of tumor necrosis factor-alpha (TNF-α) gene polymorphism at the -308G/A (rs1800629) region and vascular endothelial growth factor A (VEGFA) gene polymorphism at the -634G/C (rs 2010963) region in the development of ulcerative colitis (UC), focusing on patients from the Perm region, Russia. We examined 70 UC patients and 50 healthy donors during the active phase of the disease. Our focus was on TNF-α and VEGF concentration in the blood serum, as well as TNF-α and VEGFA gene polymorphisms at the -308G/А and -634G/C regions, respectively. We found that TNF-α and VEGF levels were significantly higher in patients with severe UC and high endoscopic activity compared to those with milder forms of the disease and low endoscopic activity. These tests could serve as additional non-invasive markers for assessing mucosal damage in the large intestine of UC patients. The frequency of allele variations in the TNF-α gene -308G/A (rs1800629) revealed a significantly higher occurrence of the unfavorable homozygote AA in UC patients compared to donors. Additionally, the major allele G and the allele pair GG were more frequent in patients with mild to moderate disease and 1-2 degree of endoscopic activity than in those with severe UC and 3-4 degree of endoscopic activity (χ2=14.19; p=0.000). We also observed a mutant allele A and the unfavorable homozygote AA associated with severe progressive UC. The occurrence of the mutant allele increased the risk of severe UC by 5 times (OR 5.03; CI 12.07-12.21). We did not find any significant differences in the frequency of the CC homozygote (χ2=1.02; p=0.6; OR=1.32) and the mutant allele C of the VEGFA gene -634G/C (rs 2010963) (χ2=0.01; p=0.913; OR=0.97) between groups of UC patients and healthy individuals. However, we detected that the mutant allele C and the unfavorable homozygote CC of the VEGFA gene were associated with more severe endoscopic changes in the colonic mucosa of UC patients (χ2=25,76; р=0,000; OR=0,15). The presence of the mutant allele increased the risk of severe UC by 6 times (OR 6,78; CI 3,13–14,7). We found a direct correlation between TNF-α and VEGFA gene polymorphisms, increased production of the same factors, disease severity, and endoscopic activity (р=0.000). Therefore, the presence of the mutant allele A and homozygote AA of the TNF-α gene at the -308G/A region and the mutant allele C and homozygote CC of the VEGFA gene at the -634G/C region are associated with risks related to an unfavorable clinical course of UC, frequent recurrences, and rapid progression. These findings should be considered when making prognoses regarding the clinical course of the disease and selecting treatment strategies. The presence of the homozygote AA in the TNF-α gene (rs1800629) is considered a sign of genetic predisposition to UC.

Keywords: gene polymorphism, TNF-α, ulcerative colitis, VEGF

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Authors: Sami Adwan, Alaa Alhaj Ismail, Claudia Girardone

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This paper examines the changes in the value relevance of book value of equity and net income of financial firms over the crisis period. It also examines how these changes vary with three variables, namely, fair value exposure, ownership concentration, and regulatory capital ratios. Using a sample of financial firms operating in the European Economic Area over 2005-2011, our findings suggest that the value relevance of book value of equity increases while that of net income decreases during the financial crisis. We find that more exposure to fair value accounting mitigates the impact of the crisis on the value relevance of book value of equity and net income. We also find that more concentrated ownership appears to have a mitigating impact on the changes in the value relevance of both book value of equity and net income in times of financial crisis. Finally, we find evidence that the level of regulatory capital ratios tends to have an attenuating effect on the changes in the value relevance of net income (but not book value of equity) in times of financial crisis.

Keywords: value relevance, financial crisis, financial firms, fair value, ownership concentration, regulatory capital

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Authors: I. Boroňová, J. Bernasovská, J. Kmec, E. Petrejčíková

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Dilated cardiomyopathy (DCM) is a primary myocardial disease, it is characterized by progressive systolic dysfunction due to cardiac chamber dilatation and inefficient myocardial contractility with estimated prevalence of 37 in 100 000 people. It is the most frequent cause of heart failure and cardiac transplantation in young adults. About one-third of all patients have a suspected familial disease indicating a genetic basis of DCM. Many candidate gene studies in humans have tested the association of single nucleotide polymorphisms (SNPs) in various genes coding for proteins with a known cardiovascular function. In our study we present the results of ZBTB17 gene rs10927875 polymorphism genotyping in relation to dilated cardiomyopathy in Slovak population. The study included 78 individuals, 39 patients with DCM and 39 healthy control persons. The mean age of patients with DCM was 50.7±11.5 years; the mean age of individuals in control group was 51.3±9.8 years. Risk factors detected at baseline in each group included age, sex, body mass index, smoking status, diabetes and blood pressure. Genomic DNA was extracted from leukocytes by a standard methodology and screened for rs10927875 polymorphism in intron of ZBTB17 gene using Real-time PCR method (Step One Applied Biosystems). The distribution of investigated genotypes for rs10927875 polymorphism in the group of patients with DCM was as follows: CC (89.74%), CT (10.26%), TT (0%), and the distribution in the control group: CC (92.31%), CT (5.13%), and TT (2.56%). Using the chi-square (χ2) test we compared genotype and allele frequencies between patients and controls. There was no difference in genotype or allele frequencies in ZBTB17 gene rs10927875 polymorphism between patients and control group (χ2=3.028, p=0.220; χ2=0.264, p=0.608). Our results represent an initial study, it can be considered as preliminary and first of its kind in Slovak population. Further studies of ZBTB17 gene polymorphisms of more numerous files and additional functional investigations are needed to fully understand the role of genetic associations.

