Search results for: gene copy number

Authors: Shiamaa Eltantawy, Gihan Sobhy, Alif Alaam

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Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disease that results in excess copper buildup in the body. It primarily affects the liver and basal ganglia of the brain, but it can affect other organ systems. Musculoskeletal abnormalities, including premature osteoarthritis, skeletal deformity, and pathological bone fractures, can occasionally be found in WD patients with a hepatic or neurologic type. The aim was to assess the prevalence of osteoporosis and osteopenia in Wilson’s disease patients. This case-control study was conducted on ninety children recruited from the inpatient ward and outpatient clinic of the Paediatric Hepatology, Gastroenterology, and Nutrition department of the National Liver Institute at Menofia University, aged from 1 to 18 years. Males were 49, and females were 41. Children were divided into three groups: (Group I) consisted of thirty patients with WD; (Group II) consisted of thirty patients with chronic liver disease other than WD; (Group III) consisted of thirty age- and sex-matched healthy The exclusion criteria were patients with hyperparathyroidism, hyperthyroidism, renal failure, Cushing's syndrome, and patients on certain drugs such as chemotherapy, anticonvulsants, or steroids. All patients were subjected to the following: 1- Full history-taking and clinical examination. 2-Laboratory investigations: (FBC,ALT,AST,serum albumin, total protein, total serum bilirubin,direct bilirubin,alkaline phosphatase, prothrombin time, serum critine,parathyroid hormone, serum calcium, serum phosphrus). 3-Bone mineral density (BMD, gm/cm2) values were measured by dual-energy X-ray absorptiometry (DEXA). The results revealed that there was a highly statistically significant difference between the three groups regarding the DEXA scan, and there was no statistically significant difference between groups I and II, but the WD group had the lowest bone mineral density. The WD group had a large number of cases of osteopenia and osteoporosis, but there was no statistically significant difference with the group II mean, while a high statistically significant difference was found when compared to group III. In the WD group, there were 20 patients with osteopenia, 4 patients with osteoporosis, and 6 patients who were normal. The percentages were 66.7%, 13.3%, and 20%, respectively. Therefore, the largest number of cases in the WD group had osteopenia. There was no statistically significant difference found between WD patients on different treatment regimens regarding DEXA scan results (Z-Score). There was no statistically significant difference found between patients in the WD group (normal, osteopenic, or osteoporotic) regarding phosphorus (mg/dL), but there was a highly statistically significant difference found between them regarding ionised Ca (mmol/L). Therefore, there was a decrease in bone mineral density when the Ca level was decreased. In summary, Wilson disease is associated with bone demineralization. The largest number of cases in the WD group in our study had osteopenia (66.7%). Different treatment regimens (zinc monotherapy, Artamin, and zinc) as well as different laboratory parameters have no effect on bone mineralization in WD cases. Decreased ionised Ca is associated with low BMD in WD patients. Children with WD should be investigated for BMD.

Keywords: wilson disease, Bone mineral density, liver disease, osteoporosis

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Authors: S. Altmeyer, B. Hof, F. Marques, J. M. Lopez

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We present numerical simulations concerning the reversal of spiraling vortices in short highly counter-rotating cylinders. Increasing the differential cylinder rotation results in global flow-inversion is which develops various different and complex flow dynamics of several quasi-periodic solutions that differ in their number of vortex cells in the bulk. The dynamics change from being dominated of the inner cylinder boundary layer with ’passive’ only responding outer one to be dominated by the outer cylinder boundary layer with only responding inner one. Solutions exist on either two or three tori invariant manifolds whereby they appear as symmetric or asymmetric states. We find for either moderate and high inner cylinder rotation speed the quasiperiodic flow to consist of only two vortex cells but differ as the vortices has opposite spiraling direction. These both flows live on 2-tori but differ in number of symmetries. While for the quasi-periodic flow (q^a_2) at lower rotation speed a pair of symmetrically related 2-tori T2 exists the quasi-periodic flow (q^s_2) at higher rotation speeds is symmetric living on a single 2-torus T2. In addition these both flows differ due to their dominant azimuthal m modes. The first is dominated by m=1 whereas for the latter m=3 contribution is largest. The 2-tori states are separated by a further quasi-periodic flow (q^a_3) living on pair of symmetrically related 3-tori T3. This flow offers a ’periodical’ competition between a two and three vortex cell states in the bulk. This flow is also an m=1 solution as for the quasiperiodic flows living on the pair of symmetrically-related 2-tori states. Moreover we find hysteresis resulting in coexisting regions of different quasiperiodic flows q^s_2 and q^a_3 with increasing and decreasing the differential rotation.

Keywords: transition, bifurcation, torus, symmetries

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Authors: Il Ho Park, Joong Seob Lee, Sung Hun Kang, Jae-Min Shin, Il Seok Park, Seok Min Hong, Seok Jin Hong

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Introduction: The human microbiota is the aggregate of microorganisms, and the bacterial microbiome of the human digestive tract contributes to both health and disease. In health, bacteria are key components in the development of mucosal barrier function and in innate and adaptive immune responses, and they also work to suppress the establishment of pathogens. In human upper airway, the sinonasal microbiota might play an important role in chronic rhinosinusitis (CRS). The purpose of this study is to investigate the human upper airway microbiome in CRS patients and to compare the sinonasal microbiome of adults with children. Materials and methods: A total of 19 samples from 19 patients (Group1; 9 CRS in children, aged 5 to 14 years versus Group 2; 10 CRS in adults aged 21 to 59 years) were examined. Swabs were collected from the middle meatus and/or anterior ethmoid region under general anesthesia during endoscopic sinus surgery or tonsillectomy. After DNA extraction from swab samples, we analysed bacterial microbiome consortia using 16s rRNA gene sequencing approach (the Illumina MiSeq platform). Results: In this study, relatively abundance of the six bacterial phyla and tremendous genus and species found in substantial amounts in the individual sinus swab samples, include Corynebacterium, Hemophilus, Moraxella, and Streptococcus species. Anaerobes like Fusobacterium and Bacteroides were abundantly present in the children group, Bacteroides and Propionibacterium were present in adults group. In genus, Haemophilus was the most common CRS microbiome in children and Corynebacterium was the most common CRS microbiome in adults. Conclusions: Our results show the diversity of human upper airway microbiome, and the findings will suggest that CRS is a polymicrobial infection. The Corynebacterium and Hemophilus may live as commensals on mucosal surfaces of sinus in the upper respiratory tract. The further study will be needed for analysis of microbiome-human interactions in upper airway and CRS.

