Search results for: flexible mechanisms

Authors: Abdulfattah A. Q. Alwah, Amal Al‑Attar, Sumyah M. Al-Fanini, Ellen Fetzer

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Cultural landscapes enhance the spiritual relationship between people and their environment. They represent civilized evidence of peoples' interaction with nature and the exploitation of its resources to build their civilization. Yemeni urban and rural environments are rich in many cultural landscape elements that reflect the ingenuity of Yemeni people in interacting with nature. Yemen's mountain cities and villages appear in harmony with mountains, with vertical tower building patterns, local building materials, and unique architectural and urban elements and features. Such cities and villages are still full of life today, such as the cities of Taiz, Ibb, Lahj, and historical Jableh and hundreds of mountain villages in the provinces of the mountainous highlands. The cultivated mountain terraces reflect the ability of Yemenis to create arable areas in the tall mountains and to use successful means of irrigation and rainwater drainage. Unfortunately, there is a severe shortage of research studies that discuss the cultural landscapes in Yemen and the mechanisms for their preservation. Therefore, this study aimed to shed light on the types of mountain cultural landscapes in Yemen and discuss the means of their preservation. The study achieved its objectives through a theoretical review of available studies and field visits to some sites in Ibb, Jableh, and Taiz cities. The study highlighted the human contribution to these sites and elements and showed the Yemenis’ skills in adapting to nature and benefiting from it ideally. This study can guide the competent authorities to assess, develop, and protect cultural landscape sites in Yemen.

Keywords: civilization, urban environment, Yemeni mountain architecture, human heritage conservation, cultural identity

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Authors: Garineh Keshishyan Siraki

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Civil society is one of the most important concepts of the twentieth century and even so far. Modern and postmodern thinkers have provided different definitions of civil society. Of course, the concept of civil society has undergone many changes over time. The relationship between government and civil society is one of the relationships that attracted the attention of many contemporary thinkers. Hegel, the thinker we discussed in this article also explores the relationship between these concepts and emphasizing the dialectical method, he has drawn three lines between family, state, and civil society. In Hegel's view, the creation of civil society will lead to a reduction of social conflict and increased social cohesion. The importance of the issue is due to the study of social cohesion and the ways to increase it. The importance of the issue is due to the study of social cohesion and the ways to increase it. This paper, which uses a descriptive-analytic method to examine Hegel's dialectical theory of civil society, after examining the relationship between the family and the state and finding the concept of civil society as the interface and the interconnected circle of these two, investigates tripartite economic, legal, and pluralistic systems. In this article, after examining the concepts of the market, the right and duty, the individual interests and the development of the exchange economy, Hegel's view is to examine the concept of freedom and its relation with civil society. The results of this survey show that, in Hegel's thought, the separation between the political system and the social system is a natural and necessary thing. In Hegel's view, because of those who are in society, they have selfish features; the community is in tension and contradiction. Therefore, the social realms within which conflicts emerge must be identified and controlled by specific mechanisms. It can also be concluded that the government can act to reduce social conflicts by legislating, using force or forming trade unions. The bottom line is that Hegel wants to reconcile between the individual, the state and civil society and it is not possible to rely on ethics.

Keywords: civil society, cohesion system, economic system, family, the legal system, state

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Authors: Keyao Li, Sai On Cheung

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Incorporation of alternative dispute resolution (ADR) mechanism has been the main feature of current trend of construction project dispute resolution (CPDR). ADR approaches have been identified as efficient mechanisms and are suitable alternatives to litigation and arbitration. Moreover, the use of ADR in this multi-tiered dispute resolution process often leads to repeated evaluations of a same dispute. Multi-tiered CPDR may become a breeding ground for cognitive biases. When completed knowledge is not available at the early tier of construction dispute resolution, disputing parties may form preconception of the dispute matter or the counterpart. This preconception would influence their information processing in the subsequent tier. Disputing parties tend to search and interpret further information in a self-defensive way to confirm their early positions. Their imbalanced information collection would boost their confidence in the held assessments. Their attitudes would be hardened and difficult to compromise. The occurrence of cognitive bias, therefore, impedes efficient dispute settlement. This study aims to explore ways to minimize bias in CPDR. Based on a comprehensive literature review, three types of bias minimizing approaches were collected: strategy-based, attitude-based and process-based. These approaches were further operationalized into bias minimizing measures. To verify the usefulness and practicability of these bias minimizing measures, semi-structured interviews were conducted with ten CPDR third party neutral professionals. All of the interviewees have at least twenty years of experience in facilitating settlement of construction dispute. The usefulness, as well as the implications of the bias minimizing measures, were validated and suggested by these experts. There are few studies on cognitive bias in construction management in general and in CPDR in particular. This study would be the first of its type to enhance the efficiency of construction dispute resolution by highlighting strategies to minimize the biases therein.

