Search results for: holographic replication

Authors: Fouzia Perveen, Rumana Qureshi

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The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

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Authors: Ahmed Mahmoud Ahmed Abouelmagd

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The diversity is the usual remedy of the transmitted signal level variations (Fading phenomena) in radio frequency channels. Diversity techniques utilize two or more copies of a signal and combine those signals to combat fading. The basic concept of diversity is to transmit the signal via several independent diversity branches to get independent signal replicas via time – frequency - space - and polarization diversity domains. Coding and decoding processes can be an alternative remedy for fading phenomena, it cannot increase the channel capacity, but it can improve the error performance. In this paper we propose the use of replication decoding with BCH code class, and Viterbi decoding algorithm with convolution coding; as examples of coding and decoding processes. The results are compared to those obtained from two optimized selection space diversity techniques. The performance of Rayleigh fading channel, as the model considered for radio frequency channels, is evaluated for each case. The evaluation results show that the coding and decoding approaches, especially the BCH coding approach with replication decoding scheme, give better performance compared to that of selection space diversity optimization approaches. Also, an approach for combining the coding and decoding diversity as well as the space diversity is considered, the main disadvantage of this approach is its complexity but it yields good performance results.

Keywords: Rayleigh fading, diversity, BCH codes, Replication decoding, ‎convolution coding, viterbi decoding, space diversity

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Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

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The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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Authors: Michael Nicolosi, Karola Dillenburger

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The University of California at Los Angeles-Young Autism Project (UCLA-YAP) provides one of the best-known and most researched comprehensive applied behavior analysis-based intervention models for young children on the autism spectrum. This paper reports a systematic literature review of replication studies over more than 30 years. The data show that the relatively high-intensity UCLA-YAP model can be greatly beneficial for children on the autism spectrum, particularly with regard to their cognitive functioning and adaptive behavior. This review concludes that, while more research is always welcome, the impact of the UCLA-YAP model on autism interventions is justified by more than 30 years of outcome evidence.

Keywords: ABA, applied behavior analysis, autism, California at Los Angeles Young Autism project, intervention, Lovaas, UCLA-YAP

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Authors: Ahmad S. Mohd Noor, Emma A. Sirajudin, Nur F. Mat Zain

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Reliability is an important property for knowledge repository system. National Marine Bioinformatics System or NABTICS is a marine knowledge repository portal aimed to provide a baseline for marine biodiversity and a tool for researchers and developers. It is intended to be a large and growing online database and also a metadata system for inputs of research analysis. The trends of present large distributed systems such as Cloud computing are the delivery of computing as a service rather than a product. The goal of this research is to make NABTICS a system of greater availability by integrating it with Cloud based Neighbor Replication and Failure Recovery (NRFR). This can be achieved by implementation of NABTICS into distributed environment. As a result, the user can experience minimum downtime while using the system should the server is having a failure. Consequently the online database application is said to be highly available.

Keywords: cloud, availability, distributed system, marine repository, database replication

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Authors: Jehad Al Dallal

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Software engineers apply different measures to quantify the quality of software design. These measures consider artifacts developed at low or high level software design phases. The results are used to point to design weaknesses and to indicate design points that have to be restructured. Understanding the relationship among the quality measures and among the design quality aspects considered by these measures is important to interpreting the impact of a measure for a quality aspect on other potentially related aspects. In addition, exploring the relationship between quality measures helps to explain the impact of different quality measures on external quality aspects, such as reliability and maintainability. In this paper, we report a replication study that empirically explores the correlation between six well known and commonly applied design quality measures. These measures consider several quality aspects, including complexity, cohesion, coupling, and inheritance. The results indicate that inheritance measures are weakly correlated to other measures, whereas complexity, coupling, and cohesion measures are mostly strongly correlated.  

Keywords: quality attribute, quality measure, software design quality, Spearman correlation

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Authors: Biki Sarmah, Priyanko Raj Mudiar

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In the modern world of remotely interactive virtual reality-based learning and teaching, including professional skill-building training and acquisition practices, as well as data acquisition and robotic systems, the revolutionary application or implementation of field-programmable neurostimulator aids and first-hand interactive sensitisation techniques into 3D holographic audio-visual platforms have been a coveted dream of many scholars, professionals, scientists, and students. Integration of 'kinaesthetic vibrotactile haptic perception' along with an actuated step magnitude contact profiloscopy in augmented reality-based learning platforms and professional training can be implemented by using an extremely calculated and well-coordinated image telemetry including remote data mining and control technique. A real-time, computer-aided (PLC-SCADA) field calibration based algorithm must be designed for the purpose. But most importantly, in order to actually realise, as well as to 'interact' with some 3D holographic models displayed over a remote screen using remote laser image telemetry and control, all spatio-physical parameters like cardinal alignment, gyroscopic compensation, as well as surface profile and thermal compositions, must be implemented using zero-order type 1 actuators (or transducers) because they provide zero hystereses, zero backlashes, low deadtime as well as providing a linear, absolutely controllable, intrinsically observable and smooth performance with the least amount of error compensation while ensuring the best ergonomic comfort ever possible for the users.

