Search results for: CRISPR/Cas systems

Authors: Qingfang Guo

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Isodon rubescens is rich in a variety of terpenes such as oridonin. It has important medicinal value. MYB transcription factors are involved in the regulation of plant secondary metabolic pathways. The combined transcriptomics and metabolomics analysis revealed that IrMYB55 might be involved in the regulation of the synthesis of terpenes. The function of IrMYB55 was further verified by establishing of a genetic transformation system by CRISPR/Cas9. Obtaining a virus-mediated Isodon rubescens gene silencing material. The main research results are as follows: (1) Screening IrMYB which can regulate the synthesis of terpenes. Metabolomics and transcriptomics analyses of materials with high (TJ)-and low (FL)-content populations which revealed significant differences in terpene content and IrMYB55 expression. Correlation analysis showed that the expression level of IrMYB55 had a significant correlation with the content of terpenes. (2) Establishment of a genetic transformation system of Isodon rubescens. The IrPDS gene could be knocked out by injection of Isodon rubescens cotyledon, and the transformed material showed obvious albino phenotype. Subsequently, IrMYB55 conversion material was obtained by this method. (3) The IrMYB55 silencing material was obtained. Subcellular localization indicated that IrMYB55 was located in the nucleus, indicating that it might regulate the synthesis of terpenoids through transcription. In summary, IrMYB55 that may regulate the synthesis of oridonin was dug out from the transcriptome and metabolome data. In this study, a genetic transformation system of Isodon rubescens was successfully established. Further studies showed that IrMYB55 regulated the transcription level of genes related to the synthesis of terpenoids, thereby promoting the accumulation of oridonin.

Keywords: isodon rubescens, MYB, oridonin, CRISPR/Cas9

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Authors: Shreya Borthakur, Adhar Sharma

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The North-east states of India are well known for their age-old practice of preparing alcoholic beer from rice and millet. They do so in a traditional way by sprinkling starter cake (inoculum) on cooked rice or millet after which the fermentation starts and eventually, forms the beer. This starter cake has a rich composition of different microbes and medicinal herbs along with the powdered rice dough or maize dough with rice bran. The starter cake microbial composition has an important role in determining the microbial succession and metabolic secretions as the fermentation proceeds from the early to its late stage, thus, giving the beer a unique aroma, taste, and other sensory properties of traditionally prepared beer. Here, We have worked on identifying and characterizing the microbial community in the starter cakes prepared by the Monpa and Galo tribes of Arunachal Pradesh. A total of 18 microbial strains have been isolated from the starter cake of Monpa tribe, while 10 microbial isolates in that of Galo tribe. A metagenomic approach was applied to enumerate the cultural and non-cultural microbes present in the starter cakes prepared by the Monpa and Galo tribes of Arunachal Pradesh. The findings of the mini-project lays foundation to understand the role of microbes present in the starter cake in the beer’s fermentation process and will aide in future research on re-formulating the starter cakes to prevent the early spoilage of the ready to consume beer as the traditional rice beer has a short shelf-life. The paper concludes with the way forward being controlled CRISPR-Cas9.

Keywords: fermentation, traditional beer, microbial succession, preservation, CRISPR-Cas, food microbiology

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Authors: Jin Young Kim, Kwon Kyoo Kang