Keywords: microbiome, upper airway, chronic rhinosinusitis, adult and children

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Authors: Robin V. Cupido

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Online dispute resolution has been identified in many countries as a viable alternative for resolving conflicts which have arisen in the so-called digital age. This system of dispute resolution is developing alongside the Internet, and as new types of transactions are made possible by our increased connectivity, new ways of resolving disputes must be explored. Developed nations, such as the United States of America and the European Union, have been involved in creating these online dispute resolution mechanisms from the outset, and currently have sophisticated systems in place to deal with conflicts arising in a number of different fields, such as e-commerce, domain name disputes, labour disputes and conflicts arising from family law. Specifically, in the field of e-commerce, the Internet’s borderless nature has served as a way to promote cross-border trade, and has created a global marketplace. Participation in this marketplace boosts a country’s economy, as new markets are now available, and consumers can transact from anywhere in the world. It would be especially advantageous for developing nations to be a part of this global marketplace, as it could stimulate much-needed investment in these nations, and encourage international co-operation and trade. However, for these types of transactions to proliferate, an effective system for resolving the inevitable disputes arising from such an increase in e-commerce is needed. Online dispute resolution scholarship and practice is flourishing in developed nations, and it is clear that the gap is widening between developed and developing nations in this regard. The potential for implementing online dispute resolution in developing countries has been discussed, but there are a number of obstacles that have thus far prevented its continued development. This paper aims to evaluate the various political, infrastructural and socio-economic challenges faced in developing nations, and to question how these have impacted the acceptance and development of online dispute resolution, scholarship and training of online dispute resolution practitioners and, ultimately, developing nations’ readiness to participate in cross-border e-commerce.

Keywords: developing countries, feasibility, online dispute resolution, progress

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Authors: Anastasia Papachristou, Anastasia Ntikoudi, Vasileios Saridakis

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The safety and health care needs of refugees have become an increasingly important issue all over the world especially during last few decades. Wars are the primary reason for refugees to leave their countries. Moreover, refugees are frequently exposed to a variety of stressors such as socioeconomic disadvantages, poverty, changes in family structure and functioning, losing social support, difficulty to access education, living in very crowded places, experiencing racism and isolation. This systematic review included research studies published between 2007-2017 from the search databases Medline, Scopus, Cinahl and PubMed, with keywords 'war survivors', 'war trauma', 'psychiatric disorders', 'refugees'. In order to meet the purpose of the systematic review, further research for complementary studies was conducted into the literature references of the research articles included in this study that would meet the criteria. Overall, 14 studies were reviewed and evaluated. The majority of them demonstrated that the most common psychiatric disorders observed among war refugees are post-traumatic stress disorder (PTSD), depression, anxiety and multiple somatic complaints. Moreover, significant relationship was shown between the number of traumatic events experienced by the refugees and sociodemographic features such as gender, age and previous family history of any psychological disorder. War violence is highly traumatic, causing multiple, long-term negative outcomes such as the aforementioned psychiatric disorders. The number of the studies reviewed in this systematic review is not representative of the problem and its significance. The need for care of the survivors and their families is vital. Further research is necessary in order to clarify the role of predictive factors in the development and maintenance of post-traumatic stress and the rest psychiatric disorders following war trauma. In conclusion, it is necessary to have large multicenter studies in the future in order to be able to draw reliable conclusions about the effects of war.

Keywords: psychiatric disorders, refugees, war survivors, war trauma

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Authors: Jordan Chamarande, Lisiane Cunat, Corentine Alauzet, Catherine Cailliez-Grimal

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Gut microbiota (GM) is now considered a new organ mainly due to the microorganism’s specific biochemical interaction with its host. Although mechanisms underlying host-microbiota interactions are not fully described, it is now well-defined that cell surface molecules and structures of the GM play a key role in such relation. The study of surface structures of GM members is also fundamental for their role in the establishment of species in the versatile and competitive environment of the digestive tract and as a potential virulence factor. Among these structures are capsular polysaccharides (CPS), fimbriae, pili and lipopolysaccharides (LPS), all well-described for their central role in microorganism colonization and communication with host epithelium. The health-promoting Parabacteroides distasonis, which is part of the core microbiome, has recently received a lot of attention, showing beneficial properties for its host and as a new potential biotherapeutic product. However, to the best of the authors’ knowledge, the cell surface molecules and structures of P. distasonis that allow its maintain within the GM are not identified. Moreover, although P. distasonis is strongly recognized as intestinal commensal species with benefits for its host, it has also been recognized as an opportunistic pathogen. In this study, we reported gene clusters potentially involved in the synthesis of the capsule, fimbriae-like and pili-like cell surface structures in 26 P. distasonis genomes and applied the new RfbA-Typing classification in order to better understand and characterize the beneficial/pathogenic behaviour related to P. distasonis strains. In context, 2 different types of fimbriae, 3 of pilus and up to 14 capsular polysaccharide loci, have been identified over the 26 genomes studied. Moreover, the addition of data to the rfbA-Type classification modified the outcome by rearranging rfbA genes and adding a fifth group to the classification. In conclusion, the strain variability in terms of external proteinaceous structure could explain the inter-strain differences previously observed in P. distasonis adhesion capacities and its potential pathogenicity.

