Search results for: isolated bridges
Commenced in January 2007
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Edition: International
Paper Count: 1919

Search results for: isolated bridges

119 Analysis and Comparison of Asymmetric H-Bridge Multilevel Inverter Topologies

Authors: Manel Hammami, Gabriele Grandi

Abstract:

In recent years, multilevel inverters have become more attractive for single-phase photovoltaic (PV) systems, due to their known advantages over conventional H-bridge pulse width-modulated (PWM) inverters. They offer improved output waveforms, smaller filter size, lower total harmonic distortion (THD), higher output voltages and others. The most common multilevel converter topologies, presented in literature, are the neutral-point-clamped (NPC), flying capacitor (FC) and Cascaded H-Bridge (CHB) converters. In both NPC and FC configurations, the number of components drastically increases with the number of levels what leads to complexity of the control strategy, high volume, and cost. Whereas, increasing the number of levels in case of the cascaded H-bridge configuration is a flexible solution. However, it needs isolated power sources for each stage, and it can be applied to PV systems only in case of PV sub-fields. In order to improve the ratio between the number of output voltage levels and the number of components, several hybrids and asymmetric topologies of multilevel inverters have been proposed in the literature such as the FC asymmetric H-bridge (FCAH) and the NPC asymmetric H-bridge (NPCAH) topologies. Another asymmetric multilevel inverter configuration that could have interesting applications is the cascaded asymmetric H-bridge (CAH), which is based on a modular half-bridge (two switches and one capacitor, also called level doubling network, LDN) cascaded to a full H-bridge in order to double the output voltage level. This solution has the same number of switches as the above mentioned AH configurations (i.e., six), and just one capacitor (as the FCAH). CAH is becoming popular, due to its simple, modular and reliable structure, and it can be considered as a retrofit which can be added in series to an existing H-Bridge configuration in order to double the output voltage levels. In this paper, an original and effective method for the analysis of the DC-link voltage ripple is given for single-phase asymmetric H-bridge multilevel inverters based on level doubling network (LDN). Different possible configurations of the asymmetric H-Bridge multilevel inverters have been considered and the analysis of input voltage and current are analytically determined and numerically verified by Matlab/Simulink for the case of cascaded asymmetric H-bridge multilevel inverters. A comparison between FCAH and the CAH configurations is done on the basis of the analysis of the DC and voltage ripple for the DC source (i.e., the PV system). The peak-to-peak DC and voltage ripple amplitudes are analytically calculated over the fundamental period as a function of the modulation index. On the basis of the maximum peak-to-peak values of low frequency and switching ripple voltage components, the DC capacitors can be designed. Reference is made to unity output power factor, as in case of most of the grid-connected PV generation systems. Simulation results will be presented in the full paper in order to prove the effectiveness of the proposed developments in all the operating conditions.

Keywords: asymmetric inverters, dc-link voltage, level doubling network, single-phase multilevel inverter

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118 ENDO-β-1,4-Xylanase from Thermophilic Geobacillus stearothermophilus: Immobilization Using Matrix Entrapment Technique to Increase the Stability and Recycling Efficiency

Authors: Afsheen Aman, Zainab Bibi, Shah Ali Ul Qader

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Introduction: Xylan is a heteropolysaccharide composed of xylose monomers linked together through 1,4 linkages within a complex xylan network. Owing to wide applications of xylan hydrolytic products (xylose, xylobiose and xylooligosaccharide) the researchers are focusing towards the development of various strategies for efficient xylan degradation. One of the most important strategies focused is the use of heat tolerant biocatalysts which acts as strong and specific cleaving agents. Therefore, the exploration of microbial pool from extremely diversified ecosystem is considerably vital. Microbial populations from extreme habitats are keenly explored for the isolation of thermophilic entities. These thermozymes usually demonstrate fast hydrolytic rate, can produce high yields of product and are less prone to microbial contamination. Another possibility of degrading xylan continuously is the use of immobilization technique. The current work is an effort to merge both the positive aspects of thermozyme and immobilization technique. Methodology: Geobacillus stearothermophilus was isolated from soil sample collected near the blast furnace site. This thermophile is capable of producing thermostable endo-β-1,4-xylanase which cleaves xylan effectively. In the current study, this thermozyme was immobilized within a synthetic and a non-synthetic matrice for continuous production of metabolites using entrapment technique. The kinetic parameters of the free and immobilized enzyme were studied. For this purpose calcium alginate and polyacrylamide beads were prepared. Results: For the synthesis of immobilized beads, sodium alginate (40.0 gL-1) and calcium chloride (0.4 M) was used amalgamated. The temperature (50°C) and pH (7.0) optima of immobilized enzyme remained same for xylan hydrolysis however, the enzyme-substrate catalytic reaction time raised from 5.0 to 30.0 minutes as compared to free counterpart. Diffusion limit of high molecular weight xylan (corncob) caused a decline in Vmax of immobilized enzyme from 4773 to 203.7 U min-1 whereas, Km value increased from 0.5074 to 0.5722 mg ml-1 with reference to free enzyme. Immobilized endo-β-1,4-xylanase showed its stability at high temperatures as compared to free enzyme. It retained 18% and 9% residual activity at 70°C and 80°C, respectively whereas; free enzyme completely lost its activity at both temperatures. The Immobilized thermozyme displayed sufficient recycling efficiency and can be reused up to five reaction cycles, indicating that this enzyme can be a plausible candidate in paper processing industry. Conclusion: This thermozyme showed better immobilization yield and operational stability with the purpose of hydrolyzing the high molecular weight xylan. However, the enzyme immobilization properties can be improved further by immobilizing it on different supports for industrial purpose.

Keywords: immobilization, reusability, thermozymes, xylanase

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117 How Restorative Justice Can Inform and Assist the Provision of Effective Remedies to Hate Crime, Case Study: The Christchurch Terrorist Attack

Authors: Daniel O. Kleinsman

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The 2019 terrorist attack on two masjidain in Christchurch, New Zealand, was a shocking demonstration of the harm that can be caused by hate crime. As legal and governmental responses to the attack struggle to provide effective remedies to its victims, restorative justice has emerged as a tool that can assist, in terms of both meeting victims’ needs and discharging the obligations of the state under the International Covenant on Civil and Political Rights (ICCPR), arts 2(3), 26, 27. Restorative justice is a model that emphasizes the repair of harm caused or revealed by unjust behavior. It also prioritises the facilitation of dialogue, the restoration of equitable relationships, and the prevention of future harm. Returning to the case study, in the remarks of the sentencing judge, the terrorist’s actions were described as a hate crime of vicious malevolence that the Court was required to decisively reject, as anathema to the values of acceptance, tolerance and mutual respect upon which New Zealand’s inclusive society is based and which the country strives to maintain. This was one of the reasons for which the terrorist received a life sentence with no possibility of parole. However, in the report of the Royal Commission of Inquiry into the Attack, it was found that victims felt the attack occurred within the context of widespread racism, discrimination and Islamophobia, where hostile behaviors, including hate-based threats and attacks, were rarely recorded, analysed or acted on. It was also found that the Government had inappropriately concentrated intelligence resources on the risk of ‘Islamist’ terrorism and had failed to adequately respond to concerns raised about threats against the Muslim community. In this light, the remarks of the sentencing judge can be seen to reflect a criminal justice system that, in the absence of other remedies, denies systemic accountability and renders hate crime an isolated incident rather than an expression of more widespread discrimination and hate to be holistically addressed. One of the recommendations of the Royal Commission was to explore with victims the desirability and design of restorative justice processes. This presents an opportunity for victims to meet with state representatives and pursue effective remedies (ICCPR art 2(3)) not only for the harm caused by the terrorist but the harm revealed by a system that has exposed the minority Muslim community in New Zealand to hate in all forms, including but not limited to violent extremism. In this sense, restorative justice can also assist the state in discharging its wider obligations to protect all persons from discrimination (art 26) and allow ethnic and religious minorities to enjoy their own culture and profess and practice their own religion (art 27). It can also help give effect to the law and its purpose as a remedy to hate crime, as expressed in this case study by the sentencing judge.

