Search results for: regulating investments

Authors: Daniela Pellin, Wilson Engelmann

Abstract:

Brazil has sought to accelerate your development through technology and innovation as a response to the global influences, which has received in internal management practices. For this, it had edited the Brazilian Law of Innovation 13.243/2016. However observing the Law overestimated economic aspects the respective application will not consider the stakeholders and the technological risks because there is no legal treatment. The economic exploitation and the technological risks must be controlled by limits of democratic system to find better social development to contribute with the economics agents for making decision to conform with global directions. The research understands this is a problem to face given the social particularities of the country because there has been the literal import of the North American Triple Helix Theory consolidated in developed countries and the negative consequences when applied in developing countries. Because of this symptomatic scenario, it is necessary to create adjustment to conduct the management of the law besides social democratic interests to increase the country development. For this, therefore, the Government will have to adopt some conducts promoting side by side with universities, civil society and companies, informational transparency, catch of partnerships, create a Confort Letter document for preparation to ensure the operation, joint elaboration of a Manual of Good Practices, make accountability and data dissemination. Also the Universities must promote informational transparency, drawing up partnership contracts and generating revenue, development of information. In addition, the civil society must do data analysis about proposals received for discussing to give opinion related. At the end, companies have to give public and transparent information about investments and economic benefits, risks and innovation manufactured. The research intends as a general objective to demonstrate that the efficiency of the propeller deployment will be possible if the innovative decision-making process goes through the institutional logic. As specific objectives, the American influence must undergo some modifications to better suit the economic-legal incentives to potentiate the development of the social system. The hypothesis points to institutional model for application to the legal system can be elaborated based on emerging characteristics of the country, in such a way that technological risks can be foreseen and there will be global conformity with attention to the full development of society as proposed by the researchers.The method of approach will be the systemic-constructivist with bibliographical review, data collection and analysis with the construction of the institutional and democratic model for the management of the Law.

Keywords: development, governance of law, institutionalization, triple helix

Procedia PDF Downloads 122

Authors: Trevor Toy, Josef Langerman

Abstract:

Around a quarter of the world’s data is generated by financial with an estimated 708.5 billion global non-cash transactions reached between 2018 and. And with Open Banking still a rapidly developing concept within the financial industry, there is an opportunity to create a secure mechanism for connecting its stakeholders to openly, legitimately and consensually share the data required to enable it. Integration and data sharing of anonymised transactional data are still operated in silos and centralised between the large corporate entities in the ecosystem that have the resources to do so. Smaller fintechs generating data and businesses looking to consume data are largely excluded from the process. Therefore there is a growing demand for accessible transactional data for analytical purposes and also to support the rapid global adoption of Open Banking. The following research has provided a solution framework that aims to provide a secure decentralised marketplace for 1.) data providers to list their transactional data, 2.) data consumers to find and access that data, and 3.) data subjects (the individuals making the transactions that generate the data) to manage and sell the data that relates to themselves. The platform also provides an integrated system for downstream transactional-related data from merchants, enriching the data product available to build a comprehensive view of a data subject’s spending habits. A robust and sustainable data market can be developed by providing a more accessible mechanism for data producers to monetise their data investments and encouraging data subjects to share their data through the same financial incentives. At the centre of the platform is the market mechanism that connects the data providers and their data subjects to the data consumers. This core component of the platform is developed on a decentralised blockchain contract with a market layer that manages transaction, user, pricing, payment, tagging, contract, control, and lineage features that pertain to the user interactions on the platform. One of the platform’s key features is enabling the participation and management of personal data by the individuals from whom the data is being generated. This framework developed a proof-of-concept on the Etheruem blockchain base where an individual can securely manage access to their own personal data and that individual’s identifiable relationship to the card-based transaction data provided by financial institutions. This gives data consumers access to a complete view of transactional spending behaviour in correlation to key demographic information. This platform solution can ultimately support the growth, prosperity, and development of economies, businesses, communities, and individuals by providing accessible and relevant transactional data for big data analytics and open banking.

Keywords: big data markets, open banking, blockchain, personal data management

Procedia PDF Downloads 48

Authors: Sara Bonetti

Abstract:

The use of quantitative data to support policies and justify investments has become imperative in many fields including the field of education. However, the topic of data literacy has only marginally touched the early care and education (ECE) field. In California, within the ECE workforce, there is a group of professionals working in policy and advocacy that use quantitative data regularly and whose educational and professional experiences have been neglected by existing research. This study aimed at analyzing these experiences in accessing, using, and producing quantitative data. This study utilized semi-structured interviews to capture the differences in educational and professional backgrounds, policy contexts, and power relations. The participants were three key professionals from county-level organizations and one working at a State Department to allow for a broader perspective at systems level. The study followed Núñez’s multilevel model of intersectionality. The key in Núñez’s model is the intersection of multiple levels of analysis and influence, from the individual to the system level, and the identification of institutional power dynamics that perpetuate the marginalization of certain groups within society. In a similar manner, this study looked at the dynamic interaction of different influences at individual, organizational, and system levels that might intersect and affect ECE professionals’ experiences with quantitative data. At the individual level, an important element identified was the participants’ educational background, as it was possible to observe a relationship between that and their positionality, both with respect to working with data and also with respect to their power within an organization and at the policy table. For example, those with a background in child development were aware of how their formal education failed to train them in the skills that are necessary to work in policy and advocacy, and especially to work with quantitative data, compared to those with a background in administration and/or business. At the organizational level, the interviews showed a connection between the participants’ position within the organization and their organization’s position with respect to others and their degree of access to quantitative data. This in turn affected their sense of empowerment and agency in dealing with data, such as shaping what data is collected and available. These differences reflected on the interviewees’ perceptions and expectations for the ECE workforce. For example, one of the interviewees pointed out that many ECE professionals happen to use data out of the necessity of the moment. This lack of intentionality is a cause for, and at the same time translates into missed training opportunities. Another interviewee pointed out issues related to the professionalism of the ECE workforce by remarking the inadequacy of ECE students’ training in working with data. In conclusion, Núñez’s model helped understand the different elements that affect ECE professionals’ experiences with quantitative data. In particular, what was clear is that these professionals are not being provided with the necessary support and that we are not being intentional in creating data literacy skills for them, despite what is asked of them and their work.

