Search results for: regional expression

Authors: Naresh Kumar Verma

Abstract:

Nuclear energy being adapted as a renewable energy source and its production by developing countries has turned into a major strategic concern and politics by the developed world. The West seem to be the sole proprietor of such energy source and any country opting for such energy production either face significant hurdles or geopolitical challenges in developing such energy source. History of West Asia is full of interference by external powers which has been integral in the incessant conflict in the region. Whether it was the creation of Israel, the Gulf war of 1991, or the invasion of Iraq in 2003, and more recently the Iranian nuclear conundrum, the soil of West Asia has always been a witness to the play of extra regional powers game. Iran, being a theocratic state has been facing such threats and challenges, regarding its intentions and its capability in such energy production. The paper will try to assess the following issues: -Politics of Renewable Energy Generation. -Geographical and strategic significance of Iran’s nuclear programme. -Challenges in the path of Iran developing nuclear energy as a RE source. -The interests of the regional and extra-regional actors in challenging Iranian Nuclear Programme.

Keywords: developing countries, geopolitics, Iran, nuclear energy, renewable energy

Procedia PDF Downloads 606

Authors: Renalda El Samra, Elie Bou-Zeid, Hamza Kunhu Bangalath, Georgiy Stenchikov, Mutasem El Fadel

Abstract:

The regional-scale impact of climate change over complex terrain was examined through high-resolution dynamic downscaling conducted using the Weather Research and Forecasting (WRF) model, with initial and boundary conditions from a High-Resolution Atmospheric Model (HiRAM). The analysis was conducted over the eastern Mediterranean, with a focus on the country of Lebanon, which is characterized by a challenging complex topography that magnifies the effect of orographic precipitation. Four year-long WRF simulations, selected based on HiRAM time series, were performed to generate future climate projections of extreme temperature and precipitation over the study area under the conditions of the Representative Concentration Pathway (RCP) 4.5. One past WRF simulation year, 2008, was selected as a baseline to capture dry extremes of the system. The results indicate that the study area might be exposed to a temperature increase between 1.0 and 3ºC in summer mean values by 2050, in comparison to 2008. For extreme years, the decrease in average annual precipitation may exceed 50% at certain locations in comparison to 2008.

Keywords: HiRAM, regional climate modeling, WRF, Representative Concentration Pathway (RCP)

Procedia PDF Downloads 376

Authors: Christantus Begealawuh Nchongayi

Abstract:

As clearly stated in goal 14 of sustainable development goals, global oceans greatly contribute to making the earth habitable for mankind. This explains why ocean governance is an important global concern today. The emerging maritime security problems and the impact of climate change on African oceans, evidenced by tropical cyclones as seen recently in the Southern region of Africa, is also an indication that maritime governance and policymaking are important elements of peace and security in Africa. Within the last decade, there have been commendable efforts towards maritime governance and policymaking in Africa, although implementation of existing maritime policies is still lacking. This paper provides a snapshot of the overall state of the maritime policymaking process in Africa. It specifically explores the challenges facing policymakers in developing national and regional maritime security strategy in the East African Community. For methodology, the paper relied on primary and secondary data. Primary data was collected from informal discussions with policymakers and key policy-making bodies in Africa, and from a survey of public opinions. The study found that the Africa Integrated Maritime Strategy (2050 AIMS) is a recent template for regional and national maritime security policymaking in Africa and that although maritime security has in the past not been prioritized in the security agenda of the East African Community, developing and aligning a regional maritime security strategy to the 2050 AIMS will result to positive regional integration outcomes in East Africa.

Keywords: 2050 Africa integrated maritime strategy, east African community, maritime policy-making, maritime security

Procedia PDF Downloads 193

Authors: Boonyalitpun P., Pruckpattranon P., Thonghom A., Rotpenpian N.

Abstract:

Osteoarthritis is a musculoskeletal and neuromuscular abnormality, masticatory muscle, and other tissue that causes pain and breaks down the articular surface of the temporomandibular joint (TMJ). The aim of this study is to investigate the change in the mandibular condyle, in terms of thickness and porosity, and osteoclast marker in the mandibular condyle of TMJ induced osteoarthritis mice (TMJ-OA mice). We investigated the bony changes in the TMJ structure of a complete Freund adjuvant (CFA)-injected TMJ in a mice model over 28 days. On day 28, we observed any change in the TMJ by a micro computed tomography scan (micro-CT scan) in the parameters of trabecular microarchitecture. Then we studied the thickness of the condyles by hematoxylin and eosin staining. Moreover, we calculated the area around the TMJ’s condylar head containing the osteoclast expression by TRAP (Tartrate-resistant acid phosphatase) immunohistochemistry staining. The result found that the parameter of a micro-CT scan was no different from microarchitecture in the TMJ compared with the control group; however, mandibular condyles of the TMJ-OA group was significantly thinner than the control groups, and the osteoclast expression significantly increased in the TMJ-OA group. Therefore, our findings suggest that CFA-induced TMJ-OA represents an expression of osteoclast mandibular condyle of the TMJ, which is the proposed mechanism for a TMJ-OA model.

