Search results for: molecular states

Authors: Fatimah Alhomaid

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The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of colon cancer in Saudi patients. Our results were carried out on 48 patients colon cancer. We obtained our data from laboratory in King Khalid university hospital. The specimens were taken (48) patients with colon cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as I in tow patients (male and female) and grade 2 in 42 patients (29 male and 13 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining , immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients of adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscularis layer. With advancing the disease, there were haemorge in blood and increase in lymphocytes and increase number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20,PCNA,P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for pcan and the grades. In our sections, there were strong reactions in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of colon cancer.

Keywords: DNA-CK20, PCNA, P53, colon cancer

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Authors: Parvaneh Mahmoudi, Ahmad Moeni, Seyed Mojtaba Khayam Nekoei, Mohsen Mardi, Mehrshad Zeinolabedini, Ghasem Hosseini Salekdeh

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Saffron (Crocus sativus L.) is one of the most important spice and medicinal plants. The three-branch style of C. sativus flowers are the most important economic part of the plant and known as saffron, which has several medicinal properties. Despite the economic and biological significance of this plant, knowledge about its molecular characteristics is very limited. In the present study, we, for the first time, constructed a comprehensive dataset for C. sativus stigma through de novo transcriptome sequencing. We performed de novo transcriptome sequencing of C. sativus stigma using the Illumina paired-end sequencing technology. A total of 52075128 reads were generated and assembled into 118075 unigenes, with an average length of 629 bp and an N50 of 951 bp. A total of 66171unigenes were identified, among them, 66171 (56%) were annotated in the non-redundant National Center for Biotechnology Information (NCBI) database, 30938 (26%) were annotated in the Swiss-Prot database, 10273 (8.7%) unigenes were mapped to 141 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, while 52560 (44%) and 40756 (34%) unigenes were assigned to Gen Ontology (GO) categories and Eukaryotic Orthologous Groups of proteins (KOG), respectively. In addition, 65 candidate genes involved in three stages of crocin biosynthesis were identified. Finally, transcriptome sequencing of saffron stigma was used to identify 6779 potential microsatellites (SSRs) molecular markers. High-throughput de novo transcriptome sequencing provided a valuable resource of transcript sequences of C. sativus in public databases. In addition, most of candidate genes potentially involved in crocin biosynthesis were identified which could be further utilized in functional genomics studies. Furthermore, numerous obtained SSRs might contribute to address open questions about the origin of this amphiploid spices with probable little genetic diversity.

Keywords: saffron, transcriptome, NGS, bioinformatic

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Authors: Tariq Ahmad Dar, Moinuddin, M. Masroor A. Khan

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There is considerable need in enhancing the content and yield of active constituents of medicinal plants keeping in view their massive demand worldwide. Different strategies have been employed to enhance the active constituents of medicinal plants and the use of phytohormones has been proved effective in this regard. Gamma-irradiated Sodium alginate (ISA) is known to elicit an array of plant defense responses and biological activities in plants. Considering the medicinal importance, a pot experiment was conducted to explore the effect of ISA and phosphorus on growth, yield and quality of fenugreek (Trigonella foenum-graecum L.). ISA spray treatments (0, 40, 80 and 120 mg L-1) were applied alone and in combination with 40 kg P ha-1 (P40). Crop performance was assessed in terms of plant growth characteristics, physiological attributes, seed yield and the content of seed trigonelline. Of the ten-treatments, P40 + 80 mg L−1 of ISA proved the best. The results showed that foliar spray of ISA alone or in combination with P40 augmented the plant vegetative growth, enzymatic activities, trigonelline content, trigonelline yield and economic yield of fenugreek. Application of 80 mg L−1 of ISA applied with P40 gave the best results for almost all the parameters studied compared to control or to 80 mg L−1 of ISA applied alone. This treatment increased the total content of chlorophyll, carotenoids, leaf -N, -P and -K and trigonelline compared to the control by 24.85 and 27.40%, 15 and 23.52%, 18.70 and 16.84%, 15.88 and 18.92%, 12 and 14.44%, at 60 and 90 DAS respectively. The combined application of 80 mg L−1 of ISA along with P40 resulted in the maximum increase in seed yield, trigonelline content and trigonelline yield by146, 34 and 232.41%, respectively, over the control. Gel permeation chromatography revealed the formation of low molecular weight fractions in ISA samples, containing even less than 20,000 molecular weight oligomers, which might be responsible for plant growth promotion in this study. Trigonelline content was determined by reverse phase high performance liquid chromatography (HPLC) with C-18 column.

