Search results for: regulatory genes

Authors: Birge Yildirim Okta

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This paper aims to narrate the story of Atatürk Cultural Center in Taksim Square, which was demolished in 2018, and discuss its architectonic as a social place of memory and its existence and demolishment as the space of politics. Focusing on the timeline starting from early republican period till today, the paper uses narrative discourse analysis to research Atatürk Cultural Center as a place of memory and a space of politics in its existence. After the establishment of Turkish Republic, one of most important implementation in Taksim Square, reflecting the internationalist style, was the construction of Opera Building in Prost Plan. The first design of the opera building belonged to Aguste Perret, which could not be implemented due to economic hardship during World War II. Later the project was designed by architects Feridun Kip and Rüknettin Güney in 1946 but could not be completed due to 1960 military coup. Later the project was shifted to another architect Hayati Tabanlıoglu, with a change in its function as a cultural center. Eventually, the construction of the building was completed in 1969 in a completely different design. AKM became a symbol of republican modernism not only with its modern architectural style but also with it is function as the first opera building of the republic, reflecting the western, modern cultural heritage by professional groups, artists and the intelligentsia. In 2005, Istanbul’s council for the protection of cultural heritage decided to list AKM as a grade 1 cultural heritage, ending a period of controversy which saw calls for the demolition of the center as it was claimed it ended its useful lifespan. In 2008 the building was announced to be closed for repairs and restoration. Over the following years, the building was demolished piece by piece silently while Taksim mosque has been built just in front of Atatürk Cultural Center. Belonging to the early republican period, AKM was a representation of a cultural production of a modern society for the emergence and westward looking, secular public space in Turkey. Its erasure from Taksim scene under the rule of the conservative government, Justice and Development Party and the construction of Taksim mosque in front of AKM’s parcel is also representational. The question of governing the city through space has always been an important aspect for governments, those holding political power since cities are the chaotic environments that are seen as a threat for the governments, carrying the tensions of proletariat or the contradictory groups. The story of AKM as a dispositive or a regulatory apparatus demonstrates how space itself is becoming a political medium, to transform the socio-political condition. The article aims to discuss the existence and demolishment of Atatürk Cultural Center by discussing the constructed and demolished building as a place of memory and a space of politics.

Keywords: space of politics, place of memory, atatürk cultural center, taksim square

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Authors: Bikash Ranjan Mishra, Lopamudra D. Satpathy

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In the wake of the phenomenal surge in international business in the last decades or more, both the developed and developing economies around the world are in massive competition to attract more and more FDI flows. While the developed countries have marched ahead in the race, the developing countries, especially those of Asian economies, have followed them at a rapid pace. While most of the previous studies have analysed the role of institutional quality in the promotion of FDI flows in developing countries, very few studies have taken an integrated approach of examining the comprehensive impact of institutional quality, globalization pattern and domestic financial development on FDI flows. In this context, the paper contributes to the literature in two important ways. Firstly, two composite indices of institutional quality and domestic financial development for the Asian countries are constructed in comparison to earlier studies that resort to a single variable for indicating the institutional quality and domestic financial development. Secondly, the impact of these variables on FDI flows through their interaction with geographical region is investigated. The study uses panel data covering the time period of 1996 to 2012 by selecting twenty Asian developing countries by emphasizing the quality of institutions from the geographical regions of eastern, south-eastern, southern and western Asia. Control of corruption, better rule of law, regulatory quality, effectiveness of the government, political stability and voice and accountability are used as indicators of institutional quality. Besides these, the study takes into account the domestic credits in the hands of public, private sectors and in stock markets as domestic financial indicators. First in the specification of model, a factor analysis is performed to reduce the vast determinants, which are highly correlated with each other, to a manageable size. Afterwards, a reduced version of the model is estimated with the extracted factors in the form of index as independent variables along with a set of control variables. It is found that the institutional quality index and index of globalization exert a significant effect on FDI inflows of the host countries; in contrast, the domestic financial index does not seem to play much worthy role. Finally, some robustness tests are performed to make sure that the results are not sensitive to temporal and spatial unobserved heterogeneity. On the basis of the above study, one general inference can be drawn from the policy prescription point of view that the government of these developing countries should strengthen their domestic institution, both financial and non-financial. In addition to these, welfare policies should also target for rapid globalization. If the financial and non-financial institutions of these developing countries become sound and grow more globalized in the economic, social and political domain, then they can appeal to more amounts of FDI inflows that will subsequently result in advancement of these economies.

Keywords: Asian developing economies, FDI, institutional quality, panel data

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Authors: Moien Mojabi, Aurelien Hospital, Daniel Potts, Chris Young, Albert Leung

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The wave analysis is an integral part of the hydrotechnical assessment carried out during the permitting and design phases for coastal structures, such as marinas. This analysis aims in quantifying: i) the Suitability of the coastal structure design against Small Craft Harbour wave tranquility safety criterion; ii) Potential environmental impacts of the structure (e.g., effect on wave, flow, and sediment transport); iii) Mooring and dock design and iv) Requirements set by regulatory agency’s (e.g., WSA section 11 application). While a complex three-dimensional hydrodynamic modelling approach can be applied on large-scale projects, the need for an efficient and reliable wave analysis method suitable for smaller scale marina projects was identified. As a result, Tetra Tech has developed and applied an integrated analysis framework (hereafter TT approach), which takes the advantage of the state-of-the-art numerical models while preserving the level of simplicity that fits smaller scale projects. The present paper aims to describe the TT approach and highlight the key advantages of using this integrated framework in lake marina projects. The core of this methodology is made by integrating wind, water level, bathymetry, and structure geometry data. To respond to the needs of specific projects, several add-on modules have been added to the core of the TT approach. The main advantages of this method over the simplified analytical approaches are i) Accounting for the proper physics of the lake through the modelling of the entire lake (capturing real lake geometry) instead of a simplified fetch approach; ii) Providing a more realistic representation of the waves by modelling random waves instead of monochromatic waves; iii) Modelling wave-structure interaction (e.g. wave transmission/reflection application for floating structures and piles amongst others); iv) Accounting for wave interaction with the lakebed (e.g. bottom friction, refraction, and breaking); v) Providing the inputs for flow and sediment transport assessment at the project site; vi) Taking in consideration historical and geographical variations of the wind field; and vii) Independence of the scale of the reservoir under study. Overall, in comparison with simplified analytical approaches, this integrated framework provides a more realistic and reliable estimation of wave parameters (and its spatial distribution) in lake marinas, leading to a realistic hydrotechnical assessment accessible to any project size, from the development of a new marina to marina expansion and pile replacement. Tetra Tech has successfully utilized this approach since many years in the Okanagan area.