Keywords: dilated cardiomyopathy, SNP polymorphism, ZBTB17 gene, bioscience

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Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le, Chi V. Phan

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Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 (13q14.3). This study aimed to investigate the gene mutation in the Vietnamese patients with WD, and make a presymptomatic diagnosis for their familial members. Forty-three WD patients and their 65 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. We recognized four mutations ([R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G) in the sum of 20 detectable mutations, accounting for 87.2% of the total. Mutation S105* was determined to have a high rate (32.6%) in this study. The hotspot regions of ATP7B were found at exons 2, 16, and 8, and intron 14, in 39.6 %, 11.6 %, 9.3%, and 7 % of patients, respectively. Among nine homozygote/compound heterozygote siblings of the patients with WD, three individuals were determined as asymptomatic by screening mutations of the probands. They would begin treatment after diagnosis. In conclusion, 20 different mutations were detected in 43 WD patients. Of this number, four novel mutations were explored, including [R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G. The mutation S105* is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD patients. Exons 2, 8, and 16, and intron 14 should be screened initially for WD patients in Vietnam. Based on risk profile for WD, genetic testing for presymptomatic patients is also useful in diagnosis and treatment.

Keywords: ATP7B gene, mutation detection, presymptomatic diagnosis, Vietnamese Wilson’s disease

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Authors: Mark Lokanan

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The paper analyzes the processing of complaints against investment brokers and dealer members through the Investment Industry Regulatory Organization of Canada (IIROC) from 2008 to 2017. IIROC is the self-regulatory organization (SRO) that is responsible for policing investment dealers and brokerage firms that trade in Canada’s securities market. Data from the study came from IIROC's enforcement annual reports for the years examined. The case processing is evaluated base on the misconduct funnel that was originally designed for street crime and applies to the enforcement of investment fraud. The misconduct funnel is used as a framework to examine IIROC’s claim that it brought in more complaints (funnel in) than government regulators and shows how these complaints are funneled out and funneled away as they are processed through IIROC’s enforcement system. The results indicate that IIROC is ineffective in disciplining its members and is unable to handle the more serious quasi-criminal and improper sales practices offenses. It is hard not to see the results of the paper being used by the legislator in Ottawa to show the importance of a federal securities regulatory agency such as the Securities and Exchange Commission (SEC) in the United States.

Keywords: investment fraud, securities regulation, compliance, enforcement

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Authors: Maryam Zafar, Sajida Rasheed, Imran Hashmi

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Water as an environmental reservoir is reported to act as a habitat and transmission route to microaerophilic bacteria such as Heliobacter pylori. It has been studied that in biofilms are the predominant dwellings for the bacteria to grow in water and protective reservoir for numerous pathogens by protecting them against harsh conditions, such as shear stress, low carbon concentration and less than optimal temperature. In this study, influence of these and many other parameters was studied on H. pylori in stagnant and moving water biofilms both in surface and underground aquatic reservoirs. H. pylori were recovered from pipe of different materials such as Polyvinyl Chloride, Polypropylene and Galvanized iron pipe cross sections from an urban water distribution network. Biofilm swabbed from inner cross section was examined by molecular biology methods coupled with gene sequencing and H. pylori 16S rRNA peptide nucleic acid probe showing positive results for H. pylori presence. Studies showed that pipe material affect growth of biofilm which in turn provide additional survival mechanism for pathogens like H. pylori causing public health concerns.