Keywords: hate crime, restorative justice, minorities, victims' rights

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116 Chronic Care Management for the Medically Vulnerable during the Pandemic: Experiences of Family Caregivers of Youth with Substance Use Disorders in Zambia

Authors: Ireen Manase Kabembo, Patrick Chanda

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Background: Substance use disorders are among the chronic conditions that affect all age groups. Worldwide, there is an increase in young people affected by SUDs, which implies that more family members are transitioning into the caregiver role. Family caregivers play a buffering role in the formal healthcare system due to their involvement in caring for persons with acute and chronic conditions in the home setting. Family carers of youth with problematic alcohol and marijuana use experience myriad challenges in managing daily care for this medically vulnerable group. In addition, the poor health-seeking behaviours of youth with SUDs characterized by eluding treatment and runaway tendencies coupled with the effects of the pandemic made caregiving a daunting task for most family caregivers. Issues such as limited and unavailable psychotropic medications, social stigma and discrimination, financial hurdles, systemic barriers in adolescent and young adult mental healthcare services, and the lack of a perceived vulnerability to Covid-19 by youth with SUDs are experiences of family caretakers. Methods: A qualitative study with 30 family caregivers of youth aged 16-24 explored their lived experiences and subjective meanings using two in-depth semi-structured interviews, a caregiving timeline, and participant observation. Findings: Results indicate that most family caregivers had challenges managing care for treatment elusive youth, let alone having them adhere to Covid-19 regulations. However, youth who utilized healthcare services and adhered to treatment regimens had positive outcomes and sustained recovery. The effects of the pandemic, such as job losses and the closure of businesses, further exacerbated the financial challenges experienced by family caregivers, making it difficult to purchase needed medications and daily necessities for the youth. The unabated stigma and discrimination of families of substance-dependent youth in Zambian communities further isolated family caregivers, leaving them with limited support. Conclusion: Since young people with SUDs have a compromised mental capacity due to the cognitive impairments that come with continued substance abuse, they often have difficulties making sound judgements, including the need to utilize SUD recovery services. Also, their tendency to not adhere to the Covid-19 pandemic requirements places them at a higher risk for adverse health outcomes in the (post) pandemic era. This calls for urgent implementation of robust youth mental health services that address prevention and recovery for these emerging adults grappling with substance use disorders. Support for their family caregivers, often overlooked, cannot be overemphasized.

Keywords: chronic care management, Covid-19 pandemic, family caregivers, youth with substance use disorders

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115 Assessing Mycotoxin Exposure from Processed Cereal-Based Foods for Children

Authors: Soraia V. M. de Sá, Miguel A. Faria, José O. Fernandes, Sara C. Cunha

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Cereals play a vital role in fulfilling the nutritional needs of children, supplying essential nutrients crucial for their growth and development. However, concerns arise due to children's heightened vulnerability due to their unique physiology, specific dietary requirements, and relatively higher intake in relation to their body weight. This vulnerability exposes them to harmful food contaminants, particularly mycotoxins, prevalent in cereals. Because of the thermal stability of mycotoxins, conventional industrial food processing often falls short of eliminating them. Children, especially those aged 4 months to 12 years, frequently encounter mycotoxins through the consumption of specialized food products, such as instant foods, breakfast cereals, bars, cookie snacks, fruit puree, and various dairy items. A close monitoring of this demographic group's exposure to mycotoxins is essential, as toxins ingestion may weaken children’s immune systems, reduce their resistance to infectious diseases, and potentially lead to cognitive impairments. The severe toxicity of mycotoxins, some of which are classified as carcinogenic, has spurred the establishment and ongoing revision of legislative limits on mycotoxin levels in food and feed globally. While EU Commission Regulation 1881/2006 addresses well-known mycotoxins in processed cereal-based foods and infant foods, the absence of regulations specifically addressing emerging mycotoxins underscores a glaring gap in the regulatory framework, necessitating immediate attention. Emerging mycotoxins have gained mounting scrutiny in recent years due to their pervasive presence in various foodstuffs, notably cereals and cereal-based products. Alarmingly, exposure to multiple mycotoxins is hypothesized to exhibit higher toxicity than isolated effects, raising particular concerns for products primarily aimed at children. This study scrutinizes the presence of 22 mycotoxins of the diverse range of chemical classes in 148 processed cereal-based foods, including 39 breakfast cereals, 25 infant formulas, 27 snacks, 25 cereal bars, and 32 cookies commercially available in Portugal. The analytical approach employed a modified QuEChERS procedure followed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. Given the paucity of information on the risk assessment of children to multiple mycotoxins in cereal and cereal-based products consumed by children of Portugal pioneers the evaluation of this critical aspect. Overall, aflatoxin B1 (AFB1) and aflatoxin G2 (AFG2) emerged as the most prevalent regulated mycotoxins, while enniatin B (ENNB) and sterigmatocystin (STG) were the most frequently detected emerging mycotoxins.

Keywords: cereal-based products, children´s nutrition, food safety, UPLC-MS/MS analysis

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114 Smart Cities, Morphology of the Uncertain: A Study on Development Processes Applied by Amazonian Cities in Ecuador

Authors: Leonardo Coloma

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The world changes constantly, every second its properties vary due either natural factors or human intervention. As the most intelligent creatures on the planet, human beings have transformed the environment and paradoxically –have allowed ‘mother nature’ to lose species, accelerate the processes of climate change, the deterioration of the ozone layer, among others. The rapid population growth, the procurement, administration and distribution of resources, waste management, and technological advances are some of the factors that boost urban sprawl whose gray stain extends over the territory, facing challenges such as pollution, overpopulation and scarcity of resources. In Ecuador, these problems are added to the social, cultural, economic and political anomalies that have historically affected it. This fact can represent a greater delay when trying to solve global problems, without having paid attention to local inconveniences –smaller ones, but ones that could be the key to project smart solutions on bigger ones. This research aims to highlight the main characteristics of the development models adopted by two Amazonian cities, and analyze the impact of such urban growth on society; to finally define the parameters that would allow the development of an intelligent city in Ecuador, prepared for the challenges of the XXI Century. Contrasts in the climate, temperature, and landscape of Ecuadorian cities are fused with the cultural diversity of its people, generating a multiplicity of nuances of an indecipherable wealth. However, we strive to apply development models that do not recognize that wealth, not understanding them and ignoring that their proposals will vary according to where they are applied. Urban plans seem to take a bit of each of the new theories and proposals of development, which, in the encounter with the informal growth of cities, with those excluded and ‘isolated’ societies, generate absurd morphologies - where the uncertain becomes tangible. The desire to project smart cities is ever growing, but it is important to consider that this concept does not only have to do with the use of information and communication technologies. Its success is achieved when advances in science and technology allow the establishment of a better relationship between people and their context (natural and built). As a research methodology, urban analysis through mappings, diagrams and geographical studies, as well as the identification of sensorial elements when living the city, will make evident the shortcomings of the urban models adopted by certain populations of the Ecuadorian Amazon. Following the vision of previous investigations started since 2014 as part of ‘Centro de Acciones Urbanas,’ the results of this study will encourage the dialogue between the city (as a physical fact) and those who ‘make the city’ (people as its main actors). This research will allow the development of workshops and meetings with different professionals, organizations and individuals in general.

Keywords: Latin American cities, smart cities, urban development, urban morphology, urban sprawl

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113 Changes of Chemical Composition and Physicochemical Properties of Banana during Ethylene-Induced Ripening

Authors: Chiun-C.R. Wang, Po-Wen Yen, Chien-Chun Huang

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Banana is produced in large quantities in tropical and subtropical areas. Banana is one of the important fruits which constitute a valuable source of energy, vitamins and minerals. The ripening and maturity standards of banana vary from country to country depending on the expected shelf life of market. The compositions of bananas change dramatically during ethylene-induced ripening that are categorized as nutritive values and commercial utilization. Nevertheless, there is few study reporting the changes of physicochemical properties of banana starch during ethylene-induced ripening of green banana. The objectives of this study were to investigate the changes of chemical composition and enzyme activity of banana and physicochemical properties of banana starch during ethylene-induced ripening. Green bananas were harvested and ripened by ethylene gas at low temperature (15℃) for seven stages. At each stage, banana was sliced and freeze-dried for banana flour preparation. The changes of total starch, resistant starch, chemical compositions, physicochemical properties, activity of amylase, polyphenolic oxidase (PPO) and phenylalanine ammonia lyase (PAL) of banana were analyzed each stage during ripening. The banana starch was isolated and analyzed for gelatinization properties, pasting properties and microscopic appearance each stage of ripening. The results indicated that the highest total starch and resistant starch content of green banana were 76.2% and 34.6%, respectively at the harvest stage. Both total starch and resistant starch content were significantly declined to 25.3% and 8.8%, respectively at the seventh stage. Soluble sugars content of banana increased from 1.21% at harvest stage to 37.72% at seventh stage during ethylene-induced ripening. Swelling power of banana flour decreased with the progress of ripening stage, but solubility increased. These results strongly related with the decreases of starch content of banana flour during ethylene-induced ripening. Both water insoluble and alcohol insoluble solids of banana flour decreased with the progress of ripening stage. Both activity of PPO and PAL increased, but the total free phenolics content decreased, with the increases of ripening stages. As ripening stage extended, the gelatinization enthalpy of banana starch significantly decreased from 15.31 J/g at the harvest stage to 10.55 J/g at the seventh stage. The peak viscosity and setback increased with the progress of ripening stages in the pasting properties of banana starch. The highest final viscosity, 5701 RVU, of banana starch slurry was found at the seventh stage. The scanning electron micrograph of banana starch showed the shapes of banana starch appeared to be round and elongated forms, ranging in 10-50 μm at the harvest stage. As the banana closed to ripe status, some parallel striations were observed on the surface of banana starch granular which could be caused by enzyme reaction during ripening. These results inferred that the highest resistant starch was found in the green banana at the harvest stage could be considered as a potential application of healthy foods. The changes of chemical composition and physicochemical properties of banana could be caused by the hydrolysis of enzymes during the ethylene-induced ripening treatment.

