Search results for: CD8+ T cell responses
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5718

Search results for: CD8+ T cell responses

1518 Bacterial Cellulose: A New Generation Antimicrobial Wound Dressing Biomaterial

Authors: Bhavana V. Mohite, Satish V. Patil

Abstract:

Bacterial cellulose (BC) is an alternative for plant cellulose (PC) that prevents global warming leads to preservation of nature. Although PC and BC have the same chemical structure, BC is superior with its properties like its size, purity, porosity, degree of polymerization, crystallinity and water holding capacity, thermal stability etc. On this background the present study focus production and applications of BC as antimicrobial wound dressing material. BC was produced by Gluconoacetobacter hansenii (strain NCIM 2529) under shaking condition and statistically enhanced upto 7.2 g/l from 3.0 g/l. BC was analyzed for its physico mechanical, structural and thermal characteristics. BC produced at shaking condition exhibits more suitable properties in support to its high performance applications. The potential of nano silver impregnated BC was determined for sustained release modern antimicrobial wound dressing material by swelling ratio, mechanical properties and antimicrobial activity against Staphylococcus aureus. BC in nanocomposite form with other synthetic polymer like PVA shows improvement in its properties such as swelling ratio (757% to 979%) and sustainable release of antibacterial agent. The high drug loading and release potential of BC was evidenced in support to its nature as antimicrobial wound dressing material. The nontoxic biocompatible nature of BC was confirmed by MTT assay on human epidermal cells with 90% cell viability that allows its application as a regenerative biomaterial. Thus, BC as a promising new generation antimicrobial wound dressing material was projected.

Keywords: agitated culture, biopolymer, gluconoacetobacter hansenii, nanocomposite

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1517 The Influence of Surface Roughness on the Flow Fields Generated by an Oscillating Cantilever

Authors: Ciaran Conway, Nick Jeffers, Jeff Punch

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With the current trend of miniaturisation of electronic devices, piezoelectric fans have attracted increasing interest as an alternative means of forced convection over traditional rotary solutions. Whilst there exists an abundance of research on various piezo-actuated flapping fans in the literature, the geometries of these fans all consist of a smooth rectangular cross section with thicknesses typically of the order of 100 um. The focus of these studies is primarily on variables such as frequency, amplitude, and in some cases resonance mode. As a result, the induced flow dynamics are a direct consequence of the pressure differential at the fan tip as well as the pressure-driven ‘over the top’ vortices generated at the upper and lower edges of the fan. Rough surfaces such as golf ball dimples or vortex generators on an aircraft wing have proven to be beneficial by tripping the boundary layer and energising the adjacent air flow. This paper aims to examine the influence of surface roughness on the airflow generation of a flapping fan and determine whether the induced wake can be manipulated or enhanced by energising the airflow around the fan tip. Particle Image Velocimetry (PIV) is carried out on mechanically oscillated rigid fans with various surfaces consisting of pillars, perforations and cell-like grids derived from the wing topology of natural fliers. The results of this paper may be used to inform the design of piezoelectric fans and possibly aid in understanding the complex aerodynamics inherent in flapping wing flight.

Keywords: aerodynamics, oscillating cantilevers, PIV, vortices

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1516 Evaluation of Weather Risk Insurance for Agricultural Products Using a 3-Factor Pricing Model

Authors: O. Benabdeljelil, A. Karioun, S. Amami, R. Rouger, M. Hamidine

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A model for preventing the risks related to climate conditions in the agricultural sector is presented. It will determine the yearly optimum premium to be paid by a producer in order to reach his required turnover. The model is based on both climatic stability and 'soft' responses of usually grown species to average climate variations at the same place and inside a safety ball which can be determined from past meteorological data. This allows the use of linear regression expression for dependence of production result in terms of driving meteorological parameters, the main ones of which are daily average sunlight, rainfall and temperature. By simple best parameter fit from the expert table drawn with professionals, optimal representation of yearly production is determined from records of previous years, and yearly payback is evaluated from minimum yearly produced turnover. The model also requires accurate pricing of commodity at N+1. Therefore, a pricing model is developed using 3 state variables, namely the spot price, the difference between the mean-term and the long-term forward price, and the long-term structure of the model. The use of historical data enables to calibrate the parameters of state variables, and allows the pricing of commodity. Application to beet sugar underlines pricer precision. Indeed, the percentage of accuracy between computed result and real world is 99,5%. Optimal premium is then deduced and gives the producer a useful bound for negotiating an offer by insurance companies to effectively protect its harvest. The application to beet production in French Oise department illustrates the reliability of present model with as low as 6% difference between predicted and real data. The model can be adapted to almost any agricultural field by changing state parameters and calibrating their associated coefficients.

Keywords: agriculture, production model, optimal price, meteorological factors, 3-factor model, parameter calibration, forward price

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1515 Aesthetic Embodiment of the Visual and/or Non-Visual: the Becoming of a Spatial Installation Exhibition Influenced by Shamanic Healing

Authors: Ningfei Xiao, Simon Twose, Hannah Hopewell

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In urban settings worldwide, artists and researchers have drawn from shamanic healing, providing insightful responses to the environment. This project is a transdisciplinary creative research project where architecture and art practice draw from shamanic healing and provide the potential to expand knowledge of public space and inspire more aesthetic explorations of public spatial visions. The research started from the encounters with the Ewengki/Evenki shaman tribe in settlement areas of northern China in 2019 and extended through the partnerships with Maori artists in Poneke Aotearoa, New Zealand, in 2023. Based on the learnings and collaborations with female indigenous tradition practitioners and the healing that the researcher received from the land, a spatial installation exhibition was developed in this project. Indigenous practices are intricately woven with contemporary technology, merging visuals, soundscapes, and other non-visual aesthetics influenced by the researcher's personal experiences of embodied shamanic healing with brainwave generative technology. This synthesis seeks to ritualize and reimagine future public spaces, encompassing streetscapes and greenscapes from China to Aotearoa, and fostering connections between urbanized human body, mind, spirit, and land. In doing so, the project presents a feminist posthuman inquiry into how individuals perceive materiality within the context of a future city. Grounded in creative research and embodied methodologies, this paper focuses on the conceptual and autoethnographic aspects of visual-non-visual aesthetics and their creative representation. Through the exploration of aesthetics beyond the visual realm within urban and spatial contexts, this project showcases the spatial installation exhibition as an example of shamanic influence and related response to public space through embodied artistry and transdisciplinary creative inquiry.