Keywords: data literacy, early childhood professionals, intersectionality, quantitative data

Procedia PDF Downloads 227

Authors: Luke Miller

Abstract:

This paper develops an options pricing methodology to value strategic pricing strategies in the services sector. More specifically, this study provides a unifying taxonomy of current service sector pricing practices, frames these pricing decisions as strategic real options, demonstrates accepted option valuation techniques to assess service sector pricing decisions, and suggests future research areas where pricing decisions and real options overlap. Enhancing revenue in the service sector requires proactive decision making in a world of uncertainty. In an effort to strategically price service products, revenue enhancement necessitates a careful study of the service costs, customer base, competition, legalities, and shared economies with the market. Pricing decisions involve the quality of inputs, manpower, and best practices to maintain superior service. These decisions further hinge on identifying relevant pricing strategies and understanding how these strategies impact a firm’s value. A relatively new area of research applies option pricing theory to investments in real assets and is commonly known as real options. The real options approach is based on the premise that many corporate decisions to invest or divest in assets are simply an option wherein the firm has the right to make an investment without any obligation to act. The decision maker, therefore, has more flexibility and the value of this operating flexibility should be taken into consideration. The real options framework has already been applied to numerous areas including manufacturing, inventory, natural resources, research and development, strategic decisions, technology, and stock valuation. Additionally, numerous surveys have identified a growing need for the real options decision framework within all areas of corporate decision-making. Despite the wide applicability of real options, no study has been carried out linking service sector pricing decisions and real options. This is surprising given the service sector comprises 80% of the US employment and Gross Domestic Product (GDP). Identifying real options as a practical tool to value different service sector pricing strategies is believed to have a significant impact on firm decisions. This paper identifies and discusses four distinct pricing strategies available to the service sector from an options’ perspective: (1) Cost-based profit margin, (2) Increased customer base, (3) Platform pricing, and (4) Buffet pricing. Within each strategy lie several pricing tactics available to the service firm. These tactics can be viewed as options the decision maker has to best manage a strategic position in the market. To demonstrate the effectiveness of including flexibility in the pricing decision, a series of pricing strategies were developed and valued using a real options binomial lattice structure. The options pricing approach discussed in this study allows service firms to directly incorporate market-driven perspectives into the decision process and thus synchronizing service operations with organizational economic goals.

Keywords: option pricing theory, real options, service sector, valuation

Procedia PDF Downloads 329

Authors: Julio Aguirre, Yohnny Campana, Elmer Guerrero, Daniel De La Torre Ugarte

Abstract:

A well-developed transportation network is a necessary condition for a country to derive full benefits from good trade and macroeconomic policies. Road infrastructure plays a key role in the economic development of rural areas of developing countries; where agriculture is the main economic activity. The ability to move agricultural production from the place of production to the market, and then to the place of consumption, greatly influence the economic value of farming activities, and of the resources involved in the production process, i.e., labor and land. Consequently, investment in transportation networks contributes to enhance or overcome the natural advantages or disadvantages that topography and location have imposed over the agricultural sector. This is of particular importance when dealing with countries, like Peru, with a great topographic diversity. The objective of this research is to estimate the impacts of road infrastructure on the performance of the agricultural sector. Specific variables of interest are changes in travel time, shifts of production for self-consumption to production for the market, changes in farmers income, and impacts on the diversification of the agricultural sector. In the study, a cross-section model with instrumental variables is the central methodological instrument. The data is obtained from agricultural and transport geo-referenced databases, and the instrumental variable specification utilized is based on the Kruskal algorithm. The results show that the expansion of road connectivity reduced farmers' travel time by an average of 3.1 hours and the proportion of output sold in the market increases by up to 40 percentage points. The increase in connectivity has an unexpected increase in the districts index of diversification of agricultural production. The results are robust to the inclusion of year and region fixed-effects, and to control for geography (i.e., slope and altitude), population variables, and mining activity. Other results are also very eloquent. For example, a clear positive impact can be seen in access to local markets, but this does not necessarily correlate with an increase in the production of the sector. This can be explained by the fact that agricultural development not only requires provision of roads but additional complementary infrastructure and investments intended to provide the necessary conditions so that producers can offer quality products (improved management practices, timely maintenance of irrigation infrastructure, transparent management of water rights, among other factors). Therefore, complementary public goods are needed to enhance the effects of roads on the welfare of the population, beyond enabling them to increase their access to markets.

Keywords: agriculture devolepment, market access, road connectivity, regional development

Procedia PDF Downloads 174

Authors: M. Benjamin Stacey

Abstract:

Energy efficiency has been increasingly recognized as a high value resource through state policies that require utility companies to implement efficiency programs. While policymakers have recognized the statewide economic, environmental, and health related value to residents who rely on this grid supplied resource, varying interests in energy efficiency between socioeconomic groups stands undifferentiated in most state legislation. Instead, the benefits are oftentimes assumed to be distributed equitably across these groups. Despite this fact, these policies are frequently sited by advocacy groups, regulatory bodies and utility companies for their ability to address the negative financial, health and other social impacts of energy poverty in low income communities. Yet, while most states like Michigan require programs that target low income consumers, oftentimes no requirements exist for the equitable investment and energy savings for low income consumers, nor does it stipulate minimal spending levels on low income programs. To further understand the impact of the absence of these factors in legislation, this study examines the distribution of program funds and energy efficiency savings to answer a fundamental energy justice concern; Are there disparities in the investment and benefits of energy efficiency programs between socioeconomic groups? This study compiles data covering the history of Michigan’s Energy Efficiency policy implementation from 2010-2016, analyzing the energy efficiency portfolios of Michigan’s two main energy providers. To make accurate comparisons between these two energy providers' investments and energy savings in low and non-low income programs, the socioeconomic variation for each utility coverage area was captured and accounted for using GIS and US Census data. Interestingly, this study found that both providers invested more equitably in natural gas efficiency programs, however, together these providers invested roughly three times less per household in low income electricity efficiency programs, which resulted in ten times less electricity savings per household. This study also compares variation in commission approved utility plans and actual spending and savings results, with varying patterns pointing to differing portfolio management strategies between companies. This study reveals that for the history of the implementation of Michigan’s Energy Efficiency Policy, that the 35% of Michigan’s population who qualify as low income have received substantially disproportionate funding and energy savings because of the policy. This study provides an overview of results from a social perspective, raises concerns about the impact on energy poverty and equity between consumer groups and is an applicable tool for law makers, regulatory agencies, utility portfolio managers, and advocacy groups concerned with addressing issues related to energy poverty.

Keywords: energy efficiency, energy justice, low income, state policy

Procedia PDF Downloads 166

Authors: Richard Grant, Landolf Rhode-Barbarigos, Shouraseni Sen Roy, Lucas Brittan, Change Li, Aiden Rowe

Abstract:

Ports are critical for the US economy, connecting farmers, manufacturers, retailers, consumers and an array of transport and storage operators. Port facilities vary widely in terms of their productivity, footprint, specializations, and governance. In this context, Port Miami is considered as one of the busiest ports providing both cargo and cruise services in connecting the wider region of the Caribbean and Mesoamerica to the global networks. It is considered as the “Cruise Capital of the World and Global Gateway of the Americas” and “leading container port in Florida.” Furthermore, it has also been ranked as one of the top container ports in the world and the second most efficient port in North America. In this regard, Port Miami has made significant investments in the strategic and capital infrastructure of about US$1 billion, including increasing the channel depth and other onshore infrastructural enhancements. Therefore, this study involves a detailed analysis of Port Miami’s network, using publicly available multiple years of data about marine vessel traffic, cargo, and connectivity and performance indices from 2015-2021. Through the analysis of cargo and cruise vessels to and from Port Miami and its relative performance at the global scale from 2015 to 2021, this study examines the port’s long-term resilience and future growth potential. The main results of the analyses indicate that the top category for both inbound and outbound cargo is manufactured products and textiles. In addition, there are a lot of fresh fruits, vegetables, and produce for inbound and processed food for outbound cargo. Furthermore, the top ten port connections for Port Miami are all located in the Caribbean region, the Gulf of Mexico, and the Southeast USA. About half of the inbound cargo comes from Savannah, Saint Thomas, and Puerto Plata, while outbound cargo is from Puerto Corte, Freeport, and Kingston. Additionally, for cruise vessels, a significantly large number of vessels originate from Nassau, followed by Freeport. The number of passenger's vessels pre-COVID was almost 1,000 per year, which dropped substantially in 2020 and 2021 to around 300 vessels. Finally, the resilience and competitiveness of Port Miami were also assessed in terms of its network connectivity by examining the inbound and outbound maritime vessel traffic. It is noteworthy that the most frequent port connections for Port Miami were Freeport and Savannah, followed by Kingston, Nassau, and New Orleans. However, several of these ports, Puerto Corte, Veracruz, Puerto Plata, and Santo Thomas, have low resilience and are highly vulnerable, which needs to be taken into consideration for the long-term resilience of Port Miami in the future.

Keywords: port, Miami, network, cargo, cruise

Procedia PDF Downloads 55

Authors: Joseph Ndegwa

Abstract:

Changes are required if energy systems are to foster long-term growth. The main problems are increasing access to inexpensive, dependable, and sufficient energy supply while addressing environmental implications at all levels. Policies can help to promote sustainable development by providing adequate and inexpensive energy sources to underserved regions, such as liquid and gaseous fuels for cooking and electricity for household and commercial usage. Promoting energy efficiency. Increased utilization of new renewables. Spreading and implementing additional innovative energy technologies. Markets can achieve many of these goals with the correct policies, pricing, and regulations. However, if markets do not work or fail to preserve key public benefits, tailored government policies, programs, and regulations can achieve policy goals. The main strategies for promoting sustainable energy systems are simple. However, they need a broader recognition of the difficulties we confront, as well as a firmer commitment to specific measures. Making markets operate better by minimizing pricing distortions, boosting competition, and removing obstacles to energy efficiency are among the measures. Complementing the reform of the energy industry with policies that promote sustainable energy. Increasing investments in renewable energy. Increasing the rate of technical innovation at each level of the energy innovation chain. Fostering technical leadership in underdeveloped nations by transferring technology and enhancing institutional and human capabilities. promoting more international collaboration. Governments, international organizations, multilateral financial institutions, and civil society—including local communities, business and industry, non-governmental organizations (NGOs), and consumers—all have critical enabling roles to play in the problem of sustainable energy. Partnerships based on integrated and cooperative approaches and drawing on real-world experience will be necessary. Setting the required framework conditions and ensuring that public institutions collaborate effectively and efficiently with the rest of society are common themes across all industries and geographical areas in order to achieve sustainable development. Powerful tools for sustainable development include energy. However, significant policy adjustments within the larger enabling framework will be necessary to refocus its influence in order to achieve that aim. Many of the options currently accessible will be lost or the price of their ultimate realization (where viable) will grow significantly if such changes don't take place during the next several decades and aren't started right enough. In any case, it would seriously impair the capacity of future generations to satisfy their demands.

Keywords: sustainable development, reliable, price, policy

Procedia PDF Downloads 40

Authors: Fatih Gundogan, Fatih Kafali, Abdullah Karadag, Alper Baloglu, Ersoy Pehlivan, Mustafa Eruyar, Osman Bayram, Orhan Karademiroglu, Wasim Shoman

Abstract:

Nowadays many cities around the world are investing their efforts and resources for the purpose of facilitating their citizen’s life and making cities more livable and sustainable by implementing newly emerged phenomena of smart city. For this purpose, related research institutions prepare and publish smart city indices or benchmarking reports aiming to measure the city’s current ‘smartness’ status. Several functional domains, various indicators along different selection and calculation methods are found within such indices and reports. The selection criteria varied for each institution resulting in inconsistency in the ranking and evaluating. This research aims to evaluate the impact of selecting such functional domains, indicators and calculation methods which may cause change in the rank. For that, six functional domains, i.e. Environment, Mobility, Economy, People, Living and governance, were selected covering 19 focus areas and 41 sub-focus (variable) areas. 60 out of 191 indicators were also selected according to several criteria. These were identified as a result of extensive literature review for 13 well known global indices and research and the ISO 37120 standards of sustainable development of communities. The values of the identified indicators were obtained from reliable sources for ten cities. The values of each indicator for the selected cities were normalized and standardized to objectively investigate the impact of the chosen indicators. Moreover, the effect of choosing an integration method to represent the values of indicators for each city is investigated by comparing the results of two of the most used methods i.e. geometric aggregation and fuzzy logic. The essence of these methods is assigning a weight to each indicator its relative significance. However, both methods resulted in different weights for the same indicator. As a result of this study, the alternation in city ranking resulting from each method was investigated and discussed separately. Generally, each method illustrated different ranking for the selected cities. However, it was observed that within certain functional areas the rank remained unchanged in both integration method. Based on the results of the study, it is recommended utilizing a common platform and method to objectively evaluate cities around the world. The common method should provide policymakers proper tools to evaluate their decisions and investments relative to other cities. Moreover, for smart cities indices, at least 481 different indicators were found, which is an immense number of indicators to be considered, especially for a smart city index. Further works should be devoted to finding mutual indicators representing the index purpose globally and objectively.

Keywords: functional domain, urban city index, indicator, smart city

Procedia PDF Downloads 123

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

Abstract:

Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

Procedia PDF Downloads 106

Authors: Annika Freudenberger, Sin Sokhong

Abstract:

In just a few years, the Face-to-Face Victory Gardens Project (F2F) in Cambodia has developed a high-impact project that has provided immediate and tangible benefits to local families. This has been accomplished with a relatively hands-off approach that relies on households’ own motivation and personal investments of time and resources -which is both unique and impressive in the landscape of NGO and government initiatives in the area. Households have been growing food both for their own consumption and to sell or exchange. Not all targeted beneficiaries are equally motivated and maximizing their involvement, but there is a clear subset of households -particularly those who serve as facilitators- whose circumstances have been transformed as a result of F2F. A number of household factors and contextual economic factors affect families’ income generation opportunities. All the households we spoke with became involved with F2F with the goal of selling some proportion of their produce (i.e., not exclusively for their own consumption). For some, this income is marginal and supplemental to their core household income; for others, it is substantial and transformative. Some engage directly with customers/buyers in their immediate community, while others sell in larger nearby markets, and others link up with intermediary vendors. All struggle, to a certain extent, to compete in a local economy flooded with cheap produce imported from large-scale growers in neighboring provinces, Thailand, and Vietnam, although households who grow and sell herbs and greens popular in Khmer cuisine have found a stronger local market. Some are content with the scale of their garden, the income they make, and the current level of effort required to maintain it; others would like to expand but are faced with land constraints and water management challenges. Households making a substantial income from selling their products have achieved success in different ways, making it difficult to pinpoint a clear “model” for replication. Within our small sample size of interviewees, it seems as though the families with a clear passion for their gardens and high motivation to work hard to bring their products to market have succeeded in doing so. Khmer greens and herbs have been the most successful; they are not high-value crops, but they are fairly easy to grow, and there is a constant demand. These crops are also not imported as much, so prices are more stable than those of crops such as long beans. Although we talked to a limited number of individuals, it also appears as though successful families either restricted their crops to those that would grow well in drought or flood conditions (depending on which they are affected by most); or benefit already from water management infrastructure such as water tanks which helps them diversify their crops and helps them build their resilience.

