Search results for: gene regulation

Authors: Ghada Al-Kafaji, Mohamed Sabry

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Mitochondria are the site of cellular respiration and produce energy in the form of adenosine triphosphate (ATP) via oxidative phosphorylation. They are the major source of intracellular reactive oxygen species (ROS) and are also direct target to ROS attack. Oxidative stress and ROS-mediated disruptions of mitochondrial function are major components involved in the pathogenicity of diabetic complications. In this work, the changes in mitochondrial DNA (mtDNA) copy number, biogenesis, gene expression of mtDNA-encoded subunits of electron transport chain (ETC) complexes, and mitochondrial function in response to hyperglycemia-induced ROS and the effect of direct inhibition of ROS on mitochondria were investigated in an in vitro model of diabetic nephropathy using human renal mesangial cells. The cells were exposed to normoglycemic and hyperglycemic conditions in the presence and absence of Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) or catalase for 1, 4 and 7 days. ROS production was assessed by the confocal microscope and flow cytometry. mtDNA copy number and PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 transcripts, were all analyzed by real-time PCR. PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 proteins, were analyzed by Western blotting. Mitochondrial function was determined by assessing mitochondrial membrane potential and adenosine triphosphate (ATP) levels. Hyperglycemia-induced a significant increase in the production of mitochondrial superoxide and hydrogen peroxide at day 1 (P < 0.05), and this increase remained significantly elevated at days 4 and 7 (P < 0.05). The copy number of mtDNA and expression of PGC-1a, NRF-1, and TFAM as well as ND2, CYTB, CO1 and ATPase 6 increased after one day of hyperglycemia (P < 0.05), with a significant reduction in all those parameters at 4 and 7 days (P < 0.05). The mitochondrial membrane potential decreased progressively at 1 to 7 days of hyperglycemia with the parallel progressive reduction in ATP levels over time (P < 0.05). MnTBAP and catalase treatment of cells cultured under hyperglycemic conditions attenuated ROS production reversed renal mitochondrial oxidative stress and improved mtDNA, mitochondrial biogenesis, and function. These results show that hyperglycemia-induced ROS caused an early increase in mtDNA copy number, mitochondrial biogenesis and mtDNA-encoded gene expression of the ETC subunits in human mesangial cells as a compensatory response to the decline in mitochondrial function, which precede the mtDNA defect and mitochondrial dysfunction with a progressive oxidative response. Protection from ROS-mediated damage to renal mitochondria induced by hyperglycemia may be a novel therapeutic approach for the prevention/treatment of DN.

Keywords: diabetic nephropathy, hyperglycemia, reactive oxygen species, oxidative stress, mtDNA, mitochondrial dysfunction, manganese superoxide dismutase, catalase

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Authors: Ragea Alqahtani

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The purpose of the study was to measure the effectiveness of the Goldstein’s social skill streaming model based on the special and general pre-service teachers’ knowledge about controlling their emotions in conflict situations. A review of previous pieces of literature guided the design and measurement of the effectiveness of the approach to the control of emotions. The teachers were assessed using the coping strategy, adult anger, and Goldstein’s skill streaming inventories. Lastly, the paper provides various recommendations on the sensitization of the Goldstein’s Social Skill streaming model to both the special and pre-service teachers to promote their knowledge about controlling emotions in conflicts.

Keywords: emotional control, Goldstein social skill streaming model, modeling technique, self- as-a-model, self-efficacy, self-regulation

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Authors: Ayse Ozge Demir, Nihat Mert

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In this research, Kilis and Honamli goats are used, which are specific local genetic resources of Turkey. The herds were independent, but they had similar care and nutrition circumstances. From each breed 30 samples were taken, in all 120 samples were collected. Erytrocyte, all blood and serum samples were used for hemoglobine (Hb), glutathione (GSH) and Tf with Cp analysis, respectively. In the analysis of this samples, Hb and Tf bands were determined by electrophoresis. However, Cp and GSH levels were analyzed by the spectrophotometer. Three Hb phenotypes (AA, BB, AB) and Six Tf phenotypes (AA, AB, AC, BB, BC, CC) were determined in this study. In addition, both the observed and the expected values of polymorphic characteristic for 2 characters were presented according to the Hardy-Weinberg Equilibrium (HWE). Cp levels were detected as 0.822 ± 0.055 mg/dl and 1.793 ± 0.109 mg/dl in Kilis and Honamli herds, respectively. GSH levels were detected as, 42,486 ± 1,034 mg/dl and 33.515 ± 0.345 mg/dl in these breeds, respectively,. On the other hand, the high and low GSH levels (GSHH and GSHh) of herds were presented.