Keywords: haptic feedback, kinaesthetic vibrotactile 3D design, medical simulation training, piezo diaphragm based actuator

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Authors: Ákos Tótin

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In crop production the most modern hybrids are available for us, therefore the yield and yield stability is determined by the agro-technology. The purpose of the experiment is to adapt the modern agrotechnology to the new type of hybrids. The long-term experiment was set up in 2015-2016 on chernozem soil in the Hajdúság (eastern Hungary). The plots were set up in 75 thousand ha-1 plant density. We examined some mainly use hybrids of Hungary. The conducted studies are: germination dynamic, growing dynamic and the effect of annual weather for the yield. We use three different sowing date as early, average and late, and measure how many plant germinated during the germination process. In the experiment, we observed the germination dynamics in 6 hybrid in 4 replication. In each replication, we counted the germinated plants in 2m long 2 row wide area. Data will be shown in the average of the 6 hybrid and 4 replication. Growing dynamics were measured from the 10cm (4-6 leaf) plant highness. We measured 10 plants’ height in two weeks replication. The yield was measured buy a special plot harvester - the Sampo Rosenlew 2010 – what measured the weight of the harvested plot and also took a sample from it. We determined the water content of the samples for the water release dynamics. After it, we calculated the yield (t/ha) of each plot at 14% of moisture content to compare them. We evaluated the data using Microsoft Excel 2015. The annual weather in each crop year define the maize germination dynamics because the amount of heat is determinative for the plants. In cooler crop year the weather is prolonged the germination. At the 2015 crop year the weather was cold in the beginning what prolonged the first sowing germination. But the second and third sowing germinated faster. In the 2016 crop year the weather was much favorable for plants so the first sowing germinated faster than in the previous year. After it the weather cooled down, therefore the second and third sowing germinated slower than the last year. The statistical data analysis program determined that there is a significant difference between the early and late sowing date growing dynamics. In 2015 the first sowing date had the highest amount of yield. The second biggest yield was in the average sowing time. The late sowing date has lowest amount of yield.

Keywords: germination, maize, sowing date, yield

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Authors: Kaddi Mohammed, A. Benatiallah, D. Benatiallah

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Data grid is a technology that has full emergence of new challenges, such as the heterogeneity and availability of various resources and geographically distributed, fast data access, minimizing latency and fault tolerance. Researchers interested in this technology address the problems of the various systems related to the industry such as task scheduling, load balancing and replication. The latter is an effective solution to achieve good performance in terms of data access and grid resources and better availability of data cost. In a system with duplication, a coherence protocol is used to impose some degree of synchronization between the various copies and impose some order on updates. In this project, we present an approach for placing replicas to minimize the cost of response of requests to read or write, and we implement our model in a simulation environment. The placement techniques are based on a cost model which depends on several factors, such as bandwidth, data size and storage nodes.

Keywords: response time, query, consistency, bandwidth, storage capacity, CERN

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Authors: Chung-Young Lee, Se-Hee Ahn, Ilhwan Kim, Du-Min Go, Dae-Yong Kim, Jun-Gu Choi, Youn-Jeong Lee, Jae-Hong Kim, Hyuk-Joon Kwon

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The polymerase of avian influenza A virus (AIV) is a heterotrimer composed of PB2, PB1 and PA. PB2 plays a role in overcoming the host barrier; however, the genetic prerequisites for avian PB2 to acquire mammalian pathogenic mutations have not been well elucidated. Here, we demonstrated that key amino acid mutations (I66M, I109V and I133V, collectively referred to as MVV) of prototypic avian PB2 increase the replication efficiency of recombinant PR8 virus carrying the mutated PB2 in both avian and mammalian hosts. The MVV mutations caused no weight loss in mice, but they did allow replication in infected lungs, and the viruses acquired fatal mammalian pathogenic mutations such as Q591R/K, E627K, or D701N in the infected lungs. The MVV mutations are located at the interfaces of the trimer and are predicted to increase the strength of this structure. Thus, gaining MVV mutations might be the first step for AIV to acquire mammalian pathogenicity. These results provide new insights into the evolution of AIV in birds and mammals.