Keywords: aesthetic, embodiment, visual and/or non-visual, spatial installation, shamanic healing, public space

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1514 Nematicidal Activity of the Cell Extract from Penicillium Sp EU0013 and Its Metabolite Profile Using High Performance Liquid Chromatograpy

Authors: Zafar Iqbal, Sana Irshad Khan

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Organic extract from newly isolated plant growth promoting fungus (PGPF) Penicillium sp EU0013 was subjected to bioassays including anti fungal (disc diffusion) cytotoxicity (brine shrimp lethality), herbicidal (Lemna minor) and nematicidal activities. Metabolite profile of the extract was also assessed using HPLC analysis with the aim to identify bioactive natural products in the extract as new drug candidate(s). The extract showed anti fungal potential against tested fungal pathogens. Growth of the Wilt pathogen Fusarium oxyosproum was inhibited up to 63% when compared to negative reference. Activity against brine shrimps was weak and mortality up to 10% was observed at concentration of 200 µg. mL-1. The extract exhibited no toxicity against Lemna minor frond at 200 µg. mL-1. Nematicidal activity was observed very potent against root knot nematode and LC50 value was calculated as 52.5 ug. mL-1 using probit analysis. Methodically assessment of metabolites profile by HPLC showed the presence of kojic acid (Rt 1.4 min) and aflatoxin B1 (Rt 5.9 min) in the mycellial extract as compared with standards. The major unidentified metabolite was eluted at Rt 8.6 along with other minor peaks. The observed high toxicity against root knot nematode was attributed to the unidentified compounds that make fungal extract worthy of further exploration for isolation and structural characterization studies for development of future commercial nematicidal compound(s).

Keywords: penicillium, nematicidal activity, metabolites, HPLC

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1513 Environmental and Socioeconomic Determinants of Climate Change Resilience in Rural Nigeria: Empirical Evidence towards Resilience Building

Authors: Ignatius Madu

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The study aims at assessing the environmental and socioeconomic determinants of climate change resilience in rural Nigeria. This is necessary because researches and development efforts on building climate change resilience of rural areas in developing countries are usually made without the knowledge of the impacts of the inherent rural characteristics that determine resilient capacities of the households. This has, in many cases, led to costly mistakes, delayed responses, inaccurate outcomes, and other difficulties. Consequently, this assessment becomes crucial not only to policymakers and people living in risk-prone environments in rural areas but also to fill the research gap. To achieve the aim, secondary data were obtained from the Annual Abstract of Statistics 2017, LSMS-Integrated Surveys on Agriculture and General Household Survey Panel 2015/2016, and National Agriculture Sample Survey (NASS), 2010/2011.Resilience was calculated by weighting and adding the adaptive, absorptive and anticipatory measures of households variables aggregated at state levels and then regressed against rural environmental and socioeconomic characteristics influencing it. From the regression, the coefficients of the variables were used to compute the impacts of the variables using the Stochastic Regression of Impacts on Population, Affluence and Technology (STIRPAT) Model. The results showed that the northern States are generally low in resilient indices and are impacted less by the development indicators. The major determining factors are percentage of non-poor, environmental protection, road transport development, landholding, agricultural input, population density, dependency ratio (inverse), household asserts, education and maternal care. The paper concludes that any effort to a successful resilient building in rural areas of the country should first address these key factors that enhance rural development and wellbeing since it is better to take action before shocks take place.

Keywords: climate change resilience; spatial impacts; STIRPAT model; Nigeria

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1512 Evaluation of Immune Checkpoint Inhibitors in Cancer Therapy

Authors: Mir Mohammad Reza Hosseini

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In new years immune checkpoint inhibitors have gathered care as being one of the greatest talented kinds of immunotherapy on the prospect. There has been a specific emphasis on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). In 2011, ipilimumab, the primary antibody obstructive an immune checkpoint (CTLA4) was authorized. It is now documented that recognized tumors have many devices of overpowering the antitumor immune response, counting manufacture of repressive cytokines, staffing of immunosuppressive immune cells, and upregulation of coinhibitory receptors recognized as immune checkpoints. This was fast followed by the growth of monoclonal antibodies directing PD1 (pembrolizumab and nivolumab) and PDL1 (atezolizumab and durvalumab). Anti-PD1/PDL1 antibodies have developed some of the greatest extensively set anticancer therapies. We also compare and difference their present place in cancer therapy and designs of immune-related toxicities and deliberate the role of dual immune checkpoint inhibition and plans for the organization of immune-related opposing proceedings. In this review, the employed code and present growth of numerous immune checkpoint inhibitors are abridged, while the communicating device and new development of Immune checkpoint inhibitors in cancer therapy-based synergistic therapies with additional immunotherapy, chemotherapy, phototherapy, and radiotherapy in important and clinical educations in the historical 5 years are portrayed and tinted. Lastly, we disapprovingly measure these methods and effort to find their fortes and faintness based on pre-clinical and clinical information.

Keywords: checkpoint, cancer therapy, PD-1, PDL-1, CTLA4, immunosuppressive

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1511 Thermodynamic and Immunochemical Studies of Antibody Biofunctionalized Gold Nanoparticles Mediated Photothermal Ablation in Human Liver Cancer Cells

Authors: Lucian Mocan, Flaviu Tabaran, Teodora Mocan, Cristian Matea, Cornel Iancu

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We present method of Gold Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinoma cell line), based on a simple gold nanoparticle carrier system, such as serum albumin (BSA), and demonstrate its selective therapeutic efficacy. Hyperspectral, contrast phase, and confocal microscopy combined immunochemical staining were used to demonstrate the selective internalization of HSA-GNPs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. We examined the ability of laser-activated carbon nanotubes to induce Hsp70 expression using confocal microscopy. Hep G2 cells heat-shocked (laser activated BSA-GNPs) to 42°C demonstrated an up-regulation of Hsp70 compared with control cells (BSA-GNPs treated cells without laser), which showed no detectable constitutive expression of Hsp70. We observed a time-dependent induction in Hsp70 expression in Hep G2 treated with BSA-GNPs and LASER irradiated. The post-irradiation apoptotic rate of HepG2 cells treated with HSA-GNPs ranged from 88.24% (for 50 mg/L) at 60 seconds, while at 30 minute the rate increased to 92.34% (50 mg/L). These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: gold nanoparticles, liver cancer, albumin, laser irradiation