Keywords: wave modelling, wind-wave, extreme value analysis, marina

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Authors: Sofia Papadimitriou

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INTRODUCTION: The differential diagnosis between acute viral and bacterial infections is an important cost-effectiveness parameter at the stage of the treatment process in order to achieve the maximum benefits in therapeutic intervention by combining the minimum cost to ensure the proper use of antibiotics.The discovery of sensitive and robust molecular diagnostic tests in response to the role of the host in infections has enhanced the accurate diagnosis and differentiation of infections. METHOD: The study used a sample of six independent blood samples (total=756) which are associated with human proteins-proteins, each of which at the transcription stage expresses a different response in the host network between viral and bacterial infections.Τhe individual blood samples are subjected to a sequence of computer filters that identify a gene panel corresponding to an autonomous diagnostic score. The data set and the correspondence of the gene panel to the diagnostic patents a new Bangalore -Viral Bacterial (BL-VB). FINDING: We use a biomarker based on the blood of 10 genes(Panel-VB) that are an important prognostic value for the detection of viruses from bacterial infections with a weighted average AUROC of 0.97(95% CL:0.96-0.99) in eleven independent samples (sets n=898). We discovered a base with a patient score (VB 10 ) according to the table, which is a significant diagnostic value with a weighted average of AUROC 0.94(95% CL: 0.91-0.98) in 2996 patient samples from 56 public sets of data from 19 different countries. We also studied VB 10 in a new cohort of South India (BL-VB,n=56) and found 97% accuracy in confirmed cases of viral and bacterial infections. We found that VB 10 (a)accurately identifies the type of infection even in unspecified cases negative to the culture (b) shows its clinical condition recovery and (c) applies to all age groups, covering a wide range of acute bacterial and viral infectious, including non-specific pathogens. We applied our VB 10 rating to publicly available COVID 19 data and found that our rating diagnosed viral infection in patient samples. RESULTS: Τhe results of the study showed the diagnostic power of the biomarker VB 10 as a diagnostic test for the accurate diagnosis of acute infections in recovery conditions. We look forward to helping you make clinical decisions about prescribing antibiotics and integrating them into your policies management of antibiotic stewardship efforts. CONCLUSIONS: Overall, we are developing a new property of the RNA-based biomarker and a new blood test to differentiate between viral and bacterial infections to assist a physician in designing the optimal treatment regimen to contribute to the proper use of antibiotics and reduce the burden on antimicrobial resistance, AMR.

Keywords: acute infections, antimicrobial resistance, biomarker, blood transcriptome, systems biology, classifier diagnostic score

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Authors: Laura Helena Caicedo Lopez, Luis Miguel Contreras Medina, Ramon Gerardo Guevara Gonzales, Juan E. Andrade

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In this study, we evaluated the effect of three different hydric stress conditions: Low (LHS), medium (MHS), and high (HHS) on capsaicinoid content and enzyme regulation of C. annuum plants. Five main peaks were detected using a 2 Hz resolution vibrometer laser (Polytec-B&K). These peaks or “characteristic frequencies” were used as acoustic emissions (AEs) treatment, transforming these signals into audible sound with the frequency (Hz) content of each hydric stress. Capsaicinoids (CAPs) are the main, secondary metabolites of chili pepper plants and are known to increase during hydric stress conditions or short drought-periods. The AEs treatments were applied in two plant stages: the first one was in the pre-anthesis stage to evaluate the genes that encode the transcription of enzymes responsible for diverse metabolic activities of C. annuum plants. For example, the antioxidant responses such as peroxidase (POD), superoxide dismutase (Mn-SOD). Also, phenyl-alanine ammonia-lyase (PAL) involved in the biosynthesis of the phenylpropanoid compounds. The chalcone synthase (CHS) related to the natural defense mechanisms and species-specific aquaporin (CAPIP-1) that regulate the flow of water into and out of cells. The second stage was at 40 days after flowering (DAF) to evaluate the biochemical effect of AEs related to hydric stress on capsaicinoids production. These two experiments were conducted to identify the molecular responses of C. annuum plants to AE. Moreover, to define AEs could elicit any increase in the capsaicinoids content after a one-week exposition to AEs treatments. The results show that all AEs treatment signals (LHS, MHS, and HHS) were significantly different compared to the non-acoustic emission control (NAE). Also, the AEs induced the up-regulation of POD (~2.8, 2.9, and 3.6, respectively). The gene expression of another antioxidant response was particularly treatment-dependent. The HHS induced and overexpression of Mn-SOD (~0.23) and PAL (~0.33). As well, the MHS only induced an up-regulation of the CHs gene (~0.63). On the other hand, CAPIP-1 gene gas down-regulated by all AEs treatments LHS, MHS, and HHS ~ (-2.4, -0.43 and -6.4, respectively). Likewise, the down-regulation showed particularities depending on the treatment. LHS and MHS induced downregulation of the SOD gene ~ (-1.26 and -1.20 respectively) and PAL (-4.36 and 2.05, respectively). Correspondingly, the LHS and HHS showed the same tendency in the CHs gene, respectively ~ (-1.12 and -1.02, respectively). Regarding the elicitation effect of AE on the capsaicinoids content, additional treatment controls were included. A white noise treatment (WN) to prove the frequency-selectiveness of signals and a hydric stressed group (HS) to compare the CAPs content. Our findings suggest that WN and NAE did not present differences statically. Conversely, HS and all AEs treatments induced a significant increase of capsaicin (Cap) and dihydrocapsaicin (Dcap) after one-week of a treatment. Specifically, the HS plants showed an increase of 8.33 times compared to the NAE and WN treatments and 1.4 times higher than the MHS, which was the AEs treatment with a larger induction of Capsaicinoids among treatments (5.88) and compared to the controls.

Keywords: acoustic emission, capsaicinoids, elicitors, hydric stress, plant signaling

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Authors: Pavitra Sharma, Anuradha Singh, Nupur Mathur

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There exist more than 100 trillion bacteria in the digestive system of human-beings. Such bacteria are referred to as gut microbiota. Gut microbiota comprises around 75% of our immune system. The bacteria that comprise the gut microbiota are unique to every individual and their composition keeps changing with time owing to factors such as the host’s age, diet, genes, environment, and external medication. Of these factors, the variable easiest to control is one’s diet. By modulating one’s diet, one can ensure an optimal composition of the gut microbiota yielding several health benefits. Prebiotics and probiotics are two compounds that have been considered as viable options to modulate the host’s diet. Prebiotics are basically plant products that support the growth of good bacteria in the host’s gut. Examples include garden asparagus, aloe vera etc. Probiotics are living microorganisms that exist in our intestines and play an integral role in promoting digestive health and supporting our immune system in general. Examples include yogurt, kimchi, kombucha etc. In the context of modulating the host’s diet, the key attribute of prebiotics is that they support the growth of probiotics. By developing the right combination of prebiotics and probiotics, food products or supplements can be created to enhance the host’s health. An effective combination of prebiotics and probiotics that yields health benefits to the host is referred to as synbiotics. Synbiotics comprise of an optimal proportion of prebiotics and probiotics, their application benefits the host’s health more than the application of prebiotics and probiotics used in isolation. When applied to food supplements, synbiotics preserve the beneficial probiotic bacteria during storage period and during the bacteria’s passage through the intestinal tract. When applied to the gastrointestinal tract, the composition of the synbiotics assumes paramount importance. Reason being that for synbiotics to be effective in the gastrointestinal tract, the chosen probiotic must be able to survive in the stomach’s acidic environment and manifest tolerance towards bile and pancreatic secretions. Further, not every prebiotic stimulates the growth of a particular probiotic. The prebiotic chosen should be one that not only maintains 2 balance in the host’s digestive system, but also provides the required nutrition to probiotics. Hence in each application of synbiotics, the prebiotic-probiotic combination needs to be carefully selected. Once the combination is finalized, the exact proportion of prebiotics and probiotics to be used needs to be considered. When determining this proportion, only that amount of a prebiotic should be used that activates metabolism of the required number of probiotics. It was observed that while probiotics are active is both the small and large intestine, the effect of prebiotics is observed primarily in the large intestine. Hence in the host’s small intestine, synbiotics are likely to have the maximum efficacy. In small intestine, prebiotics not only assist in the growth of probiotics, but they also enable probiotics to exhibit a higher tolerance to pH levels, oxygenation, and intestinal temperature

Keywords: microbiota, probiotics, prebiotics, synbiotics

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Authors: A. Ramachandra Reddy, V. Murugan, Prema Kumari