Keywords: condyle, osteoarthritis, osteoclast, temporomandibular joint

Procedia PDF Downloads 76

Authors: Xingxin Wu, Fenli Shao, Tao Tan, Yang Tan, Yang Sun, Qiang Xu

Abstract:

Psoriasis is a chronic inflammatory skin disease that affects about 2% of the world's population. IL-23 signaling plays a key role in the pathogenesis of psoriasis. Control of IL-23 release by small molecule compounds during developing psoriasis has not been well established. Here, we show that compound 1, a small molecule nature product, protected mice from imiquimod-induced psoriasis with improved skin lesions, reduced skin thickness, and reduced IL-23 mRNA expression in the skin tissue. FACS results showed compound 1 reduced the number of dendritic cells in the skin. Interestingly, compound 1 was not able to ameliorate IL-23-induced psoriasis-like skin inflammation in mice. Further, compound 1 inhibited MyD88-dependent IL-23 mRNA expression induced by LPS, CpG and imiquimod in BMDC cells, but not MyD88-independent CD80 and CD86 expression induced by LPS. The methods included real-time PCR, western blot, H & E staining, FACS and ELISA et al. In conclusion, compound 1 regulates MyD88-dependent signaling to control IL-23 release in dendritic cells, which improves imiquimod-induced psoriasis.

Keywords: dendritic cells, IL-23, toll-like receptor signaling, psoriasis

Procedia PDF Downloads 617

Authors: Hong Zhang, Runlian Miao, Min Zhang

Abstract:

Coordinated development of Beijing-Tianjin-Hebei region is of great importance and has been emphasized by the government in recent years. Beijing-Tianjin-Hebei region accumulates a large part of S&T resources of the whole country and boasts the most influential achievements. In order to improve innovation capability of the region, universities, research institutions and enterprises from Beijing, Tianjin and Hebei have cooperated in many forms, but technological innovation is not so satisfactory due to unbalanced allocation, poor sharing and low utilization efficiency of S&T resources. Therefore, it’s very necessary to promote resources sharing, optimize their overall layout, and enhance their innovation performance, which can further deepen coordination development of the region. This study focuses on S&T resources with the methods of documents research plus field investigation and qualitative research combing plus quantitive research. It starts from the macro background of promoting coordinated development of Beijing-Tianjin-Hebei region and arrives at improving regional innovation capability. Firstly, the author makes a literature review on coordinated development of Beijing-Tianjin-Hebei region and summarizes that coordinated development has been carried forward in the major fields which lay foundation for regional innovation; secondly, analyzes current S&T resources distribution and coordinated innovation by taking key industries as the examples; based on analysis of the status quo of resources sharing and innovation in the region, the author points out problems and obstacles that holdbacks coordinated innovation of the region and at last raises some suggestions to resources sharing and regional innovation. It reaches the conclusion that an efficient management mechanism, market laws, favorable environment, model innovation and incentive measures can help to accelerate resources sharing and regional innovation in the region.

Keywords: Beijing-Tianjin-Hebei region, coordinated development, innovation, S&T resources

Procedia PDF Downloads 275

Authors: Simeon Karafolas, Maciej Woźniak

Abstract:

Mostly of public financing programs at national and regional level are funded from European Union sources. EU can participate directly to a national and regional program (example LEADER initiative, URBAN…) or indirectly by funding regional or national funds. Funds from European Union are provided from EU multiannual financial framework form which the annual budget is programmed. The adjusted program 2007-2013 of the EU considered commitments of almost 1 trillion Euros for the EU-28 countries. Provisions of the new program 2014-2020 consider commitments of more than 1 trillion Euros. Sustainable growth, divided to Cohesion and Competitiveness for Growth an Employment, is one of the two principal categories; the other is the preservation and management of natural resources. Through this financing process SMEs benefited of EU and public sources by receiving grants for their investments. Most of the financial instruments are available indirectly through the national financial intermediaries. Part of them is managed by the European Investment Fund. The paper focuses on the public financing to SMEs by examining case studies on divers forms of public help. It tries to distinguish the efficiency of the examined good practices and therefore try to have some conclusions on the possibility of application to other regions.

Keywords: DIFASS, grants, SMEs, public financing

Procedia PDF Downloads 282

Authors: Liu Danping

Abstract:

Walking space has very important historical and cultural value in ancient and even modern urban development. As far as the footpath itself is concerned, it reflects the spatial organization mode and traditional architectural construction characteristics of mountain cities. In terms of the spatial nature of streets, traditional streets contain the history of urban development and the most primitive urban life. The slow walking speed allows people to carefully perceive the space and scenery along the way. The real city life in the streets often makes people feel the cultural connotation and unique charm of the city. According to the regional characteristics of pedestrian traffic in the main urban area of Chongqing, the charm of chongqing is discussed. Based on the study of chongqing characteristic walking space elements, this paper summarizes the characteristics of Chongqing urban walking traffic, analyzes the existing problems of mountain city walking traffic, and takes Yuzhong Peninsula as an example to analyze the charm promotion strategy of urban walking traffic.

Keywords: mountain city, walking space, urban charm, urban renewal, regional culture

Procedia PDF Downloads 71

Authors: Tyler D. Cesarone, Tatiana M. Wugalter

Abstract:

The movement of patients from the Global North to the Global South in pursuit of inexpensive healthcare and touristic experiences dominates the academic discourse on international medical travel (IMT). However, medical travel exists in higher numbers between Global South countries as patients who lack trust in, and feel disenfranchised by, their national healthcare systems seek treatment in nearby countries. Through a review of the existing literature, this paper examines patterns of IMT in the Middle East, Southeast Asia, and Southern Africa, distinguishing North-South medical tourism from South-South intra-regional medical mobility (IRMM). Evidence from these case studies demonstrates that notions of medical distrust and disenfranchisement, rooted in low-resourced and poor quality healthcare systems, are key drivers of IRMM in the Global South. The movement of patients from lower income to proximate higher income countries not only reveals tensions between patients and their healthcare systems but widens gaps in the quality of healthcare between departing and destination countries. In analyzing these cross-regional similarities, the paper moves beyond the current literature’s focus on singular case studies to expose global patterns of South-South IRMM. This presents a shift from the traditional focus on North-South medical tourism, demonstrating how disparities in healthcare systems both influence and are influenced by IRMM.