Keywords: avian influenza A virus, prototypic PB2, polymerase activity, mammalian pathogenicity, first-step mutations

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Authors: Parampal Kaur, Deepak Aggarwal

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In the computational Grid, fault tolerance is an imperative issue to be considered during job scheduling. Due to the widespread use of resources, systems are highly prone to errors and failures. Hence, fault tolerance plays a key role in the grid to avoid the problem of unreliability. Scheduling the task to the appropriate resource is a vital requirement in computational Grid. The fittest resource scheduling algorithm searches for the appropriate resource based on the job requirements, in contrary to the general scheduling algorithms where jobs are scheduled to the resources with best performance factor. The proposed method is to improve the fault tolerance of the fittest resource scheduling algorithm by scheduling the job in coordination with job replication when the resource has low reliability. Based on the reliability index of the resource, the resource is identified as critical. The tasks are scheduled based on the criticality of the resources. Results show that the execution time of the tasks is comparatively reduced with the proposed algorithm using real-time approach rather than a simulator.

Keywords: computational grid, fault tolerance, task replication, job scheduling

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Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: Ahmad Shukri Mohd Noor, Emma Ahmad Sirajudin, Rabiei Mamat

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Pertaining to a particular Marine interest, the process of data sampling could take years before a study can be concluded. Therefore, the need for a robust backup system for the data is invariably implicit. In recent advancement of Marine applications, more functionalities and tools are integrated to assist the work of the researchers. It is anticipated that this modality will continue as research scope widens and intensifies and at the same to follow suit with current technologies and lifestyles. The convenience to collect and share information these days also applies to the work in Marine research. Therefore, Marine system designers should be aware that high availability is a necessary attribute in Marine repository applications as well as a robust backup system for the data. In this paper, the approach to high availability is related both to hardware and software but the focus is more on software. We consider a NABTIC repository system that is primitively built on a single server and does not have replicated components. First, the system is decomposed into separate modules. The modules are placed on multiple servers to create a distributed system. Redundancy is added by placing the copies of the modules on different servers using Neighbor Caring Environment System(NCES) technique. NCER is utilizing parallel replication components mechanism. A background monitoring is established to check servers’ heartbeats to confirm their aliveness. At the same time, a critical adaptive threshold is maintained to make sure a failure is timely detected using Adaptive Fault Detection (AFD). A confirmed failure will set the recovery mode where a selection process will be done before a fail-over server is instructed. In effect, the Marine repository service is continued as the fail-over masks a recent failure. The performance of the new prototype is tested and is confirmed to be more highly available. Furthermore, the downtime is not noticeable as service is immediately restored automatically. The Marine repository system is said to have achieved fault tolerance.

Keywords: availability, fault detection, replication, fault tolerance, marine application

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Authors: José Silvestre Mendoza Figueroa, Anders Kvarnheden, Jesús Méndez Lozano, Edgar Antonio Rodríguez Negrete, Manuel Soriano García