Keywords: biofilm, gene sequencing, heliobacter pylori, pipe materials

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Authors: Mengying Wang, Dongjing Liu, Holger Schwender, Ping Wang, Hongping Zhu, Tao Wu, Terri H Beaty

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Background: Maternal smoking is a recognized risk factor for nonsyndromic cleft lip with or without cleft palate (NSCL/P). It has been reported that the effect of maternal smoking on oral clefts is mediated through genes that influence nicotine dependence. The polymorphisms of cholinergic receptor nicotinic alpha (CHRNA) and beta (CHRNB) subunits genes have previously shown strong associations with nicotine dependence. Here, we attempted to investigate whether the above genes are associated with clefting risk through testing for potential gene-gene (G×G) and gene-environment (G×E) interaction. Methods: We selected 120 markers in 14 genes associated with nicotine dependence to conduct transmission disequilibrium tests among 806 Chinese NSCL/P case-parent trios ascertained in an international consortium which conducted a genome-wide association study (GWAS) of oral clefts. We applied Cordell’s method using “TRIO” package in R to explore G×G as well as G×E interaction involving environmental tobacco smoke (ETS) based on conditional logistic regression model. Results: while no SNP showed significant association with NSCL/P after Bonferroni correction, we found signals for G×G interaction between 10 pairs of SNPs in CHRNA3, CHRNA5, and CHRNB4 (p<10-8), among which the most significant interaction was found between RS3743077 (CHRNA3) and RS11636753 (CHRNB4, p<8.2×10-12). Linkage disequilibrium (LD) analysis revealed only low level of LD between these markers. However, there were no significant results for G×ETS interaction. Conclusion: This study fails to detect association between nicotine dependence genes and NSCL/P, but illustrates the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P. This study also suggests nicotine dependence genes should be considered as important candidate genes for NSCL/P in future studies.

Keywords: Gene-Gene Interaction, Maternal Smoking, Nicotine Dependence, Non-Syndromic Cleft Lip with or without Cleft Palate

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Authors: Surinder Singh, Meenakshi

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In this paper MZI-FBG based optical add drop multiplexer is designed and its performance is analyzed in the ring network. In the ring network nodes are composed of optical add drop multiplexer, transmitter and receiver. OADM is used to add or drop any frequency at intermediate nodes without affecting other channels. In this paper the performance of the ring network is carried out by varying various kinds of fiber with or without amplifiers.

Keywords: OADM, ring network, MZI-FBG, transmitter

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Authors: Moneesh Thakur, Hridayesh Prasad, Nikitasha Bora, Parimal Roy Choudhary, A. K. Samanta, Sanjeev Kumar

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Canine demodicosis is a common parasitic condition which involves dog skin. Demodicosis in dogs is due the prominent growth of Demodex. Out of various canine Demodex spp., Demodex canis is the most often involved species. Canine demodicosis can occur as either a localized or generalized form of demodicosis severely affect the dogs and in non-treated dogs may cause death. This study was planned with the aim to screen and characterize the 18S rRNA gene of isolated Demodex canis. A total of 1200 dogs were screened during this study period. The skin scrapings of all the suspected dogs were examined under a microscope at 100X magnification for the presence of Demodex canis. The skin scrapings positive for Demodex canis were examined using PCR for confirmation. A total of 35 dogs were confirmed a positive result for D. canis based on 18S rRNA gene amplification by PCR. Further, the 18S rRNA gene of isolated Demodex canis was cloned and sequenced for genome analysis. On the sequence analysis, it was found that isolated sequence (GenBank Accession No. MK177513) had close similarity (99.7%) to that of D. canis genotype of China (Accession No. MG372254).

Keywords: PCR, phylogenetic analysis, cloning and sequening, Demodex canis

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Authors: Mohamed Aljarallah, Mohamed Nurullah, George Saridakis

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This paper aims and objectives are to investigate how the structural change of the financial regulatory bodies affect the financial supervision and how the regulators can design such a structure with taking into account; the Central Bank, the conduct of business and the prudential regulators, it will also consider looking at the structure of the international regulatory bodies and what barriers are found. There will be five questions to be answered; should conduct of business and prudential regulation be separated? Should the financial supervision and financial stability be separated? Should the financial supervision be under the Central Bank? To what extent the politician should intervene in changing the regulatory and supervisory structure? What should be the regulatory and supervisory structure when there is financial conglomerate? Semi structure interview design will be applied. This research sample selection contains a collective of financial regulators and supervisors from the emerged and emerging countries. Moreover, financial regulators and supervisors must be at a senior level at their organisations. Additionally, senior financial regulators and supervisors would come from different authorities and from around the world. For instance, one of the participants comes from the International Bank Settlements, others come from European Central Bank, and an additional one will come from Hong Kong Monetary Authority and others. Such a variety aims to fulfil the aims and objectives of the research and cover the research questions. The analysis process starts with transcription of the interview, using Nvivo software for coding, applying thematic interview to generate the main themes. The major findings of the study are as follow. First, organisational structure changes quite frequently if the mandates are not clear. Second, measuring structural change is difficult, which makes the whole process unclear. Third, effective coordination and communication are what regulators looking for when they change the structure and that requires; openness, trust, and incentive. In addition to that, issues appear during the event of crisis tend to be the reason why the structure change. Also, the development of the market sometime causes a change in the regulatory structure. And, some structural change occurs simply because of the international trend, fashion, or other countries' experiences. Furthermore, when the top management change the structure tends to change. Moreover, the structure change due to the political change, or politicians try to show they are doing something. Finally, fear of being blamed can be a driver of structural change. In conclusion, this research aims to provide an insight from the senior regulators and supervisors from fifty different countries to have a clear understanding of why the regulatory structure keeps changing from time to time through a qualitative approach, namely, semi-structure interview.

