Search results for: small molecule inhibitor
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5437

Search results for: small molecule inhibitor

5137 Neighbour Cell List Reduction in Multi-Tier Heterogeneous Networks

Authors: Mohanad Alhabo, Naveed Nawaz

Abstract:

The ongoing call or data session must be maintained to ensure a good quality of service. This can be accomplished by performing the handover procedure while the user is on the move. However, the dense deployment of small cells in 5G networks is a challenging issue due to the extensive number of handovers. In this paper, a neighbour cell list method is proposed to reduce the number of target small cells and hence minimizing the number of handovers. The neighbour cell list is built by omitting cells that could cause an unnecessary handover and handover failure because of short time of stay of the user in these cells. A multi-attribute decision making technique, simple additive weighting, is then applied to the optimized neighbour cell list. Multi-tier small cells network is considered in this work. The performance of the proposed method is analysed and compared with that of the existing methods. Results disclose that our method has decreased the candidate small cell list, unnecessary handovers, handover failure, and short time of stay cells compared to the competitive method.

Keywords: handover, HetNets, multi-attribute decision making, small cells

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5136 Zika Virus NS5 Protein Potential Inhibitors: An Enhanced in silico Approach in Drug Discovery

Authors: Pritika Ramharack, Mahmoud E. S. Soliman

Abstract:

The re-emerging Zika virus is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus already been linked to irreversible chronic central nervous system (CNS) conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA-approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of Zika virus Methyltransferase and RNA-dependent RNA polymerase. This in silico “per-residue energy decomposition pharmacophore” virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.

Keywords: NS5 protein inhibitors, per-residue decomposition, pharmacophore model, virtual screening, Zika virus

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5135 Synthesis of a Library of Substituted Isoquinolines Based on a Triazolization Strategy, and Their Anti-HIV and C-X-C Chemokine Receptor Type 4 Antagonist Activity

Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

Abstract:

Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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5134 Factors of Influence in Software Process Improvement: An ISO/IEC 29110 for Very-Small Entities

Authors: N. Wongsai, R. Wetprasit, V. Siddoo

Abstract:

The recently introduced ISO/IEC 29110 standard Lifecycle profile for Very Small Entities (VSE) has been adopted and practiced in many small and medium software companies, including in Thailand’s software industry. Many Thai companies complete their software process improvement (SPI) initiative program and have been certified. There are, however, a number of participants fail to success. This study was concerned with the factors that influence the accomplishment of the standard implementation in various VSE characteristics. In order to achieve this goal, exploring and extracting critical factors from prior studies were carried out and then the obtained factors were validated by the standard experts. Data analysis of comments and recommendations was performed using a qualitative content analysis method. This paper presents the initial set of influence factors in both positive and negative impact the ISO/IEC 29110 implementation with an aim at helping such SPI practitioners with some considerations to manage appropriate adoption approach in order to achieve its implementation.

Keywords: barriers, critical success factors, ISO/IEC 29110, Software Process Improvement, SPI, Very-Small Entity, VSE

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5133 Response Solutions of 2-Dimensional Elliptic Degenerate Quasi-Periodic Systems With Small Parameters

Authors: Song Ni, Junxiang Xu

Abstract:

This paper concerns quasi-periodic perturbations with parameters of 2-dimensional degenerate systems. If the equilibrium point of the unperturbed system is elliptic-type degenerate. Assume that the perturbation is real analytic quasi-periodic with diophantine frequency. Without imposing any assumption on the perturbation, we can use a path of equilibrium points to tackle with the Melnikov non-resonance condition, then by the Leray-Schauder Continuation Theorem and the Kolmogorov-Arnold-Moser technique, it is proved that the equation has a small response solution for many sufficiently small parameters.