Keywords: gut microbiota, Parabacteroides distasonis, capsular polysaccharide, fimbriae, pilus, O-antigen, pathogenicity, probiotic, comparative genomics

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Authors: David B. Tsuanyo, Didier Aussel, Yao Azoumah, Pierre Neveu

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An innovative concept called “Flexy-Energy”is developing at 2iE. This concept aims to produce electricity at lower cost by smartly mix different available energies sources in accordance to the load profile of the region. With a higher solar irradiation and due to the fact that Diesel generator are massively used in sub-Saharan rural areas, PV/Diesel hybrid systems could be a good application of this concept and a good solution to electrify this region, provided they are reliable, cost effective and economically attractive to investors. Presentation of the developed approach is the aims of this paper. The PV/Diesel hybrid system designed consists to produce electricity and/or heat from a coupling between Diesel gensets and PV panels without batteries storage, while ensuring the substitution of gasoil by bio-fuels available in the area where the system will be installed. The optimal design of this system is based on his technical performances; the Life Cycle Cost (LCC) and Levelized Cost of Energy are developed and use as economic criteria. The Net Present Value (NPV), the internal rate of return (IRR) and the discounted payback (DPB) are also evaluated according to dual electricity pricing (in sunny and unsunny hours). The PV/Diesel hybrid system obtained is compared to the standalone Diesel gensets. The approach carried out in this paper has been applied to Siby village in Mali (Latitude 12 ° 23'N 8 ° 20'W) with 295 kWh as daily demand. This approach provides optimal physical characteristics (size of the components, number of component) and dynamical characteristics in real time (number of Diesel generator on, their load rate, fuel specific consumptions, and PV penetration rate) of the system. The system obtained is slightly cost effective; but could be improved with optimized tariffing strategies.

Keywords: investments criteria, optimization, PV hybrid, sizing, rural electrification

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Authors: Arburim Iseni, Afrim Aliti, Nagri Rexhepi

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This paper focuses mainly on an important aspect of student-linguistic errors. It aims to explore the nature of Albanian intermediate level or B1 students’ language errors and mistakes and attempts to trace the possible sources or causes by classifying the error samples into both inter lingual and intra lingual errors. The hypothesis that intra lingua errors may be determined or induced somehow by the native language influence seems to be confirmed by the significant number of errors found in Albanian EFL students in the Study Program of the English Language and Literature at the State University of Tetova. Findings of this study have revealed that L1 interference first and then ignorance of the English Language grammar rules constitute the main sources or causes of errors, even though carelessness cannot be ruled out. Although we have conducted our study with 300 students of intermediate or B1 level, we believe that this hypothesis would need to be confirmed by further research, maybe with a larger number of students with different levels in order to draw more steady and accurate conclusions. The analysis of the questionnaires was done according to quantitative and qualitative research methods. This study was also conducted by taking written samples on different topics from our students and then distributing them with comments to the students and University teachers as well. These questionnaires were designed to gather information among 300 students and 48 EFL teachers, all of whom teach in the Study Program of English Language and Literature at the State University of Tetova. From the analyzed written samples of the students and face-to-face interviews, we could get useful insights into some important aspects of students’ error-making and error-correction. These different research methodologies were used in order to comprise a holistic research and the findings of the questionnaires helped us to come up with some more steady solutions in order to minimize the potential gap between students and teachers.

Keywords: L1 & L2, Linguistics, Applied linguistics, SLA, Albanian EFL students and teachers, Errors and Mistakes, Students’ Assessment and Self-Assessment

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Authors: Amalia Ardeljan, Lexi Frankel, Divesh Manjani, Gabriela Santizo, Maximillian Guerra, Omar Rashid

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Introduction: Cytomegalovirus (CMV) infection is a widespread infection affecting between 60-70% of people in industrialized countries. CMV has been previously correlated with a higher incidence of Hodgkin Lymphoma compared to noninfected persons. Research regarding prior CMV infection and subsequent lymphoma development is still controversial. With limited evidence, further research is needed in order to understand the relationship between previous CMV infection and subsequent lymphoma development. This study assessed the effect of CMV infection and the incidence of lymphoma afterward. Methods: A retrospective cohort study (2010-2019) was conducted through a Health Insurance Portability and Accountability Act (HIPAA) compliant national database and conducted using International Classification of Disease (ICD) 9th,10th codes, and Current Procedural Terminology (CPT) codes. These were used to identify lymphoma diagnosis in a previously CMV infected population. Patients were matched for age range and Charlson Comorbidity Index (CCI). A chi-squared test was used to assess statistical significance. Results: A total number of 14,303 patients was obtained in the CMV infected group as well as in the control population (matched by age range and CCI score). Subsequent lymphoma development was seen at a rate of 11.44% (1,637) in the CMV group and 5.74% (822) in the control group, respectively. The difference was statistically significant by p= 2.2x10-16, odds ratio = 2.696 (95% CI 2.483- 2.927). In an attempt to stratify the population by antiviral medication exposure, the outcomes were limited by the decreased number of members exposed to antiviral medication in the control population. Conclusion: This study shows a statistically significant correlation between prior CMV infection and an increased incidence of lymphoma afterward. Further exploration is needed to identify the potential carcinogenic mechanism of CMV and whether the results are attributed to a confounding bias.

Keywords: cytomegalovirus, lymphoma, cancer, microbiology

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Authors: N. Piwpuan, J. Tosalee, N. Phonkerd

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Malachite green (MG), a synthetic dye, is used in industries and aquaculture and also disposed in the effluent. Use of wastewater in irrigation increases due to water shortage. However, wastewater containing dyes, MG, are toxic to biological systems. Therefore, effects of MG on growth of vegetables were evaluated in order to utilize dye-contaminated wastewater for irrigation. In this study, Pak choy (Brassica chinensis) and Chinese convolvulus (Ipomoea aquatica) were grown in growing material (mixture of soil, coconut fiber, and compost) for four weeks and afterward kept watering with 200 ml of tap water containing MG at the concentrations of 0 (control), 1, 2, 10, and 20 mg/L. At harvest, number of leaf and shoot and root dry weight of the treated plants were measured and compared with control. For both species, their biomass values were similar among treatments and did not differ from the control plants (dry weight were 0.6-1.0 and 1.1-1.7 g/plant for B. chinensis and I. aquatica, respectively). B. chinensis treated with 2, 10, and 20 mg/L of MG produced lower number of new leaf and had smaller and shorter leaf compared to control and treatment of 1 mg/L. These results indicate the different responses between plant species, which B. chinensis is more sensitive to contaminant compared to I. aquatica. There was no sign of MG and leucomalachite green (LMG) detected in root and shoot tissues of plants treated with MG at 20 mg/L, tested by thin layer chromatography. After plant harvest, toxicity of the growing material from all treatments was tested on mung beans. Percent germination (83-97%), seedling fresh weight (0.3-0.5 g/plant), and shoot length (11-12.5 cm) were similar to the control. These indicated that contaminant in growing material did not pose detrimental effect on mung beans. Based on these results, the water contaminated with low concentration of MG, such as discharge from aquaculture, may serve as ferti-irrigation water to compensate water shortage.