Keywords: electrophoresis, gene resource, goat, spectrophotometer

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Authors: Abdulrahman S. Shryan Aldossary

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Globally, artificial intelligence (AI) is already performing legitimate tasks on behalf of humans. In Saudi Arabia, large-scale national projects, primarily based on AI technologies and receiving billions of dollars of funding, are projected for completion by 2030. However, the legal aspect of these projects is seriously vulnerable, given AI’s unprecedented ability to self-learn and act independently. This paper, therefore, identifies the critical legal aspects of AI that authorities and policymakers should be aware of, specifically whether AI can possess identity and be liable for the risk of public harm. The article begins by identifying the problematic characteristics of AI and what should be considered by legal experts when dealing with it. Also discussed are the possible competent institutions that could regulate AI in Saudi Arabia. Finally, a procedural proposal is presented for controlling AI, focused on Saudi Arabia but potentially of interest to other jurisdictions facing similar concerns about AI safety.

Keywords: regulation, artificial intelligence, tech law, automated systems

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Authors: Sofia Papadimitriou

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INTRODUCTION: The differential diagnosis between acute viral and bacterial infections is an important cost-effectiveness parameter at the stage of the treatment process in order to achieve the maximum benefits in therapeutic intervention by combining the minimum cost to ensure the proper use of antibiotics.The discovery of sensitive and robust molecular diagnostic tests in response to the role of the host in infections has enhanced the accurate diagnosis and differentiation of infections. METHOD: The study used a sample of six independent blood samples (total=756) which are associated with human proteins-proteins, each of which at the transcription stage expresses a different response in the host network between viral and bacterial infections.Τhe individual blood samples are subjected to a sequence of computer filters that identify a gene panel corresponding to an autonomous diagnostic score. The data set and the correspondence of the gene panel to the diagnostic patents a new Bangalore -Viral Bacterial (BL-VB). FINDING: We use a biomarker based on the blood of 10 genes(Panel-VB) that are an important prognostic value for the detection of viruses from bacterial infections with a weighted average AUROC of 0.97(95% CL:0.96-0.99) in eleven independent samples (sets n=898). We discovered a base with a patient score (VB 10 ) according to the table, which is a significant diagnostic value with a weighted average of AUROC 0.94(95% CL: 0.91-0.98) in 2996 patient samples from 56 public sets of data from 19 different countries. We also studied VB 10 in a new cohort of South India (BL-VB,n=56) and found 97% accuracy in confirmed cases of viral and bacterial infections. We found that VB 10 (a)accurately identifies the type of infection even in unspecified cases negative to the culture (b) shows its clinical condition recovery and (c) applies to all age groups, covering a wide range of acute bacterial and viral infectious, including non-specific pathogens. We applied our VB 10 rating to publicly available COVID 19 data and found that our rating diagnosed viral infection in patient samples. RESULTS: Τhe results of the study showed the diagnostic power of the biomarker VB 10 as a diagnostic test for the accurate diagnosis of acute infections in recovery conditions. We look forward to helping you make clinical decisions about prescribing antibiotics and integrating them into your policies management of antibiotic stewardship efforts. CONCLUSIONS: Overall, we are developing a new property of the RNA-based biomarker and a new blood test to differentiate between viral and bacterial infections to assist a physician in designing the optimal treatment regimen to contribute to the proper use of antibiotics and reduce the burden on antimicrobial resistance, AMR.