Keywords: gamma-irradiated sodium alginate, phosphorus, gel permeation chromatography, HPLC, trigonelline content, yield

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Authors: Mervat Kassem, Nourhan Fanaki, F. Dabbous, Hamida Abou-Shleib, Y. R. Abdel-Fattah

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With increasing environmental awareness and emphasis on a sustainable society in harmony with the global environment, biosurfactants are gaining prominence and have already taken over for a number of important industrial uses. They are produced by living organisms, for examples Pseudomonas aeruginosa which produces rhamnolipids, Candida (formerly Torulopsis) bombicola, which produces high yields of sophorolipids from vegetable oils and sugars and Bacillus subtilis which produces a lipopeptide called surfactin. The main goal of this work was to optimize biosurfactants production by an environmental Gram positive isolate for large scale production with maximum yield and low cost. After molecular characterization, phylogenetic tree was constructed where it was found to be B. subtilis, which close matches to B. subtilis subsp. subtilis strain CICC 10260. For optimizing its biosurfactants production, sequential statistical design using Plackett-Burman and response surface methodology, was applied where 11 variables were screened. When analyzing the regression coefficients for the 11 variables, pH, glucose, glycerol, yeast extract, ammonium chloride and ammonium nitrate were found to have a positive effect on the biosurfactants production. Ammonium nitrate, pH and glucose were further studied as significant independent variables for Box-Behnken design and their optimal levels were estimated and were found to be 7.328 pH value, 3 g% glucose and 0.21g % ammonium nitrate yielding high biosurfactants concentration that reduced the surface tension of the culture medium from 72 to 18.16 mN/m. Next, kinetics of cell growth and biosurfactants production by the tested B. subtilis isolate, in bioreactor was compared with that of shake flask where the maximum growth and specific growth (µ) in the bioreactor was higher by about 25 and 53%, respectively, than in shake flask experiment, while the biosurfactants production kinetics was almost the same in both shake flask and bioreactor experiments.

Keywords: biosurfactants, B. subtilis, molecular identification, phylogenetic trees, Plackett-Burman design, Box-Behnken design, 16S rRNA

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Authors: Kevin A. Droguett, Edwin G. Pérez, Denis Fuentealba, Margarita E. Aliaga, Angélica M. Fierro

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Supramolecular chemistry is a field of growing interest. Moreover, studying the formation of host-guest complexes between macrocycles and dyes is highly attractive due to their potential applications. Examples of the above are drug delivery, catalytic process, and sensing, among others. There are different dyes of interest in the literature; one example is the quinolinone derivatives. Those molecules have good optical properties and chemical and thermal stability, making them suitable for developing fluorescent probes. Secondly, several macrocycles can be seen in the literature. One example is the cucurbiturils. This water-soluble macromolecule family has a hydrophobic cavity and two identical carbonyl portals. Additionally, the thermodynamic analysis of those supramolecular systems could help understand the affinity between the host and guest, their interaction, and the main stabilization energy of the complex. In this work, two 7-(diethylamino) quinoline-2 (1H)-one derivative (QD1-2) and their interaction with cucurbit[7]uril (CB[7]) were studied from an experimental and in-silico point of view. For the experimental section, the complexes showed a 1:1 stoichiometry by HRMS-ESI and isothermal titration calorimetry (ITC). The inclusion of the derivatives on the macrocycle lends to an upward shift in the fluorescence intensity, and the pKa value of QD1-2 exhibits almost no variation after the formation of the complex. The thermodynamics of the inclusion complexes was investigated using ITC; the results demonstrate a non-classical hydrophobic effect with a minimum contribution from the entropy term and a constant binding on the order of 106 for both ligands. Additionally, dynamic molecular studies were carried out during 300 ns in an explicit solvent at NTP conditions. Our finding shows that the complex remains stable during the simulation (RMSD ~1 Å), and hydrogen bonds contribute to the stabilization of the systems. Finally, thermodynamic parameters from MMPBSA calculations were obtained to generate new computational insights to compare with experimental results.

Keywords: host-guest complexes, molecular dynamics, quinolin-2(1H)-one derivatives dyes, thermodynamics

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Authors: Kheira Hamaida, Mohamed Salah Halati

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In this current paper, our aim work is to link as possible the obtained simulation results and the other experimental ones, just focusing on the electronic and optical properties of ZnSe. The predictive spectra of the total and partial densities of states using the Full Potential Linearized/Augmented Plane Wave method with the newly Tran-Blaha (TB) modified Becke-Johnson (mBJ) exchange-correlation potential (EXC). So the upper valence energy (UVE) levels contain the relative contribution of Se-(4p and 3d) states with considerable contribution from the electrons of Zn-2s orbital. The dielectric function of w-ZnSe, with its two parts, appears with a noticeable anisotropy character. The microscopic origins of the electronic states that are responsible for the observed peaks in the spectrum are determined through the decomposition of the spectrum to the individual contributions of the electronic transitions between the pairs of bands, where Vi is an occupied state in the valence band, and Ci is an unoccupied state in the conduction band. X-PES (X Ray-Photo Electron Spectroscopy) is an important technique used to probe the homogeneity, stoichiometry, and purity state of the title compound. In order to check the electron transitions derived from simulations and the others from Reflected Electron Energy Loss Spectroscopy (REELS) technique which was of great sensitivity, is used to determine the interband electronic transitions. In the optical window (Eg), all the electron energy states created were also determined through the specific gaussian deconvolution of the photoluminescence spectrum (PLS) that probed under a room temperature (RT).