Keywords: ferti-irrigation, soil toxicity, triphenylmethane dye, wastewater reuse

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Authors: Eyad H. R. Fadda, Jawaher K. Al Rashdieah, Aysha H. Al Rashdieh

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Urban Sprawl is a phenomenon that many regions in the Sultanate of Oman suffer from in general and in Welayat Barka in particular. It is considered a human phenomenon that causes many negative effects as it has increased in the last time clearly, and this study aims to diagnose the current status of urban growth taking place in Walayat Barka. The objective of this study is to monitor and follow up on the most prominent changes and developments taking place in Barka in the period from 2002 to 2019 and provide suggestions to the decision-makers to reduce the negative effects of the phenomenon. The study methodology depends on the descriptive and analytical approach to describe the phenomenon and its analysis and knowledge of the factors that helped in urban expansion in the Barka, using a number of studies and interviews with the specialists, both in governmental and private institutions, as well as with individuals who own land, real estate, and others. Geographic Information Systems (GIS) and Remote Sensing (ERDAS software) have been used to analyze the satellite images that helped in obtaining results that reflect the changes Barka, in addition to knowing the natural and human determinants that stand on Urban Sprawl Expansion. The study concluded that the geographical location of Barka has a significant role in its urban expansion, as it is the closest state to the capital Muscat, as this expansion continues toward the southern and south-western directions, as this expansion has significant negative effects represented in the low number of agricultural lands due to the continuous change in land use. In addition, it was found that there are two types of natural determinants of urban expansion in Barka, which are consumed land from the Sea of Oman and from the western sands.

Keywords: GIS applications, remote sensing, urbanization, urban sprawl expansion trends

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Authors: Dmytro Zubov, Francesco Volponi

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In this paper, D-Wave quantum computing Ising model is used for the forecasting of positive extremes of daily mean air temperature. Forecast models are designed with two to five qubits, which represent 2-, 3-, 4-, and 5-day historical data respectively. Ising model’s real-valued weights and dimensionless coefficients are calculated using daily mean air temperatures from 119 places around the world, as well as sea level (Aburatsu, Japan). In comparison with current methods, this approach is better suited to predict heat wave values because it does not require the estimation of a probability distribution from scarce observations. Proposed forecast quantum computing algorithm is simulated based on traditional computer architecture and combinatorial optimization of Ising model parameters for the Ronald Reagan Washington National Airport dataset with 1-day lead-time on learning sample (1975-2010 yr). Analysis of the forecast accuracy (ratio of successful predictions to total number of predictions) on the validation sample (2011-2014 yr) shows that Ising model with three qubits has 100 % accuracy, which is quite significant as compared to other methods. However, number of identified heat waves is small (only one out of nineteen in this case). Other models with 2, 4, and 5 qubits have 20 %, 3.8 %, and 3.8 % accuracy respectively. Presented three-qubit forecast model is applied for prediction of heat waves at other five locations: Aurel Vlaicu, Romania – accuracy is 28.6 %; Bratislava, Slovakia – accuracy is 21.7 %; Brussels, Belgium – accuracy is 33.3 %; Sofia, Bulgaria – accuracy is 50 %; Akhisar, Turkey – accuracy is 21.4 %. These predictions are not ideal, but not zeros. They can be used independently or together with other predictions generated by different method(s). The loss of human life, as well as environmental, economic, and material damage, from extreme air temperatures could be reduced if some of heat waves are predicted. Even a small success rate implies a large socio-economic benefit.

Keywords: heat wave, D-wave, forecast, Ising model, quantum computing

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Authors: Abdullah Özköse, Ahmet Tamkoç

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This study aimed to determine some plant characteristics of perennial ryegrass (Lolium perenne L.) genotypes collected from the natural flora of Ankara and correlations between these characteristics. In order to evaluate for breeding purposes according to Turkey's environmental conditions, perennial ryegrass plants collected from natural pasture of Ankara at 2004 were utilized. The collected seeds of plants were sown in pots and seedlings were prepared in greenhouse. Seedlings were transplanted to the experimental field at 50x50 cm intervals in Randomized Complete Blocks Design in 2005. Data were obtained from the observations and measurements of 568 perennial ryegrasses in 2007 and 2008. Perennial ryegrass plants’ in the spring re-growth time, color, density, growth habit, tendency to inflorescences, time of inflorescence, plant height, length of upper internode, spike length, leaf length, leaf width, leaf area, leaf shape, number of spikelets per spike, seed yield per spike, and 1000 grain weight were investigated and correlation analyses were made on the data. Correlation coefficients were estimated between all paired combinations of the traits. The yield components exhibited varying trends of association among themselves. Seed yield per spike showed significant and positive association with number of spikelets per spike, 1000 grain weight, plant height, length of upper internode, spike length, leaf length, leaf width, leaf area and color, but significant and negative association with growth habit and in the spring re-growth time spring.