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Residual solvents in Pharmaceutical samples are monitored using gas chromatography with headspace (GC-HS). Based on current regulatory and compendial requirements, measuring the residual solvents are mandatory for all release testing of active pharmaceutical ingredients (API). Generally, isopropyl alcohol is used as the residual solvent in proline and tryptophan; methanol in cysteine monohydrate hydrochloride, glycine, methionine and serine; ethanol in glycine and lysine monohydrate; acetic acid in methionine. In order to have a single method for determining these residual solvents (isopropyl alcohol, ethanol, methanol and acetic acid) in all these 7 amino acids a sensitive and simple method was developed by using gas chromatography headspace technique with flame ionization detection. During development, no reproducibility, retention time variation and bad peak shape of acetic acid peaks were identified due to the reaction of acetic acid with the stationary phase (cyanopropyl dimethyl polysiloxane phase) of column and dissociation of acetic acid with water (if diluent) while applying temperature gradient. Therefore, dimethyl sulfoxide was used as diluent to avoid these issues. But most the methods published for acetic acid quantification by GC-HS uses derivatisation technique to protect acetic acid. As per compendia, risk-based approach was selected as appropriate to determine the degree and extent of the validation process to assure the fitness of the procedure. Therefore, Total error concept was selected to validate the analytical procedure. An accuracy profile of ±40% was selected for lower level (quantitation limit level) and for other levels ±30% with 95% confidence interval (risk profile 5%). The method was developed using DB-Waxetr column manufactured by Agilent contains 530 µm internal diameter, thickness: 2.0 µm, and length: 30 m. A constant flow of 6.0 mL/min. with constant make up mode of Helium gas was selected as a carrier gas. The present method is simple, rapid, and accurate, which is suitable for rapid analysis of isopropyl alcohol, ethanol, methanol and acetic acid in amino acids. The range of the method for isopropyl alcohol is 50ppm to 200ppm, ethanol is 50ppm to 3000ppm, methanol is 50ppm to 400ppm and acetic acid 100ppm to 400ppm, which covers the specification limits provided in European pharmacopeia. The accuracy profile and risk profile generated as part of validation were found to be satisfactory. Therefore, this method can be used for testing of residual solvents in amino acids drug substances.

Keywords: amino acid, head space, gas chromatography, total error

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Authors: Anita Richter

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Innovation is one of the key foundations of competitive advantage, generating growth and welfare worldwide. Consequently, all firms should innovate to bring new ideas to the market. Innovation is a vital growth driver, particularly for transition countries to move towards knowledge-based, high-income economies. However, numerous barriers, such as financial, regulatory or infrastructural constraints prevent, in particular, new and small firms in transition countries from innovating. Thus SMEs’ innovation output may benefit substantially from government support. This research paper aims to assess the effect of government interventions on innovation activities in SMEs in emerging countries. Until now academic research related to the innovation policies focused either on single country and/or high-income countries assessments and less on cross-country and/or low and middle-income countries. Therefore the paper seeks to close the research gap by providing empirical evidence from 8,500 firms in 15 transition countries (Eastern Europe, South Caucasus, South East Europe, Middle East and North Africa). Using firm-level data from the Business Environment and Enterprise Performance Survey of the World Bank and EBRD and policy data from the SME Policy Index of the OECD, the paper investigates how government interventions affect SME’s likelihood of investing in any technological and non-technological innovation. Using the Standard Linear Regression, the impact of government interventions on SMEs’ innovation output and R&D activities is measured. The empirical analysis suggests that a firm’s decision to invest into innovative activities is sensitive to government interventions. A firm’s likelihood to invest into innovative activities increases by 3% to 8%, if the innovation eco-system noticeably improves (measured by an increase of 1 level in the SME Policy Index). At the same time, a better eco-system encourages SMEs to invest more in R&D. Government reforms in establishing a dedicated policy framework (IP legislation), institutional infrastructure (science and technology parks, incubators) and financial support (public R&D grants, innovation vouchers) are particularly relevant to stimulate innovation performance in SMEs. Particular segments of the SME population, namely micro and manufacturing firms, are more likely to benefit from an increased innovation framework conditions. The marginal effects are particularly strong on product innovation, process innovation, and marketing innovation, but less on management innovation. In conclusion, government interventions supporting innovation will likely lead to higher innovation performance of SMEs. They increase productivity at both firm and country level, which is a vital step in transitioning towards knowledge-based market economies.

Keywords: innovation, research and development, government interventions, economic development, small and medium-sized enterprises, transition countries

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Authors: Aziz Ikhlef

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Most of multi-slices CT scanners are built with detectors composed of scintillator - photodiodes arrays. The photodiodes arrays are mainly based on front-illuminated technology for detectors under 64 slices and on back-illuminated photodiode for systems of 64 slices or more. The designs based on back-illuminated photodiodes were being investigated for CT machines to overcome the challenge of the higher number of runs and connection required in front-illuminated diodes. In backlit diodes, the electronic noise has already been improved because of the reduction of the load capacitance due to the routing reduction. This translated by a better image quality in low signal application, improving low dose imaging in large patient population. With the fast development of multi-detector-rows CT (MDCT) scanners and the increasing number of examinations, the clinical community has raised significant concerns on radiation dose received by the patient in both medical and regulatory community. In order to reduce individual exposure and in response to the recommendations of the International Commission on Radiological Protection (ICRP) which suggests that all exposures should be kept as low as reasonably achievable (ALARA), every manufacturer is trying to implement strategies and solutions to optimize dose efficiency and image quality based on x-ray emission and scanning parameters. The added demands on the CT detector performance also comes from the increased utilization of spectral CT or dual-energy CT in which projection data of two different tube potentials are collected. One of the approaches utilizes a technology called fast-kVp switching in which the tube voltage is switched between 80kVp and 140kVp in fraction of a millisecond. To reduce the cross-contamination of signals, the scintillator based detector temporal response has to be extremely fast to minimize the residual signal from previous samples. In addition, this paper will present an overview of detector technologies and image chain improvement which have been investigated in the last few years to improve the signal-noise ratio and the dose efficiency CT scanners in regular examinations and in energy discrimination techniques. Several parameters of the image chain in general and in the detector technology contribute in the optimization of the final image quality. We will go through the properties of the post-patient collimation to improve the scatter-to-primary ratio, the scintillator material properties such as light output, afterglow, primary speed, crosstalk to improve the spectral imaging, the photodiode design characteristics and the data acquisition system (DAS) to optimize for crosstalk, noise and temporal/spatial resolution.

Keywords: computed tomography, X-ray detector, medical imaging, image quality, artifacts

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Authors: Chang Liu, Rui Xing, Liyan Tang, Guohong Wang