Keywords: ethylene-induced ripening, banana starch, resistant starch, soluble sugars, physicochemical properties, gelatinization enthalpy, pasting characteristics, microscopic appearance

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112 Functional Ingredients from Potato By-Products: Innovative Biocatalytic Processes

Authors: Salwa Karboune, Amanda Waglay

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Recent studies indicate that health-promoting functional ingredients and nutraceuticals can help support and improve the overall public health, which is timely given the aging of the population and the increasing cost of health care. The development of novel ‘natural’ functional ingredients is increasingly challenging. Biocatalysis offers powerful approaches to achieve this goal. Our recent research has been focusing on the development of innovative biocatalytic approaches towards the isolation of protein isolates from potato by-products and the generation of peptides. Potato is a vegetable whose high-quality proteins are underestimated. In addition to their high proportion in the essential amino acids, potato proteins possess angiotensin-converting enzyme-inhibitory potency, an ability to reduce plasma triglycerides associated with a reduced risk of atherosclerosis, and stimulate the release of the appetite regulating hormone CCK. Potato proteins have long been considered not economically feasible due to the low protein content (27% dry matter) found in tuber (Solanum tuberosum). However, potatoes rank the second largest protein supplying crop grown per hectare following wheat. Potato proteins include patatin (40-45 kDa), protease inhibitors (5-25 kDa), and various high MW proteins. Non-destructive techniques for the extraction of proteins from potato pulp and for the generation of peptides are needed in order to minimize functional losses and enhance quality. A promising approach for isolating the potato proteins was developed, which involves the use of multi-enzymatic systems containing selected glycosyl hydrolase enzymes that synergistically work to open the plant cell wall network. This enzymatic approach is advantageous due to: (1) the use of milder reaction conditions, (2) the high selectivity and specificity of enzymes, (3) the low cost and (4) the ability to market natural ingredients. Another major benefit to this enzymatic approach is the elimination of a costly purification step; indeed, these multi-enzymatic systems have the ability to isolate proteins, while fractionating them due to their specificity and selectivity with minimal proteolytic activities. The isolated proteins were used for the enzymatic generation of active peptides. In addition, they were applied into a reduced gluten cookie formulation as consumers are putting a high demand for easy ready to eat snack foods, with high nutritional quality and limited to no gluten incorporation. The addition of potato protein significantly improved the textural hardness of reduced gluten cookies, more comparable to wheat flour alone. The presentation will focus on our recent ‘proof-of principle’ results illustrating the feasibility and the efficiency of new biocatalytic processes for the production of innovative functional food ingredients, from potato by-products, whose potential health benefits are increasingly being recognized.

Keywords: biocatalytic approaches, functional ingredients, potato proteins, peptides

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111 Biostratigraphic Significance of Shaanxilithes ningqiangensis from the Tal Group (Cambrian), Nigalidhar Syncline, Lesser Himalaya, India and Its GC-MS Analysis

Authors: C. A. Sharma, Birendra P. Singh

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We recovered 40 well preserved ribbon-shaped, meandering specimens of S. ningqiangensis from the Earthy Dolomite Member (Krol Group) and calcareous siltstone beds of the Earthy Siltstone Member (Tal Group) showing closely spaced annulations that lacked branching. The beginning and terminal points are indistinguishable. In certain cases, individual specimens are characterized by irregular, low-angle to high-angle sinuosity. It has been variously described as body fossil, ichnofossil and algae. Detailed study of this enigmatic fossil is needed to resolve the long standing controversy regarding its phylogenetic and stratigraphic placements, which will be an important contribution to the evolutionary history of metazoans. S. ningqiangensis has been known from the late Neoproterozoic (Ediacaran) of southern and central China (Sichuan, Shaanxi, Quinghai and Guizhou provinces and Ningxia Hui Autonomous region), Siberian platform and across Pc/C Boundary from latest Neoprterozoic to earliest Cambrian of northern India. Shaanxilithes is considered an Ediacaran organism that spans the Precambrian–Cambrian boundary, an interval marked by significant taphonomic and ecological transformations that include not only innovation but also probable extinction. All the past well constrained finds of S. ningqiangensis are restricted to Ediacaran age. However, due to the new recoveries of the fossil from Nigalidhar Syncline, the stratigraphic status of S. ningqiangensis-bearing Earthy Siltstone Member of the Shaliyan Formation of the Tal Group (Cambrian) is rendered uncertain, though the overlying Chert Member in the adjoining Korgai Syncline has yielded definite early Cambrian acritarchs. The moot question is whether the Earthy Siltstone Member represents an Ediacaran or an early Cambrian age?. It would be interesting to find if Shaanxilithes, so far known from Ediacaran sequences, could it transgress to the early Cambrian or in simple words could it withstand the Pc/C Boundary event? GC-MS data shows the S. ningqiangensis structure is formed by hydrocarbon organic compounds which are filled with inorganic elements filler like silica, Calcium, phosphorus etc. The S. ningqiangensis structure is a mixture of organic compounds of high molecular weight, containing several saturated rings with hydrocarbon chains having an occasional isolated carbon-carbon double bond and also containing, in addition, to small amounts of nitrogen, sulfur and oxygen. Data also revealed that the presence of nitrogen which would be either in the form of peptide chains means amide/amine or chemical form i.e. nitrates/nitrites etc. The formula weight and the weight ratio of C/H shows that it would be expected for algae derived organics, since algae produce fatty acids as well as other hydrocarbons such as cartenoids.

Keywords: GC-MS Analysis, lesser himalaya, Pc/C Boundary, shaanxilithes

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110 Renewable Energy and Hydrogen On-Site Generation for Drip Irrigation and Agricultural Machinery

Authors: Javier Carroquino, Nieves García-Casarejos, Pilar Gargallo, F. Javier García-Ramos

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The energy used in agriculture is a source of global emissions of greenhouse gases. The two main types of this energy are electricity for pumping and diesel for agricultural machinery. In order to reduce these emissions, the European project LIFE REWIND addresses the supply of this demand from renewable sources. First of all, comprehensive data on energy demand and available renewable resources have been obtained in several case studies. Secondly, a set of simulations and optimizations have been performed, in search of the best configuration and sizing, both from an economic and emission reduction point of view. For this purpose, it was used software based on genetic algorithms. Thirdly, a prototype has been designed and installed, that it is being used for the validation in a real case. Finally, throughout a year of operation, various technical and economic parameters are being measured for further analysis. The prototype is not connected to the utility grid, avoiding the cost and environmental impact of a grid extension. The system includes three kinds of photovoltaic fields. One is located on a fixed structure on the terrain. Another one is floating on an irrigation raft. The last one is mounted on a two axis solar tracker. Each has its own solar inverter. The total amount of nominal power is 44 kW. A lead acid battery with 120 kWh of capacity carries out the energy storage. Three isolated inverters support a three phase, 400 V 50 Hz micro-grid, the same characteristics of the utility grid. An advanced control subsystem has been constructed, using free hardware and software. The electricity produced feeds a set of seven pumps used for purification, elevation and pressurization of water in a drip irrigation system located in a vineyard. Since the irrigation season does not include the whole year, as well as a small oversize of the generator, there is an amount of surplus energy. With this surplus, a hydrolyser produces on site hydrogen by electrolysis of water. An off-road vehicle with fuel cell feeds on that hydrogen and carries people in the vineyard. The only emission of the process is high purity water. On the one hand, the results show the technical and economic feasibility of stand-alone renewable energy systems to feed seasonal pumping. In this way, the economic costs, the environmental impacts and the landscape impacts of grid extensions are avoided. The use of diesel gensets and their associated emissions are also avoided. On the other hand, it is shown that it is possible to replace diesel in agricultural machinery, substituting it for electricity or hydrogen of 100% renewable origin and produced on the farm itself, without any external energy input. In addition, it is expected to obtain positive effects on the rural economy and employment, which will be quantified through interviews.

