Search results for: gene regulation

Authors: Deepak Loura

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Production and productivity of several crops in the country continue to be adversely affected by biotic (e.g., Insect-pests and diseases) and abiotic (e.g., water temperature and salinity) stresses. Over-dependence on pesticides and other chemicals is economically non-viable for the resource-poor farmers of our country. Further, pesticides can potentially affect human and environmental safety. While traditional breeding techniques and proper- management strategies continue to play a vital role in crop improvement, we need to judiciously use biotechnology approaches for the development of genetically modified crops addressing critical problems in the improvement of crop plants for sustainable agriculture. Modern biotechnology can help to increase crop production, reduce farming costs, and improve food quality and the safety of the environment. Genetic engineering is a new technology which allows plant breeders to produce plants with new gene combinations by genetic transformation of crop plants for improvement of agronomic traits. Advances in recombinant DNA technology have made it possible to have genes between widely divergent species to develop genetically modified or genetically engineered plants. Plant genetic engineering provides the strength to harness useful genes and alleles from indigenous microorganisms to enrich the gene pool for developing genetically modified (GM) crops that will have inbuilt (inherent) resistance to insect pests, diseases, and abiotic stresses. Plant biotechnology has made significant contributions in the past 20 years in the development of genetically engineered or genetically modified crops with multiple benefits. A variety of traits have been introduced in genetically engineered crops which include (i) herbicide resistance. (ii) pest resistance, (iii) viral resistance, (iv) slow ripening of fruits and vegetables, (v) fungal and bacterial resistance, (vi) abiotic stress tolerance (drought, salinity, temperature, flooding, etc.). (vii) quality improvement (starch, protein, and oil), (viii) value addition (vitamins, micro, and macro elements), (ix) pharmaceutical and therapeutic proteins, and (x) edible vaccines, etc. Multiple genes in transgenic crops can be useful in developing durable disease resistance and a broad insect-control spectrum and could lead to potential cost-saving advantages for farmers. The development of transgenic to produce high-value pharmaceuticals and the edible vaccine is also under progress, which requires much more research and development work before commercially viable products will be available. In addition, molecular-aided selection (MAS) is now routinely used to enhance the speed and precision of plant breeding. Newer technologies need to be developed and deployed for enhancing and sustaining agricultural productivity. There is a need to optimize the use of biotechnology in conjunction with conventional technologies to achieve higher productivity with fewer resources. Therefore, genetic modification/ engineering of crop plants assumes greater importance, which demands the development and adoption of newer technology for the genetic improvement of crops for increasing crop productivity.

Keywords: biotechnology, plant genetic engineering, genetically modified, biotic, abiotic, disease resistance

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Authors: Ying Zhou, Jian-Hua Wang

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Based upon the self-determination theory and self-regulated learning theory, this study examined the predictiveness of goal orientation and self-regulated learning strategies on academic achievement of adult students in distance learning. The results show a positive relation between goal orientation and the use of self-regulated strategies, and academic achievements. A significant and positive indirect relation of mastery goal orientation through self-regulated learning strategies was also found. In addition, results pointed to a positive indirect impact of performance-approach goal orientation on academic achievement. The effort regulation strategy fully mediated this relation. The theoretical and instructional implications are discussed. Interventions can be made to motivate students’ mastery or performance approach goal orientation and help them manage their time or efforts.

Keywords: goal orientation, self-regulated strategies, achievement, adult distance students

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Authors: Ali Bayram, Burak Uz, Remzi Yiğiter

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The impairment of lipid metabolism in the central nervous system has been suggested as a critical factor of Alzheimer’s disease (AD) pathogenesis. Homo sapiens acyl-coenyme A synthetase short-chain family member 2 (ACSS2) gene encodes the enzyme acetyl-Coenzyme A synthetase (AMP forming; AceCS) providing acetyl-coenzyme A (Ac-CoA) for various physiological processes, such as cholesterol and fatty acid synthesis, as well as the citric acid cycle. We investigated ACSS2, transcript variant 1 (ACSS2*1), mRNA levels in the peripheral blood mononuclear cells (PBMC) of patients with AD and compared them with the controls. The study group comprised 50 patients with the diagnosis of AD who have applied to Gaziantep University Faculty of Medicine, and Department of Neurology. 49 healthy individuals without any neurodegenerative disease are included as controls. ACSS2 mRNA expression in PBMC of AD/control patients was 0.495 (95% confidence interval: 0.410-0.598), p= .000000001902). Further studies are needed to better clarify this association.