Keywords: bias, construction project dispute resolution, minimization, multi-tiered, semi-structured interview

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Authors: Carolin Schulze

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Characterized by a positive interdependence of learners, cooperative learning (CL) is one possibility of successfully dealing with the increasing heterogeneity of students. Various positive effects of CL on the mental, physical and social health of students have already been documented. However, this structure is still rarely used in physical education (PE). Moreover, there is a lack of information about factors that determine the successful implementation of CL in PE. Therefore, the objective of the current study was to find out factors that determine the successful implementation of CL in PE using a digital questionnaire that was conducted from November to December 2022. In addition to socio-demographic data (age, gender, teaching experience, and education level), frequency of using CL, implementation strategies (theory-led, student-centred), and positive and negative effects of CL were measured. Furthermore, teachers were asked to rate the success of implementation on a 6-point rating scale (1-very successful to 6-not successful at all). For statistical analysis, multiple linear regression was performed, setting the success of implementation as the dependent variable. A total of 224 teachers (mean age=44.81±10.60 years; 58% male) took part in the current study. Overall, 39% of participants stated that they never use CL in their PE classes. Main reasons against the implementations of CL in PE were no time for preparation (74%) or for implementation (61%) and high heterogeneity of students (55%). When using CL, most of the reported difficulties are related to uncertainties about the correct procedure (54%) and the heterogeneous performance of students (54%). The most frequently mentioned positive effect was increased motivation of students (42%) followed by an improvement of psychological abilities (e.g. self-esteem, self-concept; 36%) and improved class cohesion (31%). Reported negative effects were unpredictability (29%), restlessness (24%), confusion (24%), and conflicts between students (17%). The successful use of CL is related to a theory-based preparation (e.g., heterogeneous formation of groups, use of rules and rituals) and a flexible implementation tailored to the needs and conditions of students (e.g., the possibility of individual work, omission of CL phases). Compared to teachers who solely implemented CL theory-led or student-adapted, teachers who switched from theory-led preparation to student-centred implementation of CL reported more successful implementation (t=5.312; p<.001). Neither frequency of using CL in PE nor the gender, age, the teaching experience, or the education level of the teacher showed a significant connection with the successful use of CL. Corresponding to the results of the current study, it is advisable that teachers gather enough knowledge about CL during their education and to point out the need to adapt the learning structure according to the diversity of their students. In order to analyse implementation strategies of teachers more deeply, qualitative methods and guided interviews with teachers are needed.

Keywords: diversity, educational technology, physical education, teaching styles

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Authors: Manmeet Kaur, Madhu Vij

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The Board of Directors in a firm performs the primary role of an internal control mechanism. This Study seeks to understand the relationship between internal governance and performance of banks in India. The research paper investigates the effect of board structure (proportion of nonexecutive directors, gender diversity, board size and meetings per year) on the firm performance. This paper evaluates the impact of corporate governance mechanisms on bank’s financial performance using panel data for 28 listed banks in National Stock Exchange of India for the period of 2008-2014. Returns on Asset, Return on Equity, Tobin’s Q and Net Interest Margin were used as the financial performance indicators. To estimate the relationship among governance and bank performance initially the Study uses Pooled Ordinary Least Square (OLS) Estimation and Generalized Least Square (GLS) Estimation. Then a well-developed panel Generalized Method of Moments (GMM) Estimator is developed to investigate the dynamic nature of performance and governance relationship. The Study empirically confirms that two-step system GMM approach controls the problem of unobserved heterogeneity and endogeneity as compared to the OLS and GLS approach. The result suggests that banks with small board, boards with female members, and boards that meet more frequently tend to be more efficient and subsequently have a positive impact on performance of banks. The study offers insights to policy makers interested in enhancing the quality of governance of banks in India. Also, the findings suggest that board structure plays a vital role in the improvement of corporate governance mechanism for financial institutions. There is a need to have efficient boards in banks to improve the overall health of the financial institutions and the economic development of the country.

