Search results for: anti trafficking policy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5923

Search results for: anti trafficking policy

4093 Characteristics of Photoluminescence in Resonant Quasiperiodic Double-period Quantum Wells

Authors: C. H. Chang, R. Z. Qiu, C. W. Tsao, Y. H. Cheng, C. H. Chen, W. J. Hsueh

Abstract:

Characteristics of photoluminescence (PL) in a resonant quasi-periodic double-period quantum wells (DPQW) are demonstrated. The maximum PL intensity in the DPQW is remarkably greater than that in a traditional periodic QW (PQW) under the Bragg or anti-Bragg conditions. The optimal PL spectrum in the DPQW has an asymmetrical form instead of the symmetrical form in the PQW. Moreover, there are two large values of PL intensity in the DPQW, which also differs from the PQW.

Keywords: Photoluminescence, quantum wells, quasiperiodic structure

Procedia PDF Downloads 709
4092 An Equitable Strategy to Amend Zero-Emission Vehicles Incentives for Travelers: A Policy Review

Authors: Marie Louis

Abstract:

Even though many stakeholders are doing their very best to promote public transportation around the world, many areas are still public transportation non-accessible. With travelers purchasing and driving their private vehicles can be considered as a threat to all three aspects of the sustainability (e.g., economical, social, environmental). However, most studies that considered simultaneously all three aspects of the sustainability concept when planning and designing public transportation for a corridor have found tradeoffs among the said three aspects.One of the tradeoffs was identified by looking at tipping points of the travel demands to question whether transit agencies/and or transportation policymakers should either operate smaller buses or provide incentives to purchase Leadership in Energy and Environmental Design (LEED)-Qualified low-emission vehicles or greener vehicles (e.g., hybrid). However, how and when do the department of environmental protection (DEP) and the department of revenue (DOR) figure out how much incentives to give to each traveler who lives in a zoning that is considered as public transportation inaccessible or accessible? To answer this policy question, this study aims to compare the greenhouse gases (GHGs) emissions when hybrid and conventional cars are used to access public transportation stops/stations. Additionally, this study also intends to review previous states that have already adopted low-emissions vehicle (LEVs) or Zero-Emissions Vehicles (ZEVs) to diminish the daily GHGs pollutants.

Keywords: LEED-qualified vehicles, public transit accessibility, hybrid vehicles incentives, sustainability trade-offs

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4091 Weapon Collection Initiatives and the Threat of Small Arms and Light Weapons Proliferation in Volatile Areas of North-Eastern Nigeria as a Way Forward for National Security and Development

Authors: Halilu Babaji, Adamu Buba

Abstract:

The proliferation of small arms and light weapons (SALW) and its illicit trafficking in West Africa and Nigeria in particular, pose a major threat to peace, security and development in the Sub-region. The high circulation of these weapons in the region is a product of the interplay of several factors, which derives principally from the internal socio-economic and political dynamics compounded by globalization. The process of globalization has congealed both time and space making it easier for ideas, goods, persons, services, information, products and money to move across borders with fewer restrictions. And this has a negative effect in the entire region making it easier for arms, ammunition, insurgents, criminal and drugs to flow within national boundaries. The failure of public security in most parts of Nigeria has lead communities to indulge in different forms of ‘self-help ‘security measures, ranging from vigilante groups to community-owned arms stockpiling. Having lost confidence in the Nigerian state, parties to some of these conflicts have become entangled in a security dilemma. The quest to procure more arms to guarantee personal and community protection from perceived and real enemies is fuelling the ‘domestic arms race ‘. Therefore, as small arms remain-and proliferate – development is impeded. The impact of SALW on economic well being and national development in Nigeria is of vast significant. Therefore the need to collect these arms in circulation in Nigeria particularly the volatile area of North-east is of very important. This will hopefully contribute to government effort in building a free, secured and peaceful society.

Keywords: arms, development, proliferation, security

Procedia PDF Downloads 299
4090 Antiproliferative and Apoptotic Effects of an Enantiomerically Pure β-Dipeptide Derivative through PI3K/Akt-Dependent and -Independent Pathways in Human Hormone-Refractory Prostate Cancer Cells

Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

Abstract:

Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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4089 Demand-Side Financing for Thai Higher Education: A Reform Towards Sustainable Development

Authors: Daral Maesincee, Jompol Thongpaen

Abstract:

Thus far, most of the decisions made within the walls of Thai higher education (HE) institutions have primarily been supply-oriented. With the current supply-driven, itemized HE financing systems, the nation is struggling to systemically produce high-quality manpower that serves the market’s needs, often resulting in education mismatches and unemployment – particularly in science, technology, and innovation (STI)-related fields. With the COVID-19 pandemic challenges widening the education inequality (accessibility and quality) gap, HE becomes even more unobtainable for underprivileged students, permanently leaving some out of the system. Therefore, Thai HE needs a new financing system that produces the “right people” for the “right occupations” through the “right ways,” regardless of their socioeconomic backgrounds, and encourages the creation of non-degree courses to tackle these ongoing challenges. The “Demand-Side Financing for Thai Higher Education” policy aims to do so by offering a new paradigm of HE resource allocation via two main mechanisms: i) standardized formula-based unit-cost subsidizations that is specific to each study field and ii) student loan programs that respond to the “demand signals” from the labor market and the students, that are in line with the country’s priorities. Through in-dept reviews, extensive studies, and consultations with various experts, education committees, and related agencies, i) the method of demand signal analysis is identified, ii) the unit-cost of each student in the sample study fields is approximated, iii) the method of budget analysis is formulated, iv) the interagency workflows are established, and v) a supporting information database is created to suggest the number of graduates each HE institution can potentially produce, the study fields and skillsets that are needed by the labor market, the employers’ satisfaction with the graduates, and each study field’s employment rates. By responding to the needs of all stakeholders, this policy is expected to steer Thai HE toward producing more STI-related manpower in order to uplift Thai people’s quality of life and enhance the nation’s global competitiveness. This policy is currently in the process of being considered by the National Education Transformation Committee and the Higher Education Commission.