Keywords: Alzheimer’s disease, ACSS2 Genes, mRNA expression, RT-PCR

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Authors: Sezin Ekşioğlu

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Multilabel classification has a huge importance for several applications, it is also a challenging research topic. It is a kind of supervised learning that contains binary targets. The distance between multilabel and binary classification is having more than one class in multilabel classification problems. Features can belong to one class or many classes. There exists a wide range of applications for multi label prediction such as image labeling, text categorization, gene functionality. Even though features are classified in many classes, they may not always be properly classified. There are many ensemble methods for the classification. However, most of the researchers have been concerned about better multilabel methods. Especially little ones focus on both efficiency of classifiers and pairwise relationships at the same time in order to implement better multilabel classification. In this paper, we worked on modified ensemble methods by getting benefit from k-Nearest Neighbors and neural network structure to address issues within a beneficial way and to get better impacts from the multilabel classification. Publicly available datasets (yeast, emotion, scene and birds) are performed to demonstrate the developed algorithm efficiency and the technique is measured by accuracy, F1 score and hamming loss metrics. Our algorithm boosts benchmarks for each datasets with different metrics.

Keywords: multilabel, classification, neural network, KNN

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Authors: N. Chérif, T. Allaoui, M. Benasla, H. Chaib

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Industrialization and population growth are the prime factors for which the consumption of electricity is steadily increasing. Thus, to have a balance between production and consumption, it is necessary at first to increase the number of power plants, lines and transformers, which implies an increase in cost and environmental degradation. As a result, it is now important to have mesh networks and working close to the limits of stability in order to meet these new requirements. The transient stability studies involve large disturbances such as short circuits, loss of work or production group. The consequence of these defects can be very serious, and can even lead to the complete collapse of the network. This work focuses on the regulation means that networks can help to keep their stability when submitted to strong disturbances. The magnetic energy storage-based superconductor (SMES) comprises a superconducting coil short-circuited on it self. When such a system is connected to a power grid is able to inject or absorb the active and reactive power. This system can be used to improve the stability of power systems.

Keywords: short-circuit, power oscillations, multiband PSS, power system, SMES, transient stability

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Authors: Ilian Badjakov, Ivayla Dincheva, Violeta Kondakova, Rossitza Batchvarova

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In this study, we present our initial results on the assessment of genetic diversity among wild Bulgarian berry accessions (Rubus idaeus L. Fragaria Vesca L., Vaccinium vitis-idaea L., Vaccinium myrtillus L.) using Random Amplified Polymorphic DNA (RAPDs) markers. Leaves and fruits were collected from two natural habitats - the Balkan Mountain and the Mountain of Orpheus - Rhodope Mountain. All accessions were screened for their polymorphism using five RAPD primers. The phylogenetic distances calculated from RAPD data ranged from 0.29 to 0.82 thus indicating that a high level of gene diversity is present in the selected genotypes. In order to characterize further the structure and grouping of berry accessions, a dendrogram deriving from UPGMA cluster analysis based on the genetic similarity (GS) coefficient matrix was designed. RAPD analysis provided to be efficient for discrimination of accessions within the same species with similar morphological characters

Keywords: Bulgarian wild berries, genetic diversity, RAPD, UPGMA

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Authors: Linda Ana-Maria Ungureanu

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As space exploration opens to new actors, we are faced with the interesting question of regulating more complex structures that enable private experiments. From intellectual property implications to private and public law, there is a multitude of factors and legal structures that need to be taken into consideration when opening space, and these structures need to be harmonized with the International Space Treaties governing space exploration. In this sense, this article presents an overview of the legal and contractual framework applicable to private experiments conducted in space and/or in relation to off-world environments. Additionally, the article analyses the manner in which national space agencies regulate agreements concluded with private actors and research institutions. Finally, the article sets a series of de lege ferenda proposals for the regulation of general research and development rules and intellectual property matters that are connected to experiments and research conducted in space and/or concerning off-world environments.

Keywords: private space, intellectual property, contracts, ESA guidelines, EU legislation, Intellectual property law, international IP treaties

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Authors: Samar Saadeldin Abdelmotalab Omer, Ikram Mohamed Eltayeb Elsiddig, Saad Mohammed Hussein Ayoub