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Agroindustrial plants such as cereals and pseudo cereals offer a substantial source of biomacromolecules, as they contain large amounts per tissue-gram of proteins, polysaccharides and lipids in comparison with other plants. In particular, Amaranthus hypochondriacus seeds have high levels of proteins in comparison with other cereal and pseudo cereal species, which makes the plant a good source of bioactive molecules such as peptides. Geminiviruses are one principal class of pathogens that causes important economic losses in crops, affecting directly the development and production of the plant. One such virus is the Tomato yellow leaf curl virus (TYLCV), which affects mainly Solanacea family plants such as tomato species. The symptoms of the disease are curling of leaves, chlorosis, dwarfing and floral abortion. The aim of this work was to get peptides derived from enzymatic hydrolysis of globulins and albumins from amaranth seeds with specific recognition of the replication origin in the TYLCV genome, and to test the antiviral activity on host plants with the idea to generate a direct control of this viral infection. Globulins and albumins from amaranth were extracted, the fraction was enzymatically digested with papain, and the aromatic peptides fraction was selected for further purification. Six peptides were tested against the replication origin (OR) using affinity assays, surface resonance plasmon and fluorescent titration, and two of these peptides showed high affinity values to the replication origin of the virus, dissociation constant values were calculated and showed specific interaction between the peptide Ampep1 and the OR. An in vitro replication test of the total TYLCV DNA was performed, in which the peptide AmPep1 was added in different concentrations to the system reaction, which resulted in a decrease of viral DNA synthesis when the peptide concentration increased. Also, we showed that the peptide can decrease the complementary DNA chain of the virus in Nicotiana benthamiana leaves, confirming that the peptide binds to the OR and that its expected mechanism of action is to decrease the replication rate of the viral genome. In an infection assay, N. benthamiana plants were agroinfected with TYLCV-Israel and TYLCV-Guasave. After confirming systemic infection, the peptide was infiltrated in new infected leaves, and the plants treated with the peptide showed a decrease of virus symptoms and viral titer. In order to confirm the antiviral activity in a commercial crop, tomato plants were infected with TYLCV. After confirming systemic infection, plants were infiltrated with peptide solution as above, and the symptom development was monitored 21 days after treatment, showing that tomato plants treated with peptides had lower symptom rates and viral titer. The peptide was also tested against other begomovirus such as Pepper huasteco yellow vein virus (PHYVV-Guasave), showing a decrease of symptoms in N. benthamiana infected plants. The model of direct biochemical control of TYLCV infection shown in this work can be extrapolated to other begomovirus infections, and the methods reported here can be used for design of antiviral agrochemicals for other plant virus infections.

Keywords: agrochemical screening, antiviral, begomovirus, geminivirus, peptides, plasmon, TYLCV

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Authors: Pavel Psota, Vít Lédl, Jan Václavík, Roman Doleček, Pavel Mokrý, Petr Vojtíšek

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This paper presents advanced time average digital holography by means of frequency shift and phase modulation. This technique can measure amplitudes of vibrations at ultimate dynamic range while the amplitude distribution evaluation is done independently in every pixel. The main focus of the paper is to gain insight into behavior of the method at low amplitudes of vibrations. In order to reach that, a set of experiments was performed. Results of the experiments together with novel noise suppression show the limit of the method to be below 0.1 nm.

Keywords: acusto-optical modulator, digital holography, low amplitudes, vibrometry

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Authors: Marthese Azzopardi, Liberato Camilleri

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This research was performed to investigate the study habits and level of difficulty perceived by post-secondary students in Biology at Advanced-level topics after completing their first year of study. At the end of a two-year ‘sixth form’ course, Maltese students sit for the Matriculation and Secondary Education Certificate (MATSEC) Advanced-level biology exam as a requirement to pursue science-related studies at the University of Malta. The sample was composed of 23 students (16 taking Chemistry and seven taking some ‘Other’ subject at the Advanced Level). The cohort comprised seven males and 16 females. A questionnaire constructed by the authors, was answered anonymously during the last lecture at the end of the first year of study, in May 2016. The Chi square test revealed that gender plays no effect on the various study habits (c² (6) = 5.873, p = 0.438). ‘Reading both notes and textbooks’ was the most common method adopted by males (71.4%), whereas ‘Writing notes on each topic’ was that mostly used by females (81.3%). The Mann-Whitney U test showed no significant difference in the study habits of students and the mean assessment mark obtained at the end of the first year course (p = 0.231). Statistical difference was found with the One-ANOVA test when comparing the mean assessment mark obtained at the end of the first year course when students are clustered by their Secondary Education Certificate (SEC) grade (p < 0.001). Those obtaining a SEC grade of 2 and 3 got the highest mean assessment of 68.33% and 66.9%, respectively [SEC grading is 1-7, where 1 is the highest]. The Friedman test was used to compare the mean difficulty rating scores provided for the difficulty of each topic. The mean difficulty rating score ranges from 1 to 4, where the larger the mean rating score, the higher the difficulty. When considering the whole group of students, nine topics out of 21 were perceived as significantly more difficult than the other topics. Protein synthesis, DNA Replication and Biomolecules were the most difficult, in that order. The Mann-Whitney U test revealed that the perceived level of difficulty in comprehending Biomolecules is significantly lower for students taking Chemistry compared to those not choosing the subject (p = 0.018). Protein Synthesis was claimed as the most difficult by Chemistry students and Biomolecules by those not studying Chemistry. DNA Replication was the second most difficult topic perceived by both groups. The Mann-Whitney U test was used to examine the effect of gender on the perceived level of difficulty in comprehending various topics. It was found that females have significantly more difficulty in comprehending Biomolecules than males (p=0.039). Protein synthesis was perceived as the most difficult topic by males (mean difficulty rating score = 3.14), while Biomolecules, DNA Replication and Protein synthesis were of equal difficulty for females (mean difficulty rating score = 3.00). Males and females perceived DNA Replication as equally difficult (mean difficulty rating score = 3.00). Discovering the students’ study habits and perceived level of difficulty of specific topics is vital for the lecturer to offer guidance that leads to higher academic achievement.