Keywords: demand-side financing, higher education resource, human capital, higher education

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4088 Analysis of the Reasons behind the Deteriorated Standing of Engineering Companies during the Financial Crisis

Authors: Levan Sabauri

Abstract:

In this paper, we discuss the deteriorated standing of engineering companies, some of the reasons behind it and the problems facing engineering enterprises during the financial crisis. We show the part that financial analysis plays in the detection of the main factors affecting the standing of a company, classify internal problems and the reasons influencing efficiency thereof. The publication contains the analysis of municipal engineering companies in post-Soviet transitional economies. In the wake of the 2008 world financial crisis the issue became even more poignant. It should be said though that even before the problem had been no less acute for some post-Soviet states caught up in a lengthy transitional period. The paper highlights shortcomings in the management of transportation companies, with new, more appropriate methods suggested. In analyzing the financial stability of a company, three elements need to be considered: current assets, investment policy and structural management of the funding sources leveraging the stability, should be focused on. Inappropriate management of the three may create certain financial problems, with timely and accurate detection thereof being an issue in terms of improved standing of an enterprise. In this connection, the publication contains a diagram reflecting the reasons behind the deteriorated financial standing of a company, as well as a flow chart thereof. The main reasons behind low profitability are also discussed.

Keywords: efficiency, financial management, financial analysis funding structure, financial sustainability, investment policy, profitability, solvency, working capital

Procedia PDF Downloads 291
4087 In Response to Worldwide Disaster: Academic Libraries’ Functioning During COVID-19 Pandemic Without a Policy

Authors: Dalal Albudaiwi, Mike Allen, Talal Alhaji, Shahnaz Khadimehzadah

Abstract:

As a pandemic, COVID-19 has impacted the whole world since November 2019. In other words, every organization, industry, and institution has been negatively affected by the Coronavirus. The uncertainty of how long the pandemic will last caused chaos at all levels. As with any other institution, public libraries were affected and transmitted into online services and resources. As internationally, have been witnessed that some public libraries were well-prepared for such disasters as the pandemic, and therefore, collections, users, services, technologies, staff, and budgets were all influenced. Public libraries’ policies did not mention any plan regarding such a pandemic. Instead, there are several rules in the guidelines about disasters in general, such as natural disasters. In this pandemic situation, libraries have been involved in different uneasy circumstances. However, it has always been apparent to public libraries the role they play in serving their communities in excellent and critical times. It dwells into the traditional role public libraries play in providing information services and sources to satisfy their information-based community needs. Remarkably increasing people’s awareness of the importance of informational enrichment and enhancing society’s skills in dealing with information and information sources. Under critical circumstances, libraries play a different role. It goes beyond the traditional part of information providers to the untraditional role of being a social institution that serves the community with whatever capabilities they have. This study takes two significant directions. The first focuses on investigating how libraries have responded to COVID-19 and how they manage disasters within their organization. The second direction focuses on how libraries help their communities to act during disasters and how to recover from the consequences. The current study examines how libraries prepare for disasters and the role of public libraries during disasters. We will also propose “measures” to be a model that libraries can use to evaluate the effectiveness of their response to disasters. We intend to focus on how libraries responded to this new disaster. Therefore, this study aims to develop a comprehensive policy that includes responding to a crisis such as Covid-19. An analytical lens inside the libraries as an organization and outside the organization walls will be documented based on analyzing disaster-related literature published in the LIS publication. The study employs content analysis (CA) methodology. CA is widely used in the library and information science. The critical contribution of this work is to propose solutions it provides to libraries and planers to prepare crisis management plans/ policies, specifically to face a new global disaster such as the COVID-19 pandemic. Moreover, the study will help library directors to evaluate their strategies and to improve them properly. The significance of this study lies in guiding libraries’ directors to enhance the goals of the libraries to guarantee crucial issues such as: saving time, avoiding loss, saving budget, acting quickly during a crisis, maintaining libraries’ role during pandemics, finding out the best response to disasters, and creating plan/policy as a sample for all libraries.

Keywords: Covid-19, policy, preparedness, public libraries

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4086 Impact of the Simplification of Licensing Procedures for Industrial Complexes on Supply of Industrial Complexes and Regional Policies

Authors: Seung-Seok Bak, Chang-Mu Jung

Abstract:

An enough amount supply of industrial complexes is an important national policy in South Korea, which is highly dependent on foreign trade. A development process of the industrial complex can distinguish between the planning stage and the construction stage. The planning stage consists of the process of consulting with many stakeholders on the contents of the development of industrial complex, feasibility study, compliance with the Regional policies, and so on. The industrial complex planning stage, including licensing procedure, usually takes about three years in South Korea. The government determined that the appropriate supply of industrial complexes have been delayed, due to the long licensing period and drafted a law to shorten the license period in 2008. The law was expected to shorten the period of licensing, which was about three years, to six months. This paper attempts to show that the shortening of the licensing period does not positively affect the appropriate supply of industrial complexes. To do this, we used Interrupted Time Series Designs. As a result, it was found that the supply of industrial complexes was influenced more by other factors such as actual industrial complex demand of private sector and macro-level economic variables. In addition, the specific provisions of the law conflict with local policy and cause some problems such as damage to nature and agricultural land, traffic congestion.