Keywords: food security, Victory Gardens, nutrition, Cambodia

Procedia PDF Downloads 38

Authors: Iman Farasat, Howard M. Salis

Abstract:

Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

Procedia PDF Downloads 447

Authors: Bhargavi G. Iyer, Ojaswi Bhagat

Abstract:

It is often noted that the value of a novel idea lies in its successful implementation. However, successful implementation requires the nurturing and encouragement of innovation. Nascent competitors are a true representation of innovation in any given industry. A nascent competitor is an entity whose prospective innovation poses a future threat to an incumbent dominant competitor. While a nascent competitor benefits in several ways, it is also exposed significantly and is at greater risk of facing the brunt of exclusionary practises and abusive conduct by dominant incumbent competitors in the industry. This research paper aims to explore the risks and threats faced by nascent competitors and analyse the benefits they accrue as well as the advantages they proffer to the economy; through an analytical, critical study. In such competitive market environments, a rise of the acquisitions of nascent competitors by the incumbent dominants is observed. Therefore, this paper will examine the dynamics of nascent acquisition. Further, this paper hopes to specifically delve into the role of antitrust bodies in regulating nascent acquisition. This paper also aspires to deal with the question how to distinguish harmful from harmless acquisitions in order to facilitate ideal enforcement practice. This paper proposes mechanisms of scrutiny in order to ensure healthy market practises and efficient merger control in the context of nascent acquisitions. Taking into account the scope and nature of the topic, as well as the resources available and accessible, a combination of the methods of doctrinal research and analytical research were employed, utilising secondary sources in order to assess and analyse the subject of research. While legally evaluating the Killer Acquisition theory and the Nascent Potential Acquisition theory, this paper seeks to critically survey the precedents and instances of nascent acquisitions. In addition to affording a compendious account of the legislative framework and regulatory mechanisms in the United States, the United Kingdom, and the European Union; it hopes to suggest an internationally practicable legal foundation for domestic legislation and enforcement to adopt. This paper hopes to appreciate the complexities and uncertainties with respect to nascent acquisitions and attempts to suggest viable and plausible policy measures in antitrust law. It additionally attempts to examine the effects of such nascent acquisitions upon the consumer and the market economy. This paper weighs the argument of shifting the evidentiary burden on to the merging parties in order to improve merger control and regulation and expounds on its discovery of the strengths and weaknesses of the approach. It is posited that an effective combination of factual, legal, and economic analysis of both the acquired and acquiring companies possesses the potential to improve ex post and ex ante merger review outcomes involving nascent companies; thus, preventing anti-competitive practises. This paper concludes with an analysis of the possibility and feasibility of industry-specific identification of anti-competitive nascent acquisitions and implementation of measures accordingly.

Keywords: acquisition, antitrust law, exclusionary practises merger control, nascent competitor

Procedia PDF Downloads 133

Authors: Husham Bayazed

Abstract:

Purpose of Presentation: Obesity and overweight are among the biggest health challenges of the 21st century, according to the WHO. Obviously, obese individuals suffer different courses of disease – from infections and allergies to cancer- and even respond differently to some treatment options. Of note, obesity often seems to predispose and triggers several secondary diseases such as diabetes, arteriosclerosis, or heart attacks. Since decades it seems that immunological signals gear inflammatory processes among obese individuals with the aforementioned conditions. This review aims to shed light how obesity sparks or rewire the immune system and predisposes to such unpleasant health outcomes. Moreover, lessons from the Covid-19 pandemic ascertain that people living with pre-existing conditions such as obesity can develop severe acute respiratory syndrome (SARS), which needs to be elucidated how obesity and its adjuvant inflammatory process distortion contribute to enhancing severe COVID-19 consequences. Recent Findings: In recent clinical studies, obesity was linked to alter and sparks the immune system in different ways. Adipose tissue (AT) is considered as a secondary immune organ, which is a reservoir of tissue-resident of different immune cells with mediator release, making it a secondary immune organ. Adipocytes per se secrete several pro-inflammatory cytokines (IL-6, IL-4, MCP-1, and TNF-α ) involved in activation of macrophages resulting in chronic low-grade inflammation. The correlation between obesity and T cells dysregulation is pivotal in rewiring the immune system. Of note, autophagy occurrence in adipose tissues further rewire the immune system due to flush and outburst of leptin and adiponectin, which are cytokines and influencing pro-inflammatory immune functions. These immune alterations among obese individuals are collectively incriminated in triggering several metabolic disorders and playing role in increasing cancers incidence and susceptibility to different infections. During COVID-19 pandemic, it was verified that patients with pre-existing obesity being at greater risk of suffering severe and fatal clinical outcomes. Beside obese people suffer from increased airway resistance and reduced lung volume, ACE2 expression in adipose tissue seems to be high and even higher than that in lungs, which spike infection incidence. In essence, obesity with pre-existence of pro-inflammatory cytokines such as LI-6 is a risk factor for cytokine storm and coagulopathy among COVID-19 patients. Summary: It is well documented that obesity is associated with chronic systemic low-grade inflammation, which sparks and alter different pillars of the immune system and triggers different metabolic disorders, and increases susceptibility of infections and cancer incidence. The pre-existing chronic inflammation in obese patients with the augmented inflammatory response against the viral infection seems to increase the susceptibility of these patients to developing severe COVID-19. Although the new weight loss drugs and bariatric surgery are considered as breakthrough news for obesity treatment, but preventing is easier than treating it once it has taken hold. However, obesity and immune system link new insights dispute the role of immunotherapy and regulating immune cells treating diet-induced obesity.