Keywords: board of directors, corporate governance, GMM estimation, Indian banking

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Authors: Charles Iledun Oyewole

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The daunting challenge that the ‘man with the hoe’ is going to face in the coming decades will be complex and interwoven. With global population already above 7 billion people, it has been estimated that food (crop) production must more than double by 2050 to meet up with the world’s food requirements. Nigeria population is also expected to reach over 240 million people by 2050, at the current annual population growth of 2.61 per cent. The country’s farming population is estimated at over 65 per cent, but the country still depends on food importation to complement production. The small scale farmer, who depends on simple hand tools: hoes and cutlasses, remains the centre of agricultural production, accounting for 90 per cent of the total agricultural output and 80 per cent of the market flow. While the hoe may have been a tool for sustainable development at a time in human history, this role has been smothered by population growth, which has brought too many mouths to be fed (over 170 million), as well as many industries to fuel with raw materials. It may then be argued that the hoe is unfortunately not a tool for the coming challenges and that agricultural mechanization should be the focus. However, agriculture as an enterprise is a ‘complete wheel’ which does not work when broken, particularly, in respect to mechanization. Generally, mechanization will prompt increase production, where land is readily available; increase production, will require post-harvest handling mechanisms, crop processing and subsequent storage. An important aspect of this is readily available and favourable markets for such produce; fuel by good agricultural policies. A break in this wheel will lead to the process of mechanization crashing back to subsistence production, and probably reversal to the hoe. The focus of any agricultural policy should be to chart a course for sustainable mechanization that is environmentally friendly, that may ameliorate Nigeria’s food and raw material gaps. This is the focal point of this article.

Keywords: Crop production, Farmer, Hoes, Mechanization, Policy framework, Population, Growth, Rural areas

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Authors: Esther N. Maina, Anna Skowronska, Sridhar Chaganti, Malcolm A. Taylor, Paul G. Murray, Tatjana Stankovic

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Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human tumours of B-cell origin. The demonstration that a proportion of Hodgkin lymphomas and all Burkitt’s lymphomas harbour EBV suggests that the virus contributes to the development of these malignancies. However, the mechanisms of lymphomagenesis remain largely unknown. To determine whether EBV causes DNA damage and alters DNA damage response in cells of EBV-driven lymphoma origin, Germinal Centre (GC) B cells were infected with EBV and DNA damage responses to gamma ionising radiation (IR) assessed at early time points (12hr – 72hr) after infection and prior to establishment of lymphoblastoid (LCL) cell lines. In the presence of EBV, we observed induction of spontaneous DNA DSBs and downregulation of ATM-dependent phosphorylation in response to IR. This downregulation coincided with reduced ability of infected cells to repair IR-induced DNA double-strand breaks, as measured by the kinetics of gamma H2AX, a marker of double-strand breaks, and by the tail moment of the comet assay. Furthermore, we found that alteration of DNA damage responses coincided with the expression of LMP-1 protein. The presence of the EBV virus did not affect the localization of the ATM-dependent DNA repair proteins to sites of damage but instead lead to an increased expression of PP5, a phosphatase that regulates ATM function. The impact of the virus on DNA repair was most prominent 24h after infection, suggesting that this time point is crucial for the viral establishment in B cells. Our results suggest that during an early infection EBV virus dampens crucial cellular responses to DNA double-strand breaks which facilitate successful viral infection, but at the same time might provide the mechanism for tumor development.