Keywords: development of industrial complexes, industrial complexes, interrupted time series designs, simplification of licensing procedures for industrial complexes, time series regression

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4085 Interaction of GCN5L1 with WHAMM and KIF5B Regulates Autolysosome Tubulation

Authors: Allen Seylani

Abstract:

Lysosome-dependent autophagy is a nutrient-deprivation-induced evolutionarily conserved intracellular recycling program that sequestrates intracellular cargo into autophagosomes (AP), which then fuse with lysosomes to form autolysosomes (ALs) for cargo digestion. To restore free lysosomes, autophagic lysosome reformation (ALR) is initiated by extrusion of tubular structures from autolysosomes at the final stage of autophagy, in a process called lysosomal tubulation (LT). This project aimed to investigate the molecular mechanism of GCN5L1 in LT and the following lysosomal signaling. GCN5L1 belongs to the BORC multiprotein complexes and is involved in controlling lysosomal trafficking; however, the effect of GCN5L1 on lysosome tubulation remains largely unknown. Genetic ablation of GCN5L1 in the mouse primary hepatocytes showed dramatically increased autolysosomes (ALs), decreased lysosome regeneration and absence of lysosomal tubulation. This phenotype suggests the possibility of disruption in lysosome tubulation, which results in the disturbance of the overall lysosome homeostasis. The formation of tubulars from ALs requires kinesin motor protein KIF5B. Immunoprecipitation was employed and confirmed the interaction of GCN5L1 with the ARL8B-KIF5B complex, which recruited KIF5B to ALs. At the same time, GCN5L1 interacted with WHAMM, which promotes the actin nucleation factor, which brings actin cytoskeleton to ALs and initiates LT. Furthermore, impaired LT in GCN5L1 deficient hepatocytes was restored by overexpression of GCN5L1, and this rescue effect was attenuated by knockdown of KIF5B. Additionally, lysosomal mTORC1 activity was upregulated in GCN5L1-/- hepatocytes, while inhibition of mTORC1 abrogated the GCN5L1 mediated rescue of LT in knockout hepatocytes. Altogether these findings revealed a novel mechanism of ALR, in which a simultaneous interaction of GCN5L1 with KIF5B and WHAMM is required for LT and downstream mTORC1 signaling.

Keywords: autophagy, autolysosome, GCN5L1, lysosome

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4084 Diversifying Income Streams in Portuguese Higher Education – a Multiple Case Study

Authors: Ana Nascimento

Abstract:

For several reasons and in different countries worldwide, there is an increasing difficulty of the States to finance higher education. However, most societies consider education as a public good, so it should be a State obligation to provide this service to citizens. In Portugal, over the last decades, state has diminished its contribution to public higher education and the public higher education institutions started to look for alternative incoming sources, namely charging student’s taxes and fees, provision of services to companies, production of applied research, search for sponsors, configuring new forms of fundraising. This financial policy can raise some concerns to the scientific and pedagogical autonomy of these institutions as well as concerns in access and equity in higher education. For these reasons and in the scope of a PhD research in the area of Economy of Education, a survey is taking place in all public higher education institutions in the Great Lisbon area that intends to analyze and discuss the policy measures in each institution in the search for external financing. The research aims to understand what these measures are and what implications they might have in the institution’s autonomy as well as in higher education access by students from less favored backgrounds. The research uses a qualitative approach, namely through semi-structured interviews to presidents, directors and rectors of each institution, totalizing 50 interviews. In this paper are discussed some of the results from the interviews made so far that present the subjects opinion about higher education finance, the right to education, the search for fundraising and the possible consequences to the institution’s autonomy as well as some literature on the state of the art.

Keywords: autonomy, finance, higher education, public goods

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4083 The Conception of Implementation of Vision for European Forensic Science 2020 in Lithuania

Authors: Eglė Bilevičiūtė, Vidmantas Egidijus Kurapka, Snieguolė Matulienė, Sigutė Stankevičiūtė

Abstract:

The Council of European Union (EU Council) has stressed on several occasions the need for a concerted, comprehensive and effective solution to delinquency problems in EU communities. In the context of establishing a European Forensic Science Area and the development of forensic science infrastructure in Europe, EU Council believes that forensic science can significantly contribute to the efficiency of law enforcement, crime prevention and combating crimes. Lithuanian scientists have consolidated to implement a project named “Conception of the vision for European Forensic Science 2020 implementation in Lithuania” (the project is funded for the period of 1 March 2014 - 31 December 2016) with the objective to create a conception of implementation of the vision for European Forensic Science 2020 in Lithuania by 1) evaluating the current status of Lithuania’s forensic system and opportunities for its improvement; 2) analysing achievements and knowledge in investigation of crimes listed in conclusions of EU Council on the vision for European Forensic Science 2020 including creation of a European Forensic Science Area and the development of forensic science infrastructure in Europe: trafficking in human beings, organised crime and terrorism; 3) analysing conceptions of criminalistics, which differ in different EU member states due to the variety of forensic schools, and finding means for their harmonization. Apart from the conception of implementation of the vision for European Forensic Science 2020 in Lithuania, the project is expected to suggest provisions that will be relevant to other EU countries as well. Consequently, the presented conception of implementation of vision for European Forensic Science 2020 in Lithuania could initiate a project for a common vision of European Forensic Science and contribute to the development of the EU as an area of freedom, security and justice. The article presents main ideas of the project of the conception of the vision for European Forensic Science 2020 of EU Council and analyses its legal background, as well as prospects of and challenges for its implementation in Lithuania and the EU.

Keywords: EUROVIFOR, standardization, vision for European Forensic Science 2020, Lithuania

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4082 Optimal Dynamic Regime for CO Oxidation Reaction Discovered by Policy-Gradient Reinforcement Learning Algorithm

Authors: Lifar M. S., Tereshchenko A. A., Bulgakov A. N., Guda S. A., Guda A. A., Soldatov A. V.

Abstract:

Metal nanoparticles are widely used as heterogeneous catalysts to activate adsorbed molecules and reduce the energy barrier of the reaction. Reaction product yield depends on the interplay between elementary processes - adsorption, activation, reaction, and desorption. These processes, in turn, depend on the inlet feed concentrations, temperature, and pressure. At stationary conditions, the active surface sites may be poisoned by reaction byproducts or blocked by thermodynamically adsorbed gaseous reagents. Thus, the yield of reaction products can significantly drop. On the contrary, the dynamic control accounts for the changes in the surface properties and adjusts reaction parameters accordingly. Therefore dynamic control may be more efficient than stationary control. In this work, a reinforcement learning algorithm has been applied to control the simulation of CO oxidation on a catalyst. The policy gradient algorithm is learned to maximize the CO₂ production rate based on the CO and O₂ flows at a given time step. Nonstationary solutions were found for the regime with surface deactivation. The maximal product yield was achieved for periodic variations of the gas flows, ensuring a balance between available adsorption sites and the concentration of activated intermediates. This methodology opens a perspective for the optimization of catalytic reactions under nonstationary conditions.