Keywords: biology, perceived difficulty, post-secondary, study habits

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Authors: Manouchehr Amiri

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This article introduces a general notion of physical bit information that is compatible with the basics of quantum mechanics and incorporates the Shannon entropy as a special case. This notion of physical information leads to the Binary data matrix model (BDM), which predicts the basic results of quantum mechanics, general relativity, and black hole thermodynamics. The compatibility of the model with holographic, information conservation, and Landauer’s principles are investigated. After deriving the “Bit Information principle” as a consequence of BDM, the fundamental equations of Planck, De Broglie, Beckenstein, and mass-energy equivalence are derived.

Keywords: physical theory of information, binary data matrix model, Shannon information theory, bit information principle

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Authors: Ren-Jye Lin, Li-Hsiung Lin, Bing-Cheng Liu, Ching-Len Liao

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The human zinc finger protein 36-like protein family, containing zinc finger protein 36-like 1 (ZFP36L1) and zinc finger protein 36-like 2 (ZFP36L2), belongs to CCCH-type zinc-finger protein identified as an RNA-binding protein that participates in controlling posttranscriptional regulation via RNA decay pathways. Recently, we demonstrated that human ZFP36L1 showed potent antiviral activity against flavivirus Infection by both 5´-3´ XRN1 and 3´-5´RNA-exosome RNA decay pathways (Journal of Virology 2022 Jan 12;96(1): e0166521). However, another zinc finger protein 36-like protein member, ZFP36L2, in the host defense response against flaviviruses has yet to be addressed. Here, we also demonstrate that ZFP36L2 functions as a host innate defender against flaviviruses, including Japanese encephalitis virus (JEV) and dengue virus (DENV). Overexpression of ZFP36L2 reduced JEV and DENV infection, and ZFP36L2 knockdown significantly promoted viral replication. Distinct from the antiviral mechanism of ZFP36L1, ZFP36L2 inhibits flavivirus infection by only a 5´-3´ XRN1-mediated RNA decay pathway but not the 3´-5´RNA-exosome RNA decay pathway. Human ZFP36L1 and ZFP36L2 can restrict flavivirus replication by directly binding and destabilizing viral RNA. Thus, for the first time, human zinc finger protein 36-like family members, ZFP36L1 and ZFP36L2, are identified as host antiviral factors that can bind and degrade flavivirus viral RNA by diverse antiviral mechanisms.

Keywords: ZFP36L1, ZFP36L2, 5'-3' exonuclease XRN1, antiviral mechansim

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Authors: Jiun-Nan Hou, Tien-Huang Chen, Wei-June Chen

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Dengue viruses (DENVs) are naturally transmitted between humans by mosquito vectors. Mosquito cells usually survive DENV infection, allowing infected mosquitoes to retain an active status for virus transmission. In this study, we found that DENV2 virus infection in mosquito cells causes the unfolded protein response (UPR) that activates the protein kinase RNA-like endoplasmic reticulum kinase (PERK) signal pathway, leading to shutdown of global protein translation in infected cells which was apparently regulated by the PERK signal pathway. According to observation in this study, the PERK signal pathway in DENV2-infected C6/36 cells alleviates ER stress, and reduces initiator and effector caspases, as well as the apoptosis rate via shutdown of cellular proteins. In fact, phosphorylation of eukaryotic initiation factor 2ɑ (eIF2ɑ) by the PERK signal pathway may impair recruitment of ribosomes that bind to the mRNA 5’-cap structure, resulting in an inhibitory effect on canonical cap-dependent cellular protein translation. The resultant pro-survival “byproduct” of infected mosquito cells is undoubtedly advantageous for viral replication. This finding provides insights into elucidating the PERK-mediated modulating web that is actively involved in dynamic protein synthesis, cell survival, and viral replication in mosquito cells.