Keywords: financial regulation bodies, financial regulatory structure, global financial regulation, financial crisis

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Authors: Amir Bastani

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The result of the research in the field of human behavioural genetics demonstrates a genetic contribution of behavioural differences in aggression, violence, drug and substance abuse, antisocial personality disorder and other related traits. As the field of human behavioural genetics progresses and achieves credibility, the criminal accused continue to use its types of evidence into the criminal law. One of the most important genetic factors which controls certain neurotransmitters like dopamine and serotonin is the Monoamine Oxidase Acid A (MAOA) gene, known as the 'warrior gene'. The high-profile study by Caspi and colleagues in 2002 showed that the combination between one type of variation of the MAOA gene and childhood maltreatment noticeably predisposes a person to antisocial behaviour. Moreover, further scientific research shows that individuals with the MAOA gene have to some degree difficulties in controlling their impulses. Based on the evidence of MAOA, some criminal accused claimed difficulties in self-control. In the first case – the famous case of Mobley – the court rejected the MAOA evidence on the ground of the lack of scientific support. In contrast, in other cases after the Mobley trial, courts accepted the evidence of MAOA. In this paper, the issue of lack of impulse control produced by the MAOA gene and cases which relied on the MAOA evidence and successfully being accepted will be reviewed in detail. Finally, the anticipation of the paper for the future use of the MAOA evidence in criminal cases will be presented.

Keywords: genetic defence, criminal responsibility, MAOA, self-control

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Authors: Tanveer Hussain, Misbah Hussain, Masroor Ellahi Babar, Muhammad Traiq Pervez, Fiaz Hussain, Sana Zahoor, Rashid Saif

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Interleukin 2 (IL-2) is a cytokine which is produced by activated T cells, play important role in immune response against antigen. It act in both autocrine and paracrine manner. It can stimulate B cells and various other phagocytic cells like monocytes, lymphokine-activated killer cells and natural killer cells. Acting in autocrine fashion, IL-2 protein plays a crucial role in proliferation of T cells. IL-2 triggers the release of pro and anti- inflammatory cytokines by activating several pathways. In present study, exon 1 of IL-2 gene of four local Pakistani breeds (Dera Din Panah, Beetal, Nachi and Kamori) from two provinces was amplified by using reported Ovine IL-2 primers, yielding PCR product of 501 bp. The sequencing of all samples was done to identify the polymorphisms in amplified region of IL-2 gene. Analysis of sequencing data resulted in identification of one novel nucleotide substitution (T→A) in amplified non-coding region of IL-2 gene. Comparison of IL-2 gene sequence of all four breeds with other goat breeds showed high similarity in sequence. While phylogenetic analysis of our local breeds with other mammals showed that IL-2 is a variable gene which has undergone many substitutions. This high substitution rate can be due to the decreased or increased changed selective pressure. These rapid changes can also lead to the change in function of immune system. This pioneering study of Pakistani goat breeds urge for further studies on immune system of each targeted breed for fully understanding the functional role of IL-2 in goat immunity.

Keywords: interleukin 2, mutational analysis, phylogeny, goat breeds, Pakistan

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Authors: Fady Tawakol

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BitCoin is a decentralized cryptocurrency that can be used without the need of traditional central banks to accomplish any e-commerce trade. The use of such currency could facilitate new economic interactions and linkages. However, without effective and efficient regulations, cryptocurrency transactions are mostly used by criminals to commit crimes such as money laundering, theft, and blackmailing. And because law is one step behind technological developments, this paper discusses the importance of regulations and supervision for the BitCoin-system, to provide unified regulatory solutions for our digital future in the Middle East. It will provide a detailed analysis of the legal nature of BitCoin along with, its regulation with respect to criminal and civil law.