Keywords: artificial intelligence, catalyst, co oxidation, reinforcement learning, dynamic control

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4081 Determining the Presence of Brucella abortus Antibodies by the Indirect Elisa Method in Bovine Bulk Milk and Risk Factors in the Peri-Urban Zones of Bamenda Cameroon

Authors: Cha-ah C. N., Awah N. J., Mouiche M. M. M.

Abstract:

Brucellosis is a neglected zoonotic disease of animals and man caused by bacteria of genus Brucella. Though eradicated in some parts of the world, it remains endemic in sub-Saharan Africa including Cameroon. The aim of this study was to contribute to the epidemiology of brucellosis in the North-West region of Cameroon by detecting the presence of anti-Brucella antibodies in bovine bulk milk as this serves as a route of transmission from animals to man. A cross sectional study was conducted to determine the prevalence of Brucella abortus antibodies in bovine bulk milk in the peri-urban zones of Bamenda. One hundred bulk milk samples were collected from 100 herds and tested by milk I-ELISA test. The conducted study revealed the presence of anti-Brucella abortus antibodies in bovine bulk milk. The study revealed that bovine brucellosis is widespread in animal production systems in this area. The animal infection pressure in these systems has remained strong due to movement of livestock in search of pasture, co-existence of animal husbandry, communal sharing of grazing land, concentration of animals around water points, abortions in production systems, locality of production systems and failure to quarantine upon introduction of new animals. The circulation of Brucella abortus antibodies in cattle farms recorded in the study revealed potential public health implication and suggest economic importance of brucellosis to the cattle industry in the Northwest region of Cameroon. The risk for re-emergence and transmission of brucellosis is evident as a result of the co-existence of animal husbandry activities and social-cultural activities that promote brucellosis transmission. Well-designed countrywide, evidence-based studies of brucellosis are needed. These could help to generate reliable frequency and potential impact estimates, to identify Brucella reservoirs, and to propose control strategies of proven efficacy.

Keywords: brucellosis, bulk milk, northwest region Cameroon, prevalence

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4080 Substituted Thiazole Analogues as Anti-Tumor Agents

Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

Abstract:

Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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4079 The Increasing Importance of CFC Rules: An OECD+ Country Overview

Authors: Axel Prettl

Abstract:

This paper provides an overview of the different CFC rule settings in the OECD and 22 additional countries for the years 2004 to 2014 and compares them. In order to do so, it gives a summary of law amendments for every country, provides a comparison and afterwards all CFC rules are rated in their ”power of anti-avoidance” over time. For that rating of CFC rules, the largest common denominator of rule characteristics is used to keep it as abstract as necessary and possible. The paper points out that the CFC rules in the considered countries are very different in their specifications and they reach from very strict to very low binding. All in all these rules get more and more common and important; more countries implement a CFC legislation and the strictness of most of them rises over time.

Keywords: CFC rules, international taxation, corporate taxation, country comparison

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4078 Integration of Information and Communication Technology (ICT) for Effective Education of Adult Learners in Developing Communities in South-West Nigeria

Authors: Omotoke Omosalewa Owolowo

Abstract:

Mass literacy adult and non-formal education are part of the provisions of Nigeria’s National policy on Education. The advent of Information and Communication Technology (ICT), especially in this era of industrial revolution, calls for approaching these literacy and adult education in different perspective for community development. There is dire need of Needs Assessment for effective training of rural dwellers to actualize the policy requirement and for the purpose of aligning with the Sustainable Development Goals in South - West Nigeria. The present study is a preliminary survey designed to determine level of awareness, use and familiarity of community dwellers of social media. Adult dwellers from 24 communities from four states in Southern Nigeria constitute the sample, a total of 578 adults (380 females, 198 males) with age range between 21 and 52 years. The survey shows that 68% are aware of SMS, 21% of WhatsApp, 14% of Facebook while the remaining could not say precisely what social medium is their favorite. However, most of them (80%) could not see how their phones can be used to boost their status, improve their vacations or be used to develop them in their respective community. The study is expected to lead to a more elaborate training program on assessment of knowledge acquisition, participation and attitude of adult literate and non- literate members in communities for empowerment and to integrate ICT techniques. The results of this study provides a database for the larger study.

Keywords: mass literacy, community development, information and communication technology, adult learners

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4077 The Dilemma of Translanguaging Pedagogy in a Multilingual University in South Africa

Authors: Zakhile Somlata

Abstract:

In the context of international linguistic and cultural diversity, all languages can be used for all purposes. Africa in general and South Africa, in particular, is not an exception to multilingual and multicultural society. The multilingual and multicultural nature of South African society has a direct bearing to the heterogeneity of South African Universities in general. Universities as the centers of research, innovation, and transformation of the entire society should be at the forefront in leading multilingualism. The universities in South Africa had been using English and to a certain extent Afrikaans as the only academic languages during colonialism and apartheid regime. The democratic breakthrough of 1994 brought linguistic relief in South Africa. The Constitution of the Republic of South Africa recognizes 11 official languages that should enjoy parity of esteem for the realization of multilingualism. The elevation of the nine previously marginalized indigenous African languages as academic languages in higher education is central to multilingualism. It is high time that Afrocentric model instead of Eurocentric model should be the one which underpins education system in South Africa at all levels. Almost all South African universities have their language policies that seek to promote access and success of students through multilingualism, but the main dilemma is the implementation of language policies. This study is significant to respond to two objectives: (i) To evaluate how selected institutions use language policies for accessibility and success of students. (ii) To study how selected universities integrate African languages for both academic and administrative purposes. This paper reflects the language policy practices in one selected University of Technology (UoT) in South Africa. The UoT has its own language policy which depicts linguistic diversity of the institution and its commitment to promote multilingualism. Translanguaging pedagogy which accommodates minority languages' usage in the teaching and learning process plays a pivotal role in promoting multilingualism. This research paper employs mixed methods (quantitative and qualitative research) approach. Qualitative data has been collected from the key informants (insiders and experts), while quantitative data has been collected from a cohort of third-year students. A mixed methods approach with its convergent parallel design allows the data to be collected separately, analysed separately but with the comparison of the results. Language development initiatives have been discussed within the framework of language policy and policy implementation strategies. Theoretically, this paper is rooted in language as a problem, language as a right and language as a resource. The findings demonstrate that despite being a multilingual institution, there is a perpetuation of marginalization of African languages to be used as academic languages. Findings further display the hegemony of English. The promotion of status quo compromises the promotion of multilingualism, Africanization of Higher Education and intellectualization of indigenous African languages in South Africa under a democratic dispensation.

Keywords: afro-centric model, hegemony of English, language as a resource, translanguaging pedagogy

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4076 Anticoccidial Effects of the Herbal Mixture in Boilers after Eimeria spp. Infection

Authors: Yang-Ho Jang, Soon-Ok Jee, Hae-Chul Park, Jeong-Woo Kang, Byung-Jae So, Sung-Shik Shin, Kyu-Sung Ahn, Kwang-Jick Lee

Abstract:

Introduction: Antibiotics have been used as feed additives for the growth promotion and performance in food-producing animals. However, the possibility of selection of antimicrobial resistance and the concerns of residue in animal products led to ban the use of antibiotics in farm animals at 2011 in Korea. This strategy is also adjusted to anticoccidial drugs soon but these are still allowed for the time being to use in a diet for the treatment and control for the enteric necrosis in poultry. Therefore substantial focus has been given to find alternatives to antimicrobial agents. Several phytogenic materials have been reported to have positive effects on coccidiosis. This study was to evaluate the effects on anti-coccidial effect of oregano oil based herb mixture on Eimeria spp. in poultry. Materials and Methods: A total of one day-old boiler chickens divided into six groups (each group=30 chkckens) were used in this study. The herbal mixture was fed with water freely as follows: two groups, one infected with Eimeria spp. and the other group served as controls without herbal mixture respectively; 0.2ml/L of oregano oil; 0.2ml/L of oregano oil and Sanguisorbae radix; 0.2ml/L of Sanguisorbae radix; last group was fed with dichlazuril diet as positive control. Sporulated Eimeria spp. was infected at 14 day-old. Following infection, survival rate, bloody diarrhea, OPG (oocyst per gram) and feed conversion ratios were determined. The experimental period was lasted for 4 weeks. Results: Herbal mixture feeding groups (Group 3,4,5) showed low feed conversion ratio comparing with negative control. Oregano oil group and positive control group recorded the highest survival rate. The grade of bloody diarrhea was scored 0 to 5. Herbal mixture feeding groups showed 2, 3 and 1 score respectively however, group 2 (infection and no-treatment) showed 4. OPG results in herbal mixture feeding group were 3 to 4 times higher than diclazuril diet feeding group. Conclusions: These results showed that oregano oil and Sanguisorbae radix mixture may have an anti-coccidial effect and also affect chick performance.

Keywords: anticoccidial effects, oregano oil based herb mixture, herbal mixture, antibiotics

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4075 Reconstruction of Performace-Based Budgeting in Indonesian Local Government: Application of Soft Systems Methodology in Producing Guideline for Policy Implementation

Authors: Deddi Nordiawan

Abstract:

Effective public policy creation required a strong budget system, both in terms of design and implementation. Performance-based Budget is an evolutionary approach with two substantial characteristics; first, the strong integration between budgeting and planning, and second, its existence as guidance so that all activities and expenditures refer to measurable performance targets. There are four processes in the government that should be followed in order to make the budget become performance-based. These four processes consist of the preparation of a vision according to the bold aspiration, the formulation of outcome, the determination of output based on the analysis of organizational resources, and the formulation of Value Creation Map that contains a series of programs and activities. This is consistent with the concept of logic model which revealed that the budget performance should be placed within a relational framework of resources, activities, outputs, outcomes and impacts. Through the issuance of Law 17/2003 regarding State Finance, local governments in Indonesia have to implement performance-based budget. Central Government then issued Government Regulation 58/2005 which contains the detail guidelines how to prepare local governments budget. After a decade, implementation of performance budgeting in local government is still not fully meet expectations, though the guidance is completed, socialization routinely performed, and trainings have also been carried out at all levels. Accordingly, this study views the practice of performance-based budget at local governments as a problematic situation. This condition must be approached with a system approach that allows the solutions from many point of views. Based on the fact that the infrastructure of budgeting has already settled, the study then considering the situation as complexity. Therefore, the intervention needs to be done in the area of human activity system. Using Soft Systems Methodology, this research will reconstruct the process of performance-based budget at local governments is area of human activity system. Through conceptual models, this study will invite all actors (central government, local government, and the parliament) for dialogue and formulate interventions in human activity systems that systematically desirable and culturally feasible. The result will direct central government in revise the guidance to local government budgeting process as well as a reference to build the capacity building strategy.