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A variety of herbal medicinal plants are known to confer beneficial effects in regards to modification of cardiovascular ri’=sk factors. The anti-hypercholesterolaemic and antioxidant activities of the crude ethanolic extracts of Citrus reticulate fruit peel, Zingiber officinale rhizome and Sesamum indicum seed extracts have been demonstrated. These plants are assumed to possess biologically active principles, which impart their pharmacologic activities. GC-MS analysis of the ethanolic extracts was carried out to identify the active principles and their percentages of occurrence in the analytes. Analysis of the extracts was carried out using (GS-MS QP) type Schimadzu 2010 equipped with a capillary column RTX-50 (restec), (length 30mm, diameter 0.25mm, and thickness 0.25mm). Helium was used as a carrier gas, the temperature was programmed at 200°C for 5 minutes at a rate of 15ml/minute, and the extracts were injected using split injection mode. The identification of different components was achieved from their Mass Spectra and Retention time, compared with those in the NIST library. The results revealed the presence of 80 compounds in Sudanese locally grown C. reticulata fruit peel extract, most of which were monoterpenoid compounds including Limonene (3.03%), Alpha & Gamma - terpinenes (2.61%), Linalool (1.38%), Citral (1.72%) which are known to have profound antioxidant effects. The Sesquiterpenoids Humulene (0.26%) and Caryophyllene (1.97%) were also identified, the latter known to have profound anti-anxiety and anti-depressant activity in addition to the beneficiary effects in lipid regulation. The analysis of the locally grown S. indicum oily and water soluble portions of seed extract revealed the presence of a total of 64 compounds with considerably high percentage of the mono-unsaturated fatty acid ester methyl oleate (66.99%) in addition to methyl stearate (9.35%) and palmitate (15.71%) of oil portion, whereas, plant sterols including Gamma-sitosterol (13.5%), fucosterol (2.11%) and stigmasterol (1.95%) in addition to gamma-tocopherol (1.16%) were detected in extract water-soluble portion. The latter indicate various principles known to have valuable pharmacological benefits including antioxidant activities and beneficiary effects on intestinal cholesterol absorption and regulation of serum cholesterol levels. Z. officinale rhizome extract analysis revealed the presence of 93 compounds, the most abundant were alpha-zingeberine (16.5%), gingerol (9.25%), alpha-sesquiphellandrene (8.3%), zingerone (6.78%), beta-bisabolene (4.19%), alpha-farnesene (3.56%), ar-curcumene (3.29%), gamma-elemene (1.25%) and a variety of other compounds. The presence of these active principles reflected on the activity of the extract. Activity could be assigned to a single or a combination of two or more extract components. GC-MS analysis concluded the occurrence of compounds known to possess antioxidant activity and lipid profile effects.

Keywords: gas chromatography, indicum, officinale, reticulata

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Authors: Dominika Collett

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AI applications, such as machine learning, require access to a vast amount of data in the training phase, which can often be the subject of copyright protection. During later usage, the various content with which the application works can be recorded or made available on the basis of which it produces the resulting output. The EU has recently adopted new legislation to secure machine access to protected works under the DSM Directive; but, the issue of machine use of copyright works is not clearly addressed. However, such clarity is needed regarding the increasing importance of AI and its development. Therefore, this paper provides a basic background of the technology used in the development of applications in the field of computer creativity. The second part of the paper then will focus on a legal analysis of machine use of the authors' works from the perspective of existing European and Czech legislation. The main results of the paper discuss the potential collision of existing legislation in regards to machine use of works with special focus on exceptions and limitations. The legal regulation of machine use of copyright work will impact the development of AI technology.

Keywords: copyright, artificial intelligence, legal use, infringement, Czech law, EU law, text and data mining

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Authors: Mehmet Yahsi, Ozkan Ugurlu, Ercan Yuksekyildiz

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Assistant department among the electric and electronic officers on ships, has an important place for the maintenance of electric and electronic devices. From this perspective, ships must be employed with a sufficient number of assistant department. In this study, in order to research on the Turkish-flagged ships electric and electronic officers employment; Our national manning regulation compared with international regulations. The data used in this study were collected via visiting of the ships. 3000 gross tonnage and above engaged in international voyages 181 Turkish-flagged ship’s crew lists were compared with Minimum Safety Manning Certificates. According to the findings; employment rate, %54 electric and electronic officers. According to the results of the study; Turkish-flagged ships, although it is not obliged to electric and electronic officers, were employed on ships.

Keywords: manning, electric officer, electronic officer, minimum safety manning certificate

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Authors: He YuanYan

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In recent years, China has implemented the reform of land and space planning. As an important public policy, land and space planning plays a vital role in the construction and development of cities. Land and space planning throughout the country is in full swing, but there are still many disputes from all walks of life. The content, scope, and specific implementation process of land and space planning are also ambiguous, leading to the integration of multiple regulation problems such as unclear authority, unclear responsibilities, and poor planning results during the implementation of land and space planning. Therefore, it is necessary to sort out the development and evolution of domestic and foreign land space planning, clarify the problems and cruxes from the current situation of China's land space planning, and sort out the obstacles and countermeasures to the implementation of this policy, so as to deepen the understanding of the connotation of land space planning. It is of great practical significance for all planners to correctly understand and clarify the specific contents and methods of land space planning and to smoothly promote the implementation of land space planning at all levels.