Keywords: BitCoin, financial protection, crypto currency, money laundering

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Authors: David P. Horton, Gary Lynch-Wood

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Western populations are aging, prone to various lifestyle health problems, and increasing their demand for health and social care services. This demand has created enormous fiscal and regulatory challenges. In response, government institutions have deployed strategies of behavior modification to encourage people to exercise greater personal responsibility over their health and care needs (i.e., welfare responsibilisation). Policy strategies are underpinned by the assumption that people if properly supported, will make better health and lifestyle selections. Not only does this absolve governments of the responsibility for meeting all health and care needs, but it also enables government institutions to assert fiscal control over welfare spending. Looking at the regulation of health and social care in the UK, the authors identify and outline a suite of regulatory tools that are designed to extract and manage the resources of health and social care services users and to encourage them to make (‘better’) use of these resources. This is important for our understanding of how health and social care regulation is responding to ongoing social and economic challenges. It is also important because there has been a failure to systematically examine the relevance of resources for regulation, which is surprising given that resources are crucial to how and whether regulation succeeds or fails. In particular, drawing from the regulatory welfare state concept, the authors analyse the key legal and regulatory changes and mechanisms that have been introduced since the 2008 financial crisis, focusing on critical measures such as the Health and Social Care Act and regulations introduced under the National Health Service Act. The authors show how three types of user resources (i.e., tangible, labor, and data) are being used to assert fiscal control and increase welfare responsibilisation. Amongst other things, the paper concludes that service users have become more than rule followers and targets of behavioral modification; rather, they are producers of resources that regulatory systems have come to rely on.

Keywords: health care, regulation, resources, social care

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Authors: Belbahi Ahlam

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With the phenomenal growth in the Internet, network security has become an integral part of computer and information security. In order to come up with measures that make networks more secure, it is important to learn about the vulnerabilities that could exist in a computer network and then have an understanding of the typical attacks that have been carried out in such networks. The first half of this paper will expose the readers to the classical network attacks that have exploited the typical vulnerabilities of computer networks in the past and solutions that have been adopted since then to prevent or reduce the chances of some of these attacks. The second half of the paper will expose the readers to the different network security controls including the network architecture, protocols, standards and software/ hardware tools that have been adopted in modern day computer networks.

Keywords: network security, attacks and controls, computer and information, solutions

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Authors: Othman E. Othman, Hassan R. Darwish, Amira M. Nowier

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Lactoferrin (LF) is a multifunctional protein involved in economically production traits like milk protein composition and skeletal structure in small ruminants including sheep and goat. So, LF gene - with its genetic polymorphisms associated with production traits - is considered a candidate genetic marker used in marker-assisted selection in goats. This study aimed to identify the different alleles and genotypes of this gene in three Egyptian goat breeds using PCR-SSCP (polymerase chain reaction-single-strand conformation polymorphism) and DNA sequencing. Genomic DNA was extracted from 120 animals belonging to Barki, Zaraibi, and Damascus goat breeds. Using specific primers, PCR amplified 247-bp fragments from exon 2 of LF goat gene. The PCR products were subjected to Single-Strand Conformation Polymorphism (SSCP) technique. The results showed the presence of two genotypes GG and AG in the tested animals. The frequencies of both genotypes varied among the three tested breeds with the highest frequencies of GG genotype in all tested goat breeds. The sequence analysis of PCR products representing these two detected genotypes declared the presence of an SNP (single nucleotide polymorphisms) substitution (G/A) among G and A alleles of this gene. The association between different LF genotypes and milk composition as well as body measurement was estimated. The comparison showed that the animals possess AG genotypes are superior over those with GG genotypes for different parameters of milk protein compositions and skeletal structures. This finding declared that allele A of LF gene is considered the promising marker for the productive traits in goat. In conclusion, the Egyptian goat breeds will be needed to enhance their milk protein composition and growth trait parameters through the increasing of allele A frequency in their herds depending on the superior production traits of this allele in goats.

Keywords: lLactoferrin gene, PCR-SSCP, SNPs, Egyptian goat

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Authors: Kittitara Chunlakittiphan, Patompong Satapornpong

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Introduction: The variation of genetics affects how our body responds to pharmaceuticals elucidates the correlation between long-term use of medical cannabis and adverse drug reactions (ADRs). Medical cannabis is regarded as the treatment for chronic pain, cancer pain, acute pain, psychological disorders, multiple sclerosis and migraine management. However, previous studies have shown that delta-9-Tetrahydrocannabinol (THC), an ingredient found in cannabis, was the cause of ADRs in CB1 receptors found in humans. Previous research suggests that distributions of the cannabinoid type 1 (CB1) receptor gene and pharmacogenetic markers, which vary amongst different populations, might affect incidences of ADRs. Although there is an evident need to investigate the level of the CB1 receptor gene (rs806365), studies on the distribution of CB1-pharmacogenetics markers in Thai patients are limited. Objective: Therefore, the aim of this study is to investigate the distribution of the rs806365 polymorphism in Thai patients who have been treated with medical cannabis. Materials and Methods: We enrolled 31 Thai patients with THC-induced ADRs and 34 THC-tolerant controls to take part in this study. All patients with THC-induced ADRs were accessed through a review of medical records by physicians. EDTA blood of 3ml was collected to obtain the CNR1 gene (rs806365) and genotyping of this gene was conducted using the real-time PCR ViiA7 (ABI, Foster City, CA, USA) following the manufacturer’s instruction. Results: The sample consisted of 65 patients (40/61.54%) were females and (25/38.46%) were males, with an age range of 19-87 years, who have been treated with medical cannabis. In this study, the most common THC-induced ADRs were dry mouth and/or dry throat, tachycardia, nausea, and arrhythmia. Across the whole sample, we found that 52.31% of Thai patients carried a heterozygous variant (rs806365, CT allele). Moreover, the number of rs806365 (CC, homozygous variant) carriers totaled seventeen people (26.15%) amongst the subjects of Thai patients treated with medical cannabis. Furthermore, 17 out of 22 patients (77.27%) who experienced severe ADRs: Tachycardia and/or arrhythmia, carried an abnormal rs806365 gene (CT and CC alleles). Conclusions: The results propose that the rs806365 gene is widely distributed amongst the Thai population and there is a link between this gene and vulnerability to developing THC-induced ADRs after being treated with medical cannabis. Therefore, it is necessary to screen for the rs806365 gene before using medical cannabis to treat a patient.