Keywords: soft systems methodology, performance-based budgeting, Indonesia, public policy

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4074 Competitivity in Procurement Multi-Unit Discrete Clock Auctions: An Experimental Investigation

Authors: Despina Yiakoumi, Agathe Rouaix

Abstract:

Laboratory experiments were run to investigate the impact of different design characteristics of the auctions, which have been implemented to procure capacity in the UK’s reformed electricity markets. The experiment studies competition among bidders in procurement multi-unit discrete descending clock auctions under different feedback policies and pricing rules. Theory indicates that feedback policy in combination with the two common pricing rules; last-accepted bid (LAB) and first-rejected bid (FRB), could affect significantly the auction outcome. Two information feedback policies regarding the bidding prices of the participants are considered; with feedback and without feedback. With feedback, after each round participants are informed of the number of items still in the auction and without feedback, after each round participants have no information about the aggregate supply. Under LAB, winning bidders receive the amount of the highest successful bid and under the FRB the winning bidders receive the lowest unsuccessful bid. Based on the theoretical predictions of the alternative auction designs, it was decided to run three treatments. First treatment considers LAB with feedback; second treatment studies LAB without feedback; third treatment investigates FRB without feedback. Theoretical predictions of the game showed that under FRB, the alternative feedback policies are indifferent to the auction outcome. Preliminary results indicate that LAB with feedback and FRB without feedback achieve on average higher clearing prices in comparison to the LAB treatment without feedback. However, the clearing prices under LAB with feedback and FRB without feedback are on average lower compared to the theoretical predictions. Although under LAB without feedback theory predicts the clearing price will drop to the competitive equilibrium, experimental results indicate that participants could still engage in cooperative behavior and drive up the price of the auction. It is showed, both theoretically and experimentally, that the pricing rules and the feedback policy, affect the bidding competitiveness of the auction by providing opportunities to participants to engage in cooperative behavior and exercise market power. LAB without feedback seems to be less vulnerable to market power opportunities compared to the alternative auction designs. This could be an argument for the use of LAB pricing rule in combination with limited feedback in the UK capacity market in an attempt to improve affordability for consumers.

Keywords: descending clock auctions, experiments, feedback policy, market design, multi-unit auctions, pricing rules, procurement auctions

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4073 The Impact of Innovation Best Practices in Economic Development

Authors: Hanadi Mubarak AL-Mubaraki, Michael Busler

Abstract:

Innovation is the process of making changes, differences, and novelties in the products and services, adding values and business practices to create economic and social benefit. The purpose of this paper is to identify the strengths and weaknesses of innovation programs in developed and developing countries. We used a mixed-methods approach, quantitative as survey and qualitative as a multi-case study to examine innovation best practices in developed and developing countries. In addition, four case studies of innovation organisations based on the best practices and successful implementation in the developed and developing countries are selected for examination. The research findings provide guidance, suggestions, and recommendations for future implementation in developed and developing countries for practitioners such as policy makers, governments, funded organizations, and strategic institutions. In conclusion, innovation programs are vital tools for economic growth, knowledge, and technology transfer based on the several indicators such as creativity, entrepreneurship, role of government, role of university, strategic focus, new products, survival rate, job creation, start-up companies, and number of patents. The authors aim to conduct future research which will include a comparative study of innovation case studies between developed and developing countries for policy implications worldwide. The originality of this study makes a contribution to the current literature about the innovation best practice in developed and developing countries.

Keywords: economic development, entrepreneurship, innovation program, developed countries

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4072 Production and Valorization of Nano Lignins by Organosolv and Steam Explosion

Authors: V. Girard, I. Ziegler-Devin, H. Chapuis, N. Canilho, L. Marchal-Heussler, N. Brosse

Abstract:

Lignocellulosic biomass is made up of the three polymeric fractions that are cellulose, hemicellulose, and lignin, which are highly entangled. In this project, we are particularly interested in the under-valued lignin polymer, which is mainly used for thermal valorization. Lignin from Macro to Nanosize (LIMINA) project will first focus on the extraction of macro lignin from forestry waste (hardwood and softwood) by the mean of eco-friendly processes (organosolv and steam explosion) and then the valorization of nano lignins produced by using anti-solvent precipitation (UV-blocker, cosmetic, food products).

Keywords: nanolignin, nanoparticles, organosolv, steam explosion

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4071 India, Pakistan and the US in the Afghan Imbroglio: The Way Forward

Authors: Saroj Kumar Rath

Abstract:

When insurgency erupted in Kashmir in 1989, it was quickly backed by Pakistan. Kashmir witnessed terrorism for more than a decade till 2004 when Indian forces decimated militancy. After the US pressure in 1992, terrorist training camps of Pakistan shifted to Afghanistan and al Qaeda and the Taliban had taken over training of Kashmiri militants in Afghanistan after 1997 as part of their global jihad. The Indo-Pak rivalry over Kashmir dispute had taken a new turn in the aftermath of 9/11 developments. Islamabad viewed its Afghan policy through the prism of denying India any advantage in Kabul. Pakistan was successful in refuting Indian presence in Kabul for a decade through the Taliban. After the 9/11 attacks the Inter Services Intelligence (ISI) saw Northern Alliance, supported by the Americans and all of Pakistan’s regional rivals – India, Iran, and Russia – as claiming victory in Kabul. For Pakistan’s military regime, this was a strategic disaster and prompted the ISI to give refuge to the escaping Taliban, while denying full support to Hamid Karzai. The new development in Afghanistan prompted India to establish a foothold it had lost nearly a decade earlier. India established diplomatic contacts with Afghanistan; supported the Karzai government and funded aid programs. Pakistan alleged that Indian agents are training Baloch and Sindhi dissidents in Pakistan through Afghanistan. Kabul had suddenly become the new Kashmir – the new battleground for India-Pakistan rivalry.