Keywords: cap-dependent protein translation, dengue virus, endoplasmic reticulum stress, mosquito cells, PERK signal pathway

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Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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Authors: Amelia R. Anshar, Dini Kurnia, Muh A. Bahar

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Nowadays, there are so many incidences had been reported in pet animals regarding drug overdose caused by incorrect doses of a non-steroidal anti-inflammatory drug (NSAID), for instance, meloxicam. As supporting treatment, the avocado is used in traditional medicine to treat or prevent some health cases. The study was aimed at providing the basis for the antioxidant activity of avocado puree in animal medicine. Experimental animals used in this study were 24 male rats that were randomly divided into 4 groups (n=6). Control Group I got 1 ml CMC 1% and control II got meloxicam 30 mg/kgBB and 1 ml CMC 1%. Treatment group I got meloxicam 30 mg/kgBB and avocado 5 g/kgBB/day and treatment II got meloxicam 30 mg/kgBB and avocado 10 g/kgBB/day. The study was conducted over 8 days, then the level of Blood Urea Nitrogen and creatinine of the white rats were examined in 1st day and 8th day. The results were analyzed by ANOVA Two Way With Replication, then followed by T-test (α = 0,05) if there were a difference. Comparison test among the four groups after treatment with avocado using Anova Two Way With Replication test showed that there were significant differences between the mean of the four groups either decreased levels of Blood Urea Nitrogen and creatinine with p < 0,05. Treatment group I and II received treatment showed remarkable (p < 0,05) decreases ini Blood Urea Nitrogen level by 27,17 mg/dl and 17,83 mg/dl respectively. There was also significant decrease in the values of creatinine in Treatment group I and treatment group II by 0,983 mg/dl and 0,713 mg/dl respectively. The conclusion of this study was that avocado decreases level of Blood Urea Nitrogen and creatinine in white rats which are exposed to toxic doses of meloxicam.

Keywords: avocado, blood urea nitrogen, creatinine, meloxicam

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Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari

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Cyperus rotendus rhizomes are used as traditional medicine, including Ayurveda in chronic liver diseases and hepatitis B. We investigated the in vitro hepatoprotective and anti-hepatitis B virus (HBV) potential of Cyperus rotundus rhizome organic and aqueous fractions. Of these, the n-butanol and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-injured HepG2 cells at 48 h. DCFH-toxicated cells were recovered to about 88% and 96%, upon treatment with n-butanol and aqueous fractions (200 g/ml), respectively compared to DCFH-only treated cells. Further, C. rotundus fractions were tested for anti-HBV activities by measuring the expression levels of viral antigens (HBsAg and HBeAg) in the HepG2.2.15 culture supernatants. At 48 h post-treatment, the ethyl acetate, n-butanol and aqueous fractions showed dose-dependent inhibition wherein at a higher dose (100 g/ml), HBsAg production was reduced to 60.27%, 46.87 and 42.76%, respectively. In a time-course study, HBsAg production was inhibited up to 50% and 40% by ethyl acetate and n-butanol fractions (100 g/ml), respectively on day 5. Three three active fractions were further subjected to time-dependent inhibition of HBeAg expression, an indirect measure of HBV active DNA replication. At day 5 post-treatment, ethyl acetate and n-butanol fractions downregulated HBV replication by 44.14% and 24.70%, respectively. In conclusion, our results showed very promising hepatoprotective and anti-HBV potential of C. rotendus tubers fractions in vitro. Our data could, therefore, provide the basis for the claimed traditional use of C. rotendus for jaundice and hepatitis.

Keywords: anti-hepatitis B, cyperus rotundus, hepatitis B virus, hepatoprotection

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Authors: Lian Zeng

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Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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Authors: B. Bergström, A. Ladd, A. Jones, L. Rosso, P. Michael

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Attitudes toward treatment manuals serve as a meaningful predictor of general attitudes toward evidence-based practice. Despite demonstrating high effectiveness in treating many mental disorders, manualized treatments have been underutilized by practitioners. Thus, one can assess the state of the field regarding the adoption of evidence-based practices by surveying practitioner attitudes towards manualized treatments. This study is an adapted replication that assesses psychology graduate student attitudes towards manualized treatments, as a general marker for attitudes towards evidence-based practice. Training programs provide future clinicians with the foundation for critical skills in clinical practice. Research demonstrates that post-graduate continuing education has little to no effect on clinical practice; thus, graduate programs serve as the primary, and often final platform for all future practice. However, there are little empirical data identifying the attitudes and training of graduate students in utilizing manualized treatments. The empirical analysis of this study indicates an increase in positive attitudes among graduate student attitudes towards manualized treatments (within the United States), when compared to past surveys of professional psychologists. Findings from this study may inform graduate programs of barriers for students in developing positive attitudes toward manualized treatments and evidence-based practice. This study also serves as a preliminary predictor of the state-of-the field, in regards to professional psychologists attitudes towards evidence-based practice, if attitudes remain stable. This study indicates that the attitudes toward utilizing evidence-based practices, such as treatment manuals, has become more positive since year 2000.