Keywords: rs806365, THC-induced adverse drug reactions, CB1 receptor, Thai population

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Authors: Yong Xue, Daniel A. Menascé

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Automated and end-to-end network resource management and provisioning for virtual service networks in a multiple autonomous systems (a.k.a multi-AS) environment is a challenging and open problem. This paper proposes a novel, scalable and interoperable high-level architecture that incorporates a number of emerging enabling technologies including Software Defined Network (SDN), Network Function Virtualization (NFV), Service Oriented Architecture (SOA), and Autonomic Computing. The proposed architecture can be used to not only automate network resource management and provisioning for virtual service networks across multiple autonomous substrate networks, but also provide an adaptive capability for achieving optimal network resource management and maintaining network-level end-to-end network performance as well. The paper argues that this SDN and autonomic computing based architecture lays a solid foundation that can facilitate the development of the future Internet based on the pluralistic paradigm.

Keywords: virtual network, software defined network, virtual service network, adaptive resource management, SOA, multi-AS, inter-domain

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Authors: Umamaheswari Shanmugam, Silvia Ronchi

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Software, artificial intelligence, and machine learning can improve healthcare through innovative and advanced technologies that can use the large amount and variety of data generated during healthcare services every day; one of the significant advantages of these new technologies is the ability to get experience and knowledge from real-world use and to improve their performance continuously. Healthcare systems and institutions can significantly benefit because the use of advanced technologies improves the efficiency and efficacy of healthcare. Software-defined as a medical device, is stand-alone software that is intended to be used for patients for one or more of these specific medical intended uses: - diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of a disease, any other health conditions, replacing or modifying any part of a physiological or pathological process–manage the received information from in vitro specimens derived from the human samples (body) and without principal main action of its principal intended use by pharmacological, immunological or metabolic definition. Software qualified as medical devices must comply with the general safety and performance requirements applicable to medical devices. These requirements are necessary to ensure high performance and quality and protect patients' safety. The evolution and the continuous improvement of software used in healthcare must consider the increase in regulatory requirements, which are becoming more complex in each market. The gap between these advanced technologies and the new regulations is the biggest challenge for medical device manufacturers. Regulatory requirements can be considered a market barrier, as they can delay or obstacle the device's approval. Still, they are necessary to ensure performance, quality, and safety. At the same time, they can be a business opportunity if the manufacturer can define the appropriate regulatory strategy in advance. The abstract will provide an overview of the current regulatory framework, the evolution of the international requirements, and the standards applicable to medical device software in the potential market all over the world.

Keywords: artificial intelligence, machine learning, SaMD, regulatory, clinical evaluation, classification, international requirements, MDR, 510k, PMA, IMDRF, cyber security, health care systems

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Authors: Vijay Kumar Singh, Pooja Kushwaha, Prabhat Ranjan, Krishna Kumar Ojha, Jitendra Kumar

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Present day high-throughput genomic technologies, NGS/microarrays, are producing large volume of data that require improved analysis methods to make sense of the data. The correlation between genes and samples has been regularly used to gain insight into many biological phenomena including, but not limited to, co-expression/co-regulation, gene regulatory networks, clustering and pattern identification. However, presence of outliers and violation of assumptions underlying Pearson correlation is frequent and may distort the actual correlation between the genes and lead to spurious conclusions. Here, we report a method to measure the strength of association between genes. The method assumes that the expression values of a gene are Bernoulli random variables whose outcome depends on the sample being probed. The method considers the two genes as uncorrelated if the number of sample with same outcome for both the genes (Ns) is equal to certainly expected number (Es). The extent of correlation depends on how far Ns can deviate from the Es. The method does not assume normality for the parent population, fairly unaffected by the presence of outliers, can be applied to qualitative data and it uses the binomial distribution to assess the significance of association. At this stage, we would not claim about the superiority of the method over other existing correlation methods, but our method could be another way of calculating correlation in addition to existing methods. The method uses binomial distribution, which has not been used until yet, to assess the significance of association between two variables. We are evaluating the performance of our method on NGS/microarray data, which is noisy and pierce by the outliers, to see if our method can differentiate between spurious and actual correlation. While working with the method, it has not escaped our notice that the method could also be generalized to measure the association of more than two variables which has been proven difficult with the existing methods.