Keywords: territorial spatial planning, public policy, land space, overall planning

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Authors: D. He, Y. Pang, G. Lodewijks

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Belt conveyors play an important role in continuous dry bulk material transport, especially at the mining industry. Speed control is expected to reduce the energy consumption of belt conveyors. Transient operation is the operation of increasing or decreasing conveyor speed for speed control. According to literature review, current research rarely takes the conveyor dynamics in transient operation into account. However, in belt conveyor speed control, the conveyor dynamic behaviors are significantly important since the poor dynamics might result in risks. In this paper, the potential risks in transient operation will be analyzed. An existing finite element model will be applied to build a conveyor model, and simulations will be carried out to analyze the conveyor dynamics. In order to realize the soft speed regulation, Harrison’s sinusoid acceleration profile will be applied, and Lodewijks estimator will be built to approximate the required acceleration time. A long inclined belt conveyor will be studied with two major simulations. The conveyor dynamics will be given.

Keywords: belt conveyor , speed control, transient operation, dynamics

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Authors: Anna M. Pretorius

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The emerging markets category for portfolio investment was introduced in 1986 in an attempt to promote capital market development in less developed countries. Investors traditionally diversified their portfolios by investing in different developed markets. However, high growth opportunities forced investors to consider emerging markets as well. Examples include the rapid growth of the “Asian Tigers” during the 1980s, growth in Latin America during the 1990s and the increased interest in emerging markets during the global financial crisis. As such, portfolio flows to emerging markets have increased substantially. In 2002 7% of all equity allocations from advanced economies went to emerging markets; this increased to 20% in 2012. The stronger links between advanced and emerging markets led to increased synchronization of asset price movements. This increased level of stock market integration for emerging markets is confirmed by various empirical studies. Against the background of increased interest in emerging market assets and the increasing level of integration of emerging markets, this paper focuses on the determinants of stock market integration of emerging market countries. Various studies have linked the level of financial market integration with specific economic variables. These variables include: economic growth, local inflation, trade openness, local investment, budget surplus/ deficit, market capitalization, domestic bank credit, domestic institutional and legal environment and world interest rates. The aim of this study is to empirically investigate to what extent trade-related determinants have an impact on stock market integration. The panel data sample include data of 16 emerging market countries: Brazil, Chile, China, Colombia, Czech Republic, Hungary, India, Malaysia, Pakistan, Peru, Philippines, Poland, Russian Federation, South Africa, Thailand and Turkey for the period 1998-2011. The integration variable for each emerging stock market is calculated as the explanatory power of a multi-factor model. These factors are extracted from a large panel of global stock market returns. Trade related explanatory variables include: exports as percentage of GDP, imports as percentage of GDP and total trade as percentage of GDP. Other macroeconomic indicators – such as market capitalisation, the size of the budget deficit and the effectiveness of the regulation of the securities exchange – are included in the regressions as control variables. An initial analysis on a sample of developed stock markets could not identify any significant determinants of stock market integration. Thus the macroeconomic variables identified in the literature are much more significant in explaining stock market integration of emerging markets than stock market integration of developed markets. The three trade variables are all statistically significant at a 5% level. The market capitalisation variable is also significant while the regulation variable is only marginally significant. The global financial crisis has highlighted the urgency to better understand the link between the financial and real sectors of the economy. This paper comes to the important finding that, apart from the level of market capitalisation (as financial indicator), trade (representative of the real economy) is a significant determinant of stock market integration of countries not yet classified as developed economies.

Keywords: emerging markets, financial market integration, panel data, trade

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Authors: Zou Yihui

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The integration of the traditional landscape of the ancient city and the poet's emotions and symbolization into ancient poetry is the unique cultural gene and spiritual core of the historical city, and re-understanding the historical landscape pattern from the poetry is conducive to continuing the historical city context and improving the current situation of the gradual decline of the poetry of the modern historical urban landscape. Starting from Tang poetry uses semantic analysis methods、combined with text mining technology, entry mining, word frequency analysis, and cluster analysis of the landscape information of Tang Chang'an City were carried out, and the method framework for analyzing the urban landscape form based on poetry text was constructed. Nearly 160 poems describing the landscape of Tang Chang'an City were screened, and the poetic landscape characteristics of Tang Chang'an City were sorted out locally in order to combine with modern urban spatial development to continue the urban spatial context.

Keywords: Tang Chang'an City, poetic texts, semantic analysis, historical landscape

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Ihtisham Bukhari

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In the current study, we enrolled a 46, XY phenotypically female patient bearing testes in her inguinal canal. DNA sequencing of the AR gene detected a missense mutation C.1715A > G (p. Y572C) in exon 2 which is already known to cause Complete androgen insensitivity syndrome (CAIS). We further studied the effects of this mutation on the testicular histopathology of the patient. No spermatocytes were seen in the surface spreading of testicular tissues while H&E staining showed that seminiferous tubules predominantly have only Sertoli cells. To confirm this meiotic failure is likely due to the current AR mutation we performed mRNA expression of genes associated with AR pathway, expression and location of the associated proteins in testicular tissues. Western blot and real-time PCR data showed that the patient had high levels of expression of AMH, SOX9, and INNB in testis. Tubules were stained with SOX9 and AMH which revealed Sertoli cell maturation arrest. Therefore, we suggest that AR mutation enhances AMH expression which ultimately leads to failure in the maturation of Sertoli cells and failure in spermatogenesis.