Keywords: EBV, ATM, DNA damage, germinal center cells

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Authors: Chloe Fauchon

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In Europe, the right to a fair trial is enshrined in the European Convention on Human Rights, signed in 1950, in its famous Article 6, and, in the field of the European Union, in Article 47 of the Charter of Fundamental Rights, binding since 2009. The right to a fair trial is, therefore, a fundamental right protected by all the relevant treaties. The right to a fair trial is an "umbrella right" which encompasses various sub-rights and principles. Although this right applies in all the proceedings, it gets a special relevance in criminal matters and, particularly, regarding the defendant. In criminal proceedings, the parties are not equal: the accusation is represented by a State-organ, with specific prerogatives, and the defense does not benefit from these specific powers and is often inexperienced in criminal law. Equality of arms, and consequently the right to a fair trial, needs some specific mechanisms to be effective in criminal proceedings. For instance, the defendant benefits from some procedural rights, such as the right to a lawyer, the right to be informed of the charges against them, the right to confront witnesses, and so on. These rights aim to give the defendant the tools to dispute the accusation. The role of the defense is, therefore, very important in criminal matters to avoid unjustified convictions. This specificity of criminal matters justifies that the focus will be put on them during this study. Then this paper will also focus on French and Spanish legal orders. Indeed, if the European Court and Convention on Human Rights are the most famous instruments to protect the right to a fair trial, this right is also guaranteed at a constitutional level in European national legal orders in Europe. However, this enshrinement differs from one country to the other: for instance, in Spain, the right to a fair trial is protected explicitly by the 1978 constitutional text, whereas, in France, it is more of a case-law construction. Nevertheless, this difference between both legal orders does not imply huge variations in the substantive aspect of the right to a fair trial. This can be specifically explained by the submission of both States to the European Convention on Human Rights. This work aims to show that, although the French and Spanish legal orders differ in the way they protect the right to a fair trial, this right eventually has the same substantive meaning in both legal orders.

Keywords: right to a fair trial, constitutional law, French law, Spanish law, European Court of Human Rights

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Authors: Hadeer Ibrahiem, Mahmoud Nasr, Masarrat M. M. Migahid, Mohamed A. Ghazy

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The release of textile wastewater loaded with 1,4 dioxane into aquatic ecosystems has been associated with various human health risks and adverse environmental impacts. In parallel, phytoremediation has been recently employed to treat highly polluted wastewater because various plant species tend to produce certain enzymes as a defense mechanism against a toxic environment. To our best knowledge, this study is the first to investigate the ability of phytoremediation using Eichhornia crassipes for the removal of various pollutants, including 1,4 dioxane, from textile wastewater. A phytoremediation system composed of Eichhornia crassipes was acclimatized for 10 d, and then operated in four lab-scale hydroponic systems, viz., negative control, positive control, and two different 1,4 dioxane concentration (400 and 500 mg/L). After 11 d of operation, the phytoremediation system achieved removal efficiencies of 67.5±3.4%, 89.4±4.4%, 83.6±3.8% for 1,4 dioxane (at initial concentration 400 mg/L), chemical oxygen demand (COD) (at initial concentration 679 mg/L), and cumulative heavy metals, respectively. The removal of these pollutants was mainly supported by the phyto-sorption and phytodegradation mechanisms. The economic feasibility of this phytoremediation system was validated by estimating the capital and operating costs, requiring 4.6 USD for the treatment of 1 m3 textile wastewater. The study concluded that the phytoremediation process could be used as a practical and economical approach to treat textile wastewater laden with various organic and inorganic pollutants. Due to the observed pollution reduction and human health protection, the study objectives would fulfill the targets of SDG 3 “Good Health and Well-being” and SDG 6 “Clean Water and Sanitation”. Further studies are required to (i) investigate the ability of plant species to withstand higher concentrations of 1,4 dioxane for an extended operation time and (ii) understand the biochemical pathways for the degradation of 1,4 dioxane via the action of plant enzymes and the associated microbial community.

Keywords: 1, 4 dioxane concentrations, hydrophytes, Eichhornia crassipes, phytoremediation effectiveness, SDGs, textile industrial effluent

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Authors: Peter Olasupo Ogunjuyigbe, Sarafa Shittu