Keywords: correlation, morphological traits, Lolium perenne

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Authors: Li Yang, Yang Song, Martin Y. M. Chiang

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Objective: To experimentally substantiate the micromechanical compatibility between cell and scaffold, in the regenerative medicine approach for restoring bone volume, is essential for phenotypic transitions Methods: Through nanotechnology and electrospinning process, nanofibrous scaffolds were fabricated to host dental follicle stem cells (DFSCs). Blends (50:50) of polycaprolactone (PCL) and silk fibroin (SF), mixed with various content of cellulose nanocrystals (CNC, up to 5% in weight), were electrospun to prepare nanofibrous scaffolds with heterogeneous microstructure in terms of fiber size. Colloidal probe atomic force microscopy (AFM) and conventional uniaxial tensile tests measured the scaffold stiffness at the micro-and macro-scale, respectively. The cell elastic modulus and cell-scaffold adhesive interaction (i.e., a chemical function) were examined through single-cell force spectroscopy using AFM. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine if the mechanotransduction signal (i.e., Yap1, Wwr2, Rac1, MAPK8, Ptk2 and Wnt5a) is upregulated by the scaffold stiffness at the micro-scale (cellular scale). Results: The presence of CNC produces fibrous scaffolds with a bimodal distribution of fiber diameter. This structural heterogeneity, which is CNC-composition dependent, remarkably modulates the mechanical functionality of scaffolds at microscale and macroscale simultaneously, but not the chemical functionality (i.e., only a single material property is varied). In in vitro tests, the osteogenic differentiation and gene expression associated with mechano-sensitive cell markers correlate to the degree of micromechanical compatibility between DFSCs and the scaffold. Conclusion: Cells require compliant scaffolds to encourage energetically favorable interactions for mechanotransduction, which are converted into changes in cellular biochemistry to direct the phenotypic evolution. The micromechanical compatibility is indeed important to the efficacy of regenerative medicine.

Keywords: phenotype transition, scaffold stiffness, electrospinning, cellulose nanocrystals, single-cell force spectroscopy

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Authors: Hoora Dehghani, Meisam Shahbazi, Reza Zare

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During the previous decade, a significant evolution has occurred in the number of private educational centers and, accordingly, the increase in the number of providers and students of these centers around the world. The number of language teaching institutes in Iran that are considered private educational sectors is also growing exponentially as the request for learning foreign languages has extremely increased in recent years. This fact caused competition among the institutions in improving better services tailored to the students’ demands to win the competition. Along with the growth in the industry of education, higher education institutes should apply the marketing-related concepts and view students as customers because students’ outlooks are similar to consumers with education. Studying the influential factors in the selection of an institute has multiple benefits. Firstly, it acknowledges the institutions of the students’ choice factors. Secondly, the institutions use the obtained information to improve their marketing methods. It also helps institutions know students’ outlooks that can be applied to expand the student know-how. Moreover, it provides practical evidence for educational centers to plan useful amenities and programs, and use efficient policies to cater to the market, and also helps them execute the methods that increase students’ feeling of contentment and assurance. Thus, this study explored the influencing factors in the selection of a language learning institute by language learners and examined and compared the importance among the varying age groups and genders. In the first phase of the study, the researchers selected 15 language learners as representative cases within the specified age ranges and genders purposefully and interviewed them to explore the comprising elements in their language institute selection process and analyzed the results qualitatively. In the second phase, the researchers identified elements as specified items of a questionnaire, and 1000 English learners across varying educational contexts rated them. The TOPSIS method was used to analyze the data quantitatively by representing the level of importance of the items for the participants generally and specifically in each subcategory; genders and age groups. The results indicated that the educational quality, teaching method, duration of training course, establishing need-oriented courses, and easy access were the most important elements. On the other hand, offering training in different languages, the specialized education of only one language, the uniform and appropriate appearance of office staff, having native professors to the language of instruction, applying Computer or online tests instead of the usual paper tests respectively as the least important choice factors in selecting a language institute. Besides, some comparisons among different groups’ ratings of choice factors were made, which revealed the differences among different groups' priorities in choosing a language institute.

Keywords: choice factors, EFL institute selection, english learning, need analysis, TOPSIS

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Authors: Lorico D. S. Lapitan Jr., Yihan Xu, Yuan Guo, Dejian Zhou

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The ability of ultrasensitive detection of specific genes and discrimination of single nucleotide polymorphisms is important for clinical diagnosis and biomedical research. Herein, we report the development of a new ultrasensitive approach for label-free DNA detection using magnetic nanoparticle (MNP) assisted rapid target capture/separation in combination with signal amplification using poly-enzyme tagged polymer nanobead. The sensor uses an MNP linked capture DNA and a biotin modified signal DNA to sandwich bind the target followed by ligation to provide high single-nucleotide polymorphism discrimination. Only the presence of a perfect match target DNA yields a covalent linkage between the capture and signal DNAs for subsequent conjugation of a neutravidin-modified horseradish peroxidase (HRP) enzyme through the strong biotin-nuetravidin interaction. This converts each captured DNA target into an HRP which can convert millions of copies of a non-fluorescent substrate (amplex red) to a highly fluorescent product (resorufin), for great signal amplification. The use of polymer nanobead each tagged with thousands of copies of HRPs as the signal amplifier greatly improves the signal amplification power, leading to greatly improved sensitivity. We show our biosensing approach can specifically detect an unlabeled DNA target down to 10 aM with a wide dynamic range of 5 orders of magnitude (from 0.001 fM to 100.0 fM). Furthermore, our approach has a high discrimination between a perfectly matched gene and its cancer-related single-base mismatch targets (SNPs): It can positively detect the perfect match DNA target even in the presence of 100 fold excess of co-existing SNPs. This sensing approach also works robustly in clinical relevant media (e.g. 10% human serum) and gives almost the same SNP discrimination ratio as that in clean buffers. Therefore, this ultrasensitive SNP biosensor appears to be well-suited for potential diagnostic applications of genetic diseases.