Keywords: drip irrigation, greenhouse gases, hydrogen, renewable energy, vineyard

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109 The Hidden Mechanism beyond Ginger (Zingiber officinale Rosc.) Potent in vivo and in vitro Anti-Inflammatory Activity

Authors: Shahira M. Ezzat, Marwa I. Ezzat, Mona M. Okba, Esther T. Menze, Ashraf B. Abdel-Naim, Shahnas O. Mohamed

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Background: In order to decrease the burden of the high cost of synthetic drugs, it is important to focus on phytopharmaceuticals. The aim of our study was to search for the mechanism of ginger (Zingiber officinale Roscoe) anti-inflammatory potential and to correlate it to its biophytochemicals. Methods: Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated by protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated by assessment of rat paw oedema after carrageenan injection. Prostaglandin E2 (PGE2), certain inflammation markers (TNF-α, IL-6, IL-1α, IL-1β, INFr, MCP-1MIP, RANTES, and Nox) levels and MPO activity in the paw edema exudates were measured. Total antioxidant capacity (TAC) was also determined. Histopathological alterations of paw tissues were scored. Results: All the tested extracts showed significant (p < 0.1) anti-inflammatory activities. The highest percentage of heat induced albumin denaturation (66%) was exhibited by the 50% ethanol (250 μg/ml). The 70 and 90% ethanol extracts (500 μg/ml) were more potent as membrane stabilizers (34.5 and 37%, respectively) than diclofenac (33%). The 80 and 90% ethanol extracts (500 μg/ml) showed maximum protease inhibition (56%). The strongest anti-lipoxygenase activity was observed for the AE. It showed more significant lipoxygenase inhibition activity than that of diclofenac (58% and 52%, respectively) at the same concentration (125 μg/ml). Fractionation of AE yielded four main fractions (Fr I-IV) which showed significant in vitro anti-inflammatory. Purification of Fr-III and IV led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G2 (62.5 ug/ml), G1 (250 ug/ml), and G8 (250 ug/ml) exhibited potent anti-inflammatory activity in all studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw oedema in a dose-dependent manner. AE (at 200 mg/kg) showed significant reduction (60%) of PGE2 production. The AE at different doses (at 25-200 mg/kg) showed significant reduction in inflammatory markers except for IL-1α. AE (at 25 mg/kg) is superior to indomethacin in reduction of IL-1β. Treatment of animals with the AE (100, 200 mg/kg) or indomethacin (10 mg/kg) showed significant reduction in TNF-α, IL-6, MCP-1, and RANTES levels, and MPO activity by about (31, 57 and 32% ) (65, 60 and 57%) (27, 41 and 28%) (23, 32 and 23%) (66, 67 and 67%) respectively. AE at 100 and 200 mg/kg was equipotent to indomethacin in reduction of NOₓ level and in increasing the TAC. Histopathological examination revealed very few inflammatory cells infiltration and oedema after administration of AE (200 mg/kg) prior to carrageenan. Conclusion: Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. Moreover, it produced dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenished the total antioxidant capacity. We strongly recommend future investigations of ginger in the potential signal transduction pathways.

Keywords: anti-lipoxygenase activity, inflammatory markers, 1-dehydro-6-gingerol, 6-shogaol

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108 Indeterminacy: An Urban Design Tool to Measure Resilience to Climate Change, a Caribbean Case Study

Authors: Tapan Kumar Dhar

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How well are our city forms designed to adapt to climate change and its resulting uncertainty? What urban design tools can be used to measure and improve resilience to climate change, and how would they do so? In addressing these questions, this paper considers indeterminacy, a concept originated in the resilience literature, to measure the resilience of built environments. In the realm of urban design, ‘indeterminacy’ can be referred to as built-in design capabilities of an urban system to serve different purposes which are not necessarily predetermined. An urban system, particularly that with a higher degree of indeterminacy, can enable the system to be reorganized and changed to accommodate new or unknown functions while coping with uncertainty over time. Underlying principles of this concept have long been discussed in the urban design and planning literature, including open architecture, landscape urbanism, and flexible housing. This paper argues that the concept indeterminacy holds the potential to reduce the impacts of climate change incrementally and proactively. With regard to sustainable development, both planning and climate change literature highly recommend proactive adaptation as it involves less cost, efforts, and energy than last-minute emergency or reactive actions. Nevertheless, the concept still remains isolated from resilience and climate change adaptation discourses even though the discourses advocate the incremental transformation of a system to cope with climatic uncertainty. This paper considers indeterminacy, as an urban design tool, to measure and increase resilience (and adaptive capacity) of Long Bay’s coastal settlements in Negril, Jamaica. Negril is one of the popular tourism destinations in the Caribbean highly vulnerable to sea-level rise and its associated impacts. This paper employs empirical information obtained from direct observation and informal interviews with local people. While testing the tool, this paper deploys an urban morphology study, which includes land use patterns and the physical characteristics of urban form, including street networks, block patterns, and building footprints. The results reveal that most resorts in Long Bay are designed for pre-determined purposes and offer a little potential to use differently if needed. Additionally, Negril’s street networks are found to be rigid and have limited accessibility to different points of interest. This rigidity can expose the entire infrastructure further to extreme climatic events and also impedes recovery actions after a disaster. However, Long Bay still has room for future resilient developments in other relatively less vulnerable areas. In adapting to climate change, indeterminacy can be reached through design that achieves a balance between the degree of vulnerability and the degree of indeterminacy: the more vulnerable a place is, the more indeterminacy is useful. This paper concludes with a set of urban design typologies to increase the resilience of coastal settlements.

Keywords: climate change adaptation, resilience, sea-level rise, urban form

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107 Delusional Parasitosis (A Rare Primary Psychiatric Diagnosis)

Authors: Jaspinder Kaur, Jatinder Pal Singh

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Introduction- Delusional parasitosis is a rare psychotic illness characterized by a fixed belief of manifesting a parasite in a body when in reality, it was not. Also known as Ekbom syndrome or delusional infestations, or acarophobia. Although the patient has no primary skin pathology, but all skin findings were secondary to skin manipulation by the patient itself, which is why up to 90% of patients first seek consultation from a dermatologist. Most commonly, it was seen in older people with female to male ratio is 2:1. For treatment, the patient first need to be investigated to rule all other possible causes, as Delusional parasitosis can be caused by Vitamin B12 deficiency, pellagra, hepatic and renal disease, diabetes mellitus, multiple sclerosis, and leprosy. When all possible causes ruled out, psychiatric referral to be done. Rule out other psychiatric comorbidities, and treatment should be done accordingly. Patient with delusional parasitosis responds well to second generation antipsychotics and need to continuous medication over years, and relapse is likely if treatment is stopped. Case Presentation- A 79-year-old female, belonging to lower socio-economic status, presented with complaints of itching sensation with erythematous patches over the scalp and multiple scratch excoriations lesion over the scalp, face and neck from the past 7-8 months. She had a feeling of small insect crawling under her skin and scalp area. To reduce the itching and kill the insect, she would scratch and squeeze her skin repeatedly. When the family tried to give her explanation that there was no insect in her body, she would not get convinced, rather got angry and abuse family members for not believing her. Gradually, her sleep would remain disturbed, she would be seen awake at night, seen to be scratching her skin, pull her scalp hair, even squeeze out her healed lesions. She collected her skin debris, scalp hairs and look out for insect. Because of her continuous illness, the patient started to remain sad and had crying spells. Her appetite decreased. She became socially isolated and stopped doing her activities of daily living. Family member’s first consulted dermatologist, investigated thoroughly with routine investigations, autoimmune and malignancy workup. As all investigations were normal, following which patient was referred for psychiatric evaluation. The patient was started on Tablet Olanzapine 2.5 mg, gradually increased to 7.5 mg. Over 1 month, there was reduction in itching, skin pricking. Lesions were gradually healed, and the patient continued to take other dermatological medications and ointment and was in regular follow up with psychiatric liaison from past 2 months with 70-80 % improvement in her symptoms. Conclusion- Delusional parasitosis is a psychiatric disorder of insidious onset, seen commonly in middle and old age people. Both psychiatric and dermatology consultation liaison will help the patient for an early diagnosis and adequate treatment. If a primary psychiatric diagnosis, the patient respond well to second generation antipsychotics but always require a further evaluation and treatment management if it is secondary to some physical or other psychiatric comorbidity.

Keywords: delusional parasitosis, delusional infestations, rare, primary psychiatric diagnosis, antipsychotic agents

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106 Biotechnology Approach: A Tool of Enhancement of Sticky Mucilage of Pulicaria Incisa (Medicinal Plant) for Wounds Treatment

Authors: Djamila Chabane, Asma Rouane, Karim Arab

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Depending of the chemical substances responsible for the pharmacological effects, a future therapeutic drug might be produced by extraction from whole plants or by callus initiated from some parts. The optimized callus culture protocols now offer the possibility to use cell culture techniques for vegetative propagation and open minds for further studies on secondary metabolites and drug establishment. In Algerian traditional medicine, Pulicaria incisa (Asteraceae) is used in the treatment of daily troubles (stomachache, headhache., cold, sore throat and rheumatic arthralgia). Field findings revealed that many healers use some fresh parts (leaves, flowers) of this plant to treat skin wounds. This study aims to evaluate the healing efficiency of artisanal cream prepared from sticky mucilage isolated from calluses on dermal wounds of animal models. Callus cultures were initiated from reproductive explants (young inflorescences) excised from adult plants and transferred to a MS basal medium supplemented with growth regulators and maintained under dark for for months. Many calluses types were obtained with various color and aspect (friable, compact). Several subcultures of calli were performed to enhance the mucilage accumulation. After extraction, the mucilage extracts were tested on animal models as follows. The wound healing potential was studied by causing dermal wounds (1 cm diameter) at the dorsolumbar part of Rattus norvegicus; different samples of the cream were applied after hair removal on three rats each, including two controls (one treated by Vaseline and one without any treatment), two experimental groups (experimental group 1, treated with a reference ointment "Madecassol® and experimental group 2 treated by callus mucilage cream for a period of seventeen days. The evolution of the healing activity was estimated by calculating the percentage reduction of the area wounds treated by all compounds tested compared to the controls by using AutoCAD software. The percentage of healing effect of the cream prepared from callus mucilage was (99.79%) compared to that of Madecassol® (99.76%). For the treatment time, the significant healing activity was observed after 17 days compared to that of the reference pharmaceutical products without any wound infection. The healing effect of Madecassol® is more effective because it stimulates and regulates the production of collagen, a fibrous matrix essential for wound healing. Mucilage extracts also showed a high capacity to heal the skin without any infection. According to this pharmacological activity, we suggest to use calluses produced by in vitro culture to producing new compounds for the skin care and treatment.