Keywords: global South, healthcare quality, international medical travel (IMT), intra-regional medical mobility (IRMM), medical disenfranchisement, medical distrust, medical tourism

Procedia PDF Downloads 376

Authors: Tong Ming Liu

Abstract:

Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application, which have been used in over 1000 clinical trials to treat over 30 diseases due to multilineage differentiation potential, secretome and immunosuppression. Gene therapies of MSCs hold great promise in the treatment of many diseases due to enhanced MSC-based clinical outcomes. To identify genes for gene therapy of MSCs, by comparing gene expression profile before and after MSC differentiation following by functional screening, we have identified ZNF145 that regulated MSC differentiation. Forced expression of ZNF145 resulted in enhanced in vitro chondrogenesis of MSCs as an upstream factor of SOX9 and improved osteochondral repair upon implant into osteochondral defects in rodents. By comparing gene expression profile during differentiation of iPSCs toward MSCs, we also identified gene HOX regulating MSC stemness, which was much downregulated in late-passaged MSCs. Knockdown of this gene greatly compromised MSC stemness including abolished proliferation, decreased CFU-F, promoted senescence and reduced expression of cell surface antigens linked to the MSC phenotype. In addition, multi-linage differentiation was also greatly impaired. Notably, HOX overexpression resulted in improved multi-lineage differentiation. In the mechanism, HOX expression significantly deceased in late passage of MSCs compared with early passage of MSCs, correlating with MSC important genes. ChIP-seq data shown that HOX binds to genes related to MSC self-renewal and differentiation. Most importantly, most HOX binding sites are lost in late passage of MSCs. HOX exerts its effects by directing binding Twist1, one important gene of MSCs. The identification of the genes regulating MSC differentiation and stemness will provide and promising strategies for gene therapy of MSCs in regenerative medicine.

Keywords: mesenchymal stem cell, novel transcription factor, stemness, gene therapy, cartilage repair, signaling pathway

Procedia PDF Downloads 29

Authors: Qinke Sun, Liang Zhou

Abstract:

The ‘Dragon-Elephant Debate’ between China and India is an important manifestation of global multipolarity in the 21st century. The two rising powers have carried out economic reforms one after another in the interval of more than ten years, becoming the fastest growing developing country and emerging economy in the world. At the same time, the development differences between China and India have gradually attracted wide attention of scholars. Based on the continuous annual night light data (DMSP-OLS) from 1992 to 2012, this paper systematically compares and analyses the regional development differences between China and India by Gini coefficient, coefficient of variation, comprehensive night light index (CNLI) and hot spot analysis. The results show that: (1) China's overall expansion from 1992 to 2012 is 1.84 times that of India, in which China's change is 2.6 times and India's change is 2 times. The percentage of lights in unlighted areas in China dropped from 92% to 82%, while that in India from 71% to 50%. (2) China's new growth-oriented cities appear in Hohhot, Inner Mongolia, Ordos, and Urumqi in the west, and the declining cities are concentrated in Liaoning Province and Jilin Province in the northeast; India's new growth-oriented cities are concentrated in Chhattisgarh in the north, while the declining areas are distributed in Uttar Pradesh. (3) China's differences on different scales are lower than India's, and regional inequality of development is gradually narrowing. Gini coefficients at the regional and provincial levels have decreased from 0.29, 0.44 to 0.24 and 0.38, respectively, while regional inequality in India has slowly improved and regional differences are gradually widening, with Gini coefficients rising from 0.28 to 0.32. The provincial Gini coefficient decreased slightly from 0.64 to 0.63. (4) The spatial pattern of China's regional development is mainly east-west difference, which shows the difference between coastal and inland areas; while the spatial pattern of India's regional development is mainly north-south difference, but because the southern states are sea-dependent, it also reflects the coastal inland difference to a certain extent. (5) Beijing and Shanghai present a multi-core outward expansion model, with an average annual CNLI higher than 0.01, while New Delhi and Mumbai present the main core enhancement expansion model, with an average annual CNLI lower than 0.01, of which the average annual CNLI in Shanghai is about five times that in Mumbai.

Keywords: spatial pattern, spatial difference, DMSP-OLS, China, India

Procedia PDF Downloads 126

Authors: Yanan Wang

Abstract:

It is proposed that when people give a gift they engage in 'love accounting', so that they will spend less on it if they include a written expression of love with it. This hypothesis was tested with college students (N = 308). It was found that participants who wrote a love message to accompany a Mother's Day gift budgeted less for the gift itself than control participants (Experiment 1), and this effect was replicated for a Christmas gift (Experiment 2). The amount of effort expended by the giver on preparing the love message did not account for the effect (Experiment 3). It is concluded that a gift and its accompanying love message are mentally computed as belonging to the same love account, implying that consumers’ excessive splurging on gifts might be controlled by writing a love message before gift shopping.