Keywords: spectroscopy, WIEN2K, IIB-VIA semiconductors, dielectric function

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Authors: Tae Jin Choi, Jong Ok Kim, Sang Min Jin, Gilwon Yoon

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Analysis of EEG brainwave provides information on mental or emotional states. One of the particular states that can have various applications in human machine interface (HMI) is concentration. 8-channel EEG signals were measured and analyzed. The concentration index was compared during resting and concentrating periods. Among eight channels, locations the frontal lobe (Fp1 and Fp2) showed a clear increase of the concentration index during concentration regardless of subjects. The rest six channels produced conflicting observations depending on subjects. At this time, it is not clear whether individual difference or how to concentrate made these results for the rest six channels. Nevertheless, it is expected that Fp1 and Fp2 are promising locations for extracting control signal for HMI applications.

Keywords: concentration, EEG, human machine interface, biophysical

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Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng

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Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.

Keywords: aging, hTERT, telomerase, telomeres, human cells

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Pedro Mario Gonzalez Jimenez

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The novelties introduced by the last Notice on agreements of minor importance tighten the application of the ‘De minimis’ safe harbour in the European Union. However, the undetermined legal concept of effect on trade between the Member States becomes importance at the same time. Therefore, the current analysis that the jurist should carry out in the European Union to determine if an agreement appreciably restrict competition under Article 101 of the Treaty on the Functioning of the European Union is double. Hence, it is necessary to know how to balance the significance in competition and the significance in effect on trade between the Member States. It is a crucial issue due to the negative delimitation of restriction of competition affects the positive one. The methodology of this research is rather simple. Beginning with a historical approach to the ‘De Minimis Rule’, their main problems and uncertainties will be found. So, after the analysis of normative documents and the jurisprudence of the Court of Justice of the European Union some proposals of ‘Lege ferenda’ will be offered. These proposals try to overcome the contradictions and questions that currently exist in the European Union as a consequence of the current legal regime of agreements of minor importance. The main findings of this research are the followings: Firstly, the effect on trade is another way to analyze the importance of an agreement different from the ‘De minimis rule’. In point of fact, this concept is singularly adapted to go through agreements that have as object the prevention, restriction or distortion of competition, as it is observed in the most famous European Union case-law. Thanks to the effect on trade, as long as the proper requirements are met there is no a restriction of competition under article 101 of the Treaty on the Functioning of the European Union, even if the agreement had an anti-competitive object. These requirements are an aggregate market share lower than 5% on any of the relevant markets affected by the agreement and turnover lower than 40 million of Euros. Secondly, as the Notice itself says ‘it is also intended to give guidance to the courts and competition authorities of the Member States in their application of Article 101 of the Treaty, but it has no binding force for them’. This reality makes possible the existence of different statements among the different Member States and a confusing perception of what a restriction of competition is. Ultimately, damage on trade between the Member States could be observed for this reason. The main conclusion is that the significant effect on trade between Member States is irrelevant in agreements that restrict competition because of their effects but crucial in agreements that restrict competition because of their object. Thus, the Member States should propose the incorporation of a similar concept in their legal orders in order to apply the content of the Notice. Otherwise, the significance of the restrictive agreement on competition would not be properly assessed.

Keywords: De minimis rule, effect on trade, minor importance agreements, safe harbour

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Authors: Nurudeen Oluwasola Lasisi, Abdulkareem Afolabi Ibrahim

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Newcastle disease is an infection of domestic poultry and other bird species with virulent Newcastle disease virus (NDV). In this paper, we study the dynamics of modeling the Newcastle disease virus (NDV) using a novel quarantine-adjusted incidence. We do a comparison of Vaccination, linear incident rate, and novel quarantine adjusted incident rate in the models. The dynamics of the models yield disease free and endemic equilibrium states. The effective reproduction numbers of the models are computed in order to measure the relative impact for the individual bird or combined intervention for effective disease control. We showed the local and global stability of endemic equilibrium states of the models, and we found that stability of endemic equilibrium states of models are globally asymptotically stable if the effective reproduction numbers of the models equations are greater than a unit.