Keywords: quasi-periodic systems, KAM-iteration, degenerate equilibrium point, response solution

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5132 The Role of Social Media in Growing Small and Medium Enterprises: An Empirical Study in Jordan

Authors: Hanady Al-Zagheer

Abstract:

The purpose of this paper research is to introduce the role of the social media (face book) in growing small and medium enterprises in Jordan, Today’s developments of information technologies are dazzling. Using information technologies results in having advantages in competition, decreasing costs, gaining time, and getting and sharing information. Now it is possible to state that there are different types of usage within the information technologies. Small and medium enterprises have been grown rapidly in recent years and continue to grow. Jordanian females have played a large role in the growth of entrepreneurship and have made an impact on household economics. Virtual storefronts have allowed these women to balance roles assigned by tradition and culture while becoming successful providers. If you have a small business with a limited public relations and advertising budget, Facebook can be a cost effective way to promote your services because opening an account is free. However, this can work against you if you do not maintain the page. A Face book page without frequent updates can destroy your brand value and image. According to a 2009 Computerworld article by Lisa Hoover, having a Facebook page that looks abandoned is worse than having no page at all. You might need to hire someone or pay an employee to update your business’s Facebook page.

Keywords: social media, social media small, medium enterprises, Jordan

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5131 Dissemination of Knowledge on Quality Control for Upgrading Product Standards for Small and Micro Community Enterprises

Authors: Niyom Suwandej

Abstract:

This research paper investigated the opinions of small and micro community enterprises from Jom Pluak Subdistrict, Bangkhontee District, Samut Songkram Province towards product quality control, and the findings are aimed to disseminate knowledge on quality control for upgrading product standards for small and micro community enterprises. The study employed both qualitative and quantitative methods, in which there were 23 samples in the study. The study was divided into 2 steps which were (1) studying the opinions of the respondents towards the community’s product quality control and upgrading product standards; (2) creating development guidance for product quality control and upgrading product standards for small and micro community enterprise. The demographic findings revealed female respondents as the majority, with most above 50 years of age and married. Most had more than 15 years of working experience. The education level reported by most respondents was primary school or lower followed by secondary school or lower with most respondents was vocational certificate level. Most respondents had the highest level of satisfaction with the existing condition of product quality control knowledge management. Pertaining to opinions on the guidance of knowledge creation for product quality control for small and micro community enterprise, the respondents were willing to apply the knowledge in upgrading their product standards. For the opinions of knowledge creation for product quality control and product standards, the respondents had the highest level of satisfaction. Guidance of knowledge creation for product quality control and product standards for small and micro community enterprises received the highest level of satisfaction from the respondents. Furthermore they had knowledge and comprehension in product quality control and product standards and could apply the knowledge in improving the quality of their production and product standards for small and micro community enterprises.

Keywords: product quality control, product standards, community enterprise, marketing management

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5130 A Study on Analysis of Magnetic Field in Induction Generator for Small Francis Turbine Generator

Authors: Young-Kwan Choi, Han-Sang Jeong, Yeon-Ho Ok, Jae-Ho Choi

Abstract:

The purpose of this study is to verify validity of design by testing output of induction generator through finite element analysis before manufacture of induction generator designed. Characteristics in the operating domain of induction generator can be understood through analysis of magnetic field according to load (rotational speed) of induction generator. Characteristics of induction generator such as induced voltage, current, torque, magnetic flux density (magnetic flux saturation), and loss can be predicted by analysis of magnetic field.

Keywords: electromagnetic analysis, induction generator, small hydro power generator, small francis turbine generator

Procedia PDF Downloads 1457
5129 Combination Therapies Targeting Apoptosis Pathways in Pediatric Acute Myeloid Leukemia (AML)

Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

Abstract:

Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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5128 The Potential for Tourism Development in the Greater Chinhoyi Area in Zimbabwe: A Systems Approach in an Appetizer Destination

Authors: Phillip F. Kanokanga, Patrick W. Mamimine, Molline Mwando, Charity Mapingure

Abstract:

Tourism development tends to follow anchor attractions, including cities and their surroundings, while marginalizing small towns and their environs. This is even though the small towns and their hinterlands can also offer competitive tourism products. The Zimbabwe Tourism Authority (ZTA) gathers visitor statistics of major tourist destinations only thereby sidelining the density of tourist traffic that either passes through or visits the small towns in the country. Unless this problem is addressed, the tourism potential of small towns and their hinterlands will not be fully tapped for economic development. Using qualitative research methodology, this study investigated the opportunities for tourism development in the Greater Chinhoyi Area. The study revealed that the Greater Chinhoyi area had potential for heritage tourism, village tourism, urban tourism, educational tourism, dark tourism, recreational tourism, agrotourism, and nature tourism. There is a need to link the various tourism resources in the Greater Chinhoyi area to anchor attractions in dominant resorts, then develop and present the tourism products in transit towns as ‘appetisers’ or ‘appetisser attractions’ before one gets to the main destination.