Keywords: expression of love, gift-giving, gift-budgeting, mental accounting

Procedia PDF Downloads 307

Authors: İsmail İnce, Mustafa Fener, Sair Kahraman

Abstract:

The uniaxial compressive strength (UCS) of rocks is an important input parameter for the design of rock engineering project. Compressive strength can be determined in the laboratory using the uniaxial compressive strength (UCS) test. Although the test is relatively simple, the method is time consuming and expensive. Therefore many researchers have tried to assess the uniaxial compressive strength values of rocks via relatively simple and indirect tests (e.g. point load strength test, Schmidt Hammer hardness rebound test, P-wave velocity test, etc.). Pyroclastic rocks are widely exposed in the various regions of the world. Cappadocia region located in the Central Anatolia is one of the most spectacular cite of these regions. It is important to determine the mechanical behaviour of the pyroclastic rocks due to their ease of carving, heat insulation properties and building some civil engineering constructions in them. The purpose of this study is to estimate a widely varying uniaxial strength of pyroclastic rocks from Cappadocia region by means of point load strength, porosity, dry density and saturated density tests utilizing gene expression programming.

Keywords: pyroclastic rocks, uniaxial compressive strength, gene expression programming (GEP, Cappadocia region

Procedia PDF Downloads 305

Authors: Priti Bajpai, Mohammed Shibil

Abstract:

This paper utilizes a comparative case study design to examine a regional onion market. The particular case of onion markets is used to understand perishable product supply chains. The site for the study is Dubai, United Arab Emirates. Results from a six-month field study are outlined. In particular, the findings suggest that firms should examine adding additional destinations to their supply chain. Further, we argue that utilizing Dubai as a supply chain hub is in certain cases counterproductive. Implications for food supply chains and regional trade are discussed.

Keywords: supply chains, food markets, onion trade, field study

Procedia PDF Downloads 315

Authors: Tapiwa Shumba, Nyaradzo D. T. Karubwa

Abstract:

Dispute resolution is the plinth of regional integration initiatives anchored on the rule of law and compliance with obligations. Without effective and reliable despite resolution mechanisms, it may be difficult to foster deeper integration. Within the Southern African Development Community (SADC) legal and institutional framework exists an apparent recognition that dispute resolution is an integral part of the regional integration. Almost all legal instruments of SADC include some provision for dispute resolution. Institutionally, the somewhat now defunct SADC Tribunal is meant to be the fulcrum for resolving disputes that arise under SADC instruments. However, after a closer analysis of the substance of these legal provisions and the attendant procedural mechanisms for addressing disputes, an argument can be made that dispute resolution in SADC is somewhat scant, fragmented and neglected. In most instruments, the common provision on dispute resolution appears to be a ‘mid-night clause’. In other instruments which have specialised provisions and procedures, questions of practicality and genius cannot be avoided. Worse still there now appears to be a lack of magnanimity between the substantive provisions in various instruments and the role of the transformed Tribunal. This scant, fragmented and neglected dispute resolution system may have an impact on the observance of the rule of law and compliance with obligations in the rules-based SADC system. This all, in turn, has an effect on the common agenda for deeper regional integration. This article seeks to expose this scant, fragmented and neglected SADC dispute resolution system and to propose a harmonised system that addresses these challenges. A ‘one stop shop’ system under a strengthened SADC tribunal is proposed as a responsive solution.

Keywords: regional integration, harmonisation, SADC tribunal, dispute resolution

Procedia PDF Downloads 168

Authors: Nila Febri Wilujeng, Helda Risman

Abstract:

Enjoying stable security within its region for the last 50 years, ASEAN nowadays contends with the global context emerging dynamically, which brings about multidimensional challenges and threats such as terrorism, radicalism, armed rebellion, hijacking, and other non-traditional threats. Dealing with these circumstances, ASEAN member states tighten its capacity by enhancing regional cooperation and strategic information exchange among ASEAN member states so-called ASEAN Our Eyes. This initiative adopted for the sake of forestalling any possible threat posed by violent extremism, radicalization, and terrorism through timely strategic information exchange among ASEAN member states. By using qualitative method, this paper will utilize regional security complex and international cooperation theories in analyzing the process to examine ASEAN Our Eyes based on its terms of reference. As a result, it portrays that ASEAN Our Eyes is able to undermine the gaps in the realm of strategic information exchange in monitoring the movement of violent extremism, radicalism, foreign terrorist fighters, and crime-terror nexus. However, it remains premature as a strategic measure to encounter those threats in the years to come.

Keywords: regional cooperation, counter-terrorism, ASEAN our eyes, strategic information exchange

Procedia PDF Downloads 183

Authors: Irakli Manvelidze, Genadi Iashvili, Giga Phartenadze, Giorgi Katamadze

Abstract:

Establishment of electronic governance in the region is facing serious problems. Organizational, technical, social and methodological problems have been identified after the research. These problems currently create serious barriers and prevent the development of effective e-governance. Lack of human resources, difference in program targets of the centre and the region, lack of citizens’ awareness about the project of electronic governance are other issues that should be mentioned. In spite of positive changes the overall situation concerning development of modern information-communication technologies in Adjara is not satisfactory. The information systems in the region can be described as transforming in a democratic way which needs serious reforms. Current situation shows that unsystematic, uncoordinated actions were made which overall represents more chaotic rather than coordinated systematic process. Therefore, a strategic document ‘Adjarian Electronic Government’ should be created which will ensure systematic development of electronic governance in the region. The implementation of the strategy of ‘Adjarian Electronic Government’ should be based on not only conceptual and instrumental but also legal basics. A legal normative basis should be created which will include formation of electronic government’s instrumental basis as well as creation of united regional system of electronic document management. Meanwhile types of documents which would be used in inter institutional relations should be defined under a legal norm. Creation of regional united system of e-filing will regulate regional public institutions, relations between local self-government and public organizations as well as it will ensure coordinated work of all regional public institutions.