Keywords: acute infections, antimicrobial resistance, biomarker, blood transcriptome, systems biology, classifier diagnostic score

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Authors: Fuad M. Alkoot

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DNA data have been used in forensics for decades. However, current research looks at using the DNA as a biometric identity verification modality. The goal is to improve the speed of identification. We aim at using gene data that was initially used for autism detection to find if and how accurate is this data for identification applications. Mainly our goal is to find if our data preprocessing technique yields data useful as a biometric identification tool. We experiment with using the nearest neighbor classifier to identify subjects. Results show that optimal classification rate is achieved when the test set is corrupted by normally distributed noise with zero mean and standard deviation of 1. The classification rate is close to optimal at higher noise standard deviation reaching 3. This shows that the data can be used for identity verification with high accuracy using a simple classifier such as the k-nearest neighbor (k-NN). 

Keywords: biometrics, genetic data, identity verification, k nearest neighbor

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Authors: Yeo Leng Leng

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Blended learning, with its combination of online and face-to-face instruction, presents a unique set of challenges and opportunities in terms of cultivating student agency. While it offers flexibility and personalized learning pathways, it also demands a higher degree of self-regulation and motivation from students. This paper presents the design of blended learning in a Chinese lesson and discusses the framework involved. It also talks about the Edtech tools adopted to engage the students. Some of the students’ works will be showcased. A qualitative case study research method was employed in this paper to find out more about students’ learning experiences and to give them a voice. The purpose is to seek improvement in the blended learning design of the Chinese lessons and to encourage students’ self-directed learning.

Keywords: blended learning, student agency, ed-tech tools, self-directed learning

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Authors: Judit Vilarmau

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Generative AI is emerging rapidly and transforming higher education in many ways, occasioning new challenges and disrupting traditional models and methods. The studies and authors explored remark on the impact on the ethics, curriculum, and pedagogical methods. Students are increasingly using generative AI for study, as a virtual tutor, and as a resource for generating works and doing assignments. This point is crucial for educators to make sure that students are using generative AI with ethical considerations. Generative AI also has relevant benefits for educators and can help them personalize learning experiences and promote self-regulation. Educators must seek and explore tools like ChatGPT to innovate without forgetting an ethical and pedagogical perspective. Eighteen studies were systematically reviewed, and the findings provide implementation guidelines with pedagogical and ethical considerations.

Keywords: ethics, generative artificial intelligence, guidelines, higher education, pedagogy

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Authors: Heiko Jessen, Laura Tanus, Slobodan Ruzicic

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Objectives: The efficacy of Stribild®, an integrase strand transfer inhibitor (INSTI) -based STR, has been evaluated in randomized clinical trials and it has demonstrated durable capability in terms of achieving sustained suppression of HIV-1 RNA-levels. However, differences in monitoring frequency, existing selection bias and profile of patients enrolled in the trials, may all result in divergent efficacy of this regimen in routine clinical settings. The aim of this study was to assess the virologic outcomes, safety and tolerability profile of Stribild® in a routine clinical setting. Methods: This was a retrospective monocentric analysis on HIV-1-infected patients, who started with or were switched to Stribild®. Virological failure (VF) was defined as confirmed HIV-RNA>50 copies/ml. The minimum time of follow-up was 24 weeks. The percentage of patients remaining free of therapeutic failure was estimated using the time-to-loss-of-virologic-response (TLOVR) algorithm, by intent-to-treat analysis. Results: We analyzed the data of 197 patients (56 ART-naïve and 141 treatment-experienced patients), who fulfilled the inclusion criteria. Majority (95.9%) of patients were male. The median time of HIV-infection at baseline was 2 months in treatment-naïve and 70 months in treatment-experienced patients. Median time [IQR] under ART in treatment-experienced patients was 37 months. Among the treatment-experienced patients 27.0% had already been treated with a regimen consisting of two NRTIs and one INSTI, whereas 18.4% of them experienced a VF. The median time [IQR] of virological suppression prior to therapy with Stribild® in the treatment-experienced patients was 10 months [0-27]. At the end of follow-up (median 33 months), 87.3% (95% CI, 83.5-91.2) of treatment-naïve and 80.3% (95% CI, 75.8-84.8) of treatment-experienced patients remained free of therapeutic failure. Considering only treatment-experienced patients with baseline VL<50 copies/ml, 83.0% (95% CI, 78.5-87.5) remained free of therapeutic failure. A total of 17 patients stopped treatment with Stribild®, 5.4% (3/56) of them were treatment-naïve and 9.9% (14/141) were treatment-experienced patients. The Stribild® therapy was discontinued in 2 (1.0%) because of VF, loss to follow-up in 4 (2.0%), and drug-drug interactions in 2 (1.0%) patients. Adverse events were in 7 (3.6%) patients the reason to switch from therapy with Stribild® and further 2 (1.0%) patients decided personally to switch. The most frequently observed adverse events were gastrointestinal side effects (20.0%), headache (8%), rash events (7%) and dizziness (6%). In two patients we observed an emergence of novel resistances in integrase-gene. The N155H evolved in one patient and resulted in VF. In another patient S119R evolved either during or shortly upon switch from therapy with Stribild®. In one further patient with VF two novel mutations in the RT-gene were observed when compared to historical genotypic test result (V106I/M and M184V), whereby it is not clear whether they evolved during or already before the switch to Stribild®. Conclusions: Effectiveness of Stribild® for treatment-naïve patients was consistent with data obtained in clinical trials. The safety and tolerability profile as well as resistance development confirmed clinical efficacy of Stribild® in a daily practice setting.