Keywords: immunity, metabolic disorders, cancer, COVID-19

Procedia PDF Downloads 49

Authors: Vinod Kumar

Abstract:

Background: Tissue Plasminogen Activator (tPA) showed a level 1 benefit in acute stroke (within 3-6 hrs). Intracarotid sodium nitroprusside (ICSNP) has been studied in this context with a wide treatment window, fast recovery and affordability. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a)Retrograde Neurotransmission (acute cases): 1)Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2)Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b)Vasospasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c)Long-Term Potentıatıon (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Des’gn: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat stroke cases. Case-control prospective study. Mater’als And Methods: The experimental population included 82 stroke patients (10 patients were given control treatments without superfusion or with 5% dextrose superfusion, and 72 patients comprised the ICSNP group). The mean time for superfusion was 9.5 days post-stroke. Pre- and post-ICSNP status was monitored by NIHSS, MRI and TCD. Results: After 90 seconds in the ICSNP group, the mean change in the NIHSS score was a decrease of 1.44 points, or 6.55%; after 2 h, there was a decrease of 1.16 points; after 24 h, there was an increase of 0.66 points, 2.25%, compared to the control-group increase of 0.7 points, or 3.53%; at 7 days, there was an 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points, or 22.37%; at 2 months in ICSNP, there was a 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points, or 8.78%. TCD was documented and improvements were noted. Conclusions: ICSNP is a swift-acting drug in the treatment of stroke, acting within 90 seconds on day 9.5 post-stroke with a small decrease after 24 hours. The drug recovers from this decrease quickly.

Keywords: brain infarcts, intracarotid sodium nitroprusside, perforators, vasodilatıons, retrograde transmission, the 10, 000-fold effect

Procedia PDF Downloads 290

Authors: Priyanka Jain, Ashish K. Sharma, Esha Shukla, K. J. Mukherjee

Abstract:

We propose a paradigm shift in our approach to design improved platforms for recombinant protein production, by addressing system level issues rather than the individual steps associated with recombinant protein synthesis like transcription, translation, etc. We demonstrate that by controlling and modulating the cellular stress response (CSR), which is responsible for feedback control of protein synthesis, we can generate hyper-producing strains. We did transcriptomic profiling of post-induction cultures, expressing different types of protein, to analyze the nature of this cellular stress response. We found significant down-regulation of substrate utilization, translation, and energy metabolism genes due to generation CSR inside the host cell. However, transcription profiling has also shown that many genes are up-regulated post induction and their role in modulating the CSR is unclear. We hypothesized that these up-regulated genes trigger signaling pathways, generating the CSR and concomitantly reduce the recombinant protein yield. To test this hypothesis, we knocked out the up-regulated genes, which did not have any downstream regulatees, and analyzed their impact on cellular health and recombinant protein expression. Two model proteins i.e., GFP and L-Asparaginase were chosen for this analysis. We observed a significant improvement in expression levels, with some knock-outs showing more than 7-fold higher expression compared to control. The 10 best single knock-outs were chosen to make 45 combinations of all possible double knock-outs. A further increase in expression was observed in some of these double knock- outs with GFP levels being highest in a double knock-out ΔyhbC + ΔelaA. However, for L-Asparaginase which is a secretory protein, the best results were obtained using a combination of ΔelaA+ΔcysW knock-outs. We then tested all the knock outs for their ability to enhance the expression of a 'difficult-to-express' protein. The Rubella virus E1 protein was chosen and tagged with sfGFP at the C-terminal using a linker peptide for easy online monitoring of expression of this fusion protein. Interestingly, the highest increase in Rubella-sGFP levels was obtained in the same double knock-out ΔelaA + ΔcysW (5.6 fold increase in expression yield compared to the control) which gave the highest expression for L-Asparaginase. However, for sfGFP alone, the ΔyhbC+ΔmarR knock-out gave the highest level of expression. These results indicate that there is a fair degree of commonality in the nature of the CSR generated by the induction of different proteins. Transcriptomic profiling of the double knock out showed that many genes associated with the translational machinery and energy biosynthesis did not get down-regulated post induction, unlike the control where these genes were significantly down-regulated. This confirmed our hypothesis of these genes playing an important role in the generation of the CSR and allowed us to design a strategy for making better expression hosts by simply knocking out key genes. This strategy is radically superior to the previous approach of individually up-regulating critical genes since it blocks the mounting of the CSR thus preventing the down-regulation of a very large number of genes responsible for sustaining the flux through the recombinant protein production pathway.

Keywords: cellular stress response, GFP, knock-outs, up-regulated genes

Procedia PDF Downloads 205

Authors: Michael McCann

Abstract:

Managerial theories propose that, in joint stock companies, executives may be tempted to waste excess free cash on unprofitable projects to keep control of resources. In order to conceal their projects' poor performance, they may seek to engage in earnings management. On the one hand, managers may manipulate earnings upwards in order to post ‘good’ performances and safeguard their position. On the other, since managers pursuit of unrewarding investments are likely to lead to low long-term profitability, managers will use negative accruals to reduce current year’s earnings, smoothing earnings over time in order to conceal the negative effects. Agency models argue that boards of directors are delegated by shareholders to ensure that companies are governed properly. Part of that responsibility is ensuring the reliability of financial information. Analyses of the impact of board characteristics, particularly board independence on the misuse of free cash flow and earnings management finds conflicting evidence. However, existing characterizations of board independence do not account for such directors gaining firm-specific knowledge over time, influencing their monitoring ability. Further, there is little analysis of the influence of the relative experience of independent directors and executives on decisions surrounding the use of free cash. This paper contributes to this literature regarding the heterogeneous characteristics of boards by investigating the influence of independent director tenure on earnings management and the relative tenures of independent directors and Chief Executives. A balanced panel dataset comprising 51 companies across 11 annual periods from 2005 to 2015 is used for the analysis. In each annual period, firms were classified as conducting earnings management if they had discretionary accruals in the bottom quartile (downwards) and top quartile (upwards) of the distributed values for the sample. Logistical regressions were conducted to determine the marginal impact of independent board tenure and a number of control variables on the probability of conducting earnings management. The findings indicate that both absolute and relative measures of board independence and experience do not have a significant impact on the likelihood of earnings management. It is the level of free cash flow which is the major influence on the probability of earnings management. Higher free cash flow increases the probability of earnings management significantly. The research also investigates whether board monitoring of earnings management is contingent on the level of free cash flow. However, the results suggest that board monitoring is not amplified when free cash flow is higher. This suggests that the extent of earnings management in companies is determined by a range of company, industry and situation-specific factors.

Keywords: corporate governance, boards of directors, agency theory, earnings management

Procedia PDF Downloads 201

Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

Abstract:

Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.

Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation

Procedia PDF Downloads 342

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

Procedia PDF Downloads 40

Authors: Lopamudra D. Satpathy, Bani Chatterjee, Jitendra Mahakud

Abstract:

The rapid economic growth in terms of output and investment necessitates a substantial growth of Total Factor Productivity (TFP) of firms which is an indicator of an economy’s technological change. The strong empirical relationship between financial sector development and economic growth clearly indicates that firms financing decisions do affect their levels of output via their investment decisions. Hence it establishes a linkage between the financial factors and productivity growth of the firms. To achieve the smooth and continuous economic growth over time, it is imperative to understand the financial channel that serves as one of the vital channels. The theoretical or logical argument behind this linkage is that when the internal financial capital is not sufficient enough for the investment, the firms always rely upon the external sources of finance. But due to the frictions and existence of information asymmetric behavior, it is always costlier for the firms to raise the external capital from the market, which in turn affect their investment sentiment and productivity. This kind of financial position of the firms puts heavy pressure on their productive activities. Keeping in view this theoretical background, the present study has tried to analyze the role of both external and internal financial factors (leverage, cash flow and liquidity) on the determination of total factor productivity of the firms of manufacturing industry and its sub-industries, maintaining a set of firm specific variables as control variables (size, age and disembodied technological intensity). An estimate of total factor productivity of the Indian manufacturing industry and sub-industries is computed using a semi-parametric approach, i.e., Levinsohn- Petrin method. It establishes the relationship between financial factors and productivity growth of 652 firms using a dynamic panel GMM method covering the time period between 1997-98 and 2012-13. From the econometric analyses, it has been found that the internal cash flow has a positive and significant impact on the productivity of overall manufacturing sector. The other financial factors like leverage and liquidity also play the significant role in the determination of total factor productivity of the Indian manufacturing sector. The significant role of internal cash flow on determination of firm-level productivity suggests that access to external finance is not available to Indian companies easily. Further, the negative impact of leverage on productivity could be due to the less developed bond market in India. These findings have certain implications for the policy makers to take various policy reforms to develop the external bond market and easily workout through which the financially constrained companies will be able to raise the financial capital in a cost-effective manner and would be able to influence their investments in the highly productive activities, which would help for the acceleration of economic growth.

Keywords: dynamic panel, financial factors, manufacturing sector, total factor productivity

Procedia PDF Downloads 306

Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

Abstract:

Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

Procedia PDF Downloads 175

Authors: Alessandro Balbo, Gianvito Colucci, Matteo Nicoli, Laura Savoldi

Abstract:

Hydrogen is expected to become an undisputed player in the ecological transition throughout the next decades. The decarbonization potential offered by this energy vector provides various opportunities for the so-called “hard-to-abate” sectors, including industrial production of iron and steel, glass, refineries and the heavy-duty transport. In this regard, Italy, in the framework of decarbonization plans for the whole European Union, has been considering a wider use of hydrogen to provide an alternative to fossil fuels in hard-to-abate sectors. This work aims to assess and compare different options concerning the pathway to be followed in the development of the future Italian energy system in order to meet decarbonization targets as established by the Paris Agreement and by the European Green Deal, and to infer a techno-economic analysis of the required asset alternatives to be used in that perspective. To accomplish this objective, the Energy System Optimization Model TEMOA-Italy is used, based on the open-source platform TEMOA and developed at PoliTo as a tool to be used for technology assessment and energy scenario analysis. The adopted assessment strategy includes two different scenarios to be compared with a business-as-usual one, which considers the application of current policies in a time horizon up to 2050. The studied scenarios are based on the up-to-date hydrogen-related targets and planned investments included in the National Hydrogen Strategy and in the Italian National Recovery and Resilience Plan, with the purpose of providing a critical assessment of what they propose. One scenario imposes decarbonization objectives for the years 2030, 2040 and 2050, without any other specific target. The second one (inspired to the national objectives on the development of the sector) promotes the deployment of the hydrogen value-chain. These scenarios provide feedback about the applications hydrogen could have in the Italian energy system, including transport, industry and synfuels production. Furthermore, the decarbonization scenario where hydrogen production is not imposed, will make use of this energy vector as well, showing the necessity of its exploitation in order to meet pledged targets by 2050. The distance of the planned policies from the optimal conditions for the achievement of Italian objectives is be clarified, revealing possible improvements of various steps of the decarbonization pathway, which seems to have as a fundamental element Carbon Capture and Utilization technologies for its accomplishment. In line with the European Commission open science guidelines, the transparency and the robustness of the presented results is ensured by the adoption of the open-source open-data model such as the TEMOA-Italy.

Keywords: decarbonization, energy system optimization models, hydrogen, open-source modeling, TEMOA

Procedia PDF Downloads 44

Authors: Tobias Milz, L. Macpherson, Varvara Vetrova

Abstract:

The law is a fundamental pillar of human societies as it shapes, controls and governs how humans conduct business, behave and interact with each other. Recent advances in computer-assisted technologies such as NLP, data science and AI are creating opportunities to support the practice, research and study of this pervasive domain. It is therefore not surprising that there has been an increase in investments into supporting technologies for the legal industry (also known as “legal tech” or “law tech”) over the last decade. A sub-discipline of particular appeal is concerned with assisted legal research. Supporting law researchers and practitioners to retrieve information from the vast amount of ever-growing legal documentation is of natural interest to the legal research community. One tool that has been in use for this purpose since the early nineteenth century is legal citation indexing. Among other use cases, they provided an effective means to discover new precedent cases. Nowadays, computer-assisted network analysis tools can allow for new and more efficient ways to reveal the “hidden” information that is conveyed through citation behavior. Unfortunately, access to openly available legal data is still lacking in New Zealand and access to such networks is only commercially available via providers such as LexisNexis. Consequently, there is a need to create, analyze and provide a legal citation network with sufficient data to support legal research tasks. This paper describes the development and analysis of a legal citation Network for New Zealand containing over 300.000 decisions from 125 different courts of all areas of law and jurisdiction. Using python, the authors assembled web crawlers, scrapers and an OCR pipeline to collect and convert court decisions from openly available sources such as NZLII into uniform and machine-readable text. This facilitated the use of regular expressions to identify references to other court decisions from within the decision text. The data was then imported into a graph-based database (Neo4j) with the courts and their respective cases represented as nodes and the extracted citations as links. Furthermore, additional links between courts of connected cases were added to indicate an indirect citation between the courts. Neo4j, as a graph-based database, allows efficient querying and use of network algorithms such as PageRank to reveal the most influential/most cited courts and court decisions over time. This paper shows that the in-degree distribution of the New Zealand legal citation network resembles a power-law distribution, which indicates a possible scale-free behavior of the network. This is in line with findings of the respective citation networks of the U.S. Supreme Court, Austria and Germany. The authors of this paper provide the database as an openly available data source to support further legal research. The decision texts can be exported from the database to be used for NLP-related legal research, while the network can be used for in-depth analysis. For example, users of the database can specify the network algorithms and metrics to only include specific courts to filter the results to the area of law of interest.