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The SGR1 (STAYGREEN1) protein is a critical regulator of plant leaves in chlorophyll degradation and senescence. The functions and mechanisms of tomato SGR1 action are poorly understood and worthy of further investigation. To investigate the function of the SGR1 gene, we generated a SGR1-knockout (KO) null line via clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene editing and conducted RNA sequencing and gas chromatography tandem mass spectrometry (GC-MS/MS) analysis to identify the differentially expressed genes. The SlSGR1 (Solanum lycopersicum SGR1) knockout null line clearly showed a turbid brown color with significantly higher chlorophyll and carotenoid content compared to wild-type (WT) fruit. Differential gene expression analysis revealed 728 differentially expressed genes (DEGs) between WT and sgr1 #1-6 line, including 263 and 465 downregulated and upregulated genes, respectively, for which fold change was >2, and the adjusted p-value was <0.05. Most of the DEGs were related to photosynthesis and chloroplast function. In addition, the pigment, carotenoid changes in sgr1 #1-6 line was accumulated of key primary metabolites such as sucrose and its derivatives (fructose, galactinol, raffinose), glycolytic intermediates (glucose, G6P, Fru6P) and tricarboxylic acid cycle (TCA) intermediates (malate and fumarate). Taken together, the transcriptome and metabolite profiles of SGR1-KO lines presented here provide evidence for the mechanisms underlying the effects of SGR1 and molecular pathways involved in chlorophyll degradation and carotenoid biosynthesis.

Keywords: tomato, CRISPR/Cas9, null line, RNA-sequencing, metabolite profiling

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Authors: Yugander Arra, Florence Auguy, Melissa Stiebner, Sophie Chéron, Michael M. Wudick, Van Schepler-Luu, Sébastien Cunnac, Wolf B. Frommer, Laurence Albar

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Rice yellow mottle virus (RYMV) is one of the most important diseases affecting rice in Africa. The most promising strategy to reduce yield losses is the use of highly resistant varieties. The resistance gene RYMV2 is homolog of the Arabidopsis constitutive expression of pathogenesis related protein-5 (AtCPR5) nucleoporin gene. Resistance alleles are originating from African cultivated rice Oryza glaberrima, rarely cultivated, and are characterized by frameshifts or early stop codons, leading to a non-functional or truncated protein. Rice possesses two paralogs of CPR5 and function of these genes are unclear. Here, we evaluated the role of the two rice candidate nucleoporin paralogs OsCPR5.1 (pathogenesis-related gene 5; RYMV2) and OsCPR5.2 by CRISPR/Cas9 genome editing. Despite striking sequence and structural similarity, only loss-of-function of OsCPR5.1 led to full resistance, while loss-of-function oscpr5.2 mutants remained susceptible. Short N-terminal deletions in OsCPR5.1 also did not lead to resistance. In contrast to Atcpr5 mutants, neither OsCPR5.1 nor OsCPR5.2 knock out mutants showed substantial growth defects. Taken together, the candidate nucleoporin OsCPR5.1, but not its close homolog OsCPR5.2, plays a specific role for the susceptibility to RYMV, possibly by impairing the import of viral RNA or protein into the nucleus. Whereas gene introgression from O. glaberrima to high yielding O. sativa varieties is impaired by strong sterility barriers and the negative impact of linkage drag, genome editing of OsCPR5.1, while maintaining OsCPR5.2 activity, thus provides a promising strategy to generate O. sativa elite lines that are resistant to RYMV.

Keywords: CRISPR Cas9, genome editing, knock out mutant, recessive resistance, rice yellow mottle virus

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Sabin Aslam, Sultan Habibullah Khan, James G. Thomson, Abhaya M. Dandekar

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Losses due to viral diseases are posing a serious threat to crop production. A quick breakdown of resistance to viruses like Cotton Leaf Curl Virus (CLCuV) demands the application of a proficient technology to engineer durable resistance. Gene stacking has recently emerged as a potential approach for integrating multiple genes in crop plants. In the present study, recombinase technology has been used for site-specific gene stacking. A target vector (pG-Rec) was designed for engineering a predetermined specific site in the plant genome whereby genes can be stacked repeatedly. Using Agrobacterium-mediated transformation, the pG-Rec was transformed into Coker-312 along with Nicotiana tabacum L. cv. Xanthi and Nicotiana benthamiana. The transgene analysis of target lines was conducted through junction PCR. The transgene positive target lines were used for further transformations to site-specifically stack two genes of interest using Bxb1 and PhiC31 recombinases. In the first instance, Cas9 driven by multiplex gRNAs (for Rep gene of CLCuV) was site-specifically integrated into the target lines and determined by the junction PCR and real-time PCR. The resulting plants were subsequently used to stack the second gene of interest (AVP3 gene from Arabidopsis for enhancing cotton plant growth). The addition of the genes is simultaneously achieved with the removal of marker genes for recycling with the next round of gene stacking. Consequently, transgenic marker-free plants were produced with two genes stacked at the specific site. These transgenic plants can be potential germplasm to introduce resistance against various strains of cotton leaf curl virus (CLCuV) and abiotic stresses. The results of the research demonstrate gene stacking in crop plants, a technology that can be used to introduce multiple genes sequentially at predefined genomic sites. The current climate change scenario highlights the use of such technologies so that gigantic environmental issues can be tackled by several traits in a single step. After evaluating virus resistance in the resulting plants, the lines can be a primer to initiate stacking of further genes in Cotton for other traits as well as molecular breeding with elite cotton lines.