Keywords: androgen receptor, spermatogenesis, infertility, Sertoli cell only syndrome

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Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

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Authors: M. F. Elzarei, A. M. Alseaf

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Hundred uncorrelated animal and thirty six markers were used in this study to study the molecular characterization of Saudi native Ardi goat (BM18189, ILSTS030, INRA005, OarFCB48, BM2113, ILSTS033, INRA023, RM088, CSRD247, ILSTS034, INRA063, SRCRSP1, ILSTS002, ILSTS044, INRA172, SRCRSP5, ILSTS005, ILSTS049, MAF70, SRCRSP8, ILSTS011, ILSTS058, OarAE54, SRCRSP9, ILSTS019, ILSTS059, OARCP34, TGLA53, ILSTS022, ILSTS082, OARE129, TGLA73, ILSTS029, ILSTS087, OARE193, and RM004). Ardi goat showed high variability. The mean number of alleles per locus ranged from 5 in SRCRSP1 locus to 13.5 in CSRD247 locus. Gene diversities varied within a wide range, from 0.53 in ILSTS002 locus to 0.86 in RM088 locus. Hardy-Weinberg equilibrium was tested in order to evaluate the significance of inbreeding occurring in each locus in Ardi population. Only SRCRSP9, INRA005, ILSTS030 loci showed significance in this way.

Keywords: molecular characterization, microsatellite markers, Ardi goats, Hardy-Weinberg equilibrium

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Authors: Ilknur Tuncer, Nihayet Bizsel

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The studies in bacterial diversity and antimicrobial resistance in coastal areas are important to understand the variability in the community structures and metabolic activities. In the present study, antimicrobial susceptibility and phylogenetic analysis of bacteria isolated from stations with different depths and influenced by terrestrial and marine fluxes in eastern Aegean Sea were illustrated. 51% of the isolates were found as resistant and 14% showed high MAR index indicating the high-risk sources of contamination in the environment. The resistance and the intermediate levels and high MAR index of the study area were 38–60%, 11–38% and 0–40%, respectively. According to 16S rRNA gene analysis, it was found that the isolates belonged to two phyla Firmicutes and Gammaproteobacteria with the genera Bacillus, Halomonas, Oceanobacillus, Photobacterium, Pseudoalteromonas, Psychrobacter, and Vibrio. 47% of Bacillus strains which were dominant among all isolates were resistant. In addition to phylogenetically diverse bacteria, the variability in resistance, intermediate and high MAR index levels of the study area indicated the effect of geographical differences.

Keywords: bacterial diversity, multiple antibiotic resistance, 16S rRNA genes, Aegean Sea

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Authors: Kiseob Chung, Hyeonmin Kang

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This study aims to explore what is intercultural competency needed for teacher through their experience at the public multicultural alternative school. The public alternative multicultural school is an accredited school for immigrants or students from multicultural families who have experienced school maladjustment at public school. This school has self-regulation in curriculum and function of bridge to public school by helping their adaptation. In particular, this study answers the following questions: What are the most difficulties for teacher at the multicultural alternative school in comparison to public school? What competencies are required for teacher at the multicultural alternative school? Which competencies in cognitive, emotional and practical area should be more required in order for teacher to communicate with student effectively (successfully) in class and other activities in school? What is the background of that we called these competencies especially as ‘intercultural’? This study focuses to clarify teacher’s competency to help immigrants of students from multicultural background to adjust to school life with the term of intercultural competency.

Keywords: intercultural competency for teacher, multicultural alternative school, multicultural students, school maladjustment

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Authors: Wen-Yang Hu, Ranli Lu, Mark Maienschein-Cline, Danping Hu, Larisa Nonn, Toshi Shioda, Gail S. Prins