Keywords: calluses, Pulicaria incisa, mucilage, Wounds

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105 Auto Surgical-Emissive Hand

Authors: Abhit Kumar

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The world is full of master slave Telemanipulator where the doctor’s masters the console and the surgical arm perform the operations, i.e. these robots are passive robots, what the world needs to focus is that in use of these passive robots we are acquiring doctors for operating these console hence the utilization of the concept of robotics is still not fully utilized ,hence the focus should be on active robots, Auto Surgical-Emissive Hand use the similar concept of active robotics where this anthropomorphic hand focuses on the autonomous surgical, emissive and scanning operation, enabled with the vision of 3 way emission of Laser Beam/-5°C < ICY Steam < 5°C/ TIC embedded in palm of the anthropomorphic hand and structured in a form of 3 way disc. Fingers of AS-EH (Auto Surgical-Emissive Hand) as called, will have tactile, force, pressure sensor rooted to it so that the mechanical mechanism of force, pressure and physical presence on the external subject can be maintained, conversely our main focus is on the concept of “emission” the question arises how all the 3 non related methods will work together that to merged in a single programmed hand, all the 3 methods will be utilized according to the need of the external subject, the laser if considered will be emitted via a pin sized outlet, this radiation is channelized via a thin channel which further connect to the palm of the surgical hand internally leading to the pin sized outlet, here the laser is used to emit radiation enough to cut open the skin for removal of metal scrap or any other foreign material while the patient is in under anesthesia, keeping the complexity of the operation very low, at the same time the TIC fitted with accurate temperature compensator will be providing us the real time feed of the surgery in the form of heat image, this gives us the chance to analyze the level, also ATC will help us to determine the elevated body temperature while the operation is being proceeded, the thermal imaging camera in rooted internally in the AS-EH while also being connected to the real time software externally to provide us live feedback. The ICY steam will provide the cooling effect before and after the operation, however for more utilization of this concept we can understand the working of simple procedure in which If a finger remain in icy water for a long time it freezes the blood flow stops and the portion become numb and isolated hence even if you try to pinch it will not provide any sensation as the nerve impulse did not coordinated with the brain hence sensory receptor did not got active which means no sense of touch was observed utilizing the same concept we can use the icy stem to be emitted via a pin sized hole on the area of concern ,temperature below 273K which will frost the area after which operation can be done, this steam can also be use to desensitized the pain while the operation in under process. The mathematical calculation, algorithm, programming of working and movement of this hand will be installed in the system prior to the procedure, since this AS-EH is a programmable hand it comes with the limitation hence this AS-EH robot will perform surgical process of low complexity only.

Keywords: active robots, algorithm, emission, icy steam, TIC, laser

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104 A Cross Cultural Study of Jewish and Arab Listeners: Perception of Harmonic Sequences

Authors: Roni Granot

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Musical intervals are the building blocks of melody and harmony. Intervals differ in terms of their size, direction, or quality as consonants or dissonants. In Western music, perceptual dissonance is mostly associated with the sensation of beats or periodicity, whereas cognitive dissonance is associated with rules of harmony and voice leading. These two perceptions can be studied separately in musical cultures which include melodic with little or no harmonic structures. In the Arab musical system, there is a number of different quarter- tone intervals creating various combinations of consonant and dissonant intervals. While traditional Arab music includes only melody, today’s Arab pop music includes harmonization of songs, often using typical Western harmonic sequences. Therefore, the Arab population in Israel presents an interesting case which enables us to examine the distinction between perceptual and cognitive dissonance. In the current study, we compared the responses of 34 Jewish Western listeners and 56 Arab listeners to two types of stimuli and their relationships: Harmonic sequences and isolated harmonic intervals (dyads). Harmonic sequences were presented in synthesized piano tones and represented five levels of Harmonic prototypicality (Tonic ending; Tonic ending with half flattened third; Deceptive cadence; Half cadence; and Dissonant unrelated ending) and were rated on 5-point scales of closure and surprise. Here we report only findings related to the harmonic sequences. One-way repeated measures ANOVA with one within subjects factor with five levels (Type of sequence) and one between- subjects factor (Musical background) indicates a main effect of Type of sequence for surprise ratings F (4, 85) = 51 p<.001, and for closure ratings F (4, 78) 9.54 p < .001, no main effect of Background on either surprise or closure ratings, and a marginally significant Type X Background interaction for surprise F (4, 352) = 6.05 p = .069 and closure ratings F (4, 324) 3.89 p < .01). Planned comparisons show that the interaction of Type of sequence X Background center around surprise and closure ratings of the regular versus the half- flattened third tonic and the deceptive versus the half cadence. The half- flattened third tonic is rated as less surprising and as demanding less continuation than the regular tonic by the Arab listeners as compared to the Western listeners. In addition, the half cadence is rated as more surprising but demanding less continuation than the deceptive cadence in the Arab listeners as compared to the Western listeners. Together, our results suggest that despite the vast exposure of Arab listeners to Western harmony, sensitivity to harmonic rules seems to be partial with preference to oriental sonorities such as half flattened third. In addition, the percept of directionality which demands sensitivity to the level on which closure is obtained and which is strongly entrenched in Western harmony, may not be fully integrated into the Arab listeners’ mental harmonic scheme. Results will be discussed in terms of broad differences between Western and Eastern aesthetic ideals.

Keywords: harmony, cross cultural, Arab music, closure

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103 Collaborative Program Student Community Service as a New Approach for Development in Rural Area in Case of Western Java

Authors: Brian Yulianto, Syachrial, Saeful Aziz, Anggita Clara Shinta

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Indonesia, with a population of about two hundred and fifty million people in quantity, indicates the outstanding wealth of human resources. Hundreds of millions of the population scattered in various communities in various regions in Indonesia with the different characteristics of economic, social and unique culture. Broadly speaking, the community in Indonesia is divided into two classes, namely urban communities and rural communities. The rural communities characterized by low potential and management of natural and human resources, limited access of development, and lack of social and economic infrastructure, and scattered and isolated population. West Java is one of the provinces with the largest population in Indonesia. Based on data from the Central Bureau of Statistics in 2015 the number of population in West Java reached 46.7096 million souls spread over 18 districts and 9 cities. The big difference in geographical and social conditions of people in West Java from one region to another, especially the south to the north causing the gap is high. It is closely related to the flow of investment to promote the area. Poverty and underdevelopment are the classic problems that occur on a massive scale in the region as the effects of inequity in development. South Cianjur and Tasikmalaya area South became one of the portraits area where the existing potential has not been capable of prospering society. Tri Dharma College not only define the College as a pioneer implementation of education and research to improve the quality of human resources but also demanded to be a pioneer in the development through the concept of public service. Bandung Institute of Technology as one of the institutions of higher education to implement community service system through collaborative community work program "one of the university community" as one approach to developing villages. The program is based Community Service, where students are not only required to be able to take part in community service, but also able to develop a community development strategy that is comprehensive and integrity in cooperation with government agencies and non-government related as a real form of effort alignment potential, position and role from various parties. Areas of western Java in particular have high poverty rates and disparity. On the other hand, there are three fundamental pillars in the development of rural communities, namely economic development, community development, and the integrated infrastructure development. These pillars require the commitment of all components of community, including the students and colleges for upholding success. College’s community program is one of the approaches in the development of rural communities. ITB is committed to implement as one form of student community service as community-college programs that integrate all elements of the community which is called Kuliah Kerja Nyata-Thematic.