Keywords: anchor attractions, appetisers, heritage tourism, agrotourism, small towns, tourism corridor, systems approach, hidden treasures

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5127 The Effects of Governmental Regulation on Technological Innovation in Korean Firms

Authors: SeungKu Ahn, Sewon Lee

Abstract:

This study examines the effects of regulatory policies on corporate R&D activities and innovation and suggests regulatory directions for the enhancement of corporate performance. This study employs a regression model with R&D activities as dependent variables and the regulatory index as an independent variable. The results of this study are as follows: The regulation is negatively associated with the input and output of R&D activities. The regulation encourages small and medium-sized firms to invest in R&D. The regulation has a positive effect on patent applications for small and medium-sized firms.

Keywords: governmental regulation, research and development performance, small and medium-sized firms, technological innovation

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5126 Binding Studies of Complexes of Anticancer Drugs with DNA and Enzymes Involved in DNA Replication Using Molecular Docking and Cell Culture Techniques

Authors: Fouzia Perveen, Rumana Qureshi

Abstract:

The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

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5125 Resource Allocation of Small Agribusinesses and Entrepreneurship Development In Nigeria

Authors: Festus M. Epetimehin

Abstract:

Resources are essential materials required for production of goods and services. Effective allocation of these resources can engender the success of current business activities and its sustainability for future generation. The study examined effect of resource allocation of small agribusinesses on entrepreneurship development in Southwest Nigeria. Sample size of 385 was determined using Cochran’s formula. 350 valid copies of questionnaire were used in the analysis. In order to achieve the objective, research design (descriptive and cross sectional designs) was used to gather data for the study through the administration of questionnaire to respondents. Both descriptive and inferential statistics were used to investigate the objective of the study. The result obtained indicated that resource allocation by small agribusinesses had a substantial positive effect on entrepreneurship development with the p-value of (0.0000) which was less than the 5.0% critical value with a positive regression coefficient of 0.53. The implication of this is that the ability of the entrepreneurs to deploy their resources efficiently through adequate realization of better gross margin could enhance business activities and development. The study recommends that business owners still need some level of serious training and exposure on how to manage modern small agribusiness resources to enhance business performance. The intervention of Agricultural Development Programme (ADP) and other Agricultural institutions are needed in this regard.

Keywords: resource, resource allocation, small businesses, agriculture, entrepreneurship development

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5124 Innovation and Performance of Very Small Agri-Food Enterprises in Cameroon

Authors: Ahmed Moustapha Mfokeu

Abstract:

Agri-food VSEs in Cameroon are facing a succession of crises, lack of security, particularly in the Far North, South West, and North West regions, the consequences of the Covid 19 crisis, and the war in Ukraine . These multiple crises have benefited the reception of the prices of the raw materials. Moreover, the exacerbation of competitive pressures is driven by the technological acceleration of productive systems in emerging countries which increase the demands imposed on the markets. The Cameroonian VSE must therefore be able to meet the new challenges of international competition, especially through innovation. The objective of this research is to contribute to the knowledge of the effects of innovation on the performance of very small agribusinesses in Cameroon. On the methodological level, the data were provided from a sample of 153 companies in the cities of Douala and Yaoundé. This research uses structural equation models with latent variables. The main results show that there is a positive and significant link between innovation and the performance of very small agri-food companies, so if it is important for entrepreneurs to encourage and practice innovation, it is also necessary to make them understand and make them like this aspect in their strategic function.