Keywords: cotton, CRISPR/Cas9, gene stacking, genome editing, recombinases

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Authors: Danah S. Alabdulmohsin

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Due to the fast growth of organizational data as well as the emergence of new technologies such as artificial intelligence (AI), organizations tend to utilize these new technologies in their enterprise information systems (EIS) either to overcome the issues they struggle with or to enhance their functions. The aim of this paper is to review the potential role of AI technologies in EIS, namely: enterprise resource planning systems (ERP), customer relation management systems (CRM), supply chain management systems (SCM), knowledge systems (KM), and human resources management systems (HRM). The paper provided the definitions of these systems as well as the definitions of AI technologies that have been used in EIS. In addition, the paper discussed the challenges that organizations might face while integrating AI with their information systems and explained why some organizations fail in achieving successful implementations of the integration.

Keywords: artificial intelligence, AI, enterprise information system, EIS, integration

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Authors: Yang Xiaodong

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This article explores the application and structural characteristics of flexible and programmable systems in electronic systems, with a focus on analyzing their advantages and architectural differences in dealing with complex environments. By introducing mathematical models and simulation experiments, the performance of dynamic module combination in flexible systems and fixed path selection in programmable systems in resource utilization and performance optimization was demonstrated. This article also discusses the mutual transformation between the two in practical applications and proposes a solution to improve system flexibility and performance through dynamic reconfiguration technology. This study provides theoretical reference for the design and optimization of flexible and programmable systems.

Keywords: flexibility, programmable, electronic systems, system architecture

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Authors: S. Najafi, E. Bertini, M. Pezzotti, G.B. Tornielli, S. Zenoni

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Grapevine is an important agricultural fruit crop plant consumed worldwide and with a key role in the global economy. Grapevine is strongly affected by both biotic and abiotic stresses, which impact grape growth at different stages, such as during plant and berry development and pre- and post-harvest, consequently causing significant economic losses. Recently global warming has propelled the anticipation of the onset of berry ripening, determining the reduction of a grape color and increased volatilization of aroma compounds. Climate change could negatively alter the physiological characteristics of the grape and affect the berry and wine quality. Modern plant breeding can provide tools such as genome editing for improving grape resilience traits while maintaining intact the viticultural and oenological quality characteristics of the genotype. This study aims at developing a platform for genome editing application in grapevine plants with the final goal to improve berry quality, biotic, and abiotic resilience traits. We chose to directly deliver ribonucleoproteins (RNP, preassembled Cas protein and guide RNA) into plant protoplasts, and, from these cell structures, regenerate grapevine plants edited in specific selected genes controlling traits of interest. Edited plants regenerated by somatic embryogenesis from protoplasts will then be sequenced and molecularly characterized. Embryogenic calli of Sultana and Shiraz cultivars were initiated from unopened leaves of in-vitro shoot tip cultures and from stamens, respectively. Leaves were placed on NB2 medium while stamens on callus initiation medium (PIV) medium and incubated in the dark at 28 °C for three months. Viable protoplasts, tested by FDA staining, isolated from embryogenic calli were cultured by disc method at 1*105 protoplasts/ml. Mature well-shaped somatic embryos developed directly in the protoplast culture medium two months later and were transferred in the light into to shooting medium for further growth. Regenerated plants were then transferred to the greenhouse; no phenotypic alterations were observed when compared to non in-vitro cultured plants. The performed experiments allowed to established an efficient protocol of embryogenic calli production, protoplast isolation, and regeneration of the whole plant through somatic embryogenesis in both Sultana and Shiraz. Regenerated plants, through direct somatic embryogenesis deriving from a single cell, avoid the risk of chimerism during the regeneration process, therefore improving the genome editing process. As pre-requisite of genome editing, an efficient method for transfection of protoplast by yellow fluorescent protein (YFP) marker genes was also established and experiments of direct delivery of CRISPR–Cas9 ribonucleoproteins (RNPs) in protoplasts to achieve efficient DNA-free targeted mutations are in progress.