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Background: Genetic mutations are highly associated with increased prostate cancer risk. In addition to whole genome sequencing, somatic mutations can be identified by aligning transcriptome sequences to the human genome. Here we analyzed bulk RNAseq and single cell RNAseq data of human prostate cancer cells and their matched non-cancer cells in benign regions from 4 individual patients. Methods: Sequencing raw reads were aligned to the reference genome hg38 using STAR. Variants were annotated using Annovar with respect to overlap gene annotation information, effect on gene and protein sequence, and SIFT annotation of nonsynonymous variant effect. We determined cancer-specific novel alleles by comparing variant calls in cancer cells to matched benign cells from the same individual by selecting unique alleles that were only detected in the cancer samples. Results: In bulk RNAseq data from 3 patients, the most common variants were the noncoding mutations at UTR3/UTR5, and the major variant types were single-nucleotide polymorphisms (SNP) including frameshift mutations. C>T transversion is the most frequently presented substitution of SNP. A total of 222 genes carrying unique exonic or UTR variants were revealed in cancer cells across 3 patients but not in benign cells. Among them, transcriptome levels of 7 genes (CITED2, YOD1, MCM4, HNRNPA2B1, KIF20B, DPYSL2, NR4A1) were significantly up or down regulated in cancer stem cells. Out of the 222 commonly mutated genes in cancer, 19 have nonsynonymous variants and 11 are damaged genes with variants including SIFT, frameshifts, stop gain/loss, and insertions/deletions (indels). Two damaged genes, activating transcription factor 6 (ATF6) and histone demethylase KDM3A are of particular interest; the former is a survival factor for certain cancer cells while the later positively activates androgen receptor target genes in prostate cancer. Further, single cell RNAseq data of cancer cells and their matched non-cancer benign cells from both primary 2D and 3D tumoroid cultures were analyzed. Similar to the bulk RNAseq data, single cell RNAseq in cancer demonstrated that the exonic mutations are less common than noncoding variants, with SNPs including frameshift mutations the most frequently presented types in cancer. Compared to cancer stem cell enriched-3D tumoroids, 2D cancer cells carried 3-times higher variants, 8-times more coding mutations and 10-times more nonsynonymous SNP. Finally, in both 2D primary and 3D tumoroid cultures, cancer stem cells exhibited fewer coding mutations and noncoding SNP or insertions/deletions than non-stem cancer cells. Summary: Our study demonstrates the usefulness of bulk and single cell RNAseaq data in identifying somatic mutations in prostate cancer, providing an alternative method in screening candidate genes for prostate cancer diagnosis and potential therapeutic targets. Cancer stem cells carry fewer somatic mutations than non-stem cancer cells due to their inherited immortal stand DNA from parental stem cells that explains their long-lived characteristics.

Keywords: prostate cancer, stem cell, genomic mutation, RNAseq

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Authors: Avan Al-Saffar, Eun-Jin Kim

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Both the logistic growth model and the gompertz growth model are used to describe growth processes. Both models driven by perturbations in different cases are investigated using information theory as a useful measure of sustainability and the variability. Specifically, we study the effect of different oscillatory modulations in the system's parameters on the evolution of the system and Probability Density Function (PDF). We show the maintenance of the initial conditions for a long time. We offer Fisher information analysis in positive and/or negative feedback and explain its implications for the sustainability of population dynamics. We also display a finite amplitude solution due to the purely fluctuating growth rate whereas the periodic fluctuations in negative feedback can lead to break down the system's self-regulation with an exponentially growing solution. In the cases tested, the gompertz and logistic systems show similar behaviour in terms of information and sustainability although they develop differently in time.

Keywords: dynamical systems, fisher information, probability density function (pdf), sustainability

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Authors: Yiqi Wu, Simon Tait, Andrew Nichols

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Management of UK railway drainage assets is challenging due to the large amounts of historical assets with long asset life cycles. A major concern for asset managers is to maintain the required performance economically and efficiently while complying with the relevant regulation and legislation. As the majority of the drainage assets are buried underground and are often difficult or costly to examine, it is important for asset managers to understand and model the degradation process in order to foresee the upcoming reduction in asset performance and conduct proactive maintenance accordingly. In this research, a Markov chain approach is used to model the deterioration process of rail drainage assets. The study is based on historical condition scores and characteristics of drainage assets across the whole railway network in England, Scotland, and Wales. The model is used to examine the effect of various characteristics on the probabilities of degradation, for example, the regional difference in probabilities of degradation, and how material and shape can influence the deterioration process for chambers, channels, and pipes.

Keywords: deterioration, degradation, markov models, probability, railway drainage

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Authors: Rashad Al-Hindi

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The aims of the study were to isolate and identify potential probiotic lactic acid bacteria due to their therapeutic and food preservation importance. Sixty-three suspected lactic acid bacteria (LAB) strains were isolated from thirteen different raw milk and fermented milk product samples of various animal origins manufactured indigenously in the Kingdom of Saudi Arabia using de Man, Rogosa and Sharpe (MRS) agar medium and various incubation conditions. The identification of forty-six selected LAB strains was performed using molecular methods (16S rDNA gene sequencing). The LAB counts in certain samples were higher under microaerobic incubation conditions than under anaerobic conditions. The identified LAB belonged to the following genera: Enterococcus (16 strains), Lactobacillus (9 strains), Weissella (10 strains), Streptococcus (8 strains) and Lactococcus (3 strains), constituting 34.78%, 19.57%, 21.74%, 17.39% and 6.52% of the suspected isolates, respectively. This study noted that the raw milk and traditional fermented milk products of Saudi Arabia, especially stirred yogurt (Laban) made from camel milk, could be rich in LAB. The obtained LAB strains in this study will be tested for their probiotic potentials in another ongoing study.