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1510 Durability of Slurry Infiltrated Fiber Concrete to Corrosion in Chloride Environment: An Experimental Study, Part I

Authors: M. F. Alrubaie, S. A. Salih, W. A. Abbas

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Slurry infiltrated fiber concrete (SIFCON) is considered as a special type of high strength high-performance fiber reinforced concrete, extremely strong, and ductile. The objective of this study is to investigate the durability of SIFCON to corrosion in chloride environments. Six different SIFCON mixes were made in addition to two refinance mixes with 0% and 1.5% steel fiber content. All mixes were exposed to 10% chloride solution for 180 days. Half of the specimens were partially immersed in chloride solution, and the others were exposed to weekly cycles of wetting and drying in 10% chloride solution. The effectiveness of using corrosion inhibitors, mineral admixture, and epoxy protective coating were also evaluated as protective measures to reduce the effect of chloride attack and to improve the corrosion resistance of SIFCON mixes. Corrosion rates, half-cell potential, electrical resistivity, total permeability tests had been monitored monthly. The results indicated a significant improvement in performance for SIFCON mixes exposed to chloride environment, when using corrosion inhibitor or epoxy protective coating, whereas SIFCON mix contained mineral admixture (metakaolin) did not improve the corrosion resistance at the same level. The cyclic wetting and drying exposure were more aggressive to the specimens than the partial immersion in chloride solution although the observed surface corrosion for the later was clearer.

Keywords: chloride attack, chloride environments, corrosion inhibitor, corrosion resistance, durability, SIFCON, slurry infiltrated fiber concrete

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1509 Effects of Diabetic Duration on Platelet and Platelet Indices in Streptozotocin-Induced Diabetic Rats

Authors: Sahar Oudeh, Abbas Javaheri Vayeghan, Mahmood Ahmadi-Hamedani

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This study aimed to investigate the effect of diabetic duration on platelet and platelet indices in streptozotocin-induced diabetic male and female rats. Thirty-two healthy adult Wistar rats (16 females and 16 males) were randomly divided into 4 groups of eight, including 1) control group (4 females and 4 males who did not undergo any treatment until the end of 28 days), 2) 7-day diabetic group (4 females and 4 males who were diabetic for 7 days and were euthanized after 7 days), 3) 14-day diabetic group (4 females and 4 males who were diabetic for 14 days and were euthanized after 14 days), and 28-day diabetic group (4 females and 4 males who were diabetic for 28 days and were euthanized after 28 days). Diabetes was induced by intraperitoneal injection of streptozotocin (65 mg/kg). After induction of diabetes in the groups, blood samples were taken from their hearts after anesthesia, and platelet counts (PLT) and platelet indices were measured by an automatic blood cell counter (Nihon Kohden, Celltac Alpha VET MEK-6550, Japan). Statistical differences among groups were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s multiple tests. The results of this study showed that PLT and mean platelet volume (MPV) significantly increased in 7 and 14-day diabetic groups compared to the control group, whereas plateletcrit (PCT) and platelet distribution rate (PDW) significantly increased in 14 and 28-day diabetic groups, respectively. Significant differences were observed between female and male rats in PCT and PLT in the 14-day diabetic group and PDW in the 28-day diabetic group. According to the results of this study, measurement and analysis of platelet indices can be used as a method for the early diagnosis of diabetes and its complications.

Keywords: diabetic duration, streptozotocin, female and male rats, platelet indices

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1508 Determinants Affecting to Adoption of Climate Smart Agriculture Technologies in the Northern Bangladesh

Authors: Md. Rezaul Karim, Andreas Thiel

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Bangladesh is known as one of the most climate vulnerable countries in the world. Innovative technologies are always the key responses to the management of climate impacts. The objectives of this study are to determine the farmer’s perception of climate variability, to compare farmers’ perceptions with metrological data, and to explore the determinants that affect the likelihood of adoption of the selected Climate Smart Agricultural (CSA) technologies. Data regarding climate change perception, determinants and adoption were collected based on the household survey from stratified and randomly selected 365 farmers of the Biral sub-district under Dinajpur district in drought-prone northern Bangladesh. The likelihood of adoption of CSA technologies was analyzed following a multivariate probit model. The findings show that about 82.5% of the farmers perceived increasing temperature, and 75.1 % of farmers perceived decreasing dry season rainfall over the years, which is similarly relevant to metrological data. About 76.4.7% and 80.85% of farmers were aware of the drought tolerance crops and vermicompost, respectively; more than half of the farmers adopted these practices. Around 70.7% of farmers were aware of perching for insect control, but 46.3% of farmers adopted this practice. Although two-thirds of farmers were aware of crop diversification and pheromone trap, adoption was lower compared to the other three CSAs. Results also indicate that the likelihood of adoption of the selected CSAs is significantly influenced by different factors such as socio-economic characteristics, institutional factors and perceived technological or innovation attributes. The likelihood of adopting drought tolerance crops is affected by 11, while crop diversification and perching method by 7, pheromone trap by 9 and vermicompost by 8 determining factors. Lack of information and unavailability of input appear to be major obstacles to the non-adoption of CSA technologies. This study suggests that policy implications are necessary to promote extension services and overcome the obstacles to the non-adoption of individual CSA technologies. It further recommends that the research study should be conducted in a diverse context, nationally or globally.