Keywords: innovation, performance, very small enterprise, agrifood

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5123 Aorta Adhesion Molecules in Cholesterol-Fed Rats Supplemented with Extra Virgin Olive Oil or Sunflower Oil, in Either Commercial or Modified Forms

Authors: Ageliki I. Katsarou, Andriana C. Kaliora, Antonia Chiou, Apostolos Papalois, Nick Kalogeropoulos, Nikolaos K. Andrikopoulos

Abstract:

Chronic inflammation plays a pivotal role in CVD development, while phytochemicals have been shown to reduce CVD risk. Several studies have correlated olive oil consumption with CVD prevention and CVD risk reduction. However, the effect of individual olive oil macro- or micro-constituents and possible synergisms among them needs to be further elucidated. Herein, extra virgin olive oil (EVOO) lipidic and polar phenolics fractions were evaluated for their effect on inflammatory markers in cholesterol-fed rats. Oils combining different characteristics as to their polar phenolic content and lipid profile were used. Male Wistar rats were fed for 9 weeks on either a high-cholesterol diet (HCD) or a HCD supplemented with oils, either commercially available, i.e. EVOO, sunflower oil (SO), or modified as to their polar phenol content, i.e. phenolics deprived-EVOO (EVOOd), SO enriched with the EVOO phenolics (SOe). Post-intervention, aorta and blood samples were collected. HCD induced dyslipidemia, manifested by serum total cholesterol and low-density lipoprotein cholesterol elevation. Additionally, HCD resulted in higher adhesion molecules’ levels in rat aorta. In the case of E-selectin, this increase was attenuated by HCD supplementation with EVOO and EVOOd, while no alterations were observed in SO and SOe groups. No differences were observed between pairs of commercial and modified oils, indicating that oleates may be the components responsible for aorta E-selectin levels lowering. The same was true for vascular adhesion molecule-1 (VCAM-1); augmentation in cholesterol-fed animals was attenuated by EVOO and EVOOd diets, highlighting oleates effect. In addition, VCAM-1 levels were higher in SO group compared to the respective SOe, indicating that in the presence of phenolic compounds linoleic acid have become less prone to oxidation. Intercellular adhesion molecule-1 (ICAM-1) levels were higher in cholesterol-fed rats, however not affected by any of the oils supplemented during the intervention. Overall, EVOO was found superior in regulating adhesion molecule levels in rat aorta compared to SO. EVOO and EVOOd exhibited analogous effects on all adhesion molecules assessed, indicating that EVOO major constituents (oleates) improve E-selectin and VCAM-1 levels in rat aorta, independently from phenolics presence. Further research is needed to elucidate the effect of phenolics and oleates in other tissues.

Keywords: extra virgin olive oil, cholesterol-fed rats, polar phenolics, adhesion molecules

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5122 The Impact of Metacognitive Knowledge and Experience on Top Management Team Diversity and Small to Medium Enterprises Performance

Authors: Jo Rhodes, Peter Lok, Zahra Sadeghinejad

Abstract:

The aim of this study is to determine the impact of metacognition on top management team members and firm performance based on full team integration. A survey of 1500 small to medium enterprises (SMEs) was initiated and 140 firms were obtained in this study (with response rate of 9%). The result showed that different metacognitive abilities of managers [knowledge and experience] could enhance team decision-making and problem solving, resulting in greater firm performance. This is a significant finding for SMEs because these organisations have small teams with owner leadership and entrepreneurial orientation.

Keywords: metacognition, behavioural integration, top management team (TMT), performance

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5121 Biophysical Characterization of the Inhibition of cGAS-DNA Sensing by KicGAS, Kaposi's Sarcoma-Associated Herpesvirus Inhibitor of cGAS

Authors: D. Bhowmik, Y. Tian, Q. Yin, F. Zhu

Abstract:

Cyclic GMP-AMP synthase (cGAS), recognises cytoplasmic double-stranded DNA (dsDNA), indicative of bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. Viruses also have developed numerous strategies to antagonize the cGAS-STING pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that is the causative agent of Kaposi’s sarcoma and several other malignancies. To persist in the host, consequently causing diseases, KSHV must overcome the host innate immune responses, including the cGAS-STING DNA sensing pathway. We already found that ORF52 or KicGAS (KSHV inhibitor of cGAS), an abundant and basic gamma herpesvirus-conserved tegument protein, directly inhibits cGAS enzymatic activity. To better understand the mechanism, we have performed the biochemical and structural characterization of full-length KicGAS and various mutants in regarding binding to DNA. We observed that KicGAS is capable of self-association and identified the critical residues involved in the oligomerization process. We also characterized the DNA-binding of KicGAS and found that KicGAS cooperatively oligomerizes along the length of the double stranded DNA, the highly conserved basic residues at the c-terminal disordered region are crucial for DNA recognition. Deficiency in oligomerization also affects DNA binding. Thus DNA binding by KicGAS sequesters DNA and prevents it from being detected by cGAS, consequently inhibiting cGAS activation. KicGAS homologues also inhibit cGAS efficiently, suggesting inhibition of cGAS is evolutionarily conserved mechanism among gamma herpesvirus. These results highlight the important viral strategy to evade this innate immune sensor.