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This paper emphasizes the relevance of conjugal relationship and spousal communication towards enhancing men’s involvement in contraceptive use among the Yorubas of South Western Nigeria. An understanding of males influence and the role they play in reproductive decision making can throw better light on mechanisms through which egalitarianness of husband/wife decision making influences contraceptive use. The objective of this study was to investigate how close conjugal relationships can be a good indicator of joint decision making among couples using data derived from a survey conducted in three states of South Western Nigeria. The study sample consisted of five hundred and twenty one (521) male respondents aged 15-59 years and five hundred and forty seven (547) female respondents aged 15-49 years. The study used both quantitative and qualitative approached to elicit information from the respondents. In order that the study would be truly representative of the towns, each of the study locations in the capital cities was divided into four strata: The traditional area, the migrant area, the mixed area (i.e. traditional and migrant), and the elite area. In the rural areas, selection of the respondents was by simple random sampling technique. However, the random selection was made in such a way that all the different parts of the locations were represented. Generally, the data collected were analysed at univariate, bivariate, and multivariate levels. Logistic regression models were employed to examine the interrelationships between male reproductive behaviour, conjugal relationship and contraceptive use. The study indicates that current use of contraceptive is high among this major ethnic group in Nigeria because of the improved level of communication among couples. The problem, however, is that men still have lower exposure rate when it comes to question of family planning information, education and counseling. This has serious implications on fertility regulation in Nigeria.

Keywords: behavior, conjugal, communication, counseling, spouse

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Authors: Saranya Ganapathy, Megha N. Parajulee, Michael San Francisco, Hong Zhang

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Insect pests are a serious threat to agricultural productivity. Use of chemical pesticides, the predominant control method thus far, has resulted in environmental damage, pest resurgence, and negative effects on non-target species. Genetically modified (GM) crops offer a promising alternative, and Bacillus thuringiensis endotoxin genes have played a major role in this respect. However, to overcome insect tolerance issues and to broaden the target range, it is critical to identify alternative-insecticidal toxins working through novel mechanisms. Our research group has identified a kinase from Chilo iridescent virus (CIV; Family Iridoviridae) that has insecticidal activity and designated it as ISTK (Iridovirus Serine/Threonine Kinase). A 35 kDa truncated form of ISTK, designated iridoptin, was obtained during expression and purification of ISTK in the yeast system. This yeast-expressed CIV toxin induced 50% mortality in cotton aphids and 100% mortality in green peach aphids (GPA). Optimized viral genes (o-ISTK and o-IRI) were stably transformed into the model plant, Arabidopsis. PCR analysis of genomic DNA confirmed the presence of the gene insert (oISTK/oIRI) in selected transgenic lines. The further screening was performed to identify the PCR positive lines that showed expression of respective toxins at the polypeptide level using Western blot analysis. The stable lines expressing either of these two toxins induced moderate to very high mortality in GPAs and significantly affected GPA development and fecundity. The aphicidal potential of these transgenic Arabidopsis lines will be presented.

Keywords: Chilo iridescent virus, insecticidal toxin, iridoviruses, plant-incorporated protectants, serine/threonine kinase

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Authors: Mikael M. Johansson, Peter Stenvall, Leif Karlsson, Joel Andersson

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Sandvik Sanicro 25, UNS S31035, is an advanced high temperature austenitic stainless steel that potentially can be used in super-heaters and reheaters in the next generation of advanced ultra-super critical power plants. The material possesses both high creep strength and good corrosion resistance at temperatures up to 700°C. Its high temperature properties are positioned between other commercially available high temperature austenitic stainless steels and nickel-based alloys. It is, however, well known that an austenitic solidification mode combined with a fully austenitic microstructure exacerbate susceptibility towards hot cracking. The problem increases even more for thick walled material in multipass welding and could compromise the integrity of the welded component. Varestraint weldability testing is commonly used to evaluate susceptibility towards hot cracking of materials. In this paper, Varestraint test results are evaluated for base material of both UNS S31035 steel and are compared to those of the well-known and well-characterized UNS S31008 grade. The more creep resistant alloy, UNS S31035, is metallurgically more complicated than the UNS S31008 grade and has additions of several alloying elements to improve its high temperature properties. It benefits from both solid solution hardening as well as precipitation hardening. This investigation therefore attempts, based on the Varestraint weldability test, to understand if there are any differences in cracking mechanisms between these two grades due to the additional alloying elements used in UNS S31035. Results from Varestraint testing and crack type investigations will be presented and discussed in some detail. It is shown that hot cracking susceptibility of the UNS S31035 steel is only slightly higher than that of UNS S31008 despite the more complicated metallurgy. Weldability of the two alloys is therefore judged to be comparable making the newer alloy well suited also for critical applications.