Keywords: effective reproduction number, endemic state, mathematical model, Newcastle disease virus, novel quarantine-adjusted incidence, stability analysis

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Authors: Maryam Alimardani, Kazuo Hiraki

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This study presents a framework for development of a new generation of therapy robots that can interact with users by monitoring their physiological and mental states. Here, we focused on one of the controversial methods of therapy, hypnotherapy. Hypnosis has shown to be useful in treatment of many clinical conditions. But, even for healthy people, it can be used as an effective technique for relaxation or enhancement of memory and concentration. Our aim is to develop a robot that collects information about user’s mental and physical states using electroencephalogram (EEG) and electromyography (EMG) signals and performs costeffective hypnosis at the comfort of user’s house. The presented framework consists of three main steps: (1) Find the EEG-correlates of mind state before, during, and after hypnosis and establish a cognitive model for state changes, (2) Develop a system that can track the changes in EEG and EMG activities in real time and determines if the user is ready for suggestion, and (3) Implement our system in a humanoid robot that will talk and conduct hypnosis on users based on their mental states. This paper presents a pilot study in regard to the first stage, detection of EEG and EMG features during hypnosis.

Keywords: hypnosis, EEG, robotherapy, brain-computer interface (BCI)

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Authors: Osman Mohamed

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Over the past two decades, the global interest in the rights of persons with disabilities (PWDs) has increased that resulted in the United Nations Convention on the Rights of Persons with Disabilities (UNCRPWDs). In this regard, the Gulf States have witnessed remarkable efforts towards strengthening the rights of persons with disabilities, including enactment of laws and establishment of specialized government councils for the Persons with Disabilities. This study aims to highlight the efforts of Shafallah Foundation in strengthening the rights of persons with disabilities as a model for the Gulf States. The researcher will conduct interviews with officials at Shafallah Foundation, some persons with disabilities who have benefited from the Foundation's programmes, officials from government agencies related to Persons with disabilities. The study is expected to reveal the role of Shafallah Foundation in implementing the UNCRPWDs through its programmes and activities as well as an overview of the situation of the rights of PWDs in the Gulf States. The study is important for stakeholders, decision-makers, policy-makers, academics, and the disability’s organizations.

Keywords: GCC, Gulf Cooperation Council, Shafallah Foundation, UNCRPWDs, United Nations Convention on the Rights of Persons with Disabilities, PWDs, persons with disabilities

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Authors: Mastoor Qubra

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Cyber-attacks have frequently disrupted the critical infrastructures of the major global states and now, cyber threat has become one of the dire security risks for the states across the globe. Recently, ransomware cyber-attacks, wannacry and petya, have affected hundreds of thousands of computer servers and individuals’ private machines in more than hundred countries across Europe, Middle East, Asia, United States and Australia. Although, states are rapidly becoming aware of the destructive nature of this new security threat and counter measures are being taken but states’ isolated efforts would be inadequate to deal with this heinous security challenge, rather a global coordination and cooperation is inevitable in order to develop a credible cyber deterrence policy. Hence, the paper focuses that coordinated global approach is required to deter posed cyber threat. This paper intends to analyze the cyber security counter measures in four dimensions i.e. evaluation of prevalent strategies at bilateral level, initiatives and limitations for cooperation at global level, obstacles to combat cyber terrorism and finally, recommendations to deter the threat by applying tools of deterrence theory. Firstly, it focuses on states’ efforts to combat the cyber threat and in this regard, US-Australia Cyber Security Dialogue is comprehensively illustrated and investigated. Secondly, global partnerships and strategic and analytic role of multinational organizations, particularly United Nations (UN), to deal with the heinous threat, is critically analyzed and flaws are highlighted, for instance; less significance of cyber laws within international law as compared to other conflict prone issues. In addition to this, there are certain obstacles and limitations at national, regional and global level to implement the cyber terrorism counter strategies which are presented in the third section. Lastly, by underlining the gaps and grey areas in the current cyber security counter measures, it aims to apply tools of deterrence theory, i.e. defense, attribution and retaliation, in the cyber realm to contribute towards formulating a credible cyber deterrence strategy at global level. Thus, this study is significant in understanding and determining the inevitable necessity of counter cyber terrorism strategies.

Keywords: attribution, critical infrastructure, cyber terrorism, global cooperation

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: Shrawan Baghel, Helen Cathcart, Biall J. O'Reilly

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Amorphous drug formulations have great potential to enhance solubility and thus bioavailability of BCS class II drugs. However, the higher free energy and molecular mobility of the amorphous form lowers the activation energy barrier for crystallization and thermodynamically drives it towards the crystalline state which makes them unstable. Accurate determination of the crystallization tendency/kinetics is the key to the successful design and development of such systems. In this study, dipyridamole (DPM) and cinnarizine (CNZ) has been selected as model compounds. Thermodynamic fragility (m_T) is measured from the heat capacity change at the glass transition temperature (Tg) whereas dynamic fragility (m_D) is evaluated using methods based on extrapolation of configurational entropy to zero 〖(m〗_(D_CE )), and heating rate dependence of Tg 〖(m〗_(D_Tg)). The mean relaxation time of amorphous drugs was calculated from Vogel-Tammann-Fulcher (VTF) equation. Furthermore, the correlation between fragility and glass forming ability (GFA) of model drugs has been established and the relevance of these parameters to crystallization of amorphous drugs is also assessed. Moreover, the crystallization kinetics of model drugs under isothermal conditions has been studied using Johnson-Mehl-Avrami (JMA) approach to determine the Avrami constant ‘n’ which provides an insight into the mechanism of crystallization. To further probe into the crystallization mechanism, the non-isothermal crystallization kinetics of model systems was also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. In addition, the crystallization mechanism for DPM and CNZ at each extent of transformation has been predicted. The calculated fragility, glass forming ability (GFA) and crystallization kinetics is found to be in good correlation with the stability prediction of amorphous solid dispersions. Thus, this research work involves a multidisciplinary approach to establish fragility, GFA and crystallization kinetics as stability predictors for amorphous drug formulations.