Keywords: CRISPR-cas9, plant regeneration, protoplast isolation, Vitis vinifera

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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Authors: Salisu Ibrahim

Abstract:

The paper studies the commutativity associated with fractional order linear time-varying systems (LTVSs), which is an important area of study in control systems engineering. In this paper, we explore the properties of these systems and their ability to commute. We proposed the necessary and sufficient condition for commutativity for fractional order LTVSs. Through a simulation and mathematical analysis, we demonstrate that these systems exhibit commutativity under certain conditions. Our findings have implications for the design and control of fractional order systems in practical applications, science, and engineering. An example is given to show the effectiveness of the proposed method which is been computed by Mathematica and validated by the use of MATLAB (Simulink).

Keywords: fractional differential equation, physical systems, equivalent circuit, analog control

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Authors: Ryspek Usubamatov, Tan San Chin, Sarken Kapaeva

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Productivity of the manufacturing systems depends on technological processes, a technical data of machines and a structure of systems. Technology is presented by the machining mode and data, a technical data presents reliability parameters and auxiliary time for discrete production processes. The term structure of manufacturing systems includes the number of serial and parallel production machines and links between them. Structures of manufacturing systems depend on the complexity of technological processes. Mathematical models of productivity rate for manufacturing systems are important attributes that enable to define best structure by criterion of a productivity rate. These models are important tool in evaluation of the economical efficiency for production systems.

Keywords: productivity, structure, manufacturing systems, structural design

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Authors: Elke Mackensen

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Systems Engineering plays a key role during industrial product development of complex technical systems. The need for systems engineers in industry is growing. However, there is a gap between the industrial need and the academic education. Normally the academic education is focused on the domain specific design, implementation and testing of technical systems. Necessary systems engineering expertise like knowledge about requirements analysis, product cost estimation, management or social skills are poorly taught. Thus, there is the need of new academic concepts for teaching systems engineering skills. This paper presents a project-orientated training concept to prepare students from different technical degree programs for systems engineering activities. The training concept has been initially implemented and applied in the industrial engineering master program of the University of Applied Sciences Offenburg.

Keywords: educational systems engineering training, requirements analysis, system modelling, SysML

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Authors: Mojtaba Hakimi-Moghaddam

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Positive realness as the most important property of driving point impedance of passive electrical networks appears in the control systems stability theory in 1960’s. There are three important subsets of positive real (PR) systems are introduced by researchers, that is, loos-less positive real (LLPR) systems, weakly strictly positive real (WSPR) systems and strictly positive real (SPR) systems. In this paper, definitions, properties, lemmas, and theorems related to family of positive real systems are summarized. Properties in both frequency domain and state space representation of system are explained. Also, several illustrative examples are presented.