Keywords: development in rural area, collaborative, student community service, Kuliah Kerja Nyata-Thematic ITB

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102 Unfolding Architectural Assemblages: Mapping Contemporary Spatial Objects' Affective Capacity

Authors: Panagiotis Roupas, Yota Passia

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This paper aims at establishing an index of design mechanisms - immanent in spatial objects - based on the affective capacity of their material formations. While spatial objects (design objects, buildings, urban configurations, etc.) are regarded as systems composed of interacting parts, within the premises of assemblage theory, their ability to affect and to be affected has not yet been mapped or sufficiently explored. This ability lies in excess, a latent potentiality they contain, not transcendental but immanent in their pre-subjective aesthetic power. As spatial structures are theorized as assemblages - composed of heterogeneous elements that enter into relations with one another - and since all assemblages are parts of larger assemblages, their components' ability to engage is contingent. We thus seek to unfold the mechanisms inherent in spatial objects that allow to the constituent parts of design assemblages to perpetually enter into new assemblages. To map architectural assemblage's affective ability, spatial objects are analyzed in two axes. The first axis focuses on the relations that the assemblage's material and expressive components develop in order to enter the assemblages. Material components refer to those material elements that an assemblage requires in order to exist, while expressive components includes non-linguistic (sense impressions) as well as linguistic (beliefs). The second axis records the processes known as a-signifying signs or a-signs, which are the triggering mechanisms able to territorialize or deterritorialize, stabilize or destabilize the assemblage and thus allow it to assemble anew. As a-signs cannot be isolated from matter, we point to their resulting effects, which without entering the linguistic level they are expressed in terms of intensity fields: modulations, movements, speeds, rhythms, spasms, etc. They belong to a molecular level where they operate in the pre-subjective world of perceptions, effects, drives, and emotions. A-signs have been introduced as intensities that transform the object beyond meaning, beyond fixed or known cognitive procedures. To that end, from an archive of more than 100 spatial objects by contemporary architects and designers, we have created an effective mechanisms index is created, where each a-sign is now connected with the list of effects it triggers and which thoroughly defines it. And vice versa, the same effect can be triggered by different a-signs, allowing the design object to lie in a perpetual state of becoming. To define spatial objects, A-signs are categorized in terms of their aesthetic power to affect and to be affected on the basis of the general categories of form, structure and surface. Thus, different part's degree of contingency are evaluated and measured and finally, we introduce as material information that is immanent in the spatial object while at the same time they confer no meaning; they only convey some information without semantic content. Through this index, we are able to analyze and direct the final form of the spatial object while at the same time establishing the mechanism to measure its continuous transformation.

Keywords: affective mechanisms index, architectural assemblages, a-signifying signs, cartography, virtual

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101 Relative Expression and Detection of MUB Adhesion Domains and Plantaricin-Like Bacteriocin among Probiotic Lactobacillus plantarum-Group Strains Isolated from Fermented Foods

Authors: Sundru Manjulata Devi, Prakash M. Halami

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The immemorial use of fermented foods from vegetables, dairy and other biological sources are of great demand in India because of their health benefits. However, the diversity of Lactobacillus plantarum group (LPG) of vegetable origin has not been revealed yet, particularly with reference to their probiotic functionalities. In the present study, the different species of probiotic Lactobacillus plantarum group (LPG) i.e., L. plantarum subsp. plantarum MTCC 5422 (from fermented cereals), L. plantarum subsp. argentoratensis FG16 (from fermented bamboo shoot) and L. paraplantarum MTCC 9483 (from fermented gundruk) (as characterized by multiplex recA PCR assay) were considered to investigate their relative expression of MUB domains of mub gene (mucin binding protein) by Real time PCR. Initially, the allelic variation in the mub gene was assessed and found to encode three different variants (Type I, II and III). All the three types had 8, 9 and 10 MUB domains respectively (as analysed by Pfam database) and were found to be responsible for adhesion of bacteria to the host intestinal epithelial cells. These domains either get inserted or deleted during speciation or evolutionary events and lead to divergence. The reverse transcriptase qPCR analysis with mubLPF1+R1 primer pair supported variation in amplicon sizes with 300, 500 and 700 bp among different LPG strains. The relative expression of these MUB domains significantly unregulated in the presence of 1% mucin in overnight grown cultures. Simultaneously, the mub gene expressed efficiently by 7 fold in the culture L. paraplantarum MTCC 9483 with 10 MUB domains. An increase in the expression levels for L. plantarum subsp. plantarum MTCC 5422 and L. plantarum subsp. argentoratensis FG16 (MCC 2974) with 9 and 8 repetitive domains was around 4 and 2 fold, respectively. The detection and expression of an integrase (int) gene in the upstream region of mub gene reveals the excision and integration of these repetitive domains. Concurrently, an in vitro adhesion assay to mucin and exclusion of pathogens (such as Listeria monocytogenes and Micrococcus leuteus) was investigated and observed that the L. paraplantarum MTCC 9483 with more adhesion domains has more ability to adhere to mucin and inhibited the growth of pathogens. The production and expression of plantaricin-like bacteriocin (plnNC8 type) in MTCC 9483 suggests the pathogen inhibition. Hence, the expression of MUB domains can act as potential biomarkers in the screening of a novel probiotic LPG strain with adherence property. The present study provides a platform for an easy, rapid, less time consuming, low-cost methodology for the detection of potential probiotic bacteria. It was known that the traditional practices followed in the preparation of fermented bamboo shoots/gundruk/cereals of Indian foods contain different kinds of neutraceuticals for functional food and novel compounds with health promoting factors. In future, a detailed study of these food products can add more nutritive value, consumption and suitable for commercialization.

Keywords: adhesion gene, fermented foods, MUB domains, probiotics

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100 Leveraging Multimodal Neuroimaging Techniques to in vivo Address Compensatory and Disintegration Patterns in Neurodegenerative Disorders: Evidence from Cortico-Cerebellar Connections in Multiple Sclerosis

Authors: Efstratios Karavasilis, Foteini Christidi, Georgios Velonakis, Agapi Plousi, Kalliopi Platoni, Nikolaos Kelekis, Ioannis Evdokimidis, Efstathios Efstathopoulos

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Introduction: Advanced structural and functional neuroimaging techniques contribute to the study of anatomical and functional brain connectivity and its role in the pathophysiology and symptoms’ heterogeneity in several neurodegenerative disorders, including multiple sclerosis (MS). Aim: In the present study, we applied multiparametric neuroimaging techniques to investigate the structural and functional cortico-cerebellar changes in MS patients. Material: We included 51 MS patients (28 with clinically isolated syndrome [CIS], 31 with relapsing-remitting MS [RRMS]) and 51 age- and gender-matched healthy controls (HC) who underwent MRI in a 3.0T MRI scanner. Methodology: The acquisition protocol included high-resolution 3D T1 weighted, diffusion-weighted imaging and echo planar imaging sequences for the analysis of volumetric, tractography and functional resting state data, respectively. We performed between-group comparisons (CIS, RRMS, HC) using CAT12 and CONN16 MATLAB toolboxes for the analysis of volumetric (cerebellar gray matter density) and functional (cortico-cerebellar resting-state functional connectivity) data, respectively. Brainance suite was used for the analysis of tractography data (cortico-cerebellar white matter integrity; fractional anisotropy [FA]; axial and radial diffusivity [AD; RD]) to reconstruct the cerebellum tracts. Results: Patients with CIS did not show significant gray matter (GM) density differences compared with HC. However, they showed decreased FA and increased diffusivity measures in cortico-cerebellar tracts, and increased cortico-cerebellar functional connectivity. Patients with RRMS showed decreased GM density in cerebellar regions, decreased FA and increased diffusivity measures in cortico-cerebellar WM tracts, as well as a pattern of increased and mostly decreased functional cortico-cerebellar connectivity compared to HC. The comparison between CIS and RRMS patients revealed significant GM density difference, reduced FA and increased diffusivity measures in WM cortico-cerebellar tracts and increased/decreased functional connectivity. The identification of decreased WM integrity and increased functional cortico-cerebellar connectivity without GM changes in CIS and the pattern of decreased GM density decreased WM integrity and mostly decreased functional connectivity in RRMS patients emphasizes the role of compensatory mechanisms in early disease stages and the disintegration of structural and functional networks with disease progression. Conclusions: In conclusion, our study highlights the added value of multimodal neuroimaging techniques for the in vivo investigation of cortico-cerebellar brain changes in neurodegenerative disorders. An extension and future opportunity to leverage multimodal neuroimaging data inevitably remain the integration of such data in the recently-applied mathematical approaches of machine learning algorithms to more accurately classify and predict patients’ disease course.

Keywords: advanced neuroimaging techniques, cerebellum, MRI, multiple sclerosis

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99 Tracking Patient Pathway for Assessing Public Health and Financial Burden to Community for Pulmonary Tuberculosis: Pointer from Central India

Authors: Ashish Sinha, Pushpend Agrawal

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Background: Patients with undiagnosed pulmonary TB predominantly act as reservoirs for its transmission through 10-15 secondary infections in the next 1-5 Yrs. Delays in the diagnosis and treatment may worsen the disease with increase the risk of death. Factors responsible for such delays by tracking patient pathways to treatment may help in planning better interventions. The provision of ‘free diagnosis and treatment’ forms the cornerstone of the National Tuberculosis Elimination Programme (NTEP). OOPE is defined as the money spent by the patient during TB care other than public health facilities. Free TB care at all health facilities could reduce out-of-pocket expenses to the minimum possible levels. Material and Methods: This cross-sectional study was conducted among randomly selected 252 TB patients from Nov – Oct 2022 by taking in-depth interviews following informed verbal consent. We documented their journey from initial symptoms until they reached the public health facility, along with their ‘out-of-pocket expenditure’ (OOPE) pertaining to TB care. Results: Total treatment delay was 91±72 days on average (median: 77days, IQR: 45-104 days), while the isolated patient delay was 31±45 days (median: 15 days, IQR: 0 days to 43 days); diagnostic delay; 57±60 days (median: 42days, IQR 14-78 days), treatment delay 19 ± 18 days (median: 15days, IQR: 11-19 days). A patient delay (> 30 days) was significantly associated with ignorance about classic symptoms of pulmonary TB, adoption of self-medication, illiteracy, and middle and lower social class. Diagnostic delay was significantly higher among those who contacted private health facilities, were unaware of signs and symptoms, had >2 consultations, and not getting an appropriate referral for TB care. Most (97%) of the study participants interviewed claimed to have incurred some expenditure.Median total expenses were 6155(IQR: 2625-15175) rupees. More than half 141 (56%) of the study participants had expenses >5000 rupees. Median transport expenses were 525(IQR: 200-1012) rupees; Median consultation expenses were 700(IQR: 200-1600) rupees; Median investigation expenses were 1000(IQR: 0-3025) rupees and the Median medicine expenses were 3350(IQR: 1300-7525).OOPE for consultation, investigation, and medicine was observed to be significantly higher among patients who ignored classical signs& symptoms of TB, repeated visits to private health facilities, and due to self-medication practices. Transport expenses and delays in seeking care at facilities were observed to have an upward trend with OOP Expenses (r =1). Conclusion: Delay in TB care due to low awareness about signs and symptoms of TB and poor seeking care, lack of proper consultation, and appropriate referrals reported by the study subjects indicate the areas which need proper attention by the program managers. Despite a centrally sponsored programme, the financial burden on TB patients is still in the unacceptable range. OOPE could be reduced as low as possible by addressing the responsible factors linked to it.