Keywords: Kaposi's sarcoma-associated herpesvirus, KSHV, cGAS, DNA binding, inhibition

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5120 Rethinking the Use of Online Dispute Resolution in Resolving Cross-Border Small E-Disputes in EU

Authors: Sajedeh Salehi, Marco Giacalone

Abstract:

This paper examines the role of existing online dispute resolution (ODR) mechanisms and their effects on ameliorating access to justice – as a protected right by Art. 47 of the EU Charter of Fundamental Rights – for consumers in EU. The major focus of this study will be on evaluating ODR as the means of dispute resolution for Business-to-Consumer (B2C) cross-border small claims raised in e-commerce transactions. The authors will elaborate the consequences of implementing ODR methods in the context of recent developments in EU regulatory safeguards on promoting consumer protection. In this analysis, both non-judiciary and judiciary ODR redress mechanisms are considered, however, the significant consideration is given to – obligatory and non-obligatory – judiciary ODR methods. For that purpose, this paper will particularly investigate the impact of the EU ODR platform as well as the European Small Claims Procedure (ESCP) Regulation 861/2007 and their role on accelerating the access to justice for consumers in B2C e-disputes. Although, considerable volume of research has been carried out on ODR for consumer claims, rather less (or no-) attention has been paid to provide a combined doctrinal and empirical evaluation of ODR’s potential in resolving cross-border small e-disputes, in EU. Hence, the methodological approach taken in this study is a mixed methodology based on qualitative (interviews) and quantitative (surveys) research methods which will be mainly based on the data acquired through the findings of the Small Claims Analysis Net (SCAN) project. This project contributes towards examining the ESCP Regulation implementation and efficiency in providing consumers with a legal watershed through using the ODR for their transnational small claims. The outcomes of this research may benefit both academia and policymakers at national and international level.

Keywords: access to justice, consumers, e-commerce, small e-Disputes

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5119 Anticancer Lantadene Derivatives: Synthesis, Cytotoxic and Docking Studies

Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

Abstract:

Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

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5118 Supply Chain Technology Adoption in Textile and Apparel Industry

Authors: Zulkifli Mohamed Udin, Lee Khai-Loon, Mohamad Ghozali Hassan

Abstract:

In today’s dynamic business environment, the competition is no longer between firms, but between supply chains to gain competitive advantages. The global manufacturing sector, especially the textile and apparel industry are essentially known for its supply chain dependency. The delicate nature of its business leads to emphasis on the smooth movement of upstream and downstream supply chain. The nature of this industry, however, result in huge dynamic flow of physical, information, and financial. The dynamic management of these flows requires adoption of supply chain technologies. Even though technology is widely implemented and studied in many industries by researchers, adoption of supply chain technologies in Malaysian textile and apparel industry is limited. There is relatively a handful academic study conducted on recent developments in Malaysian textile and apparel industry and supply chain technology adoption indicate a major gap in supply chain performance studies. Considering the importance given to Third Industrial Master Plan by the government Malaysia, it is necessary to understand the power of supply chain technology adoptions. This study aims to investigate supply chain technology adoption by textile and apparel companies in Malaysia. The result highlighted the benefits perceived by textile and apparel companies from supply chain technologies. The indifference of small and medium enterprises to operation management acts as a major inhibitor to the adoption of supply chain technologies, since they have resource limitations. This study could be used as a precursor for further detailed studies on this issue.