Keywords: binomial distribution, correlation, microarray, outliers, transcriptome

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Authors: Riffat Iqbal, Sidra Ihsan, Andleeb Batool, Maryam Mukhtar

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Glaucoma is a gathering of optic neuropathies described by dynamic degeneration of retinal ganglionic cells. It is clinically and innately heterogenous illness containing a couple of particular forms each with various causes and severities. Primary open-angle glaucoma (POAG) is the most generally perceived kind of glaucoma. This study investigated the genetic association of single nucleotide polymorphisms (SNPs; rs10483727 and rs33912345) at the SIX1/SIX6 locus with primary open-angle glaucoma (POAG) in the Pakistani population. The SIX6 gene plays an important role in ocular development and has been associated with morphology of the optic nerve. A total of 100 patients clinically diagnosed with glaucoma and 100 control individuals of age over 40 were enrolled in the study. Genomic DNA was extracted by organic extraction method. The SNP genotyping was done by (i) PCR based restriction fragment length polymorphism (RFLP) and sequencing method. Significant genetic associations were observed for rs10483727 (risk allele T) and rs33912345 (risk allele C) with POAG. Hence, it was concluded that Six6 gene is genetically associated with pathogenesis of Glaucoma in Pakistan.

Keywords: genotyping, Pakistani population, primary open-angle glaucoma, SIX6 gene

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Authors: Tet H. Yeap

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An analog restricted Hopfield Network is presented in this paper. It consists of two layers of nodes, visible and hidden nodes, connected by directional weighted paths forming a bipartite graph with no intralayer connection. An energy or Lyapunov function was derived to show that the proposed network will converge to stable states. By introducing hidden nodes, the proposed network can be trained to store patterns and has increased memory capacity. Training to be an associative memory, simulation results show that the associative memory performs better than a classical Hopfield network by being able to perform better memory recall when the input is noisy.

Keywords: restricted Hopfield network, Lyapunov function, simultaneous perturbation stochastic approximation

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Authors: Liang Bai, Yandong Xiao, Haorang Wang, Songyang Lao

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The directedness of links is crucial to determine the controllability in complex networks. Even the edge directions can determine the controllability of complex networks. Obviously, for a given network, we wish to design its edge directions that make this network approach the optimal controllability. In this work, we firstly introduce two methods to enhance network by assigning edge directions. However, these two methods could not completely mitigate the negative effects of inaccessibility and dilations. Thus, to approach the optimal network controllability, the edge directions must mitigate the negative effects of inaccessibility and dilations as much as possible. Finally, we propose the edge direction for optimal controllability. The optimal method has been found to be successfully useful on real-world and synthetic networks.

Keywords: complex network, dynamics, network control, optimization

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Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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Authors: Hajar Hosseini Khorami

Abstract:

Porphyrins are organic, aromatic compounds found in heme, cytochrome, cobalamin, chlorophyll , and many other natural products with essential roles in biological processes that their cationic forms have been used as groups of favorable non-viral vectors recently. Cationic porphyrins are self-chromogenic reagents with a high capacity for modifications, great interaction with DNA and protection of DNA from nuclease during delivery of it into a cell with low toxicity. In order to have high efficient gene transfection into the cell while causing low toxicity, genetically manipulations of the non-viral vector, cationic porphyrin, would be useful. In this study newly modified cationic porphyrin derivative, 5, 10-dihexyl-15, 20bis (N-methyl-4-pyridyl) porphyrin was applied. Cytotoxicity of synthesized cationic porphyrin on Chinese Hamster Ovarian (CHO) cells was evaluated by using MTT assay. This cationic derivative is dose-dependent, with low cytotoxicity at the ranges from 100 μM to 0.01μM. It was uptake by cells at high concentration. Using direct non-viral gene transfection method and different concentration of cationic porphyrin were tested on transfection of CHO cells by applying derived transfection reagent with X-tremeGENE HP DNA as a positive control. However, no transfection observed by porphyrin derivative and the parameters tested except for positive control. Results of this study suggested that applying different protocol, and also trying other concentration of cationic porphyrins and DNA for forming a strong complex would increase the possibility of efficient gene transfection by using cationic porphyrins.