Keywords: patient pathway, delay, pulmonary tuberculosis, out of pocket expenses

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98 Telomerase, a Biomarker in Oral Cancer Cell Proliferation and Tool for Its Prevention at Initial Stage

Authors: Shaista Suhail

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As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

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97 Improving Physical, Social, and Mental Health Outcomes for People Living with an Intellectual Disability through Cycling

Authors: Sarah Faulkner, Patrick Faulkner, Caroline Ellison

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Improved mental and physical health, community connection, and increased life satisfaction has been strongly associated with bike riding for those with and without a disability. However, much evidence suggests that people living with a disability face increased barriers to engaging in cycling compared to members of the general population. People with an intellectual disability often live more sedentary and socially isolated lives that negatively impact their mental and physical health, as well as life satisfaction. This paper is based on preliminary findings from a three-year intervention cycling project funded by the South Australian Government. The cycling project was developed in partnership with community stakeholders that provided weekly instruction, training, and support to individuals living with intellectual disabilities to increase their capacity in cycling. This project aimed to support people living with intellectual disabilities to foster and facilitate improved physical and mental health, confidence, and independence and enhance social networking through their engagement in community cycling. The program applied principles of social role valorisation (SRV) theory as its guiding framework. Preliminary data collected is based on qualitative interviews with over 50 program participants, results from two participant wellness questionnaires, as well as a perceptually regulated exercise test administered throughout the project implementation. Preliminary findings are further supplemented with ethnographic analyses by the researchers who took a phenology of life experience approach. Preliminary findings of the program suggest a variety of social motivations behind participants' desire to learn cycling that acknowledges previous barriers to engagement and cycling’s role to address feelings of loneliness and social isolation. Meaningful health benefits can be achieved as demonstrated by increases in predicted V02 max measures, suggesting that physical intervention can not only improve physical health outcomes but also provide a variety of other social benefits. Initial engagement in the project has demonstrated an increase in participants' sense of confidence, well-being, and physical fitness. Implementation of the project in partnership with a variety of community stakeholders has identified a number of critical factors and processes necessary for future service replication, sustainability, and success. Findings from this intervention study contribute to the development of a knowledge base on how best to support individuals living with an intellectual disability to partake in bike riding and increase positive outcomes associated with their capacity building, social interaction, increased physical activity, physical health, and mental well-being. The initial findings of this study provide critical academic insights into the social and physical benefits of cycling for people living with a disability, as well as practical advice for future human service applications.

Keywords: cycling, disability, social inclusion, capacity building

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96 Isolation and Structural Elucidation of 20 Hydroxyecdystone from Vitex doniana Sweet Stem Bark

Authors: Mustapha A. Tijjani, Fanna I. Abdulrahman, Irfan Z. Khan, Umar K. Sandabe, Cong Li

Abstract:

Air dried sample V. doniana after collection and identification was extracted with ethanol and further partition with chloroform, ethyl acetate and n-butanol. Ethanolic extract (11.9g) was fractionated on a silica gel accelerated column chromatography using solvents such as n-hexane, ethyl acetate and methanol. Each eluent fractions (150ml aliquots) were collected and monitored with thin layer chromatography. Fractions with similar Rf values from same solvents system were pooled together. Phytochemical test of all the fractions were performed using standard procedure. Complete elution yielded 48 fractions (150ml/fraction) which were pooled to 24 fractions base on the Rf values. It was further recombined and 12 fractions were obtained on the basis on Rf values and coded Vd1 to Vd12 fractions. Vd8 was further eluted with ethylacetate and methanol and gave fourteen sub fractions Vd8-a, -Vd8-m. Fraction Vd8-a (56mg) gave a white crystal compound coded V1. It was further checked on TLC and observed under ultraviolet lamp and was found to give a single spot. The Rf values were calculated to be 0.433. The melting point was determined using Gallenkamp capillary melting point apparatus and found to be 241-243°C uncorrected. Characterization of the isolated compound coded V1 was done using FT-infra-red spectroscopy, HNMR, 13CNMR(1and 2D) and HRESI-MS. The IR spectrum of compound V1 shows prominent peaks that corresponds to OHstr (3365cm-1) and C=0 (1652cm-1) etc. This spectrum suggests that among the functional moiety in compound V1 are the carbonyl and hydroxyl group. The 1H NMR (400 MHz) spectrum of compound V1 in DMSO-d6 displayed five singlet signals at δ 0.72 (3H, s, H-18), 0.79 (3H, s, H-19), 1.03 (3H, s, H-21), 1.04 (3H, s, H-26), 1.06 (3H, s, H-27) each integrating for three protons indicating the five methyl functional groups present in the compound. It further showed a broad singlet at δ 5.58 integrated for 1 H due to an olefinic H-atom adjacent to the carbonyl carbon atom. Three signals at δ 3.10 (d, J = 9.0 Hz, H-22), 3.59 (m, 1H, 2H-a) and 3.72 (m, 1H, 3H-e), each integrating for one proton is due to oxymethine protons indicating that three oxymethine H-atoms are present in the compound. These all signals are characteristic to the ecdysteroid skeletons. The 13C-NMR spectrum showed the presence of 27 carbon atoms, suggesting that may be steroid skeleton. The DEPT-135 experiment showed the presence of five CH3, eight CH2, and seven CH groups, and seven quaternary C-atoms. The molecular formula was established as C27H44O7 by high resolution electron spray ionization-mass spectroscopy (HRESI-MS) positive ion mode m/z 481.3179. The signals in mass spectrum are 463, 445, and 427 peaks corresponding to losses of one, two, three, or four water molecules characteristic for ecdysterone skeleton reported in the literature. Based on the spectral analysis (HNMR, 13CNMR, DEPT, HMQC, IR, HRESI-MS) the compound V1 is thus concluded to have ecdysteriod skeleton and conclusively conforms with 2β, 3β 14α, 20R, 22R, 25-hexahydroxy-5 β cholest-7-ene-6- one, or 2, 3, 14, 20, 22, 25 hexahydroxy cholest-7-ene-6-one commonly known as 20-hydroxyecdysone.

Keywords: vitex, phytochemical, purification, isolation, chromatography, spectroscopy

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95 Influenza Virus Circulation among the Population of Kazakhstan in 2012-2014

Authors: N. G. Klivleyeva, T. I. Glebova, G. V. Lukmanova, S. B. Bayseit, S. Z. Taubaeva, M. K. Kalkozhaeva

Abstract:

The role of viral diseases in the general infectious disease incidence increases every year and requires special attention to the problem of interpreting the etiology of infectious agents. Influenza and acute respiratory viral infections are one of the most pressing public health issues. In the period 2012-2014, collection of 419 nasal swabs and 150 blood sera has been carried out in the patient care institutions of the various Kazakhstan regions from patients with symptoms of ARVI and pneumonia. Primary identification of biosamples for the presence of influenza viral antigens in enzyme immunoassay on nitrocellulose membrane gave positive results in 125 swabs (29.8%). Biosample screening in immunofluorescence test revealed the presence of influenza viral antigens against A/H1 in 63 samples (15.0%), A/H3 – in 70 samples (16.7%) and type B – in 9 samples (2.1%). As a result of primary infection, and successive passages in chick embryos and MDCK cell cultures, 38 HAAg were isolated from 419 samples with a clear cytopathic effect and hemagglutination titre in MDCK cell culture within 1:2-1:4, in CE - 1:8-1:256. The infectivity of isolates in chicken embryos were 3.5-6.5 lg EID50/0.2, in MDCK cell culture – 2.5-6.5 lg PFU/ml. Identification of 28 isolates was carried out in inhibition reactions of hemagglutinating activity and neuraminidase activity, showed their belonging to the influenza virus: 26 strains to A/H1N1, one - to A/H3N2, and one - to type B. Serological examination of blood sera for the presence of specific antibodies being an indirect evidence of the performed isolation and contributing to the timely interpretation of the disease etiology in the epidemics takes an important place in the comprehensive study of influenza viruses circulating among people. Serological analyzes were carried out in HAI assay using a kit consisting of 12 reference strains obtained from the WHO centre for reference and research on Influenza (CDC, Atlanta, USA) and three Kazakhstan (A/Almaty/347/09 (H1N1v), A/Almaty/462/11 (H3N2) and B/Almaty/414/10) human influenza viruses that are stored in the laboratory collection. The results of serological analysis of 150 blood sera showed that antihaemagglutinins against the A/H3N2 virus serosubtype were found in 46 samples (49.4%) out of 93 sera collected in 2012-2013. The antibody titres were within 1:160-1:320. 19 sera (20.4%) were seropositive against influenza A/H1N1 virus, the antibodies were observed in titres of 1:20-1:40. Six sera (6.4%) were positive against the influenza A/H1N1+A/H3N2 virus (mixed infection); the antibodies were recorded in titres of 1:20-1:40. Antihaemagglutinins against influenza type B virus were detected only in five sera (5.4%). The results of analysis of 57 sera collected in 2014 showed that antihaemagglutinins against A/H3N2 virus subtype were detected in 32 blood sera (56.1%) in titres of 1:160-1:640. Ten sera (17.5%) were seropositive against A/H1N1 virus; antihaemagglutinins against influenza type B virus were not detected. Therefore, virological and serological studies have shown that in Kazakhstan, as well as in the world, the influenza viruses A/H1N1, A/H3N2 and influenza B viruses were actively circulating during the epidemic seasons in 2012-2014.

Keywords: influenza, MDCK cell, serological analysis, virus

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94 Elite Netball Players’ Perspectives on Long Term Athlete Development Programmes in South Africa

Authors: Petrus Louis Nolte

Abstract:

University sport in South Africa is not isolated from the complexity of globalization and professionalization of sport, as it forms an integral part of the sport development environment in South Africa. In order to align their sport programmes with global and professional requirements, several universities opted to develop elite sport programmes; recruit specialized personnel such as coaches, administrators and athletes; provide expert coaching; scientific and medical services; sports testing; fitness, technical and tactical expertise; sport psychological and rehabilitation support; academic guidance and career assistance; and student-athlete accommodation. In addition, universities provide administrative support and high-quality physical resources (training facilities) for the benefit of the overall South African sport system. Although it is not compulsory for universities to develop elite sport programmes to prepare their teams for competitions, elite competitions such as the annual Varsity Sport, University Sport South Africa (USSA) and local club competitions and leagues within university international competitions where universities not only compete but also deliver players for representative national netball teams. The aim of this study is therefore to describe the perceptions of players of the university elite netball programmes they were participating in. This study adopted a descriptive design with a quantitative approach, utilizing a self-structured questionnaire as research technique. As this research formed part of a national research project for NSA with a population of 172 national and provincial netball players, a sample of 92 university netball players from the population was selected. Content validity of the self-structured questionnaire was secured through a test-retest process, with construct validity through a member of the Statistical Consultation Services (STATCON) of the University of Johannesburg that provided feedback on the structural format of the questionnaire. Reliability was measured utilising Cronbach Alpha on p<0.005 level of significance. A reliability score of 0.87 was measured. The research was approved by the Board of Netball South Africa and ethical conduct implemented according to the processes and procedures approved by the Ethics Committees of the Faculty of Health Sciences, University of Johannesburg with clearance number REC-01-30-2019. From the results it is evident that university elite netball programmes are professional, especially with regards to the employment of knowledgeable and competent coaches and technical officials such as team managers and sport sciences staff. These professionals have access to elite training facilities, support staff, and relatively large groups of elite players, all elements of an elite programme that could enhance the national federation’s (Netball South Africa) system. Universities could serve the dual purpose of serving as university netball clubs, as well as providing elite training services and facilities as performance hubs for national players.

Keywords: elite sport programmes, university netball, player experiences, Varsity Sport netball

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93 Learning Trajectories of Mexican Language Teachers: A Cross-Cultural Comparative Study

Authors: Alberto Mora-Vazquez, Nelly Paulina Trejo Guzmán

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This study examines the learning trajectories of twelve language teachers who were former students of a BA in applied linguistics at a Mexican state university. In particular, the study compares the social, academic and professional trajectories of two groups of teachers, six locally raised and educated ones and six repatriated ones from the U.S. Our interest in undertaking this research lies in the wide variety of students’ backgrounds we as professors in the BA program have witnessed throughout the years it has been around. Ever since the academic program started back in 2006, the student population has been made up of students whose backgrounds are highly diverse in terms of English language proficiency level, professional orientations and degree of cross-cultural awareness. Such diversity is further evidenced by the ongoing incorporation of some transnational students who have lived and studied in the United States for a significant period of time before their enrolment in the BA program. This, however, is not an isolated event as other researchers have reported this phenomenon in other TESOL-related programs of Mexican universities in the literature. Therefore, this suggests that their social and educational experiences are quite different from those of their Mexican born and educated counterparts. In addition, an informal comparison of the participation in formal teaching activities of the two groups at the beginning of their careers also suggested that significant differences in teacher training and development needs could also be identified. This issue raised questions about the need to examine the life and learning trajectories of these two groups of student teachers so as to develop an intervention plan aimed at supporting and encouraging their academic and professional advancement based on their particular needs. To achieve this goal, the study makes use of a combination of retrospective life-history research and the analysis of academic documents. The first approach uses interviews for data-collection. Through the use of a narrative life-history interview protocol, teachers were asked about their childhood home context, their language learning and teaching experiences, their stories of studying applied linguistics, and self-description. For the analysis of participants’ educational outcomes, a wide range of academic records, including reports of language proficiency exams results and language teacher training certificates, were used. The analysis revealed marked differences between the two groups of teachers in terms of academic and professional orientations. The locally educated teachers tended to graduate first, to look for further educational opportunities after graduation, to enter the language teaching profession earlier, and to expand their professional development options more than their peers. It is argued that these differences can be explained by their identities, which are made up of the interplay of influences such as their home context, their previous educational experiences and their cultural background. Implications for language teacher trainers and applied linguistics academic program administrators are provided.

Keywords: beginning language teachers, life-history research, Mexican context, transnational students

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92 Long Non-Coding RNAs Mediated Regulation of Diabetes in Humanized Mouse

Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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91 Computer Based Identification of Possible Molecular Targets for Induction of Drug Resistance Reversion in Multidrug Resistant Mycobacterium Tuberculosis

Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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90 Globalisation and Diplomacy: How Can Small States Improve the Practice of Diplomacy to Secure Their Foreign Policy Objectives?

Authors: H. M. Ross-McAlpine

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Much of what is written on diplomacy, globalization and the global economy addresses the changing nature of relationships between major powers. While the most dramatic and influential changes have resulted from these developing relationships the world is not, on deeper inspection, governed neatly by major powers. Due to advances in technology, the shifting balance of power and a changing geopolitical order, small states have the ability to exercise a greater influence than ever before. Increasingly interdependent and ever complex, our world is too delicate to be handled by a mighty few. The pressure of global change requires small states to adapt their diplomatic practices and diversify their strategic alliances and relationships. The nature and practice of diplomacy must be re-evaluated in light of the pressures resulting from globalization. This research examines: how small states can best secure their foreign policy objectives? Small state theory is used as a foundation for exploring the case study of New Zealand. The research draws on secondary sources to evaluate the existing theory in relation to modern practices of diplomacy. As New Zealand lacks the required economic and military power to play an active, influential role in international affairs what strategies are used to exert influence? Furthermore, New Zealand lies in a remote corner of the Pacific and is geographically isolated from its nearest neighbors how does this affect security and trade priorities? The findings note a significant shift since the 1970’s in New Zealand’s diplomatic relations. This shift is arguably a direct result of globalization, regionalism and a growing independence from the traditional bi-lateral relationships. The need to source predictable trade, investment and technology are an essential driving force for New Zealand’s diplomatic relations. A lack of hard power aligns New Zealand’s prosperity with a secure, rules-based international system that increases the likelihood of a stable and secure global order. New Zealand’s diplomacy and prosperity has been intrinsically reliant on its reputation. A vital component of New Zealand’s diplomacy is preserving a reputation for integrity and global responsibility. It is the use of this soft power that facilitates the influence that New Zealand enjoys on the world stage. To weave a comprehensive network of successful diplomatic relationships, New Zealand must maintain a reputation of international credibility. Globalization has substantially influenced the practice of diplomacy for New Zealand. The current world order places economic and military might in the hands of a few, subsequently requiring smaller states to use other means for securing their interests. There are clear strategies evident in New Zealand’s diplomacy practice that draw attention to how other smaller states might best secure their foreign policy objectives. While these findings are limited, as with all case study research, there is value in applying the findings to other small states struggling to secure their interests in the wake of rapid globalization.

Keywords: diplomacy, foreign policy, globalisation, small state

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