Keywords: case citation network, citation analysis, network analysis, Neo4j

Procedia PDF Downloads 80

Authors: Mandeep Singh Azad.Dibyendu Chakraborty, Vikas Vohra

Abstract:

Introduction: Poonch is one of the remotest districts of the Jammu and Kashmir (UT) and situated on international borders. This native poultry population in these areas is quite hardy and thrives well in adverse climatic conditions. Till date, no local breed from this area (Jammu Province) has been characterized thus present study was undertaken with the main objectives of molecular characterization of ChB6 gene in local native chicken of Poonch region located at international borders between India and Pakistan. The chicken B-cell marker (ChB6) gene has been proposed as a candidate gene in regulating B-cell development. Material and Method: RNA was isolated by Blood RNA Purification Kit (HiPura) and Trizol method from whole blood samples. Positive PCR products with size 1110 bp were selected for further purification, sequencing and analysis. The amplified PCR product was sequenced by Sangers dideoxy chain termination method. The obtained sequence of ChB6 gene of Poonchi chicken were compared by MEGAX software. BioEdit software was used to construct phylogenic tree, and Neighbor Joining method was used to infer evolutionary history. In order to compute evolutionary distance Maximum Composite Likelihood method was used. Results: The positively amplified samples of ChB6 genes were then subjected to Sanger sequencing with “Primer Walking. The sequences were then analyzed using MEGA X and BioEdit software. The sequence results were compared with other reported sequence from different breed of chicken and with other species obtained from the NCBI (National Center for Biotechnology Information). ClustalW method using MEGA X software was used for multiple sequence alignment. The sequence results of ChB6 gene of Poonchi chicken was compared with Centrocercus urophasianus, G. gallus mRNA for B6.1 protein, G. gallus mRNA for B6.2, G. gallus mRNA for B6.3, Gallus gallus B6.1, Halichoeres bivittatus, Miniopterus fuliginosus Ferringtonia patagonica, Tympanuchus phasianellus. The genetic distances were 0.2720, 0.0000, 0.0245, 0.0212, 0.0147, 1.6461, 2.2394, 2.0070 and 0.2363 for ChB6 gene of Poonchi chicken sequence with other sequences in the present study respectively. Sequencing results showed variations between different species. It was observed that AT content were higher then GC content for ChB6 gene. The lower AT content suggests less thermostable. It was observed that there was no sequence difference within the Poonchi population for ChB6 gene. The high homology within chicken population indicates the conservation of ChB6 gene. The maximum difference was observed with Miniopterus fuliginosus (Eastern bent-wing bat) followed by Ferringtonia patagonica and Halichoeres bivittatus. Conclusion: Genetic variation is the essential component for genetic improvement. The results of immune related gene Chb6 shows between population genetic variability. Therefore, further association studies of this gene with some prevalent diseases in large population would be helpful to identify disease resistant/ susceptible genotypes in the indigenous chicken population.

Keywords: ChB6, sequencing, ClustalW, genetic distance, poonchi chicken, SNP

Procedia PDF Downloads 39

Authors: S. Jimenez, R.Duarte, J.Sanchez-Choliz, I. Villanua

Abstract:

There is a certain consensus in economic literature about the factors that have influenced in historical differences in growth rates observed between developed and developing countries. However, it is less clear what elements have marked different paths of growth in developed economies in recent decades. R&D has always been seen as one of the major sources of technological progress, and productivity growth, which is directly influenced by technological developments. Following recent literature, we can say that ‘innovation pushes the technological frontier forward’ as well as encourage future innovation through the creation of externalities. In other words, productivity benefits from innovation are not fully appropriated by innovators, but it also spread through the rest of the economies encouraging absorptive capacities, what have become especially important in a context of increasing fragmentation of production This paper aims to contribute to this literature in two ways, first, exploring alternative indexes of R&D flows embodied in inter-country, inter-sectorial flows of good and services (as approximation to technology spillovers) capturing structural and technological characteristic of countries and, second, analyzing the impact of direct and embodied R&D on the evolution of labor productivity at the country/sector level in recent decades. The traditional way of calculation through a multiregional input-output framework assumes that all countries have the same capabilities to absorb technology, but it is not, each one has different structural features and, this implies, different capabilities as part of literature, claim. In order to capture these differences, we propose to use a weight based on specialization structure indexes; one related with the specialization of countries in high-tech sectors and the other one based on a dispersion index. We propose these two measures because, as far as we understood, country capabilities can be captured through different ways; countries specialization in knowledge-intensive sectors, such as Chemicals or Electrical Equipment, or an intermediate technology effort across different sectors. Results suggest the increasing importance of country capabilities while increasing the trade openness. Besides, if we focus in the country rankings, we can observe that with high-tech weighted R&D embodied countries as China, Taiwan and Germany arose the top five despite not having the highest intensities of R&D expenditure, showing the importance of country capabilities. Additionally, through a fixed effects panel data model we show that, in fact, R&D embodied is important to explain labor productivity increases, in fact, even more that direct R&D investments. This is reflecting that globalization is more important than has been said until now. However, it is true that almost all analysis done in relation with that consider the effect of t-1 direct R&D intensity over economic growth. Nevertheless, from our point of view R&D evolve as a delayed flow and it is necessary some time to be able to see its effects on the economy, as some authors have already claimed. Our estimations tend to corroborate this hypothesis obtaining a gap between 4-5 years.

Keywords: economic growth, embodied, input-output, technology

Procedia PDF Downloads 107

Authors: Sudeshna Sengupta

Abstract:

Women’s work lives weave a complex fabric of myriad work relations and complex structures. Lives, when seen from the lens of work, is a saga of conjugated oppression by intertwined structures that are vertically and horizontally interwoven in a very complex manner. Women interact with multiple institutions through their work. The interactions and interplay of institutions shape their organization of work. They intersperse productive work with reproductive work, unpaid economic activities with unpaid care work, and all kinds of activities with leisure and self-care. The proposed paper intends to understand how women working as home-based workers in the National Capital Region (NCR) of India are organizing their everyday work, and how the organization of work is influenced by the interplay of structures. Situating itself in a multidisciplinary theoretical framework, this paper brings out how the gendering of work is playing out in the political, economic and social domain and shaping the work-life within the family, and in the paid workspace. The paper will use a primary data source, which is qualitative in nature. It will comprise 15 qualitative interviews of women home-based workers from the National Capital Region. The research uses a life history approach. The sampling was purposive using snowballing as a method. The dataset is part of the primary data (qualitative) collected for the ongoing Ph.D. work in Gender Studies at Ambedkar University Delhi. The home-based workers interviewed were in “non-factory” wage relations based on piece rates with flexible working hours. Their workplaces were their own homes with no spatial divide between living spaces and workspaces. Home-based workers were recognized as a group in the domain of labor economics in the 1980s. When menial work was cheaper than machine work, the capital owners preferred to outsource work as home-based work to women. These production spaces are fragmented and the identity of gender is created within labor processes to favor material accumulation. Both the employers and employees acknowledged the material gain of the capital owner when work was subcontracted to women at home. Simultaneously the market reinforced women’s reproductive role by conforming to patriarchal ideology. The contractors played an important role in implementing localized control on workers and also in finding workers for fragmented, gendered production processes. Their presence helped the employers in bringing together multiple forms of oppression that ranged from creating a structure to flout laws by creating shadow employers. It created an intertwined social and economic structure as well as a workspace where the line between productive and reproductive work gets blurred. The state invisibilized itself either by keeping the sector out of the domain of laws or by not implementing its own laws regulating working conditions or social security. It allowed the local hierarchy to function and define localized working conditions. The productive reproductive continuum reveals a labor control that influenced both the productive and reproductive work of women.