Keywords: determinants, adoption, climate smart agriculture, northern Bangladesh

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1507 Early Diagnosis and Treatment of Cancer Using Synthetic Cationic Peptide

Authors: D. J. Kalita

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Cancer is one of the prime causes of early death worldwide. Mutation of the gene involve in DNA repair and damage, like BRCA2 (Breast cancer gene two) genes, can be detected efficiently by PCR-RFLP to early breast cancer diagnosis and adopt the suitable method of treatment. Host Defense Peptide can be used as blueprint for the design and synthesis of novel anticancer drugs to avoid the side effect of conventional chemotherapy and chemo resistance. The change at nucleotide position 392 of a -› c in the cancer sample of dog mammary tumour at BRCA2 (exon 7) gene lead the creation of a new restriction site for SsiI restriction enzyme. This SNP may be a marker for detection of canine mammary tumour. Support vector machine (SVM) algorithm was used to design and predict the anticancer peptide from the mature functional peptide. MTT assay of MCF-7 cell line after 48 hours of post treatment showed an increase in the number of rounded cells when compared with untreated control cells. The ability of the synthesized peptide to induce apoptosis in MCF-7 cells was further investigated by staining the cells with the fluorescent dye Hoechst stain solution, which allows the evaluation of the nuclear morphology. Numerous cells with dense, pyknotic nuclei (the brighter fluorescence) were observed in treated but not in control MCF-7 cells when viewed using an inverted phase-contrast microscope. Thus, PCR-RFLP is one of the attractive approach for early diagnosis, and synthetic cationic peptide can be used for the treatment of canine mammary tumour.

Keywords: cancer, cationic peptide, host defense peptides, Breast cancer genes

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1506 Design of an Improved Distributed Framework for Intrusion Detection System Based on Artificial Immune System and Neural Network

Authors: Yulin Rao, Zhixuan Li, Burra Venkata Durga Kumar

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Intrusion detection refers to monitoring the actions of internal and external intruders on the system and detecting the behaviours that violate security policies in real-time. In intrusion detection, there has been much discussion about the application of neural network technology and artificial immune system (AIS). However, many solutions use static methods (signature-based and stateful protocol analysis) or centralized intrusion detection systems (CIDS), which are unsuitable for real-time intrusion detection systems that need to process large amounts of data and detect unknown intrusions. This article proposes a framework for a distributed intrusion detection system (DIDS) with multi-agents based on the concept of AIS and neural network technology to detect anomalies and intrusions. In this framework, multiple agents are assigned to each host and work together, improving the system's detection efficiency and robustness. The trainer agent in the central server of the framework uses the artificial neural network (ANN) rather than the negative selection algorithm of AIS to generate mature detectors. Mature detectors can distinguish between self-files and non-self-files after learning. Our analyzer agents use genetic algorithms to generate memory cell detectors. This kind of detector will effectively reduce false positive and false negative errors and act quickly on known intrusions.

Keywords: artificial immune system, distributed artificial intelligence, multi-agent, intrusion detection system, neural network

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1505 Proteomics Application in Disease Diagnosis and Reproduction İmprovement in Cow

Authors: Abdollah Sobhani, Hossein Vaseghi-Dodaran

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Proteomics is defined as the study of the component of a cell, tissue and biological fluid. This technique has the potential to identify protein biomarkers of a disease states. In this study which was performed on bovine ovarian follicular cysts (BOFC), eight proteins are over expressed in BOFC that these proteins could be useful biomarkers for BOFC. The difference between serum proteome pattern cows affected by postpartum endometritis with healthy cows revealed that concentrations orosomucoid was decreased in endometritis. The comparison proteome of brucella abortus between laboratory adapted strains and clinical isolates could be useful to better understand this disease and vaccine development. Proteomics experiments identified new proteins and pathways that may be important in future hypothesis-driven studies of glucocorticoid-induced immunosuppression. Understanding the molecular mechanisms of effective parameters on male fertility is essential for obtaining high reproductive efficiency by decreasing cost and time. The investigations on proteome of high fertility spermatozoa indicated that expression of some proteins such as casein kinase 2 (CKII) prime poly peptide and tyrosine kinase in high fertility spermatozoa was higher compared to low fertility spermatozoa. Also, some evidence has indicated that variation in protein types and amounts in seminal fluid regulates fertility indexes in dairy bull. In conclusion, proteomics is a useful technique for discovering drugs, vaccine development, and diagnosis disease by biomarkers and improvement of reproduction efficiency.

Keywords: proteomics, reproduction, biomarker, immunity

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1504 Nabokov’s Lolita: Externalization of Contemporary Mind in the Configuration of Hedonistic Aesthetics

Authors: Saima Murtaza

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Ethics and aesthetics have invariably remained the two closely integrated artistic appurtenances for the production of any work of art. These artistic devices configure themselves into a complex synthesis in our contemporary literature. The labyrinthine integration of ethics and aesthetics, operating in the lives of human characters, to the extent of transcending all limits has resulted in an artistic puzzle for the readers. Art, no doubt, is an extrinsic expression of the intrinsic life of man. The use of aesthetics in literature pertaining to human existence; aesthetic solipsism, has resulted in the artistic objectification of these characters. The practice of the like aestheticism deprives the characters of their souls, rendering them as mere objects of aesthetic gaze at the hands of their artists-creators. Artists orchestrate their lives founding it on a plot which deviates from normal social and ethical standards. Their perverse attitude can be seen in dealing with characters, their feelings and the incidents of their lives. Morality is made to appear not as a religious construct but as an individual’s private affair. Furthermore, the idea of beauty incarnated, in other words hedonistic aesthetic does not placate a true aesthete. Ethics and aesthetics are the two most recurring motifs of our contemporary literature, especially of Nabokov’s world. The purpose of this study is to peruse these aforementioned motifs in Nabokov’s most enigmatic novel Lolita, a story of pedophilia, which is in fact reflective of our complex individual psychic and societal patterns. The narrative subverts all the traditional and hitherto known notions of aesthetics and ethics. When applied to literature, aesthetic does not simply mean ‘beautiful’ in the text. It refers to an intricate relationship between feelings and perception and also incorporates within its range wide-ranging emotional reactions to text. The term aesthetics in literature is connected with the readers whose critical responses to the text determine the merit of any work to be really a piece of art. Aestheticism is the child of ethics. Morality sets the grounds for the production of any work and the idea of aesthetics gives it transcendence.