Keywords: exposure therapy, evidence based practice, manualized treatments, student attitudes

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Authors: David Blaine, George Raschbaum

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The evaluation of DHCP has synthesized SCSI disks, and current trends suggest that the exploration of e-business that would allow for further study into robots will soon emerge. Given the current status of embedded algorithms, hackers worldwide obviously desire the exploration of replication, which embodies the confusing principles of programming languages. In our research we concentrate our efforts on arguing that erasure coding can be made "fuzzy", encrypted, and game-theoretic.

Keywords: SCHI disks, robot, algorithm, hacking, programming language

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Authors: N. R. Mohamad, H. Ono, H. Haroon, A. Salleh, N. M. Z. Hashim

Abstract:

In this research, we have studied and analyzed the modulation of light and liquid crystal in HPDLCs using Finite Domain Time Difference (FDTD) method. HPDLCs are modeled as a mixture of polymer and liquid crystals (LCs) that categorized as an anisotropic medium. FDTD method is directly solves Maxwell’s equation with less approximation, so this method can analyze more flexible and general approach for the arbitrary anisotropic media. As the results from FDTD simulation, the highest diffraction efficiency occurred at ±19 degrees (Bragg angle) using p polarization incident beam to Bragg grating, Q > 10 when the pitch is 1µm. Therefore, the liquid crystal is assumed to be aligned parallel to the grating constant vector during these parameters.

Keywords: birefringence, diffraction efficiency, finite domain time difference, nematic liquid crystals

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Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

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Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

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Authors: Lakshmidevi Sreeramareddy, Komalpreet Kaur, Nane Pothier

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Graphical-based passwords have existed for decades. Their major advantage is that they are easier to remember than an alphanumeric password. However, their disadvantage (especially recognition-based passwords) is the smaller password space, making them more vulnerable to brute force attacks. Graphical passwords are also highly susceptible to the shoulder-surfing effect. The gesture-based password method that we developed is a grid-free, template-free method. In this study, we evaluated the gesture-based passwords for usability and vulnerability. The results of the study are significant. We developed a gesture-based password application for data collection. Two modes of data collection were used: Creation mode and Replication mode. In creation mode (Session 1), users were asked to create six different passwords and reenter each password five times. In replication mode, users saw a password image created by some other user for a fixed duration of time. Three different duration timers, such as 5 seconds (Session 2), 10 seconds (Session 3), and 15 seconds (Session 4), were used to mimic the shoulder-surfing attack. After the timer expired, the password image was removed, and users were asked to replicate the password. There were 74, 57, 50, and 44 users participated in Session 1, Session 2, Session 3, and Session 4 respectfully. In this study, the machine learning algorithms have been applied to determine whether the person is a genuine user or an imposter based on the password entered. Five different machine learning algorithms were deployed to compare the performance in user authentication: namely, Decision Trees, Linear Discriminant Analysis, Naive Bayes Classifier, Support Vector Machines (SVMs) with Gaussian Radial Basis Kernel function, and K-Nearest Neighbor. Gesture-based password features vary from one entry to the next. It is difficult to distinguish between a creator and an intruder for authentication. For each password entered by the user, four features were extracted: password score, password length, password speed, and password size. All four features were normalized before being fed to a classifier. Three different classifiers were trained using data from all four sessions. Classifiers A, B, and C were trained and tested using data from the password creation session and the password replication with a timer of 5 seconds, 10 seconds, and 15 seconds, respectively. The classification accuracies for Classifier A using five ML algorithms are 72.5%, 71.3%, 71.9%, 74.4%, and 72.9%, respectively. The classification accuracies for Classifier B using five ML algorithms are 69.7%, 67.9%, 70.2%, 73.8%, and 71.2%, respectively. The classification accuracies for Classifier C using five ML algorithms are 68.1%, 64.9%, 68.4%, 71.5%, and 69.8%, respectively. SVMs with Gaussian Radial Basis Kernel outperform other ML algorithms for gesture-based password authentication. Results confirm that the shorter the duration of the shoulder-surfing attack, the higher the authentication accuracy. In conclusion, behavioral features extracted from the gesture-based passwords lead to less vulnerable user authentication.