Keywords: Afghan imbroglio, Kashmir conflict, Indo-Pak rivalry, US policy in South Asia

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4070 A Rapid Colorimetric Assay for Direct Detection of Unamplified Hepatitis C Virus RNA Using Gold Nanoparticles

Authors: M. Shemis, O. Maher, G. Casterou, F. Gauffre

Abstract:

Hepatitis C virus (HCV) is a major cause of chronic liver disease with a global 170 million chronic carriers at risk of developing liver cirrhosis and/or liver cancer. Egypt reports the highest prevalence of HCV worldwide. Currently, two classes of assays are used in the diagnosis and management of HCV infection. Despite the high sensitivity and specificity of the available diagnostic assays, they are time-consuming, labor-intensive, expensive, and require specialized equipment and highly qualified personal. It is therefore important for clinical and economic terms to develop a low-tech assay for the direct detection of HCV RNA with acceptable sensitivity and specificity, short turnaround time, and cost-effectiveness. Such an assay would be critical to control HCV in developing countries with limited resources and high infection rates, such as Egypt. The unique optical and physical properties of gold nanoparticles (AuNPs) have allowed the use of these nanoparticles in developing simple and rapid colorimetric assays for clinical diagnosis offering higher sensitivity and specificity than current detection techniques. The current research aims to develop a detection assay for HCV RNA using gold nanoparticles (AuNPs). Methods: 200 anti-HCV positive samples and 50 anti-HCV negative plasma samples were collected from Egyptian patients. HCV viral load was quantified using m2000rt (Abbott Molecular Inc., Des Plaines, IL). HCV genotypes were determined using multiplex nested RT- PCR. The assay is based on the aggregation of AuNPs in presence of the target RNA. Aggregation of AuNPs causes a color shift from red to blue. AuNPs were synthesized using citrate reduction method. Different sets of probes within the 5’ UTR conserved region of the HCV genome were designed, grafted on AuNPs and optimized for the efficient detection of HCV RNA. Results: The nano-gold assay could colorimetrically detect HCV RNA down to 125 IU/ml with sensitivity and specificity of 91.1% and 93.8% respectively. The turnaround time of the assay is < 30 min. Conclusions: The assay allows sensitive and rapid detection of HCV RNA and represents an inexpensive and simple point-of-care assay for resource-limited settings.

Keywords: HCV, gold nanoparticles, point of care, viral load

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4069 Circular Labour Migration and Its Consequences in Georgia

Authors: Manana Lobzhanidze

Abstract:

Introduction: The paper will argue that labor migration is the most important problem Georgia faces today. The structure of labor migration by age and gender of Georgia is analyzed. The main driving factors of circular labor migration during the last ten years are identified. While studying migration, it is necessary to discuss the interconnection of economic, social, and demographic features, also taking into consideration the policy of state regulations in terms of education and professional training. Methodology: Different research methods are applied in the presented paper: statistical, such as selection, grouping, observation, trend, and qualitative research methods, namely; analysis, synthesis, induction, deduction, comparison ones. Main Findings: Labour migrants are filling the labor market as a low salary worker. The main positive feedback of migration from developing countries is poverty eradication, but this process is accompanied by problems, such as 'Brain Drain'. The country loses an important part of its intellectual potential, and it is invested by households or state itself. Conclusions: Labor migration is characterized to be temporary, but socio-economic problems of the country often push the labor migration in the direction of longterm and illegal migration. Countries with developed economies try to stricter migration policy and fight illegal migration with different methods; circular migration helps solve this problem. Conclusions and recommendations are included about circular labor migration consequences in Georgia and its influence on the reduction of unemployment level.

Keywords: migration, circular labor migration, labor migration employment, unemployment

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4068 NGOs from the Promotion of Civic Participation to Public Problems Solving: Case Study Urmia, Iran

Authors: Amin Banae Babazadeh

Abstract:

In the contemporary world, NGOs are considered as important tool for motivating the community. So they committed their true mission and the promotion of civic participation and strengthen social identities. Functional characteristics of non-governmental organizations are the element to leverage the centers of political and social development of powerful governments since they are concrete and familiar with the problems of society and the operational strategies which would facilitate this process of mutual trust between the people and organizations. NGOs on the one hand offer reasonable solutions in line with approved organizations as agents to match between the facts and reality of society and on the other hand changes to a tool to have true political, social and economic behavior. However, the NGOs are active in the formulation of national relations and policy formulation in an organized and disciplined based on three main factors, i.e., resources, policies, and institutions. Organizations are not restricted to state administration in centralized system bodies and this process in the democratic system limits the accumulation of desires and expectations and at the end reaches to the desired place. Hence, this research will attempt to emphasis on field research (questionnaire) and according to the development evolution and role of NGOs analyze the effects of this center on youth. Therefore, the hypothesis is that there is a direct relationship between the Enlightenment and the effectiveness of policy towards NGOs and solving social damages.

Keywords: civic participation, community vulnerability, insightful, NGO, urmia

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4067 Evaluation of Structural Integrity for Composite Lattice Structure

Authors: Jae Moon Im, Kwang Bok Shin, Sang Woo Lee

Abstract:

In this paper, evaluation of structural integrity for composite lattice structure was conducted by compressive test. Composite lattice structure was manufactured by carbon fiber using filament winding method. In order to evaluate the structural integrity of composite lattice structure, compressive test was done using anti-buckling fixture. The delamination occurred 84 Tons of compressive load. It was found that composite lattice structure satisfied the design requirements.

Keywords: composite material, compressive test, lattice structure, structural integrity

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4066 Effect of Chitosan Oligosaccharide from Tenebrio Molitor on Prebiotics

Authors: Hyemi Kim, Jay Kim, Kyunghoon Han, Ra-Yeong Choi, In-Woo Kim, Hyung Joo Suh, Ki-Bae Hong, Sung Hee Han

Abstract:

Chitosan is used in various industries such as food and medical care because it is known to have various functions such as anti-obesity, anti-inflammatory and anti-cancer benefits. Most of the commercial chitosan is extracted from crustaceans. As the harvest rate of snow crabs and red snow crabs decreases and safety issues arise due to environmental pollution, research is underway to extract chitosan from insects. In this study, we used Response Surface Methodology (RSM) to predict the optimal conditions to produce chitosan oligosaccharides from mealworms (MCOS), which can be absorbed through the intestine as low-molecular-weight chitosan. The experimentally confirmed optimal conditions for MCOS production using chitosanase were found to be a substrate concentration of 2.5%, enzyme addition of 30 mg/g and a reaction time of 6 hours. The chemical structure and physicochemical properties of the produced MCOS were measured using MALDI-TOF mass spectra and FTIR spectra. The MALDI-TOF mass spectra revealed peaks corresponding to the dimer (375.045), trimer (525.214), tetramer (693.243), pentamer (826.296), and hexamer (987.360). In the FTIR spectra, commercial chitosan oligosaccharides exhibited a weak peak pattern at 3500-2500 cm-1, unlike chitosan or chitosan oligosaccharides. There was a difference in the peak at 3200~3500 cm-1, where different vibrations corresponding to OH and amine groups overlapped. Chitosan, chitosan oligosaccharide, and commercial chitosan oligosaccharide showed peaks at 2849, 2884, and 2885 cm-1, respectively, attributed to the absorption of the C-H stretching vibration of methyl or methine. The amide I, amide II, and amide III bands of chitosan, chitosan oligosaccharide, and commercial chitosan oligosaccharide exhibited peaks at 1620/1620/1602, 1553/1555/1505, and 1310/1309/1317 cm-1, respectively. Furthermore, the solubility of MCOS was 45.15±3.43, water binding capacity (WBC) was 299.25±4.57, and fat binding capacity (FBC) was 325.61±2.28 and the solubility of commercial chitosan oligosaccharides was 49.04±9.52, WBC was 280.55±0.50, and FBC was 157.22±18.15. Thus, the characteristics of MCOS and commercial chitosan oligosaccharides are similar. The results of investigating the impact of chitosan oligosaccharide on the proliferation of probiotics revealed increased growth in L. casei, L. acidophilus, and Bif. Bifidum. Therefore, the major short-chain fatty acids produced by gut microorganisms, such as acetic acid, propionic acid, and butyric acid, increased within 24 hours of adding 1% (p<0.01) and 2% (p<0.001) MCOS. The impact of MCOS on the overall gut microbiota was assessed, revealing that the Chao1 index did not show significant differences, but the Simpson index decreased in a concentration-dependent manner, indicating a higher species diversity. The addition of MCOS resulted in changes in the overall microbial composition, with an increase in Firmicutes and Verrucomicrobia (p<0.05) compared to the control group, while Proteobacteria and Actinobacteria (p<0.05) decreased. At the genus level, changes in microbiota due to MCOS supplementation showed an increase in beneficial bacteria like lactobacillus, Romboutsia, Turicibacter, and Akkermansia (p<0.0001) while harmful bacteria like Enterococcus, Morganella, Proterus, and Bacteroides (p<0.0001) decreased. In this study, chitosan oligosaccharides were successfully produced under established conditions from mealworms, and these chitosan oligosaccharides are expected to have prebiotic effects, similar to those obtained from crabs.

Keywords: mealworms, chitosan, chitosan oligosaccharide, prebiotics

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4065 Absolute Quantification of the Bexsero Vaccine Component Factor H Binding Protein (fHbp) by Selected Reaction Monitoring: The Contribution of Mass Spectrometry in Vaccinology

Authors: Massimiliano Biagini, Marco Spinsanti, Gabriella De Angelis, Sara Tomei, Ilaria Ferlenghi, Maria Scarselli, Alessia Biolchi, Alessandro Muzzi, Brunella Brunelli, Silvana Savino, Marzia M. Giuliani, Isabel Delany, Paolo Costantino, Rino Rappuoli, Vega Masignani, Nathalie Norais

Abstract:

The gram-negative bacterium Neisseria meningitidis serogroup B (MenB) is an exclusively human pathogen representing the major cause of meningitides and severe sepsis in infants and children but also in young adults. This pathogen is usually present in the 30% of healthy population that act as a reservoir, spreading it through saliva and respiratory fluids during coughing, sneezing, kissing. Among surface-exposed protein components of this diplococcus, factor H binding protein is a lipoprotein proved to be a protective antigen used as a component of the recently licensed Bexsero vaccine. fHbp is a highly variable meningococcal protein: to reflect its remarkable sequence variability, it has been classified in three variants (or two subfamilies), and with poor cross-protection among the different variants. Furthermore, the level of fHbp expression varies significantly among strains, and this has also been considered an important factor for predicting MenB strain susceptibility to anti-fHbp antisera. Different methods have been used to assess fHbp expression on meningococcal strains, however, all these methods use anti-fHbp antibodies, and for this reason, the results are affected by the different affinity that antibodies can have to different antigenic variants. To overcome the limitations of an antibody-based quantification, we developed a quantitative Mass Spectrometry (MS) approach. Selected Reaction Monitoring (SRM) recently emerged as a powerful MS tool for detecting and quantifying proteins in complex mixtures. SRM is based on the targeted detection of ProteoTypicPeptides (PTPs), which are unique signatures of a protein that can be easily detected and quantified by MS. This approach, proven to be highly sensitive, quantitatively accurate and highly reproducible, was used to quantify the absolute amount of fHbp antigen in total extracts derived from 105 clinical isolates, evenly distributed among the three main variant groups and selected to be representative of the fHbp circulating subvariants around the world. We extended the study at the genetic level investigating the correlation between the differential level of expression and polymorphisms present within the genes and their promoter sequences. The implications of fHbp expression on the susceptibility of the strain to killing by anti-fHbp antisera are also presented. To date this is the first comprehensive fHbp expression profiling in a large panel of Neisseria meningitidis clinical isolates driven by an antibody-independent MS-based methodology, opening the door to new applications in vaccine coverage prediction and reinforcing the molecular understanding of released vaccines.

Keywords: quantitative mass spectrometry, Neisseria meningitidis, vaccines, bexsero, molecular epidemiology

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4064 Leveraging the HDAC Inhibitory Pharmacophore to Construct Deoxyvasicinone Based Tractable Anti-Lung Cancer Agent and pH-Responsive Nanocarrier

Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

Abstract:

A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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