Keywords: real rational matrix transfer functions, positive realness property, strictly positive realness property, Hermitian form asymptotic property, pole-zero properties

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Authors: Ana Hol

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Digital systems are in the cognitive wave of the eTransformations and are now extensively aimed at meeting the individuals’ demands, both those of customers requiring services and those of service providers. It is also apparent that successful future systems will not just simply open doors to the traditional owners/users to offer and receive services such as Uber for example does today, but will in the future require more customized and cognitively enabled infrastructures that will be responsive to the system user’s needs. To be able to identify what is required for such systems, this research reviews the historical and the current effects of the eTransformation process by studying: 1. eTransitions of company websites and mobile applications, 2. Emergence of new sheared economy business models as Uber and, 3. New requirements for demand driven, cognitive systems capable of learning and just in time decision making. Based on the analysis, this study proposes a Cognitive eTransformation Framework capable of guiding implementations of new responsive and user aware systems.

Keywords: system implementations, AI supported systems, cognitive systems, eTransformation

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Authors: L. Ngowi, N. H. Mvungi

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This paper critically examines the evolution of socio-technical systems theory, its practices, and challenges in system design and development. It examines concepts put forward by researchers focusing on the application of the theory in software engineering. There are various methods developed that use socio-technical concepts based on systems engineering without remarkable success. The main constraint is the large amount of data and inefficient techniques used in the application of the concepts in system engineering for developing time-bound systems and within a limited/controlled budget. This paper critically examines each of the methods, highlight bottlenecks and suggest the way forward. Since socio-technical systems theory only explains what to do, but not how doing it, hence engineers are not using the concept to save time, costs and reduce risks associated with new frameworks. Hence, a new framework, which can be considered as a practical approach is proposed that borrows concepts from soft systems method, agile systems development and object-oriented analysis and design to bridge the gap between theory and practice. The approach will enable the development of systems using socio-technical systems theory to attract/enable the system engineers/software developers to use socio-technical systems theory in building worthwhile information systems to avoid fragilities and hostilities in the work environment.

Keywords: socio-technical systems, human centered design, software engineering, cognitive engineering, soft systems, systems engineering

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Authors: Joanna Nieżurawska, Hanna Karaszewska, Anna Dziadkiewicz

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Contemporary conditions force companies to constantly implement changes and improvements, which is connected with plasticization of their activity in all spheres. Cafeteria systems are a good example of flexible remuneration systems. Cafeteria systems are well-known and often used in the United States, Great Britain and in Western Europe. In Poland, they are hardly ever used and greater flexibility in remuneration packages refers mainly to senior managers and executives. The main aim of this article is to research the attractiveness of the cafeteria system as viewed by generation Z. The additional aim of the article is to prioritize using the importance index of particular types of cafeteria systems from the generation Z’s perspective, as well as to identify the factors which determine the development of cafeteria systems in Poland. The research was conducted in June 2015 among 185 young employees (generation Z). The paper presents some of the results.

Keywords: cafeteria, generation X, generation Y, generation Z, flexible remuneration systems, plasticization of remuneration

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Authors: Chao Wu

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Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.

Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS

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Authors: Eric Sanchis

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Although there does not exist a definitive consensus on a precise definition of a complex system, it is generally considered that a system is complex by nature. The presented work illustrates a different point of view: a system becomes complex only with regard to the question posed to it, i.e., with regard to the problem which has to be solved. A complex system is a couple (question, object). Because the number of questions posed to a given object can be potentially substantial, complexity does not present a uniform face. Two types of complex systems are clearly identified: first-order complex systems and second-order complex systems. First-order complex systems physically exist. They are well-known because they have been studied by the scientific community for a long time. In second-order complex systems, complexity results from the system composition and its articulation that are partially unknown. For some of these systems, there is no evidence of their existence. Vagueness is the keyword characterizing this kind of systems. Autonomy and free will, two mental productions of the human cognitive system, can be identified as second-order complex systems. A classification based on the properties structure makes it possible to discriminate complex properties from the others and to model this kind of second order complex systems. The final outcome is an implementable synthetic property that distinguishes the solid aspects of the actual property from those that are uncertain.