Keywords: ART, HIV, integrase inhibitor, stribild

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Authors: Chun-Chin Huang

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Individuals with prediabetes increase the risk of developing type 2 diabetes. Exercise is a potent stimulator of skeletal muscle glucose uptake and thus good for maintaining glucose homeostasis. That could be a conducive method to improve blood glucose regulation and prevent type 2 diabetes without medication intake. The aim of this study was to summarize mechanisms of insulin resistance and investigate the beneficial effects of acute and chronic aerobic exercise on glycemic control in prediabetes and type 2 diabetes. Aerobic exercise regulates glucose homeostasis and reduces blood glucose, insulin concentrations. Therefore, the type of aerobic exercise brings positive effects to prediabetes and type 2 diabetes.

Keywords: insulin resistance, glucose sensitivity, impaired fasting glucose, impaired glucose tolerance

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Authors: Yahia Massinissa, Melakhessou Med Akram, Mezahdia Mehdi, Marref Salah Eddine

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Cytokines are natural proteins which act as true intercellular communication signals in immune and inflammatory responses. Reverse signaling pathways that activate cytokines help to regulate different functions at the target cell, causing its activation, its proliferation, the differentiation, its survival or death. It was shown that malfunctioning of the cytokine regulation, particularly over-expression, contributes to the onset and development of certain serious diseases such as chronic rheumatoid arthritis, Crohn's disease, psoriasis, lupus. The action mode of Kinoid® technology is based on the principle vaccine: The patient's immune system is activated so that it neutralizes itself and the factor responsible for the disease. When applied specifically to autoimmune diseases, therapeutic vaccination allows the body to neutralize cytokines (proteins) overproduced through a highly targeted stimulation of the immune system.

Keywords: cytokines, Kinoid tech, auto-immune diseases, vaccination

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Authors: Gunta Resevica, Nikita Zrelovs, Ivars Silamikelis, Ieva Kalnciema, Helvijs Niedra, Gunārs Lācis, Toms Bartulsons, Inga Moročko-Bičevska, Arturs Stalažs, Kristīne Drevinska, Andris Zeltins, Ina Balke