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Entrepreneurial actions are based on entrepreneurial decisions. The quality of decisions influences entrepreneurial activities and subsequent new venture performance. Uncertainty of surroundings put heightened demands on the team as a whole, and each team member. Diverse team composition provides rich information, which a team can draw when making complex decisions. However, team heterogeneity may cause emotional conflicts, which is adverse to team outcomes. Thus, the effects of team heterogeneity on team outcomes are complex. Although team heterogeneity is an essential factor influencing entrepreneurial decision-making, there is a lack of empirical analysis on under what conditions team heterogeneity plays a positive role in promoting decision-making quality. Entrepreneurial teams always struggle with complex tasks. How a team shapes its teamwork is key in resolving constant issues. As a collective regulatory process, team reflexivity is characterized by continuous joint evaluation and discussion of team goals, strategies, and processes, and adapt them to current or anticipated circumstances. It enables diversified information to be shared and overtly discussed. Instead of hostile interpretation of opposite opinions team members take them as useful insights from different perspectives. Team reflexivity leads to better integration of expertise to avoid the interference of negative emotions and conflict. Therefore, we propose that team reflexivity is a conditional factor that influences the impact of team heterogeneity on high-quality entrepreneurial decisions. In this study, we identify team heterogeneity as a crucial determinant of entrepreneurial decision quality. Integrating the literature on decision-making and team heterogeneity, we investigate the relationship between team heterogeneity and entrepreneurial decision-making quality, treating team reflexivity as a moderator. We tested our hypotheses using the hierarchical regression method and the data gathered from 63 teams and 205 individual members from 45 new firms in China's first-tier cities such as Beijing, Shanghai, and Shenzhen. This research found that both teams' education heterogeneity and teams' functional background heterogeneity were significantly positively related to entrepreneurial decision-making quality, and the positive relation was stronger in teams with a high level of team reflexivity. While teams' specialization of education heterogeneity was negatively related to decision-making quality, and the negative relationship was weaker in teams with a high level of team reflexivity. We offer two contributions to decision-making and entrepreneurial team literatures. Firstly, our study enriches the understanding of the role of entrepreneurial team heterogeneity in entrepreneurial decision-making quality. Different from previous entrepreneurial decision-making literatures, which focus more on decision-making modes of entrepreneurs and the top management team, this study is a significant attempt to highlight that entrepreneurial team heterogeneity makes a unique contribution to generating high-quality entrepreneurial decisions. Secondly, this study introduced team reflexivity as the moderating variable, to explore the boundary conditions under which the entrepreneurial team heterogeneity play their roles.

Keywords: decision-making quality, entrepreneurial teams, education heterogeneity, functional background heterogeneity, specialization of education heterogeneity

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Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari

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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.

Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration

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Authors: Merab Khokhobaia

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The research of Georgian tourism policy challenges is important, as the tourism can play an increasing role for the economic growth and improvement of standard of living of the country even with scanty resources, at the expense of improved creative approaches. It is also important to make correct decisions at macroeconomic level, which will be accordingly reflected in the successful functioning of the travel companies and finally, in the improvement of economic indicators of the country. In order to correctly orient sectoral policy, it is important to precisely determine its role in the economy. Development of travel industry has been considered as one of the priorities in Georgia; the country has unique cultural heritage and traditions, as well as plenty of natural resources, which are a significant precondition for the development of tourism. Despite the factors mentioned above, the existing resources are not completely utilized and exploited. This work represents a study of subjective, as well as objective reasons of ineffective functioning of the sector. During the years of transformation experienced by Georgia, the role of travel industry in economic development of the country represented the subject of continual discussions. Such assessments were often biased and they did not rest on specific calculations. This topic became especially popular on the ground of market economy, because reliable statistical data have a particular significance in the designing of tourism policy. In order to deeply study the aforementioned issue, this paper analyzes monetary, as well as non-monetary indicators. The research widely included the tourism indicators system; we analyzed the flaws in reporting of the results of tourism sector in Georgia. Existing defects are identified and recommendations for their improvement are offered. For stable development tourism, similarly to other economic sectors, needs a well-designed policy from the perspective of national, as well as local, regional development. The tourism policy must be drawn up in order to efficiently achieve our goals, which were established in short-term and long-term dynamics on the national or regional scale of specific country. The article focuses on the role and responsibility of the state institutes in planning and implementation of the tourism policy. The government has various tools and levers, which may positively influence the processes. These levers are especially important in terms of international, as well as internal tourism development. Within the framework of this research, the regulatory documents, which are in force in relation to this industry, were also analyzed. The main attention is turned to their modernization and necessity of their compliance with European standards. It is a current issue to direct the efforts of state policy on support of business by implementing infrastructural projects, as well as by development of human resources, which may be possible by supporting the relevant higher and vocational studying-educational programs.

Keywords: regional development, tourism industry, tourism policy, transition

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Authors: Sarah J. C. Slabbert

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The uptake of research as part of the diffusion or adoption of innovation by practitioners, whether individuals or organisations, has been a popular topic in agricultural development studies for many decades. In the classical, linear model of innovation theory, the innovation originates from an expert source such as a state-supported research organisation or academic institution. The changing context of agriculture led to the development of the agricultural innovation systems model, which recognizes innovation as a complex interaction between individuals and organisations, which include private industry and collective action organisations. In terms of this model, an innovation can be developed and adopted without any input or intervention from a state or parastatal research organisation. This evolution in the diffusion of agricultural innovation has put forward new challenges for state or parastatal research organisations, which have to demonstrate the impact of their research to the legislature or a regulatory authority: Unless the organisation and the research it produces cross the knowledge paths of the intended audience, there will be no awareness, no uptake and certainly no impact. It is therefore critical for such a research organisation to base its communication strategy on a thorough understanding of the knowledge needs, information sources and knowledge networks of the intended target audience. In 2016, the South African Water Research Commission (WRC) commissioned a study to investigate the knowledge needs, information sources and knowledge networks of Water User Associations and commercial irrigators with the aim of improving uptake of its research on efficient water use in irrigation. The first phase of the study comprised face-to-face interviews with the CEOs and Board Chairs of four Water User Associations along the Orange River in South Africa, and 36 commercial irrigation farmers from the same four irrigation schemes. Intermediaries who act as knowledge conduits to the Water User Associations and the irrigators were identified and 20 of them were subsequently interviewed telephonically. The study found that irrigators interact regularly with grower organisations such as SATI (South African Table Grape Industry) and SAPPA (South African Pecan Nut Association) and that they perceive these organisations as credible, trustworthy and reliable, within their limitations. State and parastatal research institutions, on the other hand, are associated with a range of negative attributes. As a result, the awareness of, and interest in, the WRC and its research on water use efficiency in irrigated agriculture are low. The findings suggest that a communication strategy that involves collaboration with these grower organisations would empower the WRC to participate much more efficiently and with greater impact in agricultural innovation networks. The paper will elaborate on the findings and discuss partnering frameworks and opportunities to manage perceptions and uptake.

Keywords: agricultural innovation systems, communication strategy, diffusion of innovation, irrigated agriculture, knowledge paths, research organisations, target audiences, water use efficiency

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Authors: Stephanie Gracelyn Rahaman, Chew Yin Teng, Manjit Singh Sandhu

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Corporate scandals have made stakeholders apprehensive of large companies and expect greater transparency in CSR matters. However, companies find it challenging to strategically communicate CSR to intended stakeholders and in the process may fall short on maximizing on CSR efforts. Given that stakeholders have the ability to either reward good companies or take legal action or boycott against corporate brands who do not act socially responsible, companies must create shared understanding of their CSR activities. As a result, communication has become a strategy for many companies to demonstrate CSR engagement and to minimize stakeholder skepticism. The main objective of this research is to examine the types of CSR communication strategies and predictors that guide CSR communication strategies. Employing Morsing & Schultz’s guide on CSR communication strategies, the study integrates stakeholder and institutional theory to develop a conceptual framework. The conceptual framework hypothesized that stakeholder (instrumental and normative) and institutional (regulatory environment, nature of business, mimetic intention, CSR focus and corporate objectives) dimensions would drive CSR communication strategies. Preliminary findings from semi-structured interviews in Malaysia are consistent with the conceptual model in that stakeholder and institutional expectations guide CSR communication strategies. Findings show that most companies use two-way communication strategies. Companies that identified employees, the public or customers as key stakeholders have started to embrace social media to be in-sync with new trends of communication. This is especially with the Gen Y which is their priority. Some companies creatively use multiple communication channels because they recognize different stakeholders favor different communication channels. Therefore, it appears that companies use two-way communication strategies to complement the perceived limitation of one-way communication strategies as some companies prefer a more interactive platform to strategically engage stakeholders in CSR communication. In addition to stakeholders, institutional expectations also play a vital role in influencing CSR communication. Due to industry peer pressures, corporate objectives (attract international investors and customers), companies may be more driven to excel in social performance. For these reasons companies tend to go beyond the basic mandatory requirement, excel in CSR activities and be known as companies that champion CSR. In conclusion, companies use more two-way than one-way communication and companies use a combination of one and two-way communication to target different stakeholders resulting from stakeholder and institutional dimensions. Finally, in order to find out if the conceptual framework actually fits the Malaysian context, companies’ responses for expected organizational outcomes from communicating CSR were gathered from the interview transcripts. Thereafter, findings are presented to show some of the key organizational outcomes (visibility and brand recognition, portray responsible image, attract prospective employees, positive word-of-mouth, etc.) that companies in Malaysia expect from CSR communication. Based on these findings the conceptual framework has been refined to show the new identified organizational outcomes.