Keywords: cationic porphyrins, gene delivery, non-viral vectors, transfection reagents

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Authors: Asma Ben Yaghlane, Mohamed Naceur Azaiez

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We consider the problem of attacks on networks. We define the concept of system survivability in networks in the presence of intelligent threats. Our setting of the problem assumes a flow to be sent from one source node to a destination node. The attacker attempts to disable the network by preventing the flow to reach its destination while the defender attempts to identify the best path-set to use to maximize the chance of arrival of the flow to the destination node. Our concept is shown to be different from the classical concept of network reliability. We distinguish two types of network survivability related to the defender and to the attacker of the network, respectively. We prove that the defender-based-network survivability plays the role of a lower bound while the attacker-based-network survivability plays the role of an upper bound of network reliability. We also prove that both concepts almost never agree nor coincide with network reliability. Moreover, we use the shortest-path problem to determine the defender-based-network survivability and the min-cut problem to determine the attacker-based-network survivability. We extend the problem to a variety of models including the minimum-spanning-tree problem and the multiple source-/destination-network problems.

Keywords: defense/attack strategies, information, networks, reliability, survivability

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Authors: Yosia Mulumba, Klaus Schmidt

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Financial Inclusion is considered a key pillar for development in most countries around the world. Access to affordable financial services in a country’s economy can be a driver to overcome poverty and reduce income inequalities, and thus increase economic growth. Nevertheless, the number of financially excluded populations in developing countries continues to be very high. This paper explores the role of Financial Technology (Fintech) as a key driver for achieving financial inclusion in developing countries post the COVID-19 pandemic with an emphasis on four East African countries: Kenya, Tanzania, Uganda, and Rwanda. The research paper is inspired by the positive disruption caused by the pandemic, which has compelled societies in East Africa to adapt and embrace the use of financial technology innovations, specifically Mobile Money Services (MMS), to access financial services. MMS has been further migrated and integrated with other financial technology innovations such as Mobile Banking, Micro Savings, and Loans, and Insurance, to mention but a few. These innovations have been adopted across key sectors such as commerce, health care, or agriculture. The research paper will highlight the Mobile Network Operators (MNOs) that are behind MMS, along with numerous innovative products and services being offered to the customers. It will also highlight the regulatory framework under which these innovations are being governed to ensure the safety of the customers' funds.

Keywords: financial inclusion, financial technology, regulatory framework, mobile money services

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Authors: Ngoc Tu Truong, Nuong T. Bui, Ben Rao, Ya L. Shen

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Quorum sensing is a phenomenon present in many gram-negative bacteria that allows bacterial communication and controlled expression of a large suite of genes through quorum sensing signals - N-acyl homoserine lactones (AHLs). In order to investigate the ability of the rhlR/rhlI quorum sensing system in Pseudomonas aeruginosa to express the ß-Galactosidase reporter gene, an engineered E. coli strain EpHL02, was genetically engineered. This engineered E. coli strain EpHL02 responded to the presence of the N-butanoyl homoserine lactone and N-hexanoyl homoserine lactone to express the ß-Galactosidase reporter gene at a concentration limit of 5x10⁻⁸ M. This was also found to be comparable to AHLs extraction from Serratia marcescens H31. Moreover, we examined this ability of this engineered E. coli strain for respond of AHLs from extractions of Pseudomonas aeruginosa ATCC9027. The results demonstrated that the rhlR/rhlI quorum sensing system can express the ß-Galactosidase reporter gene by using the N-butanoyl homoserine lactone, N-hexanoyl homoserine lactone and AHLs from extractions of Serratia marcescens H31 and Pseudomonas aeruginosa ATCC9027 in the engineered E. coli strain EpHL02.

Keywords: N-butanoyl homoserine lactone, C4-HSL, N-hexanoyl homoserine lactone, C6-HSL, Pseudomonas aeruginosa, quorum sensing, Serratia marcescens, ß-galactosidase reporter gene

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Authors: Fatimah Opebiyi

Abstract:

Economic growth promotion, inflation reduction and consumer protection are among the core public interest aims of governments. Nevertheless, higher rates of default by consumers in relation to credit card loans and mortgages in recent times illustrate that government’s performance in balancing the protection of the economy and consumer is subpar. This thereby raises an important question on the role of government in protecting consumers during prolonged spells of inflation, particularly when such inflationary trends may be traceable to the acts of the government. Adopting a doctrinal research methodology, this article investigates the evolution of the concept of consumer protection in the United Kingdom and also brings to the fore the tensions and conflicts of interests in the aims and practices of the main regulators within the financial services industry. Relying on public interest theories of regulation and responsive regulatory theory, the article explores the limitations in the state’s ability to strike the right balance in meeting regulatory aims of the regulatory agencies at the opposite ends of the spectrum.

Keywords: financial regulation, consumer protection, prudential regulation, public interest theories of regulation, central bank

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