Keywords: dairy, LAB, probiotic, Saudi Arabia

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Authors: Inna Kornienko, Svetlana Guryeva, Anatoly Shekhter, Elena Petersen

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Transplantation is an effective treatment option for patients suffering from different end-stage diseases. However, it is plagued by a constant shortage of donor organs and the subsequent need of a lifelong immunosuppressive therapy for the patient. Currently some researchers look towards using of pig organs to replace human organs for transplantation since the matrix derived from porcine organs is a convenient substitute for the human matrix. As an initial step to create a new ex vivo tissue engineered model, optimized protocols have been created to obtain organ-specific acellular matrices and evaluated their potential as tissue engineered scaffolds for culture of normal cells and tumor cell lines. These protocols include decellularization by perfusion in a bioreactor system and immersion-agitation on an orbital shaker with use of various detergents (SDS, Triton X-100) and freezing. Complete decellularization – in terms of residual DNA amount – is an important predictor of probability of immune rejection of materials of natural origin. However, the signs of cellular material may still remain within the matrix even after harsh decellularization protocols. In this regard, the matrices obtained from tissues of low-immunogenic pigs with α3Galactosyl-tranferase gene knock out (GalT-KO) may be a promising alternative to native animal sources. The research included a study of induced effect of frozen and fresh fragments of GalT-KO skin on healing of full-thickness plane wounds in 80 rats. Commercially available wound dressings (Ksenoderm, Hyamatrix and Alloderm) as well as allogenic skin were used as a positive control and untreated wounds were analyzed as a negative control. The results were evaluated on the 4th day after grafting, which corresponds to the time of start of normal wound epithelization. It has been shown that a non-specific immune response in models treated with GalT-Ko pig skin was milder than in all the control groups. Research has been performed to measure technical skin characteristics: stiffness and elasticity properties, corneometry, tevametry, and cutometry. These metrics enabled the evaluation of hydratation level, corneous layer husking level, as well as skin elasticity and micro- and macro-landscape. These preliminary data may contribute to development of personalized transplantable organs from GalT-Ko pigs with significantly limited potential of immune rejection. By applying growth factors to a decellularized skin sample it is possible to achieve various regenerative effects based on the particular situation. In this particular research BMP2 and Heparin-binding EGF-like growth factor have been used. Ideally, a bioengineered organ must be biocompatible, non-immunogenic and support cell growth. Porcine organs are attractive for xenotransplantation if severe immunologic concerns can be bypassed. The results indicate that genetically modified pig tissues with knock-outed α3Galactosyl-tranferase gene may be used for production of low-immunogenic matrix suitable for transplantation.

Keywords: decellularization, low-immunogenic, matrix, scaffolds, transplants

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Authors: Sulasmi Sudirman, Rachmadanty Mujah Hartika

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Traffic violence is currently a big issue in Indonesia. However, the road users perceived risk that is caused by traffic violence is low. The lack of safety driving awareness is one of the factors that road users committed to traffic violence. There are several lists of common traffic violence in Indonesia such as lack of physical fitness, not wearing helmet, unfasten seatbelt, breaking through the traffic light, not holding a driving license, and some more violence. This research sought to explore the perception of road users toward traffic violence. The participants were road users in Makassar, Indonesia who were using cars and motorbikes. The method of the research was a qualitative approach by using a personal interview to collect data. The research showed that there three main ideas of perceiving traffic violence which are motives, environment that supported traffic violence, and reinforcement. The road users committed traffic violence had particular motive, for example, rushing. The road users committed to traffic violence when other road users and significant other did the same. The road users committed traffic violence when the police were not there to give a ticket. It can be concluded that the perception of road users toward traffic violence determined by internal aspect, the social aspect, and regulation.

Keywords: perception, road users, traffic, violence

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Authors: Sanguk Nam, Van Ha Nguyen, Hanjung Song