Keywords: CSR communication, CSR communication strategies, stakeholder theory, institutional theory, conceptual framework, Malaysia

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Authors: Ghita Benayad

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Asset allocation, which affects the long-term profitability of portfolios by distributing assets to fulfill a range of investment objectives, is the cornerstone of investment management in the dynamic and complicated world of financial markets. This paper offers a technique for optimizing strategic asset allocation with the goal of improving portfolio performance by addressing the inherent complexity and uncertainty of the market through the use of Principal Component Analysis (PCA) in a multi-objective modeling framework. The study's first section starts with a critical evaluation of conventional asset allocation techniques, highlighting how poorly they are able to capture the intricate relationships between assets and the volatile nature of the market. In order to overcome these challenges, the project suggests a PCA-driven methodology that isolates important characteristics influencing asset returns by decreasing the dimensionality of the investment universe. This decrease provides a stronger basis for asset allocation decisions by facilitating a clearer understanding of market structures and behaviors. Using a multi-objective optimization model, the project builds on this foundation by taking into account a number of performance metrics at once, including risk minimization, return maximization, and the accomplishment of predetermined investment goals like regulatory compliance or sustainability standards. This model provides a more comprehensive understanding of investor preferences and portfolio performance in comparison to conventional single-objective optimization techniques. While applying the PCA-driven multi-objective optimization model to historical market data, aiming to construct portfolios better under different market situations. As compared to portfolios produced from conventional asset allocation methodologies, the results show that portfolios optimized using the proposed method display improved risk-adjusted returns, more resilience to market downturns, and better alignment with specified investment objectives. The study also looks at the implications of this PCA technique for portfolio management, including the prospect that it might give investors a more advanced framework for navigating financial markets. The findings suggest that by combining PCA with multi-objective optimization, investors may obtain a more strategic and informed asset allocation that is responsive to both market conditions and individual investment preferences. In conclusion, this capstone project improves the field of financial engineering by creating a sophisticated asset allocation optimization model that integrates PCA with multi-objective optimization. In addition to raising concerns about the condition of asset allocation today, the proposed method of portfolio management opens up new avenues for research and application in the area of investment techniques.

Keywords: asset allocation, portfolio optimization, principle component analysis, multi-objective modelling, financial market

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Authors: Farouq Sule Garo, Yahaya Yusuf

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The purpose of this study is to investigate why there is a general lack of successful adoption of sustainable energy in Nigeria. This is particularly important given the current global campaign for net-zero emissions. The 26th United Nations Conference of the Parties (COP26), held in 2021, was hosted by the UK, in Glasgow, where, amongst other things, countries including Nigeria agreed to a zero emissions pact. There is, therefore, an obligation on the part of Nigeria for transition from fossil fuel-based economy to a sustainable net-zero emissions economy. The adoption of renewable energy is fundamental to achieving this ambitious target if decarbonisation of economic activities were to become a reality. Nigeria has an abundance of sources of renewable energy and yet there has been poor uptake and where attempts have been made to develop and harness renewable energy resources, there has been limited success. It is not entirely clear why this is the case. When analysts allude to corruption as the reason for failure for successful adoption of renewable energy or project implementation, it is arguable that corruption alone cannot explain the situation. Therefore, there is the need for a thorough investigation into the underlying issues surrounding poor uptake of renewable energy in Nigeria. This pilot study, drawing upon stakeholders’ theory, adopts a multi-stakeholder’ perspectives to investigate the influence and impacts of economic, political, technological, social factors in adoption of renewable energy in Nigeria. The research will also investigate how these factors shape (or fail to shape) strategies for achieving successful adoption of renewable energy in the country. A qualitative research methodology has been adopted given the nature of the research requiring in-depth studies in specific settings rather than a general population survey. There will be a number of interviews and each interview will allow thorough probing of sources. This, in addition to the six interviews that have already been conducted, primarily focused on economic dimensions of the challenges in adoption of renewable energy. The six participants in these initial interviews were all connected to the Katsina Wind Farm Project that was conceived and built with the view to diversifying Nigeria's energy mix and capitalise on the vast wind energy resources in the northern region. The findings from the six interviews provide insights into how the economic factors impacts on the wind farm project. Some key drivers have been identified, including strong governmental support and the recognition of the need for energy diversification. These drivers have played crucial roles in initiating and advancing the Katsina Wind Farm Project. In addition, the initial analysis has highlighted various challenges encountered during the project's implementation, including financial, regulatory, and environmental aspects. These challenges provide valuable lessons that can inform strategies to mitigate risks and improve future wind energy projects.

Keywords: challenges in adoption of renewable energy, economic factors, net-zero emission, political factors

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Authors: Aziz Ikhlef

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Most of multi-slices Computed Tomography (CT) scanners are built with detectors composed of scintillator - photodiodes arrays. The photodiodes arrays are mainly based on front-illuminated technology for detectors under 64 slices and on back-illuminated photodiode for systems of 64 slices or more. The designs based on back-illuminated photodiodes were being investigated for CT machines to overcome the challenge of the higher number of runs and connection required in front-illuminated diodes. In backlit diodes, the electronic noise has already been improved because of the reduction of the load capacitance due to the routing reduction. This is translated by a better image quality in low signal application, improving low dose imaging in large patient population. With the fast development of multi-detector-rows CT (MDCT) scanners and the increasing number of examinations, the clinical community has raised significant concerns on radiation dose received by the patient in both medical and regulatory community. In order to reduce individual exposure and in response to the recommendations of the International Commission on Radiological Protection (ICRP) which suggests that all exposures should be kept as low as reasonably achievable (ALARA), every manufacturer is trying to implement strategies and solutions to optimize dose efficiency and image quality based on x-ray emission and scanning parameters. The added demands on the CT detector performance also comes from the increased utilization of spectral CT or dual-energy CT in which projection data of two different tube potentials are collected. One of the approaches utilizes a technology called fast-kVp switching in which the tube voltage is switched between 80 kVp and 140 kVp in fraction of a millisecond. To reduce the cross-contamination of signals, the scintillator based detector temporal response has to be extremely fast to minimize the residual signal from previous samples. In addition, this paper will present an overview of detector technologies and image chain improvement which have been investigated in the last few years to improve the signal-noise ratio and the dose efficiency CT scanners in regular examinations and in energy discrimination techniques. Several parameters of the image chain in general and in the detector technology contribute in the optimization of the final image quality. We will go through the properties of the post-patient collimation to improve the scatter-to-primary ratio, the scintillator material properties such as light output, afterglow, primary speed, crosstalk to improve the spectral imaging, the photodiode design characteristics and the data acquisition system (DAS) to optimize for crosstalk, noise and temporal/spatial resolution.

Keywords: computed tomography, X-ray detector, medical imaging, image quality, artifacts

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Authors: Sijie Chen, Xiaofang Chen, Juan Wang, Yingying Zhang, Yu Hong, Wanyu Zhuang, Xinxin Huang, Ping Ou, Longsheng Huang

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Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex(PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n=8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membran, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity and promoting neuronal signal transduction.