Keywords: e-government, information society, public administration, reforming state governance, public institutions

Procedia PDF Downloads 258

Authors: Fei Sun, Meilan Xu, Jianghui Zhu, Maria Stefanie Dwiyanti, Cheolwoo Park, Fanjiang Kong, Baohui Liu, Tetsuya Yamada, Jun Abe

Abstract:

Reduced or lack of sensitivity to long daylengths is a key character for soybean, a short-day crop, to adapt to higher latitudinal environments. However, the photoperiod-insensitivity often results in a reduction of the duration of vegetative growth and final yield. To overcome this limitation, a photoperiod insensitive line (RIL16) was developed in this study that delayed flowering from the recombinant inbred population derived from a cross between a photoperiod-insensitive cultivar AGS292 and a late-flowering Thai cultivar K3. Expression analyses under SD and LD conditions revealed that the expression levels of FLOWERING LOCUS T (FT) orthologues, FT2a and FT5a, were lowered in RIL16 relative to AGS292, although the expression of E1, a soybean-specific suppressor for FTs, was inhibited in both conditions. A soybean orthologue of TARGET OF EAT1 (TOE1), another suppressor of FT, showed an upregulated expression in RIL16, which appeared to reflect a lower expression of miR172a. Our data suggest that the delayed flowering of RIL16 most likely is controlled by genes involved in an age-dependent pathway in flowering. The QTL analysis based on 1,125 SNPs obtained from Restriction Site Associated DNA Sequencing revealed two major QTLs for flowering dates in Chromosome 16 and two minor QTLs in Chromosome 4, all of which accounted for 55% and 48% of the whole variations observed in natural day length and artificially-induced long day length conditions, respectively. The intervals of the major QTLs harbored FT2a and FT5a, respectively, on the basis of annotated genes in the Williams 82 reference genome. Sequencing analysis further revealed a nonsynonymous mutation in FT2a and an SNP in the 3′ UTR region of FT5a. A further study may elucidate a detailed mechanism underlying the QTL for late flowering. The alleles from K3 at the two QTLs can be used singly or in combination to retain an appropriate duration of vegetative growth to maximize the final yield of photoperiod-insensitive soybeans.

Keywords: FT genes, miR72a, photoperiod-insensitive, soybean flowering

Procedia PDF Downloads 190

Authors: Alan Luo, Hunter N. B. Moseley

Abstract:

Many macromolecular structure entries in the Protein Data Bank (PDB) have a range of regional (localized) quality issues, be it derived from x-ray crystallography, Nuclear Magnetic Resonance (NMR) spectroscopy, or other experimental approaches. However, most PDB entries are judged by global quality metrics like R-factor, R-free, and resolution for x-ray crystallography or backbone phi-psi distribution statistics and average restraint violations for NMR. Regional quality is often ignored when PDB entries are re-used for a variety of structurally based analyses. The binding of ligands, especially ligands involved in energy metabolism, is of particular interest in many structurally focused protein studies. Using a regional quality metric that provides chemically interpretable information from electron density maps, a significant number of outliers in regional structural quality was detected across x-ray crystallographic PDB entries for proteins bound to biochemically critical ligands. In this study, a series of analyses was performed to evaluate both specific and general potential factors that could promote these outliers. In particular, these potential factors were the minimum distance to a metal ion, the minimum distance to a crystal contact, and the isotropic atomic b-factor. To evaluate these potential factors, Fisher’s exact tests were performed, using regional quality criteria of outlier (top 1%, 2.5%, 5%, or 10%) versus non-outlier compared to a potential factor metric above versus below a certain outlier cutoff. The results revealed a consistent general effect from region-specific normalized b-factors but no specific effect from metal ion contact distances and only a very weak effect from crystal contact distance as compared to the b-factor results. These findings indicate that no single specific potential factor explains a majority of the outlier ligand-bound regions, implying that human error is likely as important as these other factors. Thus, all factors, including human error, should be considered when regions of low structural quality are detected. Also, the downstream re-use of protein structures for studying ligand-bound conformations should screen the regional quality of the binding sites. Doing so prevents misinterpretation due to the presence of structural uncertainty or flaws in regions of interest.

Keywords: biomacromolecular structure, coenzyme, electron density discrepancy analysis, x-ray crystallography

Procedia PDF Downloads 100

Authors: Faris Mohsin Alabeedi

Abstract:

Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by the presence of autoantibodies directed against the epidermis's surface proteins. There are two forms of PV, mucocutaneous and mucosal-dominant PV. Disruption of the cell junctions is a hallmark of PV due to the autoantibodies targeting the desmosomal cadherins, desmoglein-3 (Dsg3) and desmoglein-1, leading to acantholysis in the skin and mucous membrane. Although the pathogenesis of PV is known, the detailed molecular events remain not fully understood. Our recent study has shown that both the PV sera and pathogenic anti-Dsg3 antibody AK23 can induce ROS and cause oxidative stress in cultured keratinocytes. In line with our finding, other independent studies also demonstrate oxidative stress in PV. Since Nrf2 plays a crucial role in cellular anti-oxidative stress response, we hypothesize that the expression of Nrf2 may alter in PV. Thus, treatment of cells with PV sera or AK23 may cause changes in Nrf2 expression and distribution. The purpose of this study was to examine the effect of AK23 and PV sera on Nrf2 in a normal human keratinocyte cell line, such as NTERT cells. Both a time-course and dose-dependent experiments with AK23, alongside the matched isotype control IgG, were performed in keratinocyte cultures and analysed by immunofluorescence for Nrf2 and Dsg3. Additionally, the same approach was conducted with the sera from PV patients and healthy individuals that served as a control in this study. All the fluorescent images were analysed using ImageJ software. Each experiment was repeated twice. In general, variations were observed throughout this study. In the dose-response experiments, although enhanced Dsg3 expression was consistently detected in AK23 treated cells, the expression of Nrf2 showed no consistent findings between the experiments, although changes in its expression were noticeable in cells treated with AK23. In the time-course study, a trend with induction of Nrf2 over time was shown in control cells treated with mouse isotype IgG. Treatment with AK23 showed a reduction of Nrf2 in a time-dependent manner, especially at the 24-hour time point. However, the earlier time points, such as 2 hours and 6 hours with AK23 treatments, detected somewhat variations. Finally, PV sera caused a decrease of Dsg3, but on the other hand, variations were observed in Nrf2 expression in PV sera treated cells. In general, PV sera seemed to cause a reduction of Nrf2 in the majority of PV sera treated samples. In addition, more pronounced cytoplasmic expression of Nrf2 has been observed in PV sera treated cells than those treated with AK23, suggesting that polyclonal and monoclonal IgG might induce a different effect on Nrf2 expression and distribution. Further experimental studies are crucial to obtain a more coincide global view of Nrf2-mediated gene regulation. In particular, Pemphigus Voulgaris studies assessing how the Nrf2-dependent network changes from a physiological to a pathological condition can provide insight into disease mechanisms and perhaps initiate further treatment approaches.

Keywords: pemphigus vulgaris, monoclonal antibody against desmoglein-3, Nrf2 oxidative stress, keratinocyte cultures

Procedia PDF Downloads 57

Authors: Alime Cengiz, Talip Kahyaoglu

Abstract:

Roasting process has the major importance to obtain desired aromatic taste of nuts. In this study, two kinds of roasting process were applied to hulled sesame seeds - vacuum oven and hot air roasting. Efficiency of Gene Expression Programming (GEP), a new soft computing technique of evolutionary algorithm that describes the cause and effect relationships in the data modelling system, and response surface methodology (RSM) were examined in the modelling of roasting processes over a range of temperature (120-180°C) for various times (30-60 min). Color attributes (L*, a*, b*, Browning Index (BI)), textural properties (hardness and fracturability) and moisture content were evaluated and modelled by RSM and GEP. The GEP-based formulations and RSM approach were compared with experimental results and evaluated according to correlation coefficients. The results showed that both GEP and RSM were found to be able to adequately learn the relation between roasting conditions and physical and textural parameters of roasted seeds. However, GEP had better prediction performance than the RSM with the high correlation coefficients (R2 >0.92) for the all quality parameters. This result indicates that the soft computing techniques have better capability for describing the physical changes occuring in sesame seeds during roasting process.

Keywords: genetic expression programming, response surface methodology, roasting, sesame seed

Procedia PDF Downloads 389

Authors: Petnamnueng Dettipponpong, Shuen E. Chen

Abstract:

Heat stress is known to have negative effects on reproductive functions, such as follicular development and ovulation. This study aimed to investigate the specific effects of heat stress on steroid hormone secretion of ovarian follicle cells, particularly in relation to the expression of Apolipoprotein B (ApoB) and microsomal triglyceride transfer protein (MTP). The aim of the study was to understand the impact of heat stress on steroid hormone secretion in ovarian follicle cells and to explore the role of ApoB and MTP in this process. Primary granulosa and theca cells were collected from follicles and cultured under heat stress conditions (42 °C) for various time periods. Controls were maintained under normal conditions (37.5 °C ). The culture medium was collected at different time points to measure levels of progesterone and estradiol using ELISA kits. ApoB and MTP expression levels were analyzed using homemade antibodies and western blot. Data were assessed by a one-way ANOVA comparison test with Duncan’s new multiple-range test. Results were expressed as mean±S.E. Difference was considered significant at P<0.05. The results showed that heat stress significantly increased progesterone secretion in granulosa cells, with the peak observed after 13 hours of recovery under thermoneutral conditions. Estradiol secretion by theca cells was not affected. Heat stress also had a significant negative effect on granulosa cell viability. Additionally, the expression of ApoB and MTP was found to be differentially regulated by heat stress. ApoB expression in theca cells was transiently promoted, while ApoB expression in granulosa cells was consistently suppressed. MTP expression increased after 5 hours of recovery in both cell types. These findings suggest a mechanism by which chicken follicle cells export cellular lipids as very low-density lipoprotein (VLDL) in response to thermal stress. These contribute to our understanding of the role of ApoB and MTP steroidogenesis and lipid metabolism under heat stress conditions. The study involved the collection of primary granulosa and theca cells, culture under different temperature conditions, and analysis of the culture medium for hormone levels using ELISA kits. ApoB and MTP expression levels were assessed using homemade antibodies and western blot. This study aimed to address the effects of heat stress on steroid hormone secretion in ovarian follicle cells, as well as the role of ApoB and MTP in this process. The study demonstrates that heat stress stimulates steroidogenesis in granulosa cells, affecting progesterone secretion. ApoB and MTP expression were found to be differentially regulated by heat stress, indicating a potential mechanism for the export of cellular lipids in response to thermal stress.