Keywords: amorphous, fragility, glass forming ability, molecular mobility, mean relaxation time, crystallization kinetics, stability

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Authors: Altaf Ahmed

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Unhindered progress and advancement of life are directly associated with peace and development. Unfortunately, many modern states are prone to the perilous of social challenges; Violent Extremism is the most ubiquitous adversary among all. Islam in its origin fully supports peace and security; the charter of Madina, the treaty of Hudabia and conquer of Mecca are the biggest examples in this reference. The holy Prophet Muhammad ﷺ always gave priority to peace in these cases. Today, the majority of the Muslim World faces VE and terrorism due to multiple reasons ranging from religious interpretations to political, social and economic conditions. This research will try to explore challenges for Muslim Ummah in maintaining peace and what steps have been taken by it to resolve conflicts among states. In this context, Sustainable development goals (SDGs) will be particularly analysed. SDGs were adopted by all United Nations Member States in 2015. It is an undeniable fact that these are the best peace-building tools. Although there are 17 SDGs, the paper will mainly focus on quality education, zero hunger, end of poverty (social protection), women empowerment, reduced inequalities and economic growth as the best peace-building approaches for eradication of violent extremism.

Keywords: violent extremism, Muslim Ummah, peace, modern world, education

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Authors: Ugur Cihat Sakarya

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This research focuses on psychedelic trance music events in Turkey in the context of altered states of consciousness (ASC). The fieldwork that was conducted from 2018 to 2019 is the main source of the research. Participant observation method was followed in 15 selected events. To direct the musical experiences of participants, performances were also presented as a Dj. Ten of these events are open-air festivals. Five of them are indoor parties. The observations made during fieldwork and suitable answers for inference from the interviews with participants, artists, DJs, and volunteers were selected, compiled, and presented. In the result, findings showed that these activities are perceived as temporary autonomous areas by the participants both in time and space and that these activities are suitable areas for expressing themselves as a group (psyfamily) against mainstream culture. It has been observed that the elements that complement the altered states of consciousness in these events are music, visual arts, drug use, and desire to experience spiritual experiences. It is thought that this first academic study -about this topic in Turkey- will open a door for future researches.

Keywords: consciousness, psychedelic, psytrance, rave, Turkey

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Authors: S. Pradhan, V. Kumaran

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Centrifugal gas separation processes effect separation by utilizing the difference in the mole fraction in a high speed rotating cylinder caused by the difference in molecular mass, and consequently the centrifugal force density. These have been widely used in isotope separation because chemical separation methods cannot be used to separate isotopes of the same chemical species. More recently, centrifugal separation has also been explored for the separation of gases such as carbon dioxide and methane. The efficiency of separation is critically dependent on the secondary flow generated due to temperature gradients at the cylinder wall or due to inserts, and it is important to formulate accurate models for this secondary flow. The widely used Onsager model for secondary flow is restricted to very long cylinders where the length is large compared to the diameter, the limit of high stratification parameter, where the gas is restricted to a thin layer near the wall of the cylinder, and it assumes that there is no mass difference in the two species while calculating the secondary flow. There are two objectives of the present analysis of the rarefied gas flow in a rotating cylinder. The first is to remove the restriction of high stratification parameter, and to generalize the solutions to low rotation speeds where the stratification parameter may be O (1), and to apply for dissimilar gases considering the difference in molecular mass of the two species. Secondly, we would like to compare the predictions with molecular simulations based on the direct simulation Monte Carlo (DSMC) method for rarefied gas flows, in order to quantify the errors resulting from the approximations at different aspect ratios, Reynolds number and stratification parameter. In this study, we have obtained analytical and numerical solutions for the secondary flows generated at the cylinder curved surface and at the end-caps due to linear wall temperature gradient and external gas inflow/outflow at the axis of the cylinder. The effect of sources of mass, momentum and energy within the flow domain are also analyzed. The results of the analytical solutions are compared with the results of DSMC simulations for three types of forcing, a wall temperature gradient, inflow/outflow of gas along the axis, and mass/momentum input due to inserts within the flow. The comparison reveals that the boundary conditions in the simulations and analysis have to be matched with care. The commonly used diffuse reflection boundary conditions at solid walls in DSMC simulations result in a non-zero slip velocity as well as a temperature slip (gas temperature at the wall is different from wall temperature). These have to be incorporated in the analysis in order to make quantitative predictions. In the case of mass/momentum/energy sources within the flow, it is necessary to ensure that the homogeneous boundary conditions are accurately satisfied in the simulations. When these precautions are taken, there is excellent agreement between analysis and simulations, to within 10 %, even when the stratification parameter is as low as 0.707, the Reynolds number is as low as 100 and the aspect ratio (length/diameter) of the cylinder is as low as 2, and the secondary flow velocity is as high as 0.2 times the maximum base flow velocity.