Keywords: austenitic stainless steel, hot cracking susceptibility, UNS S31035, UNS S31008, varestraint weldability testing

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Authors: Asieh Abbassi Daloii, Ahmad Abdi

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Introduction: Sports information suggests that physical inactivity increases the risk of many diseases, including atherosclerosis. Coronary heart disease, stroke and peripheral vascular disease, atherosclerosis and clinical protests. However, exercise can have beneficial effects on risk factors for atherosclerosis by reducing hyperlipidemia, hypertension, obesity, plaque density, increased insulin sensitivity and glucose tolerance is improved. Despite these findings, there is little information about the molecular mechanisms of interaction between the body and its relation to sport and there arteriosclerosis. The present study aims to investigate the effect of six weeks of progressive aerobic training and aqueous extract of crataegus monogyna on vascular endothelial growth factor (VEGF) variations and angiopoetin-1/2 (ANG- 1/2) in plasma and heart tissue in male Wistar rats. Methods: 30 male Wistar rats, 4-6 months old, were randomly divided into four groups: control crataegus monogyna (N=8), training crataegus monogyna (N=8), control saline (N=6), and training saline (N=8). The aerobic training program included running on treadmill at the speed of 34 meters per minute for 60 minutes per day. The training was conducted for six weeks, five days a week. Following each training session, both experimental and control subjects of crataegus monogyna groups were orally fed with 0.5 mg crataegus monogyna extract per gram of the body weight. The normal saline group was given the same amount of the normal saline solution (NS). Eventually, 72 hours after the last training session, blood samples were taken from inferior Verna cava. Conclusion: It is likely that crataegus monogyna extract compared with aerobic training and even combination of both training and crataegus monogyna extract is more effective on angiogenesis.

Keywords: angiopoietin 1, 2, vascular endothelial growth factor, aerobic exercise

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Authors: Ulugbek Azimov, Nearchos Stylianidis, Nobuyuki Kawahara, Eiji Tomita

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A chemical kinetics and computational fluid-dynamics (CFD) analysis was performed to evaluate the combustion of syngas derived from biomass and coke-oven solid feedstock in a micro-pilot ignited supercharged dual-fuel engine under lean conditions. For this analysis, a new reduced syngas chemical kinetics mechanism was constructed and validated by comparing the ignition delay and laminar flame speed data with those obtained from experiments and other detail chemical kinetics mechanisms available in the literature. The reaction sensitivity analysis was conducted for ignition delay at elevated pressures in order to identify important chemical reactions that govern the combustion process. The chemical kinetics of NOx formation was analyzed for H2/CO/CO2/CH4 syngas mixtures by using counter flow burner and premixed laminar flame speed reactor models. The new mechanism showed a very good agreement with experimental measurements and accurately reproduced the effect of pressure, temperature and equivalence ratio on NOx formation. In order to identify the species important for NOx formation, a sensitivity analysis was conducted for pressures 4 bar, 10 bar and 16 bar and preheat temperature 300 K. The results show that the NOx formation is driven mostly by hydrogen based species while other species, such as N2, CO2 and CH4, have also important effects on combustion. Finally, the new mechanism was used in a multidimensional CFD simulation to predict the combustion of syngas in a micro-pilot-ignited supercharged dual-fuel engine and results were compared with experiments. The mechanism showed the closest prediction of the in-cylinder pressure and the rate of heat release (ROHR).

Keywords: syngas, chemical kinetics mechanism, internal combustion engine, NOx formation

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Authors: Haiming Wen

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Grain growth is an important and consequential phenomenon that generally occurs in the presence of thermal and/or stress/strain fields. Thermally activated grain growth has been extensively studied and similarly, there are numerous experimental and theoretical studies published describing stress-induced grain growth in single-phase materials. However, studies on grain growth during the simultaneous presence of an elevated temperature and an external stress are very limited, and moreover, grain growth phenomena in materials containing second-phase particles and solute segregation at GBs have received limited attention. This lecture reports on a study of grain growth in the presence of second-phase particles and solute/impurity segregation at grain boundaries (GBs) during high-temperature deformation of an ultra-fine grained (UFG) Al alloy synthesized via consolidation of mechanically milled powders. The mechanisms underlying the grain growth were identified as GB migration and grain rotation, which were accompanied by dynamic recovery and geometric dynamic recrystallization, while discontinuous dynamic recrystallization was not operative. A theoretical framework that incorporates the influence of second-phase particles and solute/impurity segregation at GBs on grain growth in presence of both elevated temperature and external stress is formulated and discussed. The effect of second-phase particles and solute/impurity segregation at GBs on GB migration and grain rotation was quantified using the proposed theoretical framework, indicating that both second-phase particles and solutes/impurities segregated GBs reduce the velocities of GB migration and grain rotation as compared to those in commercially pure Al. Our results suggest that grain growth predicted by the proposed theoretical framework is in agreement with experimental results. Hence, the developed theoretical framework can be applied to quantify grain growth in simultaneous presence of external stress, elevated temperature, GB segregation and second-phase particles, or in presence of one or more of the aforementioned factors.