Keywords: heat stress, granulosa cells, theca cells, steroidogenesis, chicken, apolipoprotein B, microsomal triglyceride transfer protein

Procedia PDF Downloads 47

Authors: Leixuri Aguirre, Iñaki Milton-Laskibar, Elizabeth Hijona, Luis Bujanda, Agnes M. Rimando, Maria P. Portillo

Abstract:

Introduction: In recent years great attention has been paid by scientific community to phenolic compounds as active biomolecules naturally present in foodstuffs due to their beneficial effects on health. Pterostilbene is a resveratrol dimethylether derivative which shows higher biodisponibility. Objective. To analyze the effects of two doses of pterostilbene on several markers of thermogenic capacity in a model of genetic obesity, which shows reduced thermogenesis. Methods: The experiment was conducted with thirty Zucker (fa/fa) rats that were distributed in 3 experimental groups, the control group and two groups orally administered with pterostilbene at 15 and 30 mg/kg body weight/day for 6 weeks. Gene expression of Ucp1, Pgc-1α, Cpt1b, Pparα, Nfr1, Tfam and Cox-2 were assessed by RT-PCR, protein expression of UCP1 and GLUT4 by western blot and enzyme activity of carnitine palmitoyl transferase 1b and citrate synthase by spectrophotometry in interscapular brown adipose tissue (iBAT). Statistical analysis was performed by using one way ANOVA and Newman-Keuls as post-hoc test. Results: Pterostilbene did not change gene expression of Pgc-1α. However, significant increases were found in the expression of Ucp1, Pparα, Nfr-1 and Cox-2. Protein expression of UCP1 and GLUT4 was increased in animals treated with pterostilbene, as well as the activities of CPT-1b and CS. These effects were observed with both doses of pterostilbene, without differences between them. Conclusions: These results show that pterostilbene increases thermogenic and oxidative capacity of brown adipose tissue in obese rats. Whether these effects effectively contribute to the anti-obesity properties of these compound needs further research. Acknowledgments: MINECO-FEDER (AGL2015-65719-R), Basque Government (IT-572-13), University of the Basque Country (ELDUNANOTEK UFI11/32), Institut of Health Carlos III (CIBERobn). Iñaki Milton is a fellowship from the Basque Government.

Keywords: brown adipose tissue, pterostilbene, thermogenesis, uncoupling protein 1

Procedia PDF Downloads 268

Authors: Jaypraksh Show, Pooja Rawat

Abstract:

Experiences are the fundamental aspects of understanding of ourslves and the world around, leading to wisdom. In the path of wisdom, explorative reflection is the process through which we integrate our experiences, weave them into autobiographical narratives. Further, Neisser, a psychologist, and philosopher, thinks ‘ourselves’ is the wide web of different concepts which help us to understand the world, he called it the conceptual self. The conceptual self, as the storehouse of experiences and different concepts, develops a wiser individual narrative. Thus, Wisdom can be conceived as the expression of the Self. Drawing from this, the current work explores the autobiographies of young adults, focusing on their narrative self and foundations of wisdom through narrative analysis. Using the corresponding interview data, we will shed light on the way they exploratively reflect on challenging situations and use their narrative experiences and conceptual understanding. The aim of this study is to understand the ‘conceptual wiser-self’.

Keywords: wisdom, self, conceptual self, narrative self, autobiography, narrative analysis

Procedia PDF Downloads 122

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

Abstract:

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

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

Procedia PDF Downloads 205

Authors: Chirag Raval, Jimmy Toussaint, Tieuvi Nguyen, Hadi Fadaifard, George Wolberg, Steven Quarfordt, Kung-ming Jan, David S. Rumschitzki

Abstract:

Numerous studies examine aquaporins’ role in osmotic water transport in various systems but virtually none focus on aquaporins’ role in hydrostatically-driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here we investigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genomically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry, and function by measuring the pressure driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We use them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2h forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis. Numerous studies examine aquaporins’ role in osmotic water transport in various systems but virtually none focus on aquaporins’ role in hydrostatically-driven water transport involving mammalian cells save for our laboratory’s recent study of aortic endothelial cells. Here we investigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat models of hypertension, the spontaneously hypertensive genomically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery. We measured aquaporin-1 expression in aortic endothelial cells from whole rat aortas by quantitative immunohistochemistry, and function by measuring the pressure driven hydraulic conductivities of excised rat aortas with both intact and denuded endothelia on the same vessel. We use them to calculate the effective intimal hydraulic conductivity, which is a combination of endothelial and subendothelial components. We observed well-correlated enhancements in aquaporin-1 expression and function in both hypertensive rat models as well as in aortas from normotensive rats whose expression was upregulated by 2h forskolin treatment. Upregulated aquaporin-1 expression and function may be a response to hypertension that critically determines conduit artery vessel wall viability and long-term susceptibility to atherosclerosis.