Keywords: rotating flows, generalized onsager and carrier-Maslen model, DSMC simulations, rarefied gas flow

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Authors: Deepshikha Verma, V. N. Rajasekharan Pillai

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The present study reports the synthesis of cyclic PNC-28 peptides with solid-phase peptide synthesis method. In the first step, we synthesize the linear PNC-28 Peptide and in the second step, we cyclize (N-to-C or head-to-tail cyclization) the linear PNC-28 peptide. The molecular formula of cyclic PNC-28 peptide is C64H88N12O16 and its m/z mass is ≈1233.64. Elemental analysis of cyclic PNC-28 is C, 59.99; H, 6.92; N, 13.12; O, 19.98. The characterization of LC-MS, CD, FT-IR, and 1HNMR has been done to confirm the successful synthesis and cyclization of linear PNC-28 peptides.

Keywords: CD, FTIR, 1HNMR, cyclic peptide

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Authors: Ranadhir Roy

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Inverse problems arise in medical (molecular) imaging. These problems are characterized by large in three dimensions, and by the diffusion equation which models the physical phenomena within the media. The inverse problems are posed as a nonlinear optimization where the unknown parameters are found by minimizing the difference between the predicted data and the measured data. To obtain a unique and stable solution to an ill-posed inverse problem, a priori information must be used. Mathematical conditions to obtain stable solutions are established in Tikhonov’s regularization method, where the a priori information is introduced via a stabilizing functional, which may be designed to incorporate some relevant information of an inverse problem. Effective determination of the Tikhonov regularization parameter requires knowledge of the true solution, or in the case of optical imaging, the true image. Yet, in, clinically-based imaging, true image is not known. To alleviate these difficulties we have applied the penalty/modified barrier function (PMBF) method instead of Tikhonov regularization technique to make the inverse problems well-posed. Unlike the Tikhonov regularization method, the constrained optimization technique, which is based on simple bounds of the optical parameter properties of the tissue, can easily be implemented in the PMBF method. Imposing the constraints on the optical properties of the tissue explicitly restricts solution sets and can restore uniqueness. Like the Tikhonov regularization method, the PMBF method limits the size of the condition number of the Hessian matrix of the given objective function. The accuracy and the rapid convergence of the PMBF method require a good initial guess of the Lagrange multipliers. To obtain the initial guess of the multipliers, we use a least square unconstrained minimization problem. Three-dimensional images of fluorescence absorption coefficients and lifetimes were reconstructed from contact and noncontact experimentally measured data.

Keywords: constrained minimization, ill-conditioned inverse problems, Tikhonov regularization method, penalty modified barrier function method

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Authors: Stacie Nelson Colling, Adele Cummings

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The United States Supreme Court recently announced that it is unconstitutional to sentence a child to life without parole for non-homicide offenses, and that each child so situated must be afforded a meaningful opportunity for release from prison in his lifetime. The Court also declared that it is unconstitutional to impose a mandatory sentence of life without parole on a child for homicide offenses. Across the United States, attorneys and advocates continue to litigate issues surrounding the implementation of these legal principles. Some states have held that any sentence to a finite term of years, no matter how long, is not the same as ‘life’ and therefore does not violate the constitution. Other states have held that a sentence to a term of years that is less than the expected life of that particular child is not unconstitutional. In Colorado, the courts have routinely looked to life expectancy estimates from governmental organizations to determine how long a particular child is expected to live. They then compare that the date that the child is expected to be eligible for parole, and if the child is expected to still be living when he is eligible for parole, the sentence is deemed constitutional. This paper argues that it is inappropriate, reckless, unconstitutional and not scientifically sound to use such estimates in determining whether a child will have a meaningful opportunity for release from prison and life outside of prison before he dies. This paper argues that the opportunity for release must mean more than a probability that a child will be released before his death, and that it must include an opportunity for a meaningful life outside of prison (not just the opportunity to be released and then die on the outside). The paper further argues that life expectancy estimates cannot guide a court or a legislature in determining whether a sentence is or is not constitutional.