Keywords: autism spectrum disorder, acupuncture, animal behavior, RNA sequencing, transmission electron microscope

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Authors: Sanjeev Kumar Appicharla

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This paper presents the results of the modelling and analysis of the European Railway Traffic Management (ERTMS) safety-critical incident to raise awareness of biases in the systems engineering process on the Cambrian Railway in the UK using the RAIB 17/2019 as a primary input. The RAIB, the UK independent accident investigator, published the Report- RAIB 17/2019 giving the details of their investigation of the focal event in the form of immediate cause, causal factors, and underlying factors and recommendations to prevent a repeat of the safety-critical incident on the Cambrian Line. The Systems for Investigation of Railway Interfaces (SIRI) is the methodology used to model and analyze the safety-critical incident. The SIRI methodology uses the Swiss Cheese Model to model the incident and identify latent failure conditions (potentially less than adequate conditions) by means of the management oversight and risk tree technique. The benefits of the systems for investigation of railway interfaces methodology (SIRI) are threefold: first is that it incorporates the “Heuristics and Biases” approach advanced by 2002 Nobel laureate in Economic Sciences, Prof Daniel Kahneman, in the management oversight and risk tree technique to identify systematic errors. Civil engineering and programme management railway professionals are aware of the role “optimism bias” plays in programme cost overruns and are aware of bow tie (fault and event tree) model-based safety risk modelling techniques. However, the role of systematic errors due to “Heuristics and Biases” is not appreciated as yet. This overcomes the problems of omission of human and organizational factors from accident analysis. Second, the scope of the investigation includes all levels of the socio-technical system, including government, regulatory, railway safety bodies, duty holders, signaling firms and transport planners, and front-line staff such that lessons are learned at the decision making and implementation level as well. Third, the author’s past accident case studies are supplemented with research pieces of evidence drawn from the practitioner's and academic researchers’ publications as well. This is to discuss the role of system thinking to improve the decision-making and risk management processes and practices in the IEC 15288 systems engineering standard and in the industrial context such as the GB railways and artificial intelligence (AI) contexts as well.

Keywords: accident analysis, AI algorithm internal audit, bounded rationality, Byzantine failures, heuristics and biases approach

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Authors: Juan Peña Aguilar, Lilia Villasana, Rodrigo Valencia, Alberto Pastrana, Martin Vivanco, Juan Peña C

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Each year a growing number of companies entering Mexico in search of the domestic market share. These activities, including stores, telephone long distance and local raw materials and energy, and particularly the financial sector, have managed to significantly increase its weight in the flows of FDI in Mexico , however, you should consider whether these trends FDI are positive for the Mexican economy and these activities increase Mexican exports in the medium term , and its share in GDP , gross fixed capital formation and employment. In general stresses that these activities, by far, have been unable to significantly generate linkages with the rest of the economy, a process that has not favored with competitiveness policies and activities aimed at these neutral or horizontal. Since the nineties foreign direct investment (FDI) has shown a remarkable dynamism, both internationally and in Latin America and in Mexico. Only in Mexico the first recipient of FDI in importance in Latin America during 1990-1995 and was displaced by Brazil since FDI increased from levels below 1 % of GDP during the eighties to around 3 % of GDP during the nineties. Its impact has been significant not only from a macroeconomic perspective , it has also allowed the generation of a new industrial production structure and organization, parallel to a significant modernization of a segment of the economy. The case of Mexico also is particularly interesting and relevant because the destination of FDI until 1993 had focused on the purchase of state assets during privatization process. This paper aims to present FDI flows in Mexico and analyze the different business strategies that have been touched and encouraged by the FDI. On the one hand, looking briefly discuss regulatory issues and source and recipient of FDI sectors. Furthermore, the paper presents in more detail the impacts and changes that generated the FDI contribution of FDI in the Mexican economy , besides the macroeconomic context and later legislative changes that resulted in the current regulations is examined around FDI in Mexico, including aspects of the Free Trade Agreement (NAFTA). It is worth noting that foreign investment can not only be considered from the perspective of the receiving economic units. Instead, these flows also reflect the strategic interests of transnational corporations (TNCs) and other companies seeking access to markets and increased competitiveness of their production networks and global distribution, among other reasons. Similarly it is important to note that foreign investment in its various forms is critically dependent on historical and temporal aspects. Thus, the same functionality can vary significantly depending on the specific characteristics of both receptor units as sources of FDI, including macroeconomic, institutional, industrial organization, and social aspects, among others.

Keywords: foreign direct investment (FDI), competitiveness, neoliberal regime, globalization, gross domestic product (GDP), NAFTA, macroeconomic

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Authors: Vidar Hepsø

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The energy and oil companies on the Norwegian Continental shelf come from a situation where each asset control and manage their energy supply (island mode) and move towards a situation where the assets need to collaborate and coordinate energy use with others due to increased cost and scarcity of electric energy sharing the energy that is provided. Currently, several areas are electrified either with an onshore grid cable or are receiving intermittent energy from offshore wind-parks. While the onshore grid in Norway is well regulated, the offshore grid is still in the making, with several oil and gas electrification projects and offshore wind development just started. The paper will describe the shift in the mindset that comes with operating this new offshore grid. This transition process heralds an increase in collaboration across boundaries and integration of energy management across companies, businesses, technical disciplines, and engagement with stakeholders in the larger society. This transition will be described as a function of the new challenges with increased complexity of the energy mix (wind, oil/gas, hydrogen and others) coupled with increased technical and organization complexity in energy management. Organizational complexity denotes an increasing integration across boundaries, whether these boundaries are company, vendors, professional disciplines, regulatory regimes/bodies, businesses, and across numerous societal stakeholders. New practices must be developed, made legitimate and institutionalized across these boundaries. Only parts of this complexity can be mitigated technically, e.g.: by use of batteries, mixing energy systems and simulation/ forecasting tools. Many challenges must be mitigated with legitimated societal and institutionalized governance practices on many levels. Offshore electrification supports Norway’s 2030 climate targets but is also controversial since it is exploiting the larger society’s energy resources. This means that new systems and practices must also be transparent, not only for the industry and the authorities, but must also be acceptable and just for the larger society. The paper report from ongoing work in Norway, participant observation and interviews in projects and people working with offshore grid development in Norway. One case presented is the development of an offshore floating windfarm connected to two offshore installations and the second case is an offshore grid development initiative providing six installations electric energy via an onshore cable. The development of the offshore grid is analyzed using a capability platform framework, that describes the technical, competence, work process and governance capabilities that are under development in Norway. A capability platform is a ‘stack’ with the following layers: intelligent infrastructure, information and collaboration, knowledge sharing & analytics and finally business operations. The need for better collaboration and energy forecasting tools/capabilities in this stack will be given a special attention in the two use cases that are presented.