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Newly discovered viruses provide novel knowledge for basic phytovirus research, serve as tools for biotechnology and can be helpful in identification of epidemic outbreaks. Blackcurrant-associated rhabdovirus (BCaRV) have been discovered in USA germplasm collection samples from Russia and France. As it was reported in one accession originating from France it is unclear whether the material was already infected when it entered in the USA or it became infected while in collection in the USA. Due to that BCaRV was definite as non-EU viruses. According to ICTV classification BCaRV is representative of Blackcurrant betanucleorhabdovirus specie in genus Betanucleorhabdovirus (family Rhabdoviridae). Nevertheless, BCaRV impact on the host, transmission mechanisms and vectors are still unknown. In RNA-seq data pool from Ribes plants resistance gene study by high throughput sequencing (HTS) we observed differences between sample group gene transcript heat maps. Additional analysis of the whole data pool (total 393660492 of 150 bp long read pairs) by rnaSPAdes v 3.13.1 resulted into 14424 bases long contig with an average coverage of 684x with shared 99.5% identity to the previously reported first complete genome of BCaRV (MF543022.1) using EMBOSS Needle. This finding proved BCaRV presence in EU and indicated that it might be relevant pathogen. In this study leaf tissue from twelve asymptomatic blackcurrant cv. Mara Eglite plants (negatively tested for blackcurrant reversion virus (BRV)) from Dobele, Latvia (56°36'31.9"N, 23°18'13.6"E) was collected and used for total RNA isolation with RNeasy Plant Mini Kit with minor modifications, followed by plant rRNA removal by a RiboMinus Plant Kit for RNA-Seq. HTS libraries were prepared using MGI Easy RNA Directional Library Prep Set for 16 reactions to obtain 150 bp pair-end reads. Libraries were pooled, circularized and cleaned and sequenced on DNBSEQ-G400 using PE150 flow cell. Additionally, all samples were tested by RT-PCR, and amplicons were directly sequenced by Sanger-based method. The contig representing the genome of BCaRV isolate Mara Eglite was deposited at European Nucleotide Archive under accession number OU015520. Those findings indicate a second evidence on the presence of this particular virus in the EU and further research on BCaRV prevalence in Ribes from other geographical areas should be performed. As there are no information on BCaRV impact on the host this should be investigated, regarding the fact that mixed infections with BRV and nucleorhabdoviruses are reported.

Keywords: BCaRV, Betanucleorhabdovirus, Ribes, RNA-seq

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Authors: Suchao Donpudsa, Anchalee Tassanakajon, Vichien Rimphanitchayakit

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A crustin gene, LV-SWD1, previously found in the hemocyte cDNA library of Litopenaeus vannamei, contains the open reading frames of 288 bp encoding a putative protein of 96 amino acid residues. The putative signal peptides of the LV-SWD1 were identified using the online SignalP 3.0 with predicted cleavage sites between Ala24-Val25, resulting in 72 residue mature protein with calculated molecular mass of 7.4 kDa and predicted pI of 8.5. This crustin contains a Arg-Pro rich region at the amino-terminus and a single whey acidic protein (WAP) domain at the carboxyl-terminus. In order to characterize their properties and biological activities, the recombinant crustin protein was produced in the Escherichia coli expression system. Antimicrobial assays showed that the growth of Bacillus subtilis was inhibited by this recombinant crustin with MIC of about 25-50 µM.

Keywords: crustin, single whey acidic protein, Litopenaeus vannamei, antimicrobial activity

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Authors: Dae-Hee Son, Sang-Hee Kang, Soon-Ryul Nam

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In this paper, we develop a dynamic modeling of wind farms in the Jeju power system. The dynamic model of wind farms is developed to study their dynamic effects on the Jeju power system. PSS/E is used to develop the dynamic model of a wind farm composed of 1.5-MW doubly fed induction generators. The output of a wind farm is regulated based on pitch angle control, in which the two controllable parameters are speed and power references. The simulation results confirm that the pitch angle is successfully controlled, regardless of the variation in wind speed and output regulation.

Keywords: dynamic model, Jeju power system, online limitation, pitch angle control, wind farm

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Authors: Howard Chitimira

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In Australia, the market abuse prohibition is generally well accepted by the investing and non-investing public as well as by the government. This co-operative and co-ordinated approach on the part of all the relevant stakeholders has to date given rise to an increased awareness and commendable combating of market abuse activities in the Australian corporations, companies, and securities markets. It is against this background that this article seeks to comparatively explore the general enforcement approaches that are employed to combat market abuse (insider trading and market manipulation) activity in Australia and South Africa. In relation to this, the role of selected enforcement authorities and possible enforcement methods which may be learnt from both the Australian and South African experiences will be isolated where necessary for consideration by such authorities, especially, in the South African market abuse regulatory framework.