Keywords: supply chain technology adoption, supply chain performance, textile, apparel industry

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5117 Characterization of Dota-Girentuximab Conjugates for Radioimmunotherapy

Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

Abstract:

Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

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5116 Normal Coordinate Analysis, Molecular Structure, Vibrational, Electronic Spectra, and NMR Investigation of 4-Amino-3-Phenyl-1H-1,2,4-Triazole-5(4H)-Thione by Ab Initio HF and DFT Method

Authors: Khaled Bahgat

Abstract:

In the present work, the characterization of 4-Amino-3-phenyl-1H-1,2,4-triazole-5(4H)-thione (APTT) molecule was carried out by quantum chemical method and vibrational spectral techniques. The FT-IR (4000–400 cm_1) and FT-Raman (4000–100 cm_1) spectra of APTT were recorded in solid phase. The UV–Vis absorption spectrum of the APTT was recorded in the range of 200–400 nm. The molecular geometry, harmonic vibrational frequencies and bonding features of APTT in the ground state have been calculated by HF and DFT methods using 6-311++G(d,p) basis set. The complete vibrational frequency assignments were made by normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology (SQMF). The molecular stability and bond strength were investigated by applying the natural bond orbital analysis (NBO) and natural localized molecular orbital (NLMO) analysis. The electronic properties, such as excitation energies, absorption wavelength, HOMO and LUMO energies were performed by time depended DFT (TD-DFT) approach. The 1H and 13C nuclear magnetic resonance chemical shift of the molecule were calculated using the gauge-including atomic orbital (GIAO) method and compared with experimental results. Finally, the calculation results were analyzed to simulate infrared, FT-Raman and UV spectra of the title compound which shows better agreement with observed spectra.

Keywords: 4-amino-3-phenyl-1H-1, 2, 4-triazole-5(4H)-thione, vibrational assignments, normal coordinate analysis, quantum mechanical calculations

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5115 Predisposition of Small Scale Businesses in Fagge, Kano State, Nigeria, Towards Profit and Loss Sharing Mode of Finance

Authors: Farida, M. Shehu, Shehu U. R. Aliyu

Abstract:

Access to finance has been recognized in the literature as one of the major impediments confronting small scale businesses (SSBs). This largely arises due to high lending rate, religious inclinations, collateral, etc. Islamic mode finance operates under Profit and Loss Sharing (PLS) arrangement between a borrower (business owner) and a lender (Islamic bank). This paper empirically assesses the determinants of predisposition of small scale business operators in Fagge local government area, Kano State, Nigeria, towards the PLS. Cross-sectional data from a sample of 291 small scale business operators was analyzed using logit and probit regression models. Empirical results reveal that while awareness and religion inclination positively drive interest towards the PLS, lending rate and collateral work against it. The paper, therefore, strongly recommends more advocacy campaigns and setting up of more Islamic banks in the country to cater for the financing and religious needs of SSBs in the study area.

Keywords: Islamic finance, logit and probit models, profit and loss sharing small scale businesses, finance, commerce

Procedia PDF Downloads 360
5114 Determination of Biomolecular Interactions Using Microscale Thermophoresis

Authors: Lynn Lehmann, Dinorah Leyva, Ana Lazic, Stefan Duhr, Philipp Baaske

Abstract:

Characterization of biomolecular interactions, such as protein-protein, protein-nucleic acid or protein-small molecule, provides critical insights into cellular processes and is essential for the development of drug diagnostics and therapeutics. Here we present a novel, label-free, and tether-free technology to analyze picomolar to millimolar affinities of biomolecular interactions by Microscale Thermophoresis (MST). The entropy of the hydration shell surrounding molecules determines thermophoretic movement. MST exploits this principle by measuring interactions using optically generated temperature gradients. MST detects changes in the size, charge and hydration shell of molecules and measures biomolecule interactions under close-to-native conditions: immobilization-free and in bioliquids of choice, including cell lysates and blood serum. Thus, MST measures interactions under close-to-native conditions, and without laborious sample purification. We demonstrate how MST determines the picomolar affinities of antibody::antigen interactions, and protein::protein interactions measured from directly from cell lysates. MST assays are highly adaptable to fit to the diverse requirements of different and complex biomolecules. NanoTemper´s unique technology is ideal for studies requiring flexibility and sensitivity at the experimental scale, making MST suitable for basic research investigations and pharmaceutical applications.