Keywords: DNA detection, polymer beads, signal amplification, single nucleotide polymorphisms

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Authors: Asrat M.Belachew, Tiago Pereira, Institute of Mathematics, Computer Sciences, Avenida Trabalhador São Carlense, 400, São Carlos, 13566-590, Brazil

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Infectious diseases are among the most prominent threats to human beings. They cause morbidity and mortality to an individual and collapse the social, economic, and political systems of the whole world collectively. Mathematical models are fundamental tools and provide a comprehensive understanding of how infectious diseases spread and designing the control strategy to mitigate infectious diseases from the host population. Modeling the spread of infectious diseases using a compartmental model of inhomogeneous populations is good in terms of complexity. However, in the real world, there is a situation that accounts for heterogeneity, such as ages, locations, and contact patterns of the population which are ignored in a homogeneous setting. In this work, we study how classical an SEIR infectious disease spreading of the compartmental model can be extended by incorporating the mobility of population between heterogeneous cities during an outbreak of infectious disease. We have formulated an SEIR multi-cities epidemic spreading model using a system of 4k ordinary differential equations to describe the disease transmission dynamics in k-cities during the day and night. We have shownthat the model is epidemiologically (i.e., variables have biological interpretation) and mathematically (i.e., a unique bounded solution exists all the time) well-posed. We constructed the next-generation matrix (NGM) for the model and calculated the basic reproduction number R0for SEIR-epidemic spreading model with cities mobility. R0of the disease depends on the spectral radius mobility operator, and it is a threshold between asymptotic stability of the disease-free equilibrium and disease persistence. Using the eigenvalue perturbation theorem, we showed that sending a fraction of the population between cities decreases the reproduction number of diseases in interconnected cities. As a result, disease transmissiondecreases in the population.

Keywords: SEIR-model, mathematical model, city mobility, epidemic spreading

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Authors: Esther Van Andel, Stefanie C. Lange, Maarten M. J. Smulders, Han Zuilhof

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False outcomes of diagnostic tests are a major concern in medical health care. To improve the reliability of surface-based diagnostic tests, it is of crucial importance to diminish background signals that arise from the non-specific binding of biomolecules, a process called fouling. The aim is to create surfaces that repel all biomolecules except the molecule of interest. This can be achieved by incorporating antifouling protein repellent coatings in between the sensor surface and it’s recognition elements (e.g. antibodies, sugars, aptamers). Zwitterionic polymer brushes are considered excellent antifouling materials, however, to be able to bind the molecule of interest, the polymer brushes have to be functionalized and so far this was only achieved at the expense of either antifouling or binding capacity. To overcome this limitation, we combined both features into one single monomer: a zwitterionic sulfobetaine, ensuring antifouling capabilities, equipped with a clickable azide moiety which allows for further functionalization. By copolymerizing this monomer together with a standard sulfobetaine, the number of azides (and with that the number of recognition elements) can be tuned depending on the application. First, the clickable azido-monomer was synthesized and characterized, followed by copolymerizing this monomer to yield functionalizable antifouling brushes. The brushes were fully characterized using surface characterization techniques like XPS, contact angle measurements, G-ATR-FTIR and XRR. As a proof of principle, the brushes were subsequently functionalized with biotin via strain-promoted alkyne azide click reactions, which yielded a fully zwitterionic biotin-containing 3D-functionalized coating. The sensing capacity was evaluated by reflectometry using avidin and fibrinogen containing protein solutions. The surfaces showed excellent antifouling properties as illustrated by the complete absence of non-specific fibrinogen binding, while at the same time clear responses were seen for the specific binding of avidin. A great increase in signal-to-noise ratio was observed, even when the amount of functional groups was lowered to 1%, compared to traditional modification of sulfobetaine brushes that rely on a 2D-approach in which only the top-layer can be functionalized. This study was performed on stoichiometric silicon nitride surfaces for future microring resonator based assays, however, this methodology can be transferred to other biosensor platforms which are currently being investigated. The approach presented herein enables a highly efficient strategy for selective binding with retained antifouling properties for improved signal-to-noise ratios in binding assays. The number of recognition units can be adjusted to a specific need, e.g. depending on the size of the analyte to be bound, widening the scope of these functionalizable surface coatings.

Keywords: antifouling, signal-to-noise ratio, surface functionalization, zwitterionic polymer brushes

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Authors: Rahul Malhotra

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Fiber based access networks can deliver performance that can support the increasing demands for high speed connections. One of the new technologies that have emerged in recent years is Passive Optical Networks. This paper is targeted to show the simultaneous delivery of triple play service (data, voice and video). The comparative investigation and suitability of various data rates is presented. It is demonstrated that as we increase the data rate, number of users to be accommodated decreases due to increase in bit error rate.

Keywords: BER, PON, TDMPON, GPON, CWDM, OLT, ONT

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Authors: C. Flynn, Q. Yuan, C. Reinhardt

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting broad areas of the cerebral cortex and hippocampus. More than 95% of AD cases are representative of sporadic AD, where both genetic and environmental risk factors play a role. The main pathological features of AD include the widespread deposition of amyloid-beta and neurofibrillary tau tangles in the brain. The earliest brain pathology related to AD has been defined as hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons, characterized by Braak. However, the cause of this pathology and the ultimate progression of AD is not understood. Increasing research points to a connection between the gut microbiota and the brain, and mounting evidence has shown that there is a bidirectional interaction between the two, known as the gut-brain axis. This axis can allow for bidirectional movement of neuroinflammatory cytokines and pathogenic misfolded proteins, as seen in AD. Prebiotics and probiotics have been shown to have a beneficial effect on gut health and can strengthen the gut-barrier as well as the blood-brain barrier, preventing the spread of these pathogens across the gut-brain axis. Our laboratory has recently established a pretangle tau rat model, in which we selectively express pseudo-phosphorylated human tau (htauE14) in the LC neurons of TH-Cre rats. LC htauE14 produced pathological changes in rats resembling those of the preclinical AD pathology (reduced olfactory discrimination and LC degeneration). In this work, we will investigate the effects of pre/probiotic ingestion on AD behavioral deficits, blood inflammation/cytokines, and various brain markers in our experimental rat model of AD. Rats will be infused with an adeno-associated viral vector containing a human tau gene pseudophosphorylated at 14 sites (common in LC pretangles) into 2-3 month TH-Cre rats. Fecal and blood samples will be taken at pre-surgery, and various post-surgery time points. A collection of behavioral tests will be performed, and immunohistochemistry/western blotting techniques will be used to observe various biomarkers. This work aims to elucidate the relationship between gut health and AD progression by strengthening gut-brain relationship and aims to observe the overall effect on tau formation and tau pathology in AD brains.

Keywords: alzheimer’s disease, aging, gut microbiome, neurodegeneration

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Authors: R. A. Deshpande, P. Chandhra Sekhar, V. Sankar

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In this paper, we discussed the basic reliability evaluation techniques needed to evaluate the reliability of distribution systems which are applied in distribution system planning and operation. Basically, the reliability study can also help to predict the reliability performance of the system after quantifying the impact of adding new components to the system. The number and locations of new components needed to improve the reliability indices to certain limits are identified and studied.