Keywords: ethics, aesthetics and hedonistic aesthetic, nymphet syndrome, pedophilia

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1503 A Survey for Different Approaches in the Diagnosis and Treatment of PCOS Among Adult and Pediatric Endocrinologist

Authors: Fariha Salman, Helmet Steinberg, Hiba Al-Zubeidi

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OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common cause of infertility, with a prevalence of 5-10 % in women of reproductive age. There is evidence for differences between adult and pediatric endocrinologists and other specialists in their approach to the diagnosis and management of PCOS. METHODS: A survey consisting of 37 questions was distributed among adult and pediatric endocrinologists, aiming to understand the current practice for the diagnosis and management of PCOS. A total of 100 responses were available for final analysis; 36 % from adult endocrinologists (AE) and 64 % from pediatric endocrinologists(PE). RESULTS: The majority (64%) of respondents to the survey were endocrinologists from a multispecialty group. For both adults and adolescents with PCOS, the most commonly reported presenting symptoms were menstrual irregularities, obesity and hirsutism. The most common features used for diagnostic criteria were clinical or biochemical hyperandrogenism and ovulatory dysfunction. Most AE and PE screened for PCOS with total testosterone (83%) and free Testosterone (71%), screening for prolactin excess in 70 % and congenital adrenal hyperplasia (83 %), 66 % of AE will obtain pelvic US for evaluation vs 45 % of PE. Only 20 % of all respondents will obtain a midluteal progesterone for documentation of anovulation. In terms of treatment of hyperandrogenism and menstrual irregularities in adolescents, the most common form used is oral contraceptive pills, followed by metformin, then spironolactone. A similar approach was used in adults however the use of spironolactone was higher, 53 % vs 21 % in adolescents. The most common modality used for infertility was lifestyle interventions followed by metformin and clomiphene citrate. Screening of OSA and depression was not done by most of the endocrinologists (never + sometimes), 72 % and 76 %, respectively. Though screening for diabetes/metabolic syndrome and insulin resistance was done by most of the endocrinologists (always+often), 95 and 68 %, respectively. DISCUSSION: There are multiple diagnostic criteria used for PCOS diagnosis, however, given the wide variation in presentation and approach to diagnosis in adults and adolescents, there has not been a consensus on which is the gold standard criteria. CONCLUSION: Our survey showed the most common trends in diagnosing and treating PCOS among adult and pediatric endocrinologists. Further studies and trials need to be conducted to compare different treatment modalities used for hyperandrogenism, menstrual irregularities and infertility, as PCOS, if not treated earlier, can lead to long-term complications.

Keywords: PCOS, adolescents, diagnosis, treatment

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1502 Response Development of larvae Portunus pelagicus to Artificial Feeding Predigest

Authors: Siti Aslamyah, Yushinta Fujaya, Okto Rimaldi

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One of the problems faced in the crab hatchery operations is the reliance on the use of natural feed. This study aims to analyze the response of larval development and determine the initial stages crab larvae begin to fully able to accept artificial feeding predigest with the help of probiotic Bacillus sp. The experiment was conducted in June 2014 through July 2014 at the location of the scale backyard hatcheries, Bojo village Mallusettasi sub-district, district Barru. This study was conducted in two stages larval rearing. The first stage is designed in a completely randomized design with 5 treatments and each with 3 repetitions, ie, without the use of artificial feeding; predigest feed given from zoea 1 - megalopa; predigest feed given since zoea 2 - megalopa; predigest feed given from zoea 3 - megalopa; and feed predigest given since zoea 4 - megalopa. The second stage of the two treatments, i.e. comparing artificial feeding without and with predigest. The results showed that the artificial feeding predigest able to replace the use of natural feed started zoea 3 generated based on the survival rate. Artificial feeding predigest provide a higher survival rate (16%) compared to artificial diets without predigest only 10.8%. However, feed predigest not give a different effect on the rate of development of stadia. Cell activity in larvae that received artificial feed predigest higher with RNA-DNA ratio of 8.88 compared with no predigest only 5:36. This research is very valuable information for crab hatchery hatchery scale households have limitations in preparing natural food.

Keywords: artificial feeding, development of stadia, larvae Portunus pelagicus, predigest

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1501 Hash Based Block Matching for Digital Evidence Image Files from Forensic Software Tools

Authors: M. Kaya, M. Eris

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Internet use, intelligent communication tools, and social media have all become an integral part of our daily life as a result of rapid developments in information technology. However, this widespread use increases crimes committed in the digital environment. Therefore, digital forensics, dealing with various crimes committed in digital environment, has become an important research topic. It is in the research scope of digital forensics to investigate digital evidences such as computer, cell phone, hard disk, DVD, etc. and to report whether it contains any crime related elements. There are many software and hardware tools developed for use in the digital evidence acquisition process. Today, the most widely used digital evidence investigation tools are based on the principle of finding all the data taken place in digital evidence that is matched with specified criteria and presenting it to the investigator (e.g. text files, files starting with letter A, etc.). Then, digital forensics experts carry out data analysis to figure out whether these data are related to a potential crime. Examination of a 1 TB hard disk may take hours or even days, depending on the expertise and experience of the examiner. In addition, it depends on examiner’s experience, and may change overall result involving in different cases overlooked. In this study, a hash-based matching and digital evidence evaluation method is proposed, and it is aimed to automatically classify the evidence containing criminal elements, thereby shortening the time of the digital evidence examination process and preventing human errors.

Keywords: block matching, digital evidence, hash list, evaluation of digital evidence

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1500 Evaluating and Improving Healthcare Staff Knowledge of the [NG179] NICE Guidelines on Elective Surgical Care during the COVID-19 Pandemic: A Quality Improvement Project