Keywords: insider trading, market abuse, market manipulation, regulation

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Authors: Sachinkumar Patil, Sonali Patil, Shitalkumar Patil

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Nanoparticles played important role in the biomedicine. New advanced methods having great potential apllication in the diagnosis and therapy of cancer. Now a day’s magnetic nanoparticles used in cancer therapy. Cancer is the major disease causes death. Magnetic nanoparticles show response to the magnetic field on the basis of this property they are used in cancer therapy. Cancer treated with hyperthermia by using magnetic nanoparticles it is unconventional but more safe and effective method. Magnetic nanoparticles prepared by using different innovative techniques that makes particles in uniform size and desired effect. Magnetic nanoparticles already used as contrast media in magnetic resonance imaging. A magnetic nanoparticle has been great potential application in cancer diagnosis and treatment as well as in gene therapy. In this review we will discuss the progress in cancer therapy based on magnetic nanoparticles, mainly including magnetic hyperthermia, synthesis and characterization of magnetic nanoparticles, mechanism of magnetic nanoparticles and application of magnetic nanoparticles.

Keywords: magnetic nanoparticles, synthesis, characterization, cancer therapy, hyperthermia, application

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Authors: Mahmoud Samkan

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Dispersed Generation (DG) is a promising solution to many power system problems such as voltage regulation and power loss. This paper proposes a heuristic two-step method to optimize the location and size of DG for reducing active power losses and, therefore, improve the voltage profile in radial distribution networks. In addition to a DG placed at the system load gravity center, this method consists in assigning a DG to each lateral of the network. After having determined the central DG placement, the location and size of each lateral DG are predetermined in the first step. The results are then refined in the second step. This method is tested for 33-bus system for 100% DG penetration. The results obtained are compared with those of other methods found in the literature.

Keywords: optimal location, optimal size, dispersed generation (DG), radial distribution networks, reducing losses

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Authors: Soo Dong Cho, In-Ohk Ouh, Byeong Sul Kang, Seyeon Park, In-Soo Cho, Jae Young Song

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An VP2 gene from the current prevalent CPV (Canine Parvovirus) strain (new CPV-2a) in the Republic of Korea was expressed in a baculovirus expression system. Genomic DNA was extracted from the isolate strain CPV-2a. The recombinant baculovirus, containing the coding sequences of VP2 with the histidine tag at the N-terminus, were generated by using the Bac-to-Bac system. For production of the recombinant VP2 proteins, SF9 cells were transfection into 6 wells. Propagation of recombinant baculoviruses and expression of the VP2 protein were performed in the Sf9 cell line maintained. The proteins were detected to Western blot anlaysis. CPV-2a VP2 was detected by Western blotting the monoclonal antibodies recognized 6x His and the band had a molecular weight of 65 KDa. We demonstrated that recombinant CPV-2a VP2 expression in baculovirus. The recombinant CPV-2a VP2 may able to development of specific diagnostic test and vaccination of against CPV2. This study provides a foundation for application of CPV2 on the development of new CPV2 subunit vaccine.

Keywords: baculovirus, canine parvovirus 2a, Dog, Korea

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Authors: Expedito J. S. Parente Jr., Italo C. Rios, Joao Paulo C. Marques, Rosana M. A. Saboya, F. Murilo T. Luna, Célio L. Cavalcante Jr.

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Increasing constraints of environmental regulation around the world have led to higher demand for biodegradable products. Vegetable oils present some properties that may favor their use as biolubricants; however, there are others, such as resistance to oxidation and pour point, which affect possible commercial applications. In this study, the physicochemical properties of biolubricants synthesized from different vegetable oils were evaluated and compared with petroleum-based lubricant and pure vegetable oil. Chemical modifications applied to the original vegetable oil improved their oxidative stability and pour point significantly. The addition of commercial antioxidants to the bio-based lubricants was evaluated, yielding values of oxidative stability close to those of mineral basestock oil.