Keywords: authentication, gesture-based passwords, machine learning algorithms, shoulder-surfing attacks, usability

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Authors: Murad Ghanim

Abstract:

The citrus greening disease, also known as Huanglongbing, caused by the phloem-limited bacterium Candidatus Liberibacter asiaticus (CLas) has resulted in tremendous losses and the death of millions of citrus trees worldwide. CLas is transmitted by the Asian citrus psyllid (ACP) Diaphorina citri. The closely-related bacterium Candidatus Liberibacter solanacearum (CLso), which is associated with vegetative disorders in carrots and the zebra chips disease in potatoes, is transmitted by other psyllid species including Bactericera trigonica in carrots and B. ckockerelli in potatoes. Chemical sprays are currently the prevailing method for managing these diseases for limiting psyllid populations; however, they are limited in their effectiveness. A promising approach to prevent the transmission of these pathogens is to interfere with the vector-pathogen interactions, but our understanding of these processes is very limited. CLas induces changes in the nuclear architecture in the midgut of ACP and activates programmed cell death (apoptosis) in this organ. Strikingly, CLso displayed an opposite effect in the gut of B. trigonica, showing limited apoptosis, but widespread necrosis. Electron and fluorescent microscopy further showed that CLas induced the formation of Endoplasmic reticulum (ER) inclusion- and replication-like bodies, in which it increases and multiplies. ER involvement in bacterial replication is hypothesized to be the first stage of an immune response leading to the apoptotic and necrotic responses. ER exploitation and the subsequent events that lead to these cellular and stress responses might activate a cascade of molecular responses ending up with apoptosis and necrosis. Understanding the molecular interactions that underlay the necrotic/apoptotic responses to the bacteria will increase our knowledge of ACP-CLas, and BT-CLso interactions, and will set the foundation for developing novel, and efficient strategies to disturb these interactions and inhibit the transmission.

Keywords: Liberibacter, psyllid, transmission, apoptosis, necrosis

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Authors: Henry Lau, Dilupa Nakandala, Li Zhao

Abstract:

In today’s business, it is well-recognized that risk is an important factor that needs to be taken into consideration before a decision is made. Studies indicate that both the number of risks faced by organizations and their potential consequences are growing. Supply chain risk management has become one of the major concerns for practitioners and researchers. Supply chain leaders and scholars are now focusing on the importance of managing supply chain risk. In order to meet the challenge of managing and mitigating supply chain risk (SCR), we must first identify the different dimensions of SCR and assess its relevant probability and severity. SCR has been classified in many different ways, and there are no consistently accepted dimensions of SCRs and several different classifications are reported in the literature. Basically, supply chain risks can be classified into two dimensions namely disruption risk and operational risk. Disruption risks are those caused by events such as bankruptcy, natural disasters and terrorist attack. Operational risks are related to supply and demand coordination and uncertainty, such as uncertain demand and uncertain supply. Disruption risks are rare but severe and hard to manage, while operational risk can be reduced through effective SCM activities. Other SCRs include supply risk, process risk, demand risk and technology risk. In fact, the disorganized classification of SCR has created confusion for SCR scholars. Moreover, practitioners need to identify and assess SCR. As such, it is important to have an overarching framework tying all these SCR dimensions together for two reasons. First, it helps researchers use these terms for communication of ideas based on the same concept. Second, a shared understanding of the SCR dimensions will support the researchers to focus on the more important research objective: operationalization of SCR, which is very important for assessing SCR. In general, fresh food supply chain is subject to certain level of risks, such as supply risk (low quality, delivery failure, hot weather etc.) and demand risk (season food imbalance, new competitors). Effective strategies to mitigate fresh food supply chain risk are required to enhance operations. Before implementing effective mitigation strategies, we need to identify the risk sources and evaluate the risk level. However, assessing the supply chain risk is not an easy matter, and existing research mainly use qualitative method, such as risk assessment matrix. To address the relevant issues, this paper aims to analyze the risk factor of the fresh food supply chain using an approach comprising both fuzzy logic and hierarchical holographic modeling techniques. This novel approach is able to take advantage the benefits of both of these well-known techniques and at the same time offset their drawbacks in certain aspects. In order to develop this integrated approach, substantial research work is needed to effectively combine these two techniques in a seamless way, To validate the proposed integrated approach, a case study in a fresh food supply chain company was conducted to verify the feasibility of its functionality in a real environment.

Keywords: fresh food supply chain, fuzzy logic, hierarchical holographic modelling, operationalization, supply chain risk

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