Authors: Stavroula Stavropoulou-Tatla, Danyal Awal, Mohammad Ayaz Hossain

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The first wave of the COVID-19 pandemic saw several countries issue guidance postponing all non-urgent diagnostic evaluations and operations, leading to an estimated backlog of 28 million cases worldwide and over 4 million in the UK alone. In an attempt to regulate the resumption of elective surgical activity, the National Institute for Health and Care Excellence (NICE) introduced the ‘COVID-19 rapid guideline [NG179]’. This project aimed to increase healthcare staff knowledge of the aforementioned guideline to a targeted score of 100% in the disseminated questionnaire within 3 months at the Royal Free Hospital. A standardized online questionnaire was used to assess the knowledge of surgical and medical staff at baseline and following each 4-week-long Plan-Study-Do-Act (PDSA) cycle. During PDSA1, the A4 visual summary accompanying the guideline was visibly placed in all relevant clinical areas and the full guideline was distributed to the staff in charge together with a short briefing on the salient points. PDSA2 involved brief small-group teaching sessions. A total of 218 responses was collected. Mean percentage scores increased significantly from 51±19% at baseline to 81±16% after PDSA1 (t=10.32, p<0.0001) and further to 93±8% after PDSA2 (t=4.9, p<0.0001), with 54% of participants achieving a perfect score. In conclusion, the targeted distribution of guideline printouts and visual aids, combined with small-group teaching sessions, were simple and effective ways of educating healthcare staff about the new standards of elective surgical care at the time of COVID-19. This could facilitate the safe restoration of surgical activity, which is critical in order to mitigate the far-reaching consequences of surgical delays on an unprecedented scale during a time of great crisis and uncertainty.

Keywords: COVID-19, elective surgery, NICE guidelines, quality improvement

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1499 A Comparative Study on the Thermophysical and Lubricity Characteristics of Multiwall Carbon Nanotube/Oil and Nanoclay/Oil Nanofluids

Authors: H. Singh, H. Bhowmick

Abstract:

Now-a-days, particle based lubricants have been widely used to enhance the lubrication performance. Use of tailor made micro/nanofluids can reduce the friction losses and dissipate heat in a better way. Use of Carbon Nanotubes (CNTs) has gained interests because of its structure that can endure much better in a system mechanically or thermally in comparison to any other additive in oil. On the other hand, nanoclays have been characterized mechanically and tribologically for the use of clay/polymer composite, and they have been gaining huge interest. Hence it is interesting to be investigated the effect of nanoclays as additive in oil. Thermophysical characteristics of lubricant play a predominant role in defining the friction and wear characteristics of lubricated contacts. However, very limited studies have been carried out to correlate the thermophysical properties of nanolubricants with their lubricity characteristics. Besides, most of the lubricant formulations till dates are found to be optimized for steel/steel contacts. In the present study, Multiwall Carbon Nanotube (MWCNT) and nanoclay are used as particle additives in mineral oil to develop nanofluids of various concentrations. The prepared lubricants are tested for their rheological, thermal and lubricity characteristics under aluminium-steel contacts. From the thermophysical investigation, it is observed that nanoclay particles significantly improve the viscosity of lubricant with an insignificant improvement in thermal conductivity. On the other hand, MWCNT particles moderately increase the viscosity but significantly increase the thermal conductivity of the base oil. Frictional responses of the nanofluids are characterized using a Pin-on-Disc tribometer which reveal some interesting facts. The findings from this study will greatly aid in formulating the particle based lubricants for cutting fluid in metal forming industries as well as fully developed nanolubricants for aluminium and Aluminium Metal Matrix Composite (AMMC) tribocontact for the use in the automotive and their allied industries.

Keywords: MWCNT, Multiwall Carbon Nanotube, nanoclay, nanolubricant, rheology, thermal conductivity

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1498 Using LTE-Sim in New Hanover Decision Algorithm for 2-Tier Macrocell-Femtocell LTE Network

Authors: Umar D. M., Aminu A. M., Izaddeen K. Y.

Abstract:

Deployments of mini macrocell base stations also referred to as femtocells, improve the quality of service of indoor and outdoor users. Nevertheless, mobility management remains a key issue with regards to their deployment. This paper is leaned towards this issue, with an in-depth focus on the most important aspect of mobility management -handover. In handover management, making a handover decision in the LTE two-tier macrocell femtocell network is a crucial research area. Decision algorithms in this research are classified and comparatively analyzed according to received signal strength, user equipment speed, cost function, and interference. However, it was observed that most of the discussed decision algorithms fail to consider cell selection with hybrid access policy in a single macrocell multiple femtocell scenario, another observation was a majority of these algorithms lack the incorporation of user equipment residence parameter. Not including this parameter boosts the number of unnecessary handover occurrence. To deal with these issues, a sophisticated handover decision algorithm is proposed. The proposed algorithm considers the user’s velocity, received signal strength, residence time, as well as the femtocell base station’s access policy. Simulation results have shown that the proposed algorithm reduces the number of unnecessary handovers when compared to conventional received signal strength-based handover decision algorithm.

Keywords: user-equipment, radio signal service, long term evolution, mobility management, handoff

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1497 Facilitating Factors for the Success of Mobile Service Providers in Bangkok Metropolitan

Authors: Yananda Siraphatthada

Abstract:

The objectives of this research were to study the level of influencing factors, leadership, supply chain management, innovation, competitive advantages, business success, and affecting factors to the business success of the mobile phone system service providers in Bangkok Metropolitan. This research was done by the quantitative approach and the qualitative approach. The quantitative approach was used for questionnaires to collect data from the 331 mobile service shop managers franchised by AIS, Dtac and TrueMove. The mobile phone system service providers/shop managers were randomly stratified and proportionally allocated into subgroups exclusive to the number of the providers in each network. In terms of qualitative method, there were in-depth interviews of 6 mobile service providers/managers of Telewiz and Dtac and TrueMove shop to find the agreement or disagreement with the content analysis method. Descriptive Statistics, including Frequency, Percentage, Means and Standard Deviation were employed; also, the Structural Equation Model (SEM) was used as a tool for data analysis. The content analysis method was applied to identify key patterns emerging from the interview responses. The two data sets were brought together for comparing and contrasting to make the findings, providing triangulation to enrich result interpretation. It revealed that the level of the influencing factors – leadership, innovation management, supply chain management, and business competitiveness had an impact at a great level, but that the level of factors, innovation and the business, financial success and nonbusiness financial success of the mobile phone system service providers in Bangkok Metropolitan, is at the highest level. Moreover, the business influencing factors, competitive advantages in the business of mobile system service providers which were leadership, supply chain management, innovation management, business advantages, and business success, had statistical significance at .01 which corresponded to the data from the interviews.