Keywords: distribution system, reliability indices, urban feeder, rural feeder

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Authors: Atara Shriki, Ilana Lavy

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In a rapidly changing technological society, creativity is considered as an engine of economic and social progress. No doubt the education system has a central role in nurturing all students’ creativity, however, it is normally not encouraged at school. The causes of this reality are related to a variety of circumstances, among them: external pressures to cover the curriculum and succeed in standardized tests that mostly require algorithmic thinking and implementation of rules; teachers’ tendency to teach similarly to the way they themselves were taught as school students; relating creativity to giftedness, and therefore avoid nurturing all students' creativity; lack of adequate learning materials and accessible tools for following and evaluating the development of students’ creativity; and more. Since success in academic studies requires, among other things, creativity, lecturers in higher education institutions should consider appropriate ways to nurture students’ creative thinking and assess its development. Obviously, creativity has a multifaceted nature, numerous definitions, various perspectives for studying its essence (e.g., process, personality, environment, and product), and several approaches aimed at evaluating and assessing creative expressions (e.g., cognitive, social-personal, and psychometric). In this framework, we suggest nurturing students’ creativity through engaging them in problem posing activities that are part of inquiry assignments. In order to assess the development of their creativity, we propose to employ a model that was designed for this purpose, based on the psychometric approach, viewing the posed problems as the “creative product”. The model considers four measurable aspects- fluency, flexibility, originality, and organization, as well as a total score of creativity that reflects the relative weights of each aspect. The scores given to learners are of two types: (1) Total scores- the absolute number of posed problems with respect to each of the four aspects, and a final score of creativity; (2) Relative scores- each absolute number is transformed into a number that relates to the relative infrequency of the posed problems in student’s reference group. Through converting the scores received over time into a graphical display, students can assess their progress both with respect to themselves and relative to their reference group. Course lecturers can get a picture of the strengths and weaknesses of each student as well as the class as a whole, and to track changes that occur over time in response to the learning environment they had generated. Such tracking may assist lecturers in making pedagogical decisions about emphases that should be put on one or more aspects of creativity, and about the students that should be given a special attention. Our experience indicates that schoolteachers and lecturers in higher education institutes find the combination of engaging learners in problem posing along with self-assessment of their progress through utilizing the graphical display of accumulating total and relative scores has the potential to realize most learners’ creative potential.

Keywords: creativity, problem posing, psychometric model, self-assessment

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Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

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Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

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Authors: Joseph E. Cobbinah, Abigail A. Aryeh-Adjei

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Over the years, entry into the academia in any Ghanaian university requires an advanced research degree, more preferably traditional doctorate (PhD or DPhil). It is however argued that PhD is more research intensive, so since university teaching involves a lot of research, those having traditional doctorate have good research background to teach in a university and are thus recruited as lecturers. However, in the last ten years, a reasonable number of academics enter Ghanaian universities with professional doctorate degrees, which hitherto was considered to be only suitable for industry, because it gives individuals with just basic research skills needed for professional practice, unlike the traditional PhD which is research intensive degree. Currently, there are a reasonable number of professional doctorate degree holders with qualifications like DBA, EdD, PsychD, DPharm, EngD, among others in various departments in many Ghanaian universities. Maybe, because such degree holders also use the title Dr, some university authorities put them at par with their counterparts with traditional doctorate, although some lecturers with PhD seem to look down upon those with traditional doctorate degrees and this has created some tension amongst those academics. This makes their promotions and holding of university academic positions very problematic in some ways. This paper therefore seeks to investigate the types of professional doctorate degree holders working as lecturers in some selected universities in Ghana and the challenges associated with their recruitment, acceptability and proper integration into universities’ teaching and learning. The paper adopted qualitative research methodology. In all, respondents from three state-owned and privately owned universities were involved in the study. Administrators, lecturers, heads of departments and deans of faculty were interviewed to assess the challenges associated with the recruitment of professional doctorate degree holders and any problems they face in the departments they work. It became evident that, although some lecturers enter the academia with professional doctorate degrees, their counterparts seem not to give them the recognition and respect they deserve. Although there is little or no evidence that professional doctorate degree holders are under performing, recruiting professional doctorate degree holders does not only become a challenge, but also their progression into the university’s promotion ladder become very slow compared to their counterparts with traditional PhD degrees.

Keywords: professional doctorate, academia, lecturers, Ghanaian universities, orate

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Authors: Sundus Mona, Atif Adnan, Babar Ali, Fareeha Arshad, Allah Rakha

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Molecular diversity is the variation in the abundance of species. Forensic entomology is a neglected field in Pakistan. Insects collected from the crime scene should be handled by forensic entomologists who are currently virtually non-existent in Pakistan. Correct identification of insect specimen along with knowledge of their biodiversity can aid in solving many problems related to complicated forensic cases. Inadequate morphological identification and insufficient thermal biological studies limit the entomological utility in Forensic Medicine. Recently molecular identification of entomological evidence has gained attention globally. DNA barcoding is the latest and established method for species identification. Only proper identification can provide a precise estimation of postmortem intervals. Arthropods are known to be the first tourists scavenging on decomposing dead matter. The objective of the proposed study was to identify species by molecular techniques and analyze their phylogenetic importance with barcoded necrophagous insect species of early succession on human cadavers. Based upon this identification, the study outcomes will be the utilization of established DNA bar codes to identify carrion feeding insect species for concordant estimation of post mortem interval. A molecular identification method involving sequencing of a 658bp ‘barcode’ fragment of the mitochondrial cytochrome oxidase subunit 1 (CO1) gene from collected specimens of unknown dipteral species from cadavers of Lahore was evaluated. Nucleotide sequence divergences were calculated using MEGA 7 and Arlequin, and a neighbor-joining phylogenetic tree was generated. Three species were identified, Chrysomya megacephala, Chrysomya saffranea, and Chrysomya rufifacies with low genetic diversity. The fixation index was 0.83992 that suggests a need for further studies to identify and classify forensically relevant insects in Pakistan. There is an exigency demand for further research especially when immature forms of arthropods are recovered from the crime scene.