Keywords: informal sector, paid work, women workers, labor processes

Procedia PDF Downloads 145

Authors: Hideaki Endo, Mika Goto

Abstract:

The global outbreak of the COVID-19 pandemic has seriously affected railway businesses. The number of railway passengers decreased due to the decline in the number of commuters and business travelers to avoid crowded trains and a sharp drop in inbound tourists visiting Japan. This has affected not only railway businesses but also related businesses, including hotels, leisure businesses, and retail businesses at station buildings. In 2021, the companies were divided into profitable and loss-making companies. This division suggests that railway companies, particularly loss-making companies, needed to decrease operational inefficiency. To measure the impact of COVID-19 and discuss the sustainable management strategies of railway companies, we examine the cost inefficiency of Japanese listed railway companies by applying stochastic frontier analysis (SFA) to their operational and financial data. First, we employ the stochastic frontier cost function approach to measure inefficiency. The cost frontier function is formulated as a Cobb–Douglas type, and we estimated parameters and variables for inefficiency. This study uses panel data comprising 26 Japanese-listed railway companies from 2005 to 2020. This period includes several events deteriorating the business environment, such as the financial crisis from 2007 to 2008 and the Great East Japan Earthquake of 2011, and we compare those impacts with those of the COVID-19 pandemic after 2020. Second, we identify the characteristics of the best-practice railway companies and examine the drivers of cost inefficiencies. Third, we analyze the factors influencing cost inefficiency by comparing the profiles of the top 10 railway companies and others before and during the pandemic. Finally, we examine the relationship between cost inefficiency and the implementation of efficiency measures for each railway company. We obtained the following four findings. First, most Japanese railway companies showed the lowest cost inefficiency (most efficient) in 2014 and the highest in 2020 (least efficient) during the COVID-19 pandemic. The second worst occurred in 2009 when it was affected by the financial crisis. However, we did not observe a significant impact of the 2011 Great East Japan Earthquake. This is because no railway company was influenced by the earthquake in this operating area, except for JR-EAST. Second, the best-practice railway companies are KEIO and TOKYU. The main reason for their good performance is that both operate in and near the Tokyo metropolitan area, which is densely populated. Third, we found that non-best-practice companies had a larger decrease in passenger kilometers than best-practice companies. This indicates that passengers made fewer long-distance trips because they refrained from inter-prefectural travel during the pandemic. Finally, we found that companies that implement more efficiency improvement measures had higher cost efficiency and they effectively used their customer databases through proactive DX investments in marketing and asset management.

Keywords: COVID-19 pandemic, stochastic frontier analysis, railway sector, cost efficiency

Procedia PDF Downloads 36

Authors: Mohammadjavad Sotoudeheian

Abstract:

Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

Procedia PDF Downloads 47

Authors: Nawal Alawad, Passent Ibrahim Tantawi, Mohamed Abdel Salam Ragheb

Abstract:

Providing customers with quality experiences has been confirmed to be a sustainable, competitive advantage with a distinct financial impact for companies. The success of service providers now relies on their ability to provide customer-centric services. The importance of perceived service quality and customer experience is widely recognized. The focus of this research is in the area of mobile and fixed broadband services. This study is of dual importance both academically and practically. Academically, this research applies a new model investigating the impact of customer experience quality on loyalty based on modifying the multiple-item scale for measuring customers’ service experience in a new area and did not depend on the traditional models. The integrated scale embraces four dimensions: service experience, outcome focus, moments of truth and peace of mind. In addition, it gives a scientific explanation for this relationship so this research fill the gap in such relations in which no one correlate or give explanations for these relations before using such integrated model and this is the first time to apply such modified and integrated new model in telecom field. Practically, this research gives insights to marketers and practitioners to improve customer loyalty through evolving the experience quality of broadband customers which is interpreted to suggested outcomes: purchase, commitment, repeat purchase and word-of-mouth, this approach is one of the emerging topics in service marketing. Data were collected through 412 questionnaires and analyzed by using structural equation modeling.Findings revealed that both outcome focus and moments of truth have a significant impact on loyalty while both service experience and peace of mind have insignificant impact on loyalty.In addition, it was found that 72% of the variation occurring in loyalty is explained by the model. The researcher also measured the net prompters score and gave explanation for the results. Furthermore, assessed customer’s priorities of broadband services. The researcher recommends that the findings of this research will extend to be considered in the future plans of Telecom Egypt Group. In addition, to be applied in the same industry especially in the developing countries that have the same circumstances with similar service settings. This research is a positive contribution in service marketing, particularly in telecom industry for making marketing more reliable as managers can relate investments in service experience directly with the performance closest to income for instance, repurchasing behavior, positive word of mouth and, commitment. Finally, the researcher recommends that future studies should consider this model to explain significant marketing outcomes such as share of wallet and ultimately profitability.

Keywords: broadband services, customer experience quality, loyalty, net promoters score

Procedia PDF Downloads 246

Authors: Kim Anema, Matthias Max, Chris Zevenbergen

Abstract:

For any flood risk manager the 'safety paradox' has to be a familiar concept: low probability leads to a sense of safety, which leads to more investments in the area, which leads to higher potential consequences: keeping the aggregated risk (probability*consequences) at the same level. Therefore, it is important to mitigate potential consequences apart from probability. However, when the (perceived) probability is so low that there is no recognizable trend for society to adapt to, addressing the potential consequences will always be the lagging point on the agenda. Preparedness programs fail because of lack of interest and urgency, policy makers are distracted by their day to day business and there's always a more urgent issue to spend the taxpayer's money on. The leading question in this study was how to address the social consequences of flooding in a context of (perceived) low probability. Disruptions of everyday urban life, large or small, can be caused by a variety of (un)expected things - of which flooding is only one possibility. Variability like this is typically addressed with resilience - and we used the concept of Community Resilience as the framework for this study. Drawing on face to face interviews, an extensive questionnaire and publicly available statistical data we explored the 'whole society response' to two recent urban flood events; the Brisbane Floods (AUS) in 2011 and the Dresden Floods (GE) in 2013. In Brisbane, we studied how the societal impacts of the floods were counteracted by both authorities and the public, and in Dresden we were able to validate our findings. A large part of the reactions, both public as institutional, to these two urban flood events were not fuelled by preparedness or proper planning. Instead, more important success factors in counteracting social impacts like demographic changes in neighborhoods and (non-)economic losses were dynamics like community action, flexibility and creativity from authorities, leadership, informal connections and a shared narrative. These proved to be the determining factors for the quality and speed of recovery in both cities. The resilience of the community in Brisbane was good, due to (i) the approachability of (local) authorities, (ii) a big group of ‘secondary victims’ and (iii) clear leadership. All three of these elements were amplified by the use of social media and/ or web 2.0 by both the communities and the authorities involved. The numerous contacts and social connections made through the web were fast, need driven and, in their own way, orderly. Similarly in Dresden large groups of 'unprepared', ad hoc organized citizens managed to work together with authorities in a way that was effective and speeded up recovery. The concept of community resilience is better fitted than 'social adaptation' to deal with the potential consequences of an (im)probable flood. Community resilience is built on capacities and dynamics that are part of everyday life and which can be invested in pre-event to minimize the social impact of urban flooding. Investing in these might even have beneficial trade-offs in other policy fields.

Keywords: community resilience, disaster response, social consequences, preparedness

Procedia PDF Downloads 331