Keywords: mobile service providers, facilitating factors, Bangkok Metropolitan, business success

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1496 Prioritization Ranking for Managing Moisture Problems in a Building

Authors: Sai Amulya Gollapalli, Dilip A. Patel, Parth Patel K., Lukman E. Mansuri

Abstract:

Accumulation of moisture is one of the most worrisome aspects of a building. Architects and engineers tend to ignore its vitality during the designing and construction stage. Major fatalities in buildings can be caused by it. People avoid spending a lot of money on waterproofing. If the same mistake is repeated, no deep thinking is done. The quality of workmanship and construction is depleting due to negligence. It is important to do an analysis of the water maintenance issues happening in the current buildings and give a database for all the factors that are causing the defect. In this research, surveys are done with two waterproofing consultants, two client engineers, and two project managers. The survey was based on a matrix that was based on the causes of water maintenance issues. There were around 100 causes that were identified. The causes were categorized into six, namely, manpower, finance, method, management, environment, and material. In the matrices, the causes on the x-direction matched with the causes on the y-direction. 3 Likert scale was used to make a pairwise comparison between causes on each cell. Matrices were evaluated for the main categories and for each category separately. A final ranking was done by the weights achieved, and ‘cracks arriving from various construction joints’ was the highest with 0.57 relative significance, and ‘usage of the material’ was the lowest with 0.03 relative significance. Twelve defects due to water leakage were identified, and interviewees were asked to make a pairwise comparison of them, too, to understand the priorities. When the list of causes is achieved, the prioritization as per the stratification analysis is done. This will be beneficial to the consultants and contractors as they will get a primary idea of which causes to focus on.

Keywords: water leakage, survey, causes, matrices, prioritization

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1495 Poly(Amidoamine) Dendrimer-Cisplatin Nanocomplex Mixed with Multifunctional Ovalbumin Coated Iron Oxide Nanoparticles for Immuno-Chemotherapeutics with M1 Polarization of Macrophages

Authors: Tefera Worku Mekonnen, Hiseh Chih Tsai

Abstract:

Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR) based tumor targeted 4.5 (4.5G) poly(amidoamine) dendrimer-cisplatin nanocomplex (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs have been examined by FTIR, X-ray diffraction, Raman, and X-ray photoelectron spectroscopy. The conjugation of cisplatin (Cis-pt) with 4.5GDP was confirmed using carbon NMR. The tumor-specific 4.5GDP-Cis-pt NC provided ~45% and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed when the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NP was biocompatible in different cell lines, even at a high concentration (200 µg mL−1). In contrast, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL−1) significantly increased the cytotoxicity against the cancer cells, which is dose-dependent on the concentration of AC-IO-Ova NPs. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, the efficiency of anticancer cells may be further assisted by induction of an innate immune response via M1 macrophage polarization due to the presence of AC-IO-Ova NPs. We provide a better synergestic chemoimmunotherapeutic strategy to enhance the efficiency of anticancer of cisplatin via chemotherapeutic agent 4.5GDP-Cis-pt NC and induction of proinflammatory cytokines to stimulate innate immunity through AC-IO-Ova NPs against tumors.

Keywords: cisplatin-release, iron oxide, ovalbumin, poly(amidoamine) dendrimer

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1494 Re-Thinking and Practicing Critical Pedagogy in Education through Art

Authors: Dalya Markovich

Abstract:

In the last decade art-educators strive to integrate critical pedagogy within the art classroom. Critical pedagogy aims to deconstruct the oppressive social reality and the false consciousness in which learners from both privileged and underprivileged groups are caught. Understanding oppression as a product of socio-political conditions seeks to instigate processes of change anchored in the student's views. Yet, growing empirical evidence show that these efforts often has resulted in art projects in which art teachers play an active role in the process of critical teaching, while the students remain passive listeners. In this common scenario, the teachers/artists become authoritarian moral guides of critical thinking and acting, while the students are often found to be indifferent or play along to satisfy the teachers'/artists aspirations. These responses indicate that the message of critical pedagogy – transforming the students' way of thinking and acting – mostly do not fulfill its emancipation goals. The study analyses the critical praxis embedded in new art projects and their influence on the participants. This type of projects replaces the individual producer with a collaborative work; switch the finite work with an ongoing project; and transforms the passive learner to an engaged co-producer. The research delves into the pedagogical framework of two of these art projects by using qualitative methods. In-depth interviews were conducted with 4 of the projects' initiator and managers, in order to access understandings of the art projects goals and pedagogical methods. Field work included 4 participant observation (two in each project) during social encounters in the project's settings, focusing on how critical thinking is enacted (or not) by the participants. The analysis exposes how the new art projects avoid the prepackaged "critical" assumptions and praxis, thus turning the participants from passive carriers of critical thinking to agents that actively use criticism. Findings invite researchers to explore new avenues for understanding critical pedagogy and developing various ways to implement critical pedagogy during art education, in view of the growing need of critical thinking and acting in school/society.

Keywords: critical pedagogy, education through art, collaborative work, agency

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1493 Effect of Post Circuit Resistance Exercise Glucose Feeding on Energy and Hormonal Indexes in Plasma and Lymphocyte in Free-Style Wrestlers

Authors: Miesam Golzadeh Gangraj, Younes Parvasi, Mohammad Ghasemi, Ahmad Abdi, Saeid Fazelifar

Abstract:

The purpose of the study was to determine the effect of glucose feeding on energy and hormonal indexes in plasma and lymphocyte immediately after wrestling – base techniques circuit exercise (WBTCE) in young male freestyle wrestlers. Sixteen wrestlers (weight = 75/45 ± 12/92 kg, age = 22/29 ± 0/90 years, BMI = 26/23 ± 2/64 kg/m²) were randomly divided into two groups: control (water), glucose (2 gr per kg body weight). Blood samples were obtained before, immediately, and 90 minutes of the post-exercise recovery period. Glucose (2 g/kg of body weight, 1W/5V) and water (equal volumes) solutions were given immediately after the second blood sampling. Data were analyzed by using an ANOVA (a repeated measure) and a suitable post hoc test (LSD). A significant decrease was observed in lymphocytes glycogen immediately after exercise (P < 0.001). In the experimental group, increase Lymphocyte glycogen concentration (P < 0.028) than in the control group in 90 min post-exercise. Plasma glucose concentrations increased in all groups immediately after exercise (P < 0.05). Plasma insulin concentrations in both groups decreased immediately after exercise, but at 90 min after exercise, its level was significantly increased only in glucose group (P < 0.001). Our results suggested that WBTCE protocol could be affected cellular energy sources and hormonal response. Furthermore, Glucose consumption can increase the lymphocyte glycogen and better energy within the cell.