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For low-power applications such as adapters for portable devices and USB chargers, the primary side regulation (PSR) fly-back converter is widely used in lieu of the conventional fly-back converter using opto-coupler because of its simpler structure and lower cost. In the literature, there has been studies focusing on the design of PSR circuit; however, the conventional sensing method in PSR circuit using RC delay has a lower accuracy as compared to the conventional fly-back converter using opto-coupler. In this paper, we propose a novel PWM/PFM controller using new sensing technique for the PSR fly-back converter which can control an accurate output voltage. The conventional PSR circuit can sense the output voltage information from the auxiliary winding to regulate the duty cycle of the clock that control the output voltage. In the sensing signal waveform, there has two transient points at time the voltage equals to Vout+VD and Vout, respectively. In other to sense the output voltage, the PSR circuit must detect the time at which the current of the diode at the output equals to zero. In the conventional PSR flyback-converter, the sensing signal at this time has a non-sharp-negative slope that might cause a difficulty in detecting the output voltage information since a delay of sensing signal or switching clock may exist which brings out an unstable operation of PSR fly-back converter. In this paper instead of detecting output voltage at a non-sharp-negative slope, a sharp-positive slope is used to sense the proper information of the output voltage. The proposed PRS circuit consists of a saw-tooth generator, a summing circuit, a sample and hold circuit and a peak detector. Besides, there is also the start-up circuit which protects the chip from high surge current when the converter is turned on. Additionally, to reduce the standby power loss, a second mode which operates in a low frequency is designed beside the main mode at high frequency. In general, the operation of the proposed PSR circuit can be summarized as following: At the time the output information is sensed from the auxiliary winding, a saw-tooth signal from the saw-tooth generator is generated. Then, both of these signals are summed using a summing circuit. After this process, the slope of the peak of the sensing signal at the time diode current is zero becomes positive and sharp that make the peak easy to detect. The output of the summing circuit then is fed into a peak detector and the sample and hold circuit; hence, the output voltage can be properly sensed. By this way, we can sense more accurate output voltage information and extend margin even circuit is delayed or even there is the existence of noise by using only a simple circuit structure as compared with conventional circuits while the performance can be sufficiently enhanced. Circuit verification was carried out using 0.35μm 700V Magnachip process. The simulation result of sensing signal shows a maximum error of 5mV under various load and line conditions which means the operation of the converter is stable. As compared to the conventional circuit, we achieved very small error only used analog circuits compare with conventional circuits. In this paper, a PWM/PFM controller using a simple and effective sensing method for PSR fly-back converter has been presented in this paper. The circuit structure is simple as compared with the conventional designs. The gained results from simulation confirmed the idea of the design

Keywords: primary side regulation, PSR, sensing technique, peak detector, PWM/PFM control, fly-back converter

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Authors: C. I. Boshoff, S. Steenkamp-Jonker

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Cystic echinococcosis (CE), caused by Echinococcus granulosus is an important parasitic infection in livestock worldwide, with severe zoonotic potential. It is important to understand the variability of Echinococcus granulosus, as genotype variations may influence lifecycle patterns, development rate, and transmission. Cystic Echinococcus samples were collected from domestic animals in Eastern Cape Province, South Africa. A molecular study was performed on 14 hydatid cysts obtained from caprine, ovine and bovine livers in order to determine the Echinococcus granulosus strain present in these hosts. The sequencing of the mitochondrial cytochrome C oxidase subunit I (coxI) gene of the hydatid cysts produced sequences of 400 bp for each sample analysed. These sequences were aligned with those present in GenBank and a phylogenetic tree was constructed. Based on coxI genotype the isolates could be grouped into E. granulosus sensu stricto. The findings of the study represent a pilot molecular study on Echinococcus from domestic animals undertaken in South Africa.

Keywords: Echinococcus granulosus, genotypes, livestock, South Africa

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Authors: Mahmoud Said Jneid, Péter Harth

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EVs with independent wheel driving greatly improve vehicle stability in poor road conditions. Wheel torques can be precisely controlled through electric motors driven using advanced technologies. As a result, various types of advanced chassis assistance systems (ACAS) can be implemented. This paper proposes an integrated torque vectoring control based on wheel slip regulation in both braking and traction modes. For generating the corrective yaw moment, the vehicle yaw rate and sideslip angle are monitored. The corrective yaw moment is distributed into traction and braking torques based on an equal-opposite components approach. The proposed torque vectoring control scheme is validated in simulation and the results show its superiority when compared to conventional schemes.

Keywords: all-wheel-drive, electric vehicle, torque vectoring, regenerative braking, stability control, traction control, yaw rate control

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Authors: Robby Dwiko Juliardi, Queena K. Qian

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Economic, environmental, and human considerations, as sustainable building design principles, are to be balanced and integrated into building design strategy. Building codes often suggest the efficient and sustainable building products, such as energy-efficient fixtures. However, building departments sometimes fail to manage the full range of requirements in the building assessment, such as siting, neighborhood proximity, and public facility, etc. Hence, it shows roadmap develops the future, an extended look at the future of a chosen field of inquiry composed from the collective knowledge and imagination of the brightest drivers of change in that field. This paper is taken from the best practice of green building implementation in a few countries of Asia (China, Malaysia, and India). Sustainable development will be presented on developing the roadmap of sustainability development of a country. Findings on the similarities and dissimilarities of those countries will show: (1) A general knowledge development on the sustainable green roadmap in Asia, (2) What are the components of developing the roadmap, and (3) What affects the government regulation in a political ecology.

Keywords: developing roadmap, green building, political ecology, sustainable development

Procedia PDF Downloads 320