Keywords: autonomy, free will, synthetic property, vaporous complex systems

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Authors: Tappei Yotsumoto, Atsushi Nomura, Kozo Tanigawa, Kenichi Takahashi, Takao Kawamura, Kazunori Sugahara

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In a human tracking system, expanding a monitoring range of one system is complicating the management of devices and increasing its cost. Therefore, we propose a method to realize a wide-range human tracking by connecting small systems. In this paper, we examined an agent deploy method and information contents across the heterogeneous human tracking systems. By implementing the proposed method, we can construct a human tracking system across heterogeneous systems, and the system can track a target continuously between systems.

Keywords: human tracking system, mobile agent, monitoring, heterogeneous systems

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Authors: Shideh Mohseni Movahed, Mansoureh Safari

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Intelligent drug delivery systems (IDDS) are innovative technological innovations and clinical way to advance current treatments. These systems differ in technique of therapeutic administration, intricacy, materials and patient compliance to address numerous clinical conditions that require different pharmacological therapies. IDDS capable of releasing an active molecule at the proper site and at a amount that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism is particularly appealing. In this paper, we describe the most recent advances in the development of intelligent drug delivery systems.

Keywords: drug delivery systems, IDDS, medicine, health

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Authors: R. B. Ogunrinde, C. C. Jibunoh

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In this paper, a spectral decomposition method is developed for the direct integration of stiff and nonstiff homogeneous linear (ODE) systems with linear, constant, or zero right hand sides (RHSs). The method does not require iteration but obtains solutions at any random points of t, by direct evaluation, in the interval of integration. All the numerical solutions obtained for the class of systems coincide with the exact theoretical solutions. In particular, solutions of homogeneous linear systems, i.e. with zero RHS, conform to the exact analytical solutions of the systems in terms of t.

Keywords: spectral decomposition, linear RHS, homogeneous linear systems, eigenvalues of the Jacobian

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Authors: Salisu Ibrahim

Abstract:

The paper studies the commutativity associated with fractional order linear time-varying systems (LTVSs), which is an important area of study in control systems engineering. In this paper, we explore the properties of these systems and their ability to commute. We proposed the necessary and sufficient condition for commutativity for fractional order LTVSs. Through a simulation and mathematical analysis, we demonstrate that these systems exhibit commutativity under certain conditions. Our findings have implications for the design and control of fractional order systems in practical applications, science, and engineering. An example is given to show the effectiveness of the proposed method which is been computed by Mathematica and validated by the use of Matlab (Simulink).

Keywords: fractional differential equation, physical systems, equivalent circuit, and analog control

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Authors: Edward B. Ssekulima, Amir Etemadi

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This paper presents a Systems Thinking and System of Systems (SoS) viewpoint for managing requirements complexity in the grid integration of Variable Renewable Energy (VRE). To achieve a SoS approach, it is often necessary to inculcate a Systems Thinking (ST) perspective in the planning and design of the attendant system. We show how this approach can support the enhanced integration of VRE (wind, solar small hydro) for which intermittency is a key inhibiting factor to their sustainable grid integration. The results indicate that a ST and SoS approach are a critical tool for decision makers in the planning, design and deployment of VRE Sources for their sustainable grid-integration in accordance with relevant techno-economic, social and environmental requirements.

Keywords: sustainable grid-integration, system of systems, systems thinking, variable energy resources

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Authors: B. N. Asare, O. A. Ajigini

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Information systems (IS) are highly important in the operation of private and public organisations in developing and developed countries. Developing countries are saddled with many project failures during the implementation of information systems. However, successful information systems are greatly needed in developing countries in order to enhance their economies. This paper is highly important in view of the high failure rate of information systems in developing countries which needs to be reduced to minimum acceptable levels by means of recommended interventions. This paper centres on a review of IS development in developing countries. The paper presents evidences of the IS successes and failures in developing countries and posits a model to address the IS failures. The proposed model can then be utilised by developing countries to reduce their IS project implementation failure rate. A comparison is drawn between IS development in developing countries and developed countries. The paper provides valuable information to assist in reducing IS failure, and developing IS models and theories on IS development for developing countries.