Keywords: biochemistry, biophysics, molecular interactions, quantitative techniques

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5113 Design and Analysis of Blade Length and Number of Blades of Small Horizontal Axis Wind Turbine

Authors: Ali Gul, Bhart Kumar, Samiullah Ansari

Abstract:

The current research is focused on the study of various lengths of blades (i.e. 1 to 5m) and several bladed rotors (3,5,7 & 9) of small horizontal axis wind turbine under low wind conditions usingQBlade software. Initially, the rotor was designed using airfoil SG6043 with five different lengths of the blades. Subsequently, simulations were carried out in which, under low wind regimes, the power output was observed. Further, four rotors having 3,5,7 & 9 blades were analyzed. However, the most promising coefficient of performance (CP) was observed at the 3-bladed rotor. Both studies established a clear view of harvesting wind energy at low wind speeds that can be mobilized in the energy sector. That suggests the utilization of wind energy at the domestic levelwhich is acceleratory growing in the last few decades.

Keywords: small HAWT, QBlade, BEM, CFD

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5112 Mini Coal Gasifier for Fulfilling Small-Scale Industries Energy Consumption in Indonesia

Authors: Muhammad Ade Andriansyah Efendi, Ika Monika

Abstract:

Mini coal gasifier (GasMin) is a small reactor that could convert coal into combustible gas or producer gas which is designed to fulfill energy needs of small-scale industries. The producer gas can be utilized for both external and internal combustion. The design of coal gasifier is suitable for community require because it is easy to handle, affordable and environmentally friendly. The feasibility study shows that the substitution of 12 kg LPG or specially 50 kg LPG into GasMin of 20 kg coal capacity per hour is very attractive. The estimation price of 20 kg coal per hour capacity GasMin is 40 million rupiahs. In the year 2016, the implementation of GasMin conducted at alumunium industry and batik industry at Yogyakarta, Indonesia.

Keywords: biomass, coal, energy, gasification

Procedia PDF Downloads 317
5111 A Rare Case of Endometriosis Lesion in Caecum Causing Acute Small Bowel Obstruction

Authors: Freda Halim

Abstract:

Endometriosis in bowel is rare condition, about 3-37% of endometriosis cases. Most of bowel endometriosis rising in the rectosigmoid (90% of bowel endometriosis). The incidence of caecal endometriosis is very low ( < 5% of bowel endometriosis) and almost never causing acute small bowel obstruction. The aim of this paper is to show that although bowel obstruction caused by caecal endometriosis is difficult to diagnose as it is rare, and may require laparotomy to make definite diagnosis, but it should be considered in infertile female patient. The case is 37 years old woman infertile woman with intestinal obstruction with pre-operative diagnosis total acute small bowel obstruction caused by right colonic mass, with sepsis as the complication. Before the acute small bowel obstruction, she complained of chronic right lower quadrant pain with chronic constipation alternate with chronic diarrhea, symptoms that happened both in bowel endometriosis and colorectal malignancy. She also complained of chronic pelvic pain and dysmenorrhea. She was married for 10 years with no child. The patient was never diagnosed with endometriosis and never seek medical attention for infertility and the chronic pelvic pain. The patient underwent Abdominal CT Scan, with results: massive small bowel obstruction, and caecal mass that causing acute small bowel obstruction. Diagnosis of acute small bowel obstruction due to right colonic mass was made, and exploratory laparotomy was performed in the patient. During the laparotomy, mass at caecum and ileocaecal that causing massive small bowel obstruction was found and standard right hemicolectomy and temporary ileostomy were performed. The pathology examination showed ectopic endometriosis lesions in caecum and ileocaecal valve. The histopathology also confirmed with the immunohistochemistry, in which positive ER, PR, CD 10 and CD7 was found the ileocaecal and caecal mass. In the second operation, reanastomosis of the ileum was done 3 months after the first operation. The chronic pelvic pain is decreasing dramatically after the first and second operation. In conclusion, although bowel obstruction caused by caecal endometriosis is a rare cause of intestinal obstruction, but it can be considered as a cause in infertile female patient

Keywords: acute, bowel obstruction, caecum, endometriosis

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5110 An Inverse Docking Approach for Identifying New Potential Anticancer Targets

Authors: Soujanya Pasumarthi

Abstract:

Inverse docking is a relatively new technique that has been used to identify potential receptor targets of small molecules. Our docking software package MDock is well suited for such an application as it is both computationally efficient, yet simultaneously shows adequate results in binding affinity predictions and enrichment tests. As a validation study, we present the first stage results of an inverse-docking study which seeks to identify potential direct targets of PRIMA-1. PRIMA-1 is well known for its ability to restore mutant p53's tumor suppressor function, leading to apoptosis in several types of cancer cells. For this reason, we believe that potential direct targets of PRIMA-1 identified in silico should be experimentally screened for their ability to inhibitcancer cell growth. The highest-ranked human protein of our PRIMA-1 docking results is oxidosqualene cyclase (OSC), which is part of the cholesterol synthetic pathway. The results of two followup experiments which treat OSC as a possible anti-cancer target are promising. We show that both PRIMA-1 and Ro 48-8071, a known potent OSC inhibitor, significantly reduce theviability of BT-474 breast cancer cells relative to normal mammary cells. In addition, like PRIMA-1, we find that Ro 48-8071 results in increased binding of mutant p53 to DNA in BT- 474cells (which highly express p53). For the first time, Ro 48-8071 is shown as a potent agent in killing human breast cancer cells. The potential of OSC as a new target for developing anticancer therapies is worth further investigation.

Keywords: inverse docking, in silico screening, protein-ligand interactions, molecular docking

Procedia PDF Downloads 433
5109 Forecast of the Small Wind Turbines Sales with Replacement Purchases and with or without Account of Price Changes

Authors: V. Churkin, M. Lopatin

Abstract:

The purpose of the paper is to estimate the US small wind turbines market potential and forecast the small wind turbines sales in the US. The forecasting method is based on the application of the Bass model and the generalized Bass model of innovations diffusion under replacement purchases. In the work an exponential distribution is used for modeling of replacement purchases. Only one parameter of such distribution is determined by average lifetime of small wind turbines. The identification of the model parameters is based on nonlinear regression analysis on the basis of the annual sales statistics which has been published by the American Wind Energy Association (AWEA) since 2001 up to 2012. The estimation of the US average market potential of small wind turbines (for adoption purchases) without account of price changes is 57080 (confidence interval from 49294 to 64866 at P = 0.95) under average lifetime of wind turbines 15 years, and 62402 (confidence interval from 54154 to 70648 at P = 0.95) under average lifetime of wind turbines 20 years. In the first case the explained variance is 90,7%, while in the second - 91,8%. The effect of the wind turbines price changes on their sales was estimated using generalized Bass model. This required a price forecast. To do this, the polynomial regression function, which is based on the Berkeley Lab statistics, was used. The estimation of the US average market potential of small wind turbines (for adoption purchases) in that case is 42542 (confidence interval from 32863 to 52221 at P = 0.95) under average lifetime of wind turbines 15 years, and 47426 (confidence interval from 36092 to 58760 at P = 0.95) under average lifetime of wind turbines 20 years. In the first case the explained variance is 95,3%, while in the second –95,3%.

Keywords: bass model, generalized bass model, replacement purchases, sales forecasting of innovations, statistics of sales of small wind turbines in the United States

Procedia PDF Downloads 339
5108 Assessment of Access to Water, Sanitation and Hygiene, in Relation to the SDG 6, in Small Towns in Senegal: The Case of the Town of Foundiougne

Authors: Elhadji Mamadou Sonko, Ndiogou Sankhare, Jean Birane Gning, Cheikh Diop

Abstract:

In Senegal, small towns have problems of access to water, hygiene, and sanitation. This study aims to assess the situation in Foundiougne. The methodology includes a literature review, semi-structured interviews with stakeholders, surveys of 100 households, and observation. The results show that 35% of households have unimproved water services, 46% have limited service, and 19% have basic service. Regarding sanitation, 77% of households have basic sanitation services, and 23% have limited sanitation services. Manual emptying alone is practiced by 4% of households, while 17% combine it with mechanical emptying. Household wastewater is disposed of in streets, vacant land, and concession yards. The emptied sludge is discharged into the environment without treatment. Hand washing is practiced by 98% of households. These results show that there is real work to be done at the small towns level to close the water and sanitation gap in order to achieve SDG 6 targets in Senegal.

Keywords: foundiougne, SDG 6, senegal, small towns, water sanitation ang hygiene

Procedia PDF Downloads 112