Keywords: acute hypertension, aquaporin-1, hydraulic conductivity, hydrostatic pressure, aortic endothelial cells, transcellular flow

Procedia PDF Downloads 208

Authors: Claus Bier, Dennis Binder, Alexander Gruenberger, Dagmar Drobietz, Dietrich Kohlheyer, Anita Loeschcke, Karl Erich Jaeger, Thomas Drepper, Joerg Pietruszka

Abstract:

Light absorbing chromophoric systems are important optogenetic tools for biotechnical and biophysical investigations. Processes such as fluorescence or photolysis can be triggered by light-absorption of chromophores. These play a central role in life science. Photocaged compounds belong to such chromophoric systems. The photo-labile protecting groups enable them to release biologically active substances with high temporal and spatial resolution. The properties of photocaged compounds are specified by the characteristics of the caging group as well as the characteristics of the linked effector molecule. In our research, we work with different types of photo-labile protecting groups and various effector molecules giving us possible access to a large library of caged compounds. As a function of the caged effector molecule, a nearly limitless number of biological systems can be directed. Our main interest focusses on photocaging carbohydrates (e.g. arabinose) and their derivatives as effector molecules. Based on these resulting photocaged compounds a precisely controlled photoinduced gene expression will give us access to studies of numerous biotechnological and synthetic biological applications. It could be shown, that the regulation of gene expression via light is possible with photocaged carbohydrates achieving a higher-order control over this processes. With the one-step cleavable photocaged carbohydrate, a homogeneous expression was achieved in comparison to free carbohydrates.

Keywords: bacterial gene expression, biotechnology, caged compounds, carbohydrates, optogenetics, photo-removable protecting group

Procedia PDF Downloads 198

Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

Abstract:

Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

Procedia PDF Downloads 231

Authors: May Khei Hu, Kevin Leong, Fu Siong Ng, Nicholas Peter

Abstract:

Introduction: Sympathetic stimulation has been recognised as a potent stimulus of arrhythmogenesis in various cardiac pathologies, possibly by augmenting dispersion of repolarisation. The effects of sympathetic stimulation in healthy subjects however remain unclear. It is, therefore, crucial to first establish the effects of physiological stress on dispersion of repolarisation in healthy subjects before understanding these effects in pathological cardiac conditions. We hypothesised that activation-recovery interval (ARI; which is a surrogate of action potential duration) and dispersion of repolarisation decrease on sympathetic stimulation. Methods: Eight patients aged 18-55 years with structurally normal hearts underwent head-up tilt test (HUTT) and exercise tolerance test (ETT) while wearing the electrocardiographic imaging (ECGi) vest. Patients later underwent CT scan and the epicardial potentials are reconstructed using the ECGi software. Activation and recovery times were determined from the acquired electrograms. ARI was calculated and later corrected using Bazett’s formula. Global and regional dispersion of repolarisation were determined from standard deviation of the corrected ARI (ARIc). One-way analysis of variance (ANOVA) and Wilcoxon test were used to evaluate statistical significance. Results: Global ARIc increased significantly [p<0.01] when patients were tilted upwards but decreased significantly after five minutes [p<0.01]. A subsequent post- hoc analysis revealed that the decrease in R-R was more substantial compared to the change in ARI, resulting in the observed increase in ARIc. Global ARIc decreased on peak exercise [p<0.01] but increased on recovery [p<0.01]. Global dispersion increased significantly on peak exercise [p<0.05] although there were no significant changes in regional dispersion. There were no significant changes in both global and regional dispersion during tilt. Conclusion: ARIc decreases upon sympathetic stimulation in healthy subjects. Global dispersion of repolarisation increases upon exercise although there were no changes in global or regional dispersion during orthostatic stress.

Keywords: dispersion of repolarisation, sympathetic stimulation, Head-up tilt test (HUTT), Exercise tolerance test (ETT), Electrocardiographic imaging (ECGi)

Procedia PDF Downloads 176

Authors: Taisiia Gorshkova

Abstract:

Since the 1980s, spatial correlation models have been used more often to model regional indicators. An increasingly popular method for studying regional indicators is modeling taking into account spatial relationships between objects that are part of the same economic zone. In 2000s the new class of model – spatial vector autoregressions was developed. The main difference between standard and spatial vector autoregressions is that in the spatial VAR (SpVAR), the values of indicators at time t may depend on the values of explanatory variables at the same time t in neighboring regions and on the values of explanatory variables at time t-k in neighboring regions. Thus, VAR is a special case of SpVAR in the absence of spatial lags, and the spatial panel data model is a special case of spatial VAR in the absence of time lags. Two specifications of SpVAR were applied to Russian regional data for 2000-2017. The values of GRP and regional CPI are used as endogenous variables. The lags of GRP, CPI and the unemployment rate were used as explanatory variables. For comparison purposes, the standard VAR without spatial correlation was used as “naïve” model. In the first specification of SpVAR the unemployment rate and the values of depending variables, GRP and CPI, in neighboring regions at the same moment of time t were included in equations for GRP and CPI respectively. To account for the values of indicators in neighboring regions, the adjacency weight matrix is used, in which regions with a common sea or land border are assigned a value of 1, and the rest - 0. In the second specification the values of depending variables in neighboring regions at the moment of time t were replaced by these values in the previous time moment t-1. According to the results obtained, when inflation and GRP of neighbors are added into the model both inflation and GRP are significantly affected by their previous values, and inflation is also positively affected by an increase in unemployment in the previous period and negatively affected by an increase in GRP in the previous period, which corresponds to economic theory. GRP is not affected by either the inflation lag or the unemployment lag. When the model takes into account lagged values of GRP and inflation in neighboring regions, the results of inflation modeling are practically unchanged: all indicators except the unemployment lag are significant at a 5% significance level. For GRP, in turn, GRP lags in neighboring regions also become significant at a 5% significance level. For both spatial and “naïve” VARs the RMSE were calculated. The minimum RMSE are obtained via SpVAR with lagged explanatory variables. Thus, according to the results of the study, it can be concluded that SpVARs can accurately model both the actual values of macro indicators (particularly CPI and GRP) and the general situation in the regions

Keywords: forecasting, regional data, spatial econometrics, vector autoregression

Procedia PDF Downloads 116