Keywords: developing countries, information systems, IS development, information systems failure, information systems success, information systems success model

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Authors: Haitham S. Hamza, Mohamed Maher, Shourok Alaa, Aya Khattab, Hadeal Ismail, Kamilia Hosny

Abstract:

Radio Frequency Identification (RFID) has become a key technology in the margining concept of Internet of Things (IoT). Naturally, business applications would require the deployment of various RFID systems that are developed by different vendors and use various data formats. This heterogeneity poses a real challenge in developing large-scale IoT systems with RFID as integration is becoming very complex and challenging. Semantic integration is a key approach to deal with this challenge. To do so, ontology for RFID systems need to be developed in order to annotated semantically RFID systems, and hence, facilitate their integration. Accordingly, in this paper, we propose ontology for RFID systems. The proposed ontology can be used to semantically enrich RFID systems, and hence, improve their usage and reasoning. The usage of the proposed ontology is explained through a simple scenario in the health care domain.

Keywords: RFID, semantic technology, ontology, sparql query language, heterogeneity

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Authors: Aouiche Abdelaziz, Soudani Mouhamed Salah, Aouiche El Moundhe

Abstract:

The present paper addresses the utilization of Artificial Neural Networks (ANNs) and Fuzzy Inference Systems (FISs) for the identification and control of dynamical systems with some degree of uncertainty. Because ANNs and FISs have an inherent ability to approximate functions and to adapt to changes in input and parameters, they can be used to control systems too complex for linear controllers. In this work, we show how ANNs and FISs can be put in order to form nets that can learn from external data. In sequence, it is presented structures of inputs that can be used along with ANNs and FISs to model non-linear systems. Four systems were used to test the identification and control of the structures proposed. The results show the ANNs and FISs (Back Propagation Algorithm) used were efficient in modeling and controlling the non-linear plants.

Keywords: non-linear systems, fuzzy set Models, neural network, control law

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Authors: Arcady Ponosov

Abstract:

A novel mathematical approach is suggested, which facilitates a compressed representation and efficient validation of parameter-rich ordinary differential equation models describing the dynamics of complex, especially biology-related, systems and which is based on identification of the system's latent variables. In particular, an efficient parameter estimation method for the compressed non-linear dynamical systems is developed. The method is applied to the so-called 'power-law systems' being non-linear differential equations typically used in Biochemical System Theory.

Keywords: generalized law of mass action, metamodels, principal components, synergetic systems

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Authors: Ali E. Abbas

Abstract:

This paper summarizes some of the discussions that occurred in a workshop in West Virginia, U.S.A which was sponsored by the National Science Foundation (NSF) in February 2016. The goal of the workshop was to explore the opportunities and challenges for applying systems engineering in large enterprises, and some of the issues that still persist. The main topics of the discussion included challenges with elaboration and abstraction in large systems, interfacing physical and social systems, and the need for axiomatic frameworks for large enterprises. We summarize these main points of discussion drawing parallels with decision making in organizations to instigate research in these discussion areas.

Keywords: decision analysis, systems engineering, framing, value creation

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Authors: Takashi Shimizu, Tomoaki Hashimoto

Abstract:

A class of implicit systems is known as a more generalized class of systems than a class of explicit systems. To establish a control method for such a generalized class of systems, we adopt model predictive control method which is a kind of optimal feedback control with a performance index that has a moving initial time and terminal time. However, model predictive control method is inapplicable to systems whose all state variables are not exactly known. In other words, model predictive control method is inapplicable to systems with limited measurable states. In fact, it is usual that the state variables of systems are measured through outputs, hence, only limited parts of them can be used directly. It is also usual that output signals are disturbed by process and sensor noises. Hence, it is important to establish a state estimation method for nonlinear implicit systems with taking the process noise and sensor noise into consideration. To this purpose, we apply the model predictive control method and unscented Kalman filter for solving the optimization and estimation problems of nonlinear implicit systems, respectively. The objective of this study is to establish a model predictive control with unscented Kalman filter for nonlinear implicit systems.

Keywords: optimal control, nonlinear systems, state estimation, Kalman filter

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