Keywords: capability platform, electrification, carbon footprint, control rooms, energy forecsting, operational model

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Reham Algheshairy, Khaled Tayeb, Christopher Smith, Rebecca Gregg, Haruna Musa

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Background: Diabetes is a medical condition that refers to the pancreas’ inability to secrete sufficient insulin levels, a hormone responsible for controlling glucose levels in the body. Any surplus glucose in the blood stream is excreted through the urinary system. Insulin resistance in blood cells can also cause this condition despite the fact that the pancreas is producing the required amount of insulin A number of researchers claim that the prevalence of diabetes in Saudi Arabia has reached epidemic proportions, although one study did observe one positive in the rise in the awareness of diabetes, possibly indicative of Saudi Arabia’s improving healthcare system. While a number of factors can cause diabetes, the ever-increasing incidence of the disease in Saudi Arabia has been blamed primarily on low levels of physical activity and high levels of obesity. Objectives: The project has two aims. The first aim of the project is to investigate the regulatory effects of consumption of Nigella seeds and Ajwah dates on blood glucose levels in diabetic patients with type 2 diabetes. The second aim of the project is to investigate whether these dietary factors may have potentially beneficial effects in controlling the complications that associated with type 2 diabetes. Methods: This use a random-cross intervention trail of 75 Saudi male and female with type 2 diabetes in Al-Noor hospital in Makkah ( KSA) aged between 18 and 70 years were divided into 3 groups. Group 1 will consume 2g of Nigella Sativa seeds daily along with a modified diet for 12 weeks, group 2 will be given Ajwah dates daily with a modified diet for 12 weeks and group 3 will follow a modified diet for 12 weeks. Anthropometric measurements were taken at baseline, along with bloods for HbA1c, fasting blood sugar and at the end of 12 weeks. Results: This study found significant decrease in blood level (FBG & 2PPBG) and HbA1c in the groups with diet and Nigella seeds) compared to Ajwa date. However, there is no significant change were found in HbA1c, FBG and 2hrpp regarding Ajwa group. Conclusion: This study illustrated a significant improvement in some markers of glycaemia following 2 g of Ns and diet for 12 weeks. The dose of 2g/day of consumed Nigella seeds was found to be more effective in controlling BGL and HbA1c than control and Ajwa groups. This suggests that Nigella seeds and following a diet may have a potential effect (a role in controlling outcomes for type 2 diabetes and controlling the disease). Further research is needed on a large scale to determine the optimum dose and duration of Nigella and Ajwa in order to achieve the desired results.

Keywords: type 2 diabetes, Nigella seeds, Ajwa dates, fasting blood glucose, control

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Authors: Jin Sheng

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This paper addresses a promising area of insurance sector to develop in Asia. Captive insurance, which provides risk-mitigation services for its parent company, has great potentials to develop in energy, infrastructure, agriculture, logistics, catastrophe, and alternative risk transfer (ART), and will greatly affect the framework of insurance industry. However, the Asian captive insurance market only takes a small proportion in the global market. The recent supply chain interruption case of Hanjin Shipping indicates the significance of risk management for an Asian company’s sustainability and resilience. China has substantial needs and great potentials to develop captive insurance, on account of the currency volatility, enterprises’ credit risks, and legal and operational risks of the Belt and Road initiative. Up to date, Mainland Chinese enterprises only have four offshore captives incorporated by CNOOC, Sinopec, Lenovo and CGN Power), three onshore captive insurance companies incorporated by CNPC, China Railway, and COSCO, as well as one industrial captive insurance organization - China Ship-owners Mutual Assurance Association. Its captive market grows slowly with one or two captive insurers licensed yearly after September 2011. As an international financial center, Hong Kong has comparative advantages in taxation, professionals, market access and well-established financial infrastructure to develop a functional captive insurance market. For example, Hong Kong’s income tax for an insurance company is 16.5%; while China's income tax for an insurance company is 25% plus business tax of 5%. Furthermore, restrictions on market entry and operations of China’s onshore captives make establishing offshore captives in international or regional captive insurance centers such as Singapore, Hong Kong, and other overseas jurisdictions to become attractive options. Thus, there are abundant business opportunities in this area. Using methodology of comparative studies and case analysis, this paper discusses the incorporation, regulatory issues, taxation and prospect of captive insurance market in Hong Kong, China and Singapore. Hong Kong and Singapore are both international financial centers with prominent advantages in tax concessions, technology, implementation, professional services, and well-functioning legal system. Singapore, as the domicile of 71 active captives, has been the largest captive insurance hub in Asia, as well as an established reinsurance hub. Hong Kong is an emerging captive insurance hub with 5 to 10 newly licensed captives each year, according to the Hong Kong Financial Services Development Council. It is predicted that Hong Kong will become a domicile for 50 captive insurers by 2025. This paper also compares the formation of a captive in Singapore with other jurisdictions such as Bermuda and Vermont.

Keywords: Alternative Risk Transfer (ART), captive insurance company, offshore captives, risk management, reinsurance, self-insurance fund

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Authors: Sandra Smieszek, Jonathan Haines

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Introduction: Numerous research efforts have focused on searching for ‘longevity genes’. However, attempting to decipher the genetic component of the longevous phenotype have resulted in limited success and the mechanisms governing longevity remain to be explained. We conducted a genome-wide homozygosity analysis (GWHA) of the founder population of the Amish community in central Ohio. While genome-wide association studies using unrelated individuals have revealed many interesting longevity associated variants, these variants are typically of small effect and cannot explain the observed patterns of heritability for this complex trait. The Amish provide a large cohort of extended kinships allowing for in depth analysis via family-based approach excellent population due to its. Heritability of longevity increases with age with significant genetic contribution being seen in individuals living beyond 60 years of age. In our present analysis we show that the heritability of longevity is estimated to be increasing with age particularly on the paternal side. Methods: The present analysis integrated both phenotypic and genotypic data and led to the discovery of a series of variants, distinct for stratified populations across ages and distinct for paternal and maternal cohorts. Specifically 5437 subjects were analyzed and a subset of 893 successfully genotyped individuals was used to assess CHIP heritability. We have conducted the homozygosity analysis to examine if homozygosity is associated with increased risk of living beyond 90. We analyzed AMISH cohort genotyped for 614,957 SNPs. Results: We delineated 10 significant regions of homozygosity (ROH) specific for the age group of interest (>90). Of particular interest was ROH on chromosome 13, P < 0.0001. The lead SNPs rs7318486 and rs9645914 point to COL4A2 and our lead SNP. COL25A1 encodes one of the six subunits of type IV collagen, the C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. The second region of interest points to IRS2. Furthermore we built a classifier using the obtained SNPs from the significant ROH region with 0.945 AUC giving ability to discriminate between those living beyond to 90 years of age and beyond. Conclusion: In conclusion our results suggest that a history of longevity does indeed contribute to increasing the odds of individual longevity. Preliminary results are consistent with conjecture that heritability of longevity is substantial when we start looking at oldest fifth and smaller percentiles of survival specifically in males. We will validate all the candidate variants in independent cohorts of centenarians, to test whether they are robustly associated with human longevity. The identified regions of interest via ROH analysis could be of profound importance for the understanding of genetic underpinnings of longevity.

Keywords: regions of homozygosity, longevity, SNP, Amish

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Authors: Deniz Dincel, Sena Ardicli, Hale Samli, Mustafa Ogan, Faruk Balci