Keywords: biolubricant, vegetable oil, oxidative stability, pour point, antioxidants

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Authors: Daniel Suarez Alonso

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Cybercrime is a growing international threat and a challenge for law enforcement agencies and judicial systems worldwide. International cooperation is necessary to solve this problem because cybercrime knows no borders and often involves multiple jurisdictions, being related to organised crime. The purpose of this article is to analyse international cooperation in the investigation and prosecution of cybercrime, focusing on the framework of the Regulation of the European Union Agency for Law Enforcement Cooperation (EUROPOL), cooperation that takes place between police authorities from different countries. It examines the legal and operational mechanisms in place to facilitate international cooperation in Europe in this area and assesses their effectiveness in the fight against cybercrime. In addition, the study of a Spanish investigation where cooperation with EUROPOL took place will be examined, analyzing how international cooperation was carried out to investigate and track down criminals. Lessons learned from this case will be discussed and recommendations for improving international cooperation in the fight against cybercrime will be proposed.

Keywords: Europol, international cooperation, cybercrime, computer crime, law

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Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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Authors: Sivaraman Karthikeyan

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Due to rapidly developing power electronics devices and technologies such as power line communication or self-commutating converters, voltage and current distortion, as well as interferences, have increased in the frequency range of 2 kHz to 150 kHz; there is an urgent need for regulation of electromagnetic compatibility (EMC) standards in this frequency range. Measuring or testing compliance with emission and immunity limitations necessitates the use of precise, repeatable measuring methods. Appropriate filters to minimize the fundamental component and its harmonics below 2 kHz in the measuring signal would improve the measurement accuracy in this frequency range leading to better analysis. This paper discusses filter suggestions in the current measurement standard and proposes an infinite impulse response (IIR) filter design that is optimized for a low number of poles, strong fundamental damping, and high accuracy above 2 kHz. The new filter’s transfer function is delivered as a result. An analog implementation is derived from the overall design.

Keywords: supraharmonics, 2 kHz, 150 kHz, filter, analog filter

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Authors: Alina Parincu, Giuseppe Empoli, Alexandru Capatina

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The purpose of this paper is to identify the most influential predictors of emotional intelligence skills, in the case of 20 business innovation coaches, on the co-creation of knowledge through coaching services delivered to innovative start-ups from Europe, funded through Horizon 2020 – SME Instrument. We considered the emotional intelligence skills (self-awareness, self-regulation, motivation, empathy and social skills) as antecedent conditions of the outcome: the quality of coaching services, perceived by the entrepreneurs who received funding within SME instrument, using fuzzy-sets qualitative comparative analysis (fsQCA) approach. The findings reveal that emotional intelligence skills, trained with neuro-management techniques, were associated with increased goal-focused business coaching skills.

Keywords: neuro-management, innovative start-ups, business coaching, fsQCA

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Authors: Bing Yan

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Nanomaterials are widely used in various industrial sectors, biomedicine, and more than 1300 consumer products. Although there is still no standard safety regulation, their potential toxicity is a major concern worldwide. We discovered that nanoparticles target and enter human cells1, perturb cellular signaling pathways2, affect various cell functions3, and cause malfunctions in animals4,5. Because the majority of atoms in nanoparticles are on the surface, chemistry modification on their surface may change their biological properties significantly. We modified nanoparticle surface using nano-combinatorial chemistry library approach6. Novel nanoparticles were discovered to exhibit significantly reduced toxicity6,7, enhance cancer targeting ability8, or re-program cellular signaling machineries7. Using computational chemistry, quantitative nanostructure-activity relationship (QNAR) is established and predictive models have been built to predict biocompatible nanoparticles.

Keywords: nanoparticle, nanotoxicity, nano-bio, nano-combinatorial chemistry, nanoparticle library

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Authors: Zhao Haoyue

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Due to the combined effects of climate change, urban expansion, and population growth, various environmental issues, such as urban heat islands and pollution, arise. Therefore, reliable information on urban environmental climate is needed to address and mitigate the negative effects. The emergence of urban climate maps provides a practical basis for urban climate regulation and improvement. This article takes Shapingba District, Chongqing City, as an example to study the construction method of urban thermal environment climate maps based on GIS spatial analysis technology. The thermal load, ventilation potential analysis map, and thermal environment comprehensive analysis map were obtained. Based on the classification criteria obtained from the climate map, corresponding protection and planning mitigation measures have been proposed.