Keywords: molecular diversity, DNA barcoding, species identification, forensically relevant

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Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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Authors: M. Shokry Rashwan

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This study follows a number of experiments conducted at Red River College (RRC) to investigate the short term properties of tire derived aggregate (TDA) produced from shredding off-the-road (OTR) wasted tires in a proposed new application. The application targets replacing natural material used under concrete slabs and as backfills for residential homes’ basement slabs and walls, respectively, with TDA. The experimental work included determining: compressibility, gradation distribution, unit weight, hydraulic conductivity and lateral pressure. Based on the results of those short term properties; it was decided to move forward to study the long-term performance of this otherwise waste material through on-site demonstration. A full-scale basement replicating a typical Manitoba home was therefore built at RRC where both TDA and Natural Materials (NM) were used side-by-side. A large number of sensing and measuring systems are used to compare between the performances of each material when exposed to the typical ground and weather conditions. Parameters monitored and measured include heat losses, moisture migration, drainage ability, lateral pressure, relative movements of slabs and walls, an integrity of ground water and radon emissions. Up-to-date results have confirmed part of the conclusions reached from the earlier laboratory experiments. However, other results have shown that construction practices; such as placing and compaction, may need some adjustments to achieve more desirable outcomes. This presentation provides a review of both short-term tests as well as up-to-date analysis of the on-site demonstration.

Keywords: tire derived aggregate (TDA), basement construction, TDA material properties, lateral pressure of TDA, hydraulic conductivity of TDA

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Authors: Lohendy Munoz-Vargas, Stephen O. Opiyo, Rose Digianantonio, Michele L. Williams, Asela Wijeratne, Gregory Habing

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Non-typhoidal Salmonella enterica is a zoonotic pathogen with critical importance in animal and public health. The persistence of Salmonella on farms affects animal productivity and health, and represents a risk for food safety. The intestinal microbiota plays a fundamental role in the colonization and invasion of this ubiquitous microorganism. To overcome the colonization resistance imparted by the gut microbiome, Salmonella uses invasion strategies and the host inflammatory response to survive, proliferate, and establish infections with diverse clinical manifestations. Cattle serve as reservoirs of Salmonella, and periparturient cows have high prevalence of Salmonella shedding; however, to author`s best knowledge, little is known about the association between the gut microbiome and the onset of Salmonella shedding during the periparturient period. Thus, the objective of this study was to assess the association between changes in bacterial communities and the onset of Salmonella shedding in cattle approaching parturition. In a prospective cohort study, fecal samples from 98 dairy cows originating from four different farms were collected at four time points relative to calving (-3 wks, -1 wk, +1 wk, +3 wks). All 392 samples were cultured for Salmonella. Sequencing of the V4 region of the 16S rRNA gene using the Illumina platform was completed to evaluate the fecal microbiome in a selected sample subset. Analyses of microbial composition, diversity, and structure were performed according to time points, farm, and Salmonella onset status. Individual cow fecal microbiomes, predominated by Bacteroidetes, Firmicutes, Spirochaetes, and Proteobacteria phyla, significantly changed before and after parturition. Microbial communities from different farms were distinguishable based on multivariate analysis. Although there were significant differences in some bacterial taxa between Salmonella positive and negative samples, our results did not identify differences in the fecal microbial diversity or structure for cows with and without the onset of Salmonella shedding. These data suggest that determinants other than the significant changes in the fecal microbiome influence the periparturient onset of Salmonella shedding in dairy cattle.

Keywords: dairy cattle, microbiome, periparturient, Salmonella

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Authors: Parastou Kharazmi

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In this paper, rehabilitation methods for pipeline by advanced polymeric coating such as relining are reviewed. A number of diverse methods which are globally used are described and a brief summary of advances in technology, methods and materials is provided. The paper explains why it is claimed that sewerage rehabilitation with relining in residential buildings is environmentally friendly and economical, the importance of the quality control procedure is discussed and several quality tests are proposed.

Keywords: buildings, composite, material, renovation

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Authors: Lydia Foucan, Laurent Larifla, Emmanuelle Durand, Christine Rambhojan, Veronique Dhennin, Jean-Marc Lacorte, Philippe Froguel, Amelie Bonnefond

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In the population of Guadeloupe Island (472,124 inhabitants and 80% of subjects of African descent), overweight and obesity were estimated at 23% and 9% respectively among children. High prevalence of diabetes has been reported (~10%) in the adult population. Nevertheless, no study has investigated the contribution of gene mutations to childhood obesity in this population. We aimed to investigate rare genetic mutations in genes involved in monogenic obesity or diabetes in obese Afro-Caribbean children from Guadeloupe Island using next-generation sequencing. The present investigation included unrelated obese children, from a previous study on overweight conducted in Guadeloupe Island in 2013. We sequenced coding regions of 59 genes involved in monogenic obesity or diabetes. A total of 25 obese schoolchildren (with Z-score of body mass index [BMI]: 2.0 to 2.8) were screened for rare mutations (non-synonymous, splice-site, or insertion/deletion) in 59 genes. Mean age of the study population was 12.4 ± 1.1 years. Seventeen children (68%) had insulin-resistance (HOMA-IR > 3.16). A family history of obesity (mother or father) was observed in eight children and three of the accompanying parent presented with type 2 diabetes. None of the children had gonadotrophic abnormality or mental retardation. We detected five rare heterozygous mutations, in four genes involved in monogenic obesity, in five different obese children: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations which were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations which were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutation in ABCC8 or KCNJ11 (involved in monogenic diabetes), which were of uncertain significance (KCNJ11 p.Val13Met, KCNJ11 p.Val151Met, ABCC8 p.Lys1521Asn and ABCC8 p.Ala625Val). Rare pathogenic or likely pathogenic mutations, linked to severe obesity were detected in more than 15% of this Afro-Caribbean population at high risk of obesity and type 2 diabetes.

Keywords: childhood obesity, MC4R, monogenic obesity, SIM1

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