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The aim of the study was to determine the effects of some environmental and genetic factors on growth, fertility traits, milk yield and composition in Saanen goats. For this purpose, the total of 173 Saanen goats and kids were investigated for growth, fertility and milk traits in Marmara Region of Turkey. Fertility parameters (n=70) were evaluated during two years. Milk samples were collected during the lactation and the milk yield/components (n=59) of each goat were calculated. In terms of CSN3 and AGPAT6 gene; the genotypes were defined by PCR-RFLP. Saanen kids (n=86-112) were measured from birth to 6 months of life. The birth, weaning, 60ᵗʰ, 90ᵗʰ, 120ᵗʰ and 180tᵗʰ days of average live weights were calculated. The effects of maternal age on pregnancy rate (p < 0.05), birth rate (p < 0.05), infertility rate (p < 0.05), single born kidding (p < 0.001), twinning rate (p < 0.05), triplet rate (p < 0.05), survival rate of kids until weaning (p < 0.05), number of kids per parturition (p < 0.01) and number of kids per mating (p < 0.01) were found significant. The impacts of year on birth rate (p < 0.05), abortion rate (p < 0.001), single born kidding (p < 0.01), survival rate of kids until weaning (p < 0.01), number of kids per mating (p < 0.01) were found significant for fertility traits. The impacts of lactation length on all milk yield parameters (lactation milk, protein, fat, totally solid, solid not fat, casein and lactose yield) (p < 0.001) were found significant. The effects of age on all milk yield parameters (lactation milk, protein, fat, total solid, solid not fat, casein and lactose yield) (p < 0.001), protein rate (p < 0.05), fat rate (p < 0.05), total solid rate (p < 0.01), solid not fat rate (p < 0.05), casein rate (p < 0.05) and lactation length (p < 0.01), were found significant too. However, the effect of AGPAT6 gene on milk yield and composition was not found significant in Saanen goats. The herd was found monomorphic (FF) for CSN3 gene. The effects of sex on live weights until 90ᵗʰ days of life (birth, weaning and 60ᵗʰ day of average weight) were found significant statistically (p < 0.001). The maternal age affected only birth weight (p < 0,001). The effects month at birth on all of the investigated day [the birth, 120ᵗʰ, 180ᵗʰ days (p < 0.05); the weaning, 60ᵗʰ, 90ᵗʰ days (p < 0,001)] were found significant. The birth type was found significant on the birth (p < 0,001), weaning (p < 0,01), 60ᵗʰ (p < 0,01) and 90ᵗʰ (p < 0,01) days of average live weights. As a result, screening the other regions of CSN3, AGPAT6 gene and also investigation the phenotypic association of them should be useful to clarify the efficiency of target genes. Environmental factors such as maternal age, year, sex and birth type were found significant on some growth, fertility and milk traits in Saanen goats. So consideration of these factors could be used as selection criteria in dairy goat breeding.

Keywords: fertility, growth, milk yield, Saanen goats

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Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel

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Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.

Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant

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Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

Abstract:

Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

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Authors: Sinead Morrison, Ann Swillen, Therese Van Amelsvoort, Samuel Chawner, Elfi Vergaelen, Michael Owen, Marianne Van Den Bree

Abstract:

22q11.2 Deletion Syndrome (22q11.2DS) is caused by the deletion of approximately 60 genes on chromosome 22 and is associated with high rates of neurodevelopmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD). The presentation of these disorders in 22q11.2DS is reported to be comparable to idiopathic forms and therefore presents a valuable model for understanding mechanisms of neurodevelopmental disorders. Cognitive deficits are thought to be a core feature of neurodevelopmental disorders, and possibly manifest in behavioural and emotional problems. There have been mixed findings in 22q11.2DS on whether the presence of ADHD or ASD is associated with greater cognitive deficits. Furthermore, the influence of developmental stage has never been taken into account. The aim was therefore to examine whether the presence of ADHD or ASD was associated with cognitive deficits in childhood and/or adolescence in 22q11.2DS. We conducted the largest study to date of this kind in 22q11.2DS. The same battery of tasks measuring processing speed, attention and spatial working memory were completed by 135 participants with 22q11.2DS. Wechsler IQ tests were completed, yielding Full Scale (FSIQ), Verbal (VIQ) and Performance IQ (PIQ). Age-standardised difference scores were produced for each participant. Developmental stages were defined as children (6-10 years) and adolescents (10-18 years). ADHD diagnosis was ascertained from a semi-structured interview with a parent. ASD status was ascertained from a questionnaire completed by a parent. Interaction and main effects of cognitive performance of those with or without a diagnosis of ADHD or ASD in childhood or adolescence were conducted with 2x2 ANOVA. Significant interactions were followed up with t-tests of simple effects. Adolescents with ASD displayed greater deficits in all measures (processing speed, p = 0.022; sustained attention, p = 0.016; working memory, p = 0.006) than adolescents without ASD; there was no difference between children with and without ASD. There were no significant differences on IQ measures. Both children and adolescents with ADHD displayed greater deficits on sustained attention (p = 0.002) than those without ADHD. There were no significant differences on any other measures for ADHD. Magnitude of cognitive deficit in individuals with 22q11.2DS varied by cognitive domain, developmental stage and presence of neurodevelopmental disorder. Adolescents with 22q11.2DS and ASD showed greater deficits on all measures, which suggests there may be a sensitive period in childhood to acquire these domains, or reflect increasing social and academic demands in adolescence. The finding of poorer sustained attention in children and adolescents with ADHD supports previous research and suggests a specific deficit which can be separated from processing speed and working memory. This research provides unique insights into the association of ASD and ADHD with cognitive deficits in a group at high genomic risk of neurodevelopmental disorders.

Keywords: 22q11.2 deletion syndrome, attention deficit hyperactivity disorder, autism spectrum disorder, cognitive development

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Authors: Thais O. de Paula, Marjorie R. A. Sarmiento, Francis M. Borges, Alessandra B. Ferreira-Machado, Juliana A. Resende, Dioneia E. Cesar, Vania L. Silva, Claudio G. Diniz

Abstract:

Obesity is currently a worldwide public health threat, being considered a pandemic multifactorial disease related to the human gut microbiota (GM). Add to that GM is considered an important reservoir of antimicrobial resistance genes (ARG) and little is known on GM and ARG in obesity, considering the altered physiology and xenobiotics intake. As regional and social behavior may play important roles in GM modulation, and most of the studies are based on small sample size and various methodological approaches resulting in difficulties for data comparisons, this study was focused on the investigation of GM bacterial diversity in obese (OB), overweight (OW) and eutrophic individuals (ET) considering their nutritional, clinical and social characteristics; and comparative screening of AGR related to their physiology and xenobiotics intake. Microbial community was accessed by FISH considering phyla as a taxonomic level, and PCR-DGGE followed by dendrograms evaluation (UPGMA method) from fecal metagenome of 72 volunteers classified according to their body mass index (BMI). Nutritional, clinical, social parameters and xenobiotics intake were recorded for correlation analysis. The fecal metagenome was also used as template for PCR targeting 59 different ARG. Overall, 62% of OB were hypertensive, and 12% or 4% were, regarding the OW and ET individuals. Most of the OB were rated as low income (80%). Lower relative bacterial densities were observed in the OB compared to ET for almost all studied taxa (p < 0.05) with Firmicutes/Bacteroidetes ratio increased in the OB group. OW individuals showed a bacterial density representative of GM more likely to the OB. All the participants were clustered in 3 different groups based on the PCR-DGGE fingerprint patterns (C1, C2, C3), being OB mostly grouped in C1 (83.3%) and ET mostly grouped in C3 (50%). The cluster C2 showed to be transitional. Among 27 ARG detected, a cluster of 17 was observed in all groups suggesting a common core. In general, ARG were observed mostly within OB individuals followed by OW and ET. The ratio between ARG and bacterial groups may suggest that AGR were more related to enterobacteria. Positive correlations were observed between ARG and BMI, calories and xenobiotics intake (especially use of sweeteners). As with nutritional and clinical characteristics, our data may suggest that GM of OW individuals behave in a heterogeneous pattern, occasionally more likely to the OB or to the ET. Regardless the regional and social behaviors of our population, the methodological approaches in this study were complementary and confirmatory. The imbalance of GM over the health-disease interface in obesity is a matter of fact, but its influence in host's physiology is still to be clearly elucidated to help understanding the multifactorial etiology of obesity. Although the results are in agreement with observations that GM is altered in obesity, the altered physiology in OB individuals seems to be also associated to the increased xenobiotics intake and may interfere with GM towards antimicrobial resistance, as observed by the fecal metagenome and ARG screening. Support: FAPEMIG, CNPQ, CAPES, PPGCBIO/UFJF.

Keywords: antimicrobial resistance, bacterial diversity, gut microbiota, obesity

Procedia PDF Downloads 170