Keywords: urban climate, GIS, heat island analysis, urban thermal environment

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Authors: Tamriko Pavliashvili

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Marriage is such an important institution of family law, which is an indicator of the development of society. Although a family can be created by the birth of a child between an unmarried couple, marriage is still the main basis for the creation of a family, during which the rights and duties imposed require legal regulation. At present, in the conditions of globalization, there are different types of marriage, although in the main countries, it is still a union of a woman and a man, which involves voluntary cohabitation and assuming and fulfilling the norms and responsibilities established on the basis of the law. Modern society is at the stage where there is a need to create a family, and therefore marriage provides the best opportunity for relationships and existence between people. The mentioned paper about the state institution - marriage gives us the opportunity to get more information about the existing habits, legal norms from the ancient times to the modern period in Georgia, and also through comparison we will see what the differences and commonalities were and are in the marriage law of the countries of the world and Georgia.

Keywords: marriage, family law, the union of man and woman, church law

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Authors: Rob Waddle

Abstract:

We study an economy with weak justice and security systems and with weak public policy and regulation or little capacity to implement them, and with high barriers to profitable sectors. We look at growth and development opportunities based on the derived demand. We show that there is hope for such an economy to grow up and to generate a win-win situation for all stakeholders if the derived demand is supplied. We then investigate conditions that could stimulate the derived demand supply. We show that little knowledge of public, private and international expenditures in the economy and academic tools are enough to trigger the derived demand supply. Our model can serve as guidance to donor and NGO working in developing countries, and show to media the best way to help is to share information about existing and accessible opportunities. It can also provide direction to vocational schools and universities that could focus more on providing tools to seize existing opportunities.

Keywords: growth, development, monopoly, oligopoly, inequality

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Authors: Kakali Bhadra

Abstract:

Harmalol administration caused remarkable reduction in proliferation of HepG₂ cells with GI₅₀ of 14.2 mM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism and differential scanning calorimetric analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 ^oC. Binding constant and stoichiometry was also calculated using the above biophysical techniques. Further, dose dependent apoptotic induction ability of harmalol was studied in HepG₂ cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub G_o/G₁ population made the cancer cell, HepG₂, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of harmalol.

Keywords: apoptosis, beta carboline alkaloid, comet assay, cytotoxicity, ROS

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Authors: Yung-Chung Chuang

Abstract:

Current situation and accumulated development of archaeological sites have very high impacts on the preservation value of the site. This research set 3 archaeological sites in Taiwan as study areas. Assessment of the degree of destruction of cultural layers due to land use change and geomorphological change were conducted with aerial photographs (1976-1978; 2016-2017) and digital aerial survey technology on 2D and 3D geographic information system platforms. The results showed that the archaeological sites were all seriously influenced due to the high land use intensity between 1976-2017. Geomorphological changes caused by human cultivation and engineering construction were main causes of site destruction, especially in private lands. Therefore, urban planning methods for land acquisition or land regulation are necessary.

Keywords: archaeological sites, accumulated development, destruction of cultural layers, geomorphological changes

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Authors: Kholil Kholil, Aniwidayati

Abstract:

MDS (Multi-Dimensional Scaling) is one method that has been widely used to evaluate the use of natural resources. By using Raffish software tool, we will able to analyze sustainability level of the natural resources use. This paper will discuss the level of sustainability of the reservoir using MDS (Multi-Dimensional Scaling) based on five dimensions: (1) Ecology & Layout, (2) Economics, (3) Social & Culture, (4) Regulations & Institutional, and (5) Infrastructure and Technology. MDS analysis results show that the dimension of ecological and layout, institutional and the regulation are lack of sustainability due to the low index score of 45.76 and 42.24. While for the economic, social and culture, and infrastructure and technology dimension reach each score of 63.12, 64.42, and 68.64 (only the sufficient sustainability category). It means that the sustainability performance of Cirata Reservoir seriously threatened.

Keywords: MDS, cirata reservoir, carrying capacity, water quality, sustainable development, sedimentation, sustainability index

Procedia PDF Downloads 376