Keywords: glucose feeding, lymphocyte, Wrestling – base techniques circuit , exercise

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1492 Prevalence of Disability among Children Two to Fourteen Years at Selected Districts in Greater Accra Region of Ghana

Authors: Yvonne Nanaama Brew, Bismark Jampim Abrokwah

Abstract:

Children with disabilities in Ghana are not routinely registered, and this can imply that they may be neglected in national policy planning since global estimates may not be near the exact numbers. Although there are some studies with reports on the prevalence of disability among children in Ghana, reliable information on the prevalence, types of disability in children, and children who die with disabilities in the Greater Accra region are lacking. The current study seeks to investigate the incidence of disability among children two to fourteen years at selected districts in the Greater Accra region of Ghana. A cross-sectional design is adapted with a quantitative method for this study. Parents with disabled children who access child welfare clinics at the Greater Accra regional hospital, Maamobi hospital, Ga west, and Ga south district hospitals will be selected through purposive sampling for the study. An adapted UNICEF structured Ten Questions will be used to collect relevant data about participants. The responses to the questions will be either 'Yes' or 'No'. Parents with children who answer 'Yes' to a disability and purposively sampled parents with children who answer 'No' to disability will be invited to Child Health Clinic at the Greater Accra regional hospital for a free clinical assessment. Data will be entered into Microsoft Office Excel 2013 and imported into STATA version 15 for analysis. The study is expected to provide reliable disaggregated data on less than fourteen years of children with disabilities in the Greater Accra region. The findings and recommendations of the study will demonstrate the importance of early detection of disability and facilitate more quality and holistic planning of appropriate programmes that best safeguard the rights of children with disabilities in Ghana. It will help in policy and decision-making on children less than fourteen years with disabilities in Ghana. Also, findings will be useful for health facilities in Ghana to plan services for disabled children. Finally, the study is expected to add to the guides for the National Council of Persons with Disabilities to fulfill its legal mandate for disabled persons in Ghana.

Keywords: prevalence, disability, children, Ghana

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1491 Ethiopia as a Tourist Destination, An Exploration of German Tourists' Market Demand

Authors: Dagnew Dessie Mengie

Abstract:

The purpose of this study was to investigate German tourists' demand for Ethiopian tourism destinations. The author has made every effort to identify the differences in the preferences of German visitors’ demand in Ethiopia comparing with Egypt, Kenya, Tanzania, and South African tourism sectors if they are invited to visit at the same time. However, the demand of international tourism for Ethiopia currently lags behind these African countries. Therefore, to offer demand-driven tourism products, the Ethiopian government, Tour & Travel operators need to understand the important factors that affect international tourists’ decision to visit Ethiopian tourist destinations. The aim of this study was intended to analyze German Tourists’ Demand towards Ethiopian destination. The researcher aimed to identify the demand for German tourists’ preference to Ethiopian tourist destinations comparing to the above-mentioned African countries. For collecting and analysing data for this study, both quantitative and qualitative methods of research are being used in this study. The most significant data are collected by using the primary data collection method i.e. survey and interviews which are the most and large number of potential responses and feedback from nine German active tourists,12 Ethiopian tourism officials, four African embassies, and four well functioning private tour companies and secondary data collected from books, journals, previous research and electronic websites. based on the data analysis of the information gathered from interviews and questionnaires, the study disclosed that majority of German tourists have not that much high demand on Ethiopian Tourist destinations due to the following reasons; Many Germans are fascinated by adventures, safari and simply want to lie on the beach and relax. These interests have leaded them to look for other African countries which have these accesses. Uncomfortable infrastructure and transport problems attributed for the decreasing the number of German tourists in the country. Inadequate marketing operation of Ethiopian Tourism Authority and its delegates in advertising and clarifying the above irregularities which are raised by the tourists.

Keywords: environmental benefits of tourism, social benefits of tourism, economical benefits of tourism, political factors in tourism

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1490 Biomphalaria alexandrina Snail as a Bio-Indicator of Pollution With Manganese Metal and Its Effect on Physiological, Immunological, Histopathological Parameters and Larvicidal Potencies

Authors: Amina M. Ibrahim, Ahmed A. Abdel-Haleem, Rania G. Taha

Abstract:

Metal pollution results in many dangerous consequences to the environment and human health due to the bioaccumulation in their tissues. The present study aims to measure the bioaccumulation factor of the Manganese (Mn) heavy metal in Biomphlaria alexandrina snails' tissues and water samples. The present results showed the concentration of Mn heavy metal in water (87.5 mg/l) and its bioaccumulation factor in Helisoma duryi tissue was higher than that in tissues of Physa acuta and B. alexandrina snails. Results showed that 87.5 mg/l Mn concentration had miracidial and cercaricidal activities. Also, this concentration decreased the mean total number of the hemocytes after exposure for 24h or 48h, while increased both the mean mortality and phagocytic indices of the hemocytes of exposed snails. It caused alterations in the cytomorphology of the hemocytes of exposed snails after 24 or 48h, where, the granulocytes had irregular cell membrane, and forming pseudopodia. Besides, both levels of Testosterone (T) and Estradiol (E) were increased after exposure to 87.5mg/l Mn metal compared to the control group. Also, it increased MDA (Malonaldehyde) and TAC (Total antioxidant capacity) contents, while, decreased SOD (superoxide dismutase). Besides, it caused great histopathological damages in both hermaphrodite and digestive glands, represented in the degeneration of the gonadal, digestive, secretory cells and the connective tissues. Therefore, B. alexandrina might be used as sensitive bio-indicator of pollution with Mn heavy metal to avoid ethics rules; beside they are easily available and large in number.

Keywords: manganese metal, B. alexandrina, hormonal alterations, histopathology

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1489 Identification of Potential Small Molecule Regulators of PERK Kinase

Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

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PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

Procedia PDF Downloads 483