Keywords: life without parole, life expectancy, juvenile sentencing, meaningful opportunity for release from prison

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Authors: Murat Sengoz, Mustafa Kemal Topcu

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This study aims to contribute to efforts of Turkey to increase research and development to overcome mid-income level trap by discussing regulations on patenting and licensing. Knowledge and technology transfer from universities to business world is attached great significance to increase innovation. Through literature survey, it is observed that the States accomplished to boost the economy and increase welfare by the Bayh-Dole Act enacted in 1980. Thus, this good practice is imitated by other nations to make technological developments. The Act allows universities to acquire patent right in research programs funded by government to increase technology transfer from universities whilst motivating real sector to use research pools in the universities. An act similar with Bayh-Dole could be beneficial to Turkey since efforts in Turkey are to promote research, development and innovation. Towards this end, the impact of Bayh-Dole Act on the patent system for universities in the Sates is deliberately examined, applicability in Turkey is discussed. However, it is conceded that success rate of applying Bayh-Dole Act in Turkey would be low once Turkey mainly differs from the States regarding social, economic and cultural traits.

Keywords: Bayh-Dole Act, knowledge transfer, license, patent, spin-off

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Authors: Yunus Onur Yildiz, Mesut Kirca

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In this study, mechanical properties of a nanoporous metal coated with a different metallic material are studied through a new atomistic modelling technique and molecular dynamics (MD) simulations. This new atomistic modelling technique is based on the Voronoi tessellation method for the purpose of geometric representation of the ligaments. With the proposed technique, atomistic models of nanoporous metals which have randomly oriented ligaments with non-uniform mass distribution along the ligament axis can be generated by enabling researchers to control both ligament length and diameter. Furthermore, by the utilization of this technique, atomistic models of coated nanoporous materials can be numerically obtained for further mechanical or thermal characterization. In general, this study consists of two stages. At the first stage, we use algorithms developed for generating atomic coordinates of the coated nanoporous material. In this regard, coordinates of randomly distributed points are determined in a controlled way to be employed in the establishment of the Voronoi tessellation, which results in randomly oriented and intersected line segments. Then, line segment representation of the Voronoi tessellation is transformed to atomic structure by a special process. This special process includes generation of non-uniform volumetric core region in which atoms can be generated based on a specific crystal structure. As an extension, this technique can be used for coating of nanoporous structures by creating another volumetric region encapsulating the core region in which atoms for the coating material are generated. The ultimate goal of the study at this stage is to generate atomic coordinates that can be employed in the MD simulations of randomly organized coated nanoporous structures. At the second stage of the study, mechanical behavior of the coated nanoporous models is investigated by examining deformation mechanisms through MD simulations. In this way, the effect of coating on the mechanical behavior of the selected material couple is investigated.

Keywords: atomistic modelling, molecular dynamic, nanoporous metals, voronoi tessellation

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Authors: Jeongil Kim

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The present study examined the effects of arts-mediated mother-child dyads mindfulness-based intervention for Korean children with attention deficit hyperactivity disorder (ADHD) and their mothers, on behaviors in children and subjective psychological states in mothers. Four elementary school boys with ADHD and their mothers participated in the study. Using a multiple baseline design across four mother-child dyads, data were collected on the target behaviors (disruptive behavior, on-task behavior, and compliance in class) in children using a 10-second partial interval recording system and on the subjective psychological states in mothers using four questionnaires (on perceived stress, burnout, mindfulness, and satisfaction with life). The intervention consisted of a) mindfulness training, b) mindfulness practice, and c) mindful management of body and feeling. The arts activities, making a coiled clay pot and Korean traditional music performance, were utilized to facilitate the environment to help each participant to understand the content and progress of the intervention program. The results showed that all four dyads showed improvement in adaptive behaviors in the children (increase in on-task behavior; decrease in disruptive behavior) and positive change in subjective psychological states in the mothers (increase in scores of mindfulness and satisfaction with life; decrease in scores of perceived stress and burnout). The changes in the children’s behaviors and in the mothers’ subjective psychological states were maintained when the intervention was drawn and generalized in novel settings. The results suggest that arts-mediated mother-child dyads mindfulness-based intervention would be a mutual benefiting strategy to support both children with ADHD and their mothers who experience diverse challenges in behavioral and psychological aspects.

Keywords: mindfulness, attention deficit hyperactivity disorder (ADHD), arts-mediated, behavior, psychological well-being, child-mother

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Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji

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Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.

Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking

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Authors: Mona Alharbi

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Melioidosis has emerged as a lethal disease. Unfortunately, the molecular mechanisms of virulence and pathogenicity of Burkholderia pseudomallei remain unknown. However, proteomics research has selected putative targets in B. pseudomallei that might play roles in the B. pseudomallei virulence. BPSL 2418 putative protein has been predicted as a free methionine sulfoxide reductase and interestingly there is a link between the level of the methionine sulfoxide in pathogen tissues and its virulence. Therefore in this work, we describe the cloning expression, purification, and crystallization of BPSL 2418 and the solution of its 3D structure using X-ray crystallography. Also, we aimed to identify the substrate binding and reduced forms of the enzyme to understand the role of BPSL 2418. The gene encoding BPSL2418 from B. pseudomallei was amplified by PCR and reclone in pETBlue-1 vector and transformed into E. coli Tuner DE3 pLacI. BPSL2418 was overexpressed using E. coli Tuner DE3 pLacI and induced by 300μM IPTG for 4h at 37°C. Then BPS2418 purified to better than 95% purity. The pure BPSL2418 was crystallized with PEG 4000 and PEG 6000 as precipitants in several conditions. Diffraction data were collected to 1.2Å resolution. The crystals belonged to space group P2 21 21 with unit-cell parameters a = 42.24Å, b = 53.48Å, c = 60.54Å, α=γ=β= 90Å. The BPSL2418 binding MES was solved by molecular replacement with the known structure 3ksf using PHASER program. The structure is composed of six antiparallel β-strands and four α-helices and two loops. BPSL2418 shows high homology with the GAF domain fRMsrs enzymes which suggest that BPSL2418 might act as methionine sulfoxide reductase. The amino acids alignment between the fRmsrs including BPSL 2418 shows that the three cysteines that thought to catalyze the reduction are fully conserved. BPSL 2418 contains the three conserved cysteines (Cys⁷⁵, Cys⁸⁵ and Cys¹⁰⁹). The active site contains the six antiparallel β-strands and two loops where the disulfide bond formed between Cys⁷⁵ and Cys¹⁰⁹. X-ray structure of free methionine sulfoxide binding and native forms of BPSL2418 were solved to increase the understanding of the BPSL2418 catalytic mechanism.

Keywords: X-Ray Crystallography, BPSL2418, Burkholderia pseudomallei, Melioidosis

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Authors: Ly Nguyen, Vidit Munshi

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During the Covid-19 recession, the United States government has implemented several instruments to mitigate the impacts and revitalize the economy. This paper explores the effects of the various government policy decisions on stock returns, housing prices, and investor psychology during the pandemic in the United States. A numerous previous literature studies on this subject, yet very few focus on the context similar to what we are currently experiencing. Our monthly data covering the period from January 2019 through July 2021 were collected from Datastream. Utilizing the VAR model, we document a dynamic relationship between the market and policy actions throughout the period. In particular, the movements of Unemployment, Stock returns, and Housing prices are strongly sensitive to changes in government policies. Our results also indicate that changes in production level, stock returns, and interest rates decisions influence how investors perceived future market risk and expectations. We do not find any significant nexus between monetary and fiscal policy. Our findings imply that information on government policy and stock market performance provide useful feedback to one another in order to make better decisions in the current and future pandemic. Understanding how the market responds to a shift in government practices has important implications for authorities in implementing policy to avoid assets bubbles and market overreactions. The paper also provides useful implications for investors in evaluating the effectiveness of different policies and diversifying portfolios to minimize systematic risk and maximize returns.

Keywords: Covid-19 recession, United States, government policies, investor psychology, housing prices, stock market returns

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Authors: Ayyoub Jamali

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At the first glance, it seems that the African Court on Human and People’s Rights has achieved a tremendous development in the protection of human rights in Africa. Since its first judgement in 2009, the court has taken a robust approach/ assertive stance, showing its strength by finding states to be in violation of the Africana Charter and other human rights treaties. This paper seeks to discuss various challenges and resistance that the Court has faced since the adoption of the Founding Protocol to the Establishment of the African Court on Human and People’s Rights. The outcome of the paper casts shadow on the legitimacy and effectiveness of the African Court as the guarantor of human rights within the African continent.

Keywords: African Court on Human and People’s Rights, African Union, African regional human rights system, compliance

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Authors: S. Ramia, N. Melhem, K. Kreidieh

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The world is facing an unprecedented displacement crisis. Recently, over 1.1 million asylum seekers have been granted protection status in the European Union (EU). The majority of these asylum seekers were from countries of the Middle East and North Africa (MENA) region.This influx carries with it a potential introduction of infectious diseases that have been eliminated in the EU, which poses a challenge for EU health authorities. Compared to MENA region countries where Hepatitis A Virus (HAV) endemicity is high to intermediate, member states of the EU show very low (Western Europe) to low (Eastern Europe) levels of HAV endemicity. Because of this situation, there is an ongoing public health concern in high-income countries, like members of the EU, that many adults remain susceptible to HAV outbreaks. The overwhelming majority of the EU members’ states do not include HAV vaccine in their immunization calendars. Hence, this paper urgently calls for the implementation of new policies regarding HAV in EU members’ states.

Keywords: European union, hepatitis A, MENA region refugees, vaccine preventable diseases

Procedia PDF Downloads 263