Keywords: nanocrystalline materials, ultra-fine grained materials, grain growth, grain boundary migration, grain rotation

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Authors: Dalia G. Aseel

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The potato (Solanum tubersum, L.) has become one of the major vegetable crops in Egypt and all over the world. Potato leafroll virus(PLRV) was observed on potato plants collected from different governorates in Egypt. Three cultivars, Spunta, Diamont, and Cara, infected with PLRV were collected; RNA was extracted and subjected to Real-Time PCR using the coat protein gene primers. The results showed that the expression of the coat protein was 39.6-fold, 12.45-fold, and 47.43-fold, respectively, for Spunta, Diamont, and Cara cultivars. Differential Display Polymerase Chain Reaction (DD-PCR) using pathogenesis-related protein 1 (PR-1), β-1,3-glucanases (PR-2), chitinase (PR-3), peroxidase (POD), and polyphenol oxidase (PPO) forward primers for pathogenesis-related proteins (PR). The obtained data revealed different banding patterns depending on the viral type and the region of infection. Regarding PLRV, 58 up-regulated and 19 down-regulated genes were detected. Sequence analysis of the up-and down-regulated genes revealed that infected plants were observed in comparison with the healthy control. Sequence analysis of the up-regulated gene was performed, and the encoding sequence analysis showed that the obtained genes include: induced stolen tip protein. On the other hand, two down-regulated genes were identified: disease resistance RPP-like protein and non-specific lipid-transfer protein. In this study, the expressions of PR-1, PR-2, PR-3, POD, and PPO genes in the infected leaves of three potato cultivars were estimated by quantitative real-time PCR. We can conclude that the PLRV-infection of potato plants inhibited the expression of the five PR genes. On the contrary, infected leaves by PLRV elevated the expression of some defense genes. This interaction may also induce and/or suppress the expression of some genes responsible for the plant's defense mechanisms.

Keywords: PLRV, pathogenesis-related proteins (PRs), DD-PCR, sequence, real-time PCR

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Authors: Yinebeb Mezgebu Dagnachew, Hwee Ying Lim, Liao Wupeng, Sheau Yng Lim, Lim Sheng Jie Natalie, Veronique Angeli

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Collagen is essential for maintaining lung structure and function, and its remodeling has been associated with respiratory diseases, including chronic obstructive pulmonary disease (COPD). However, the cellular mechanisms driving collagen remodeling and the functional implications of this process in the pathophysiology of pulmonary diseases remain poorly understood. Using a mouse model of Lyve-1 expressing macrophage depletion, we found that the absence of this subpopulation of tissue-resident macrophage led to the preferential deposition of type I collagen fibers around the alveoli and bronchi in the steady state. Further analysis by polarized light microscopy revealed that the collagen fibers accumulating in the lungs depleted of Lyve-1+ macrophages were thicker and crosslinked. A decrease in MMP-9 gene expression and proteolytic activity, together with an increase in Col1a1, Timp-3 and Lox gene expression, accompanied the collagen alterations. Next, we investigated the effect of the collagen remodeling on the pathophysiology of COPD and airway function in mouse lacking Lyve-1+ macrophage exposed chronically to cigarette smoke (CS), a well-established animal model of COPD. We showed that the deposition of collagen protected mouse against the destruction of alveoli (emphysema) and bronchi thickening after CS exposure and prevented loss of airway function. Thus, we demonstrate that interstitial Lyve-1+ macrophages regulate the composition, amount, and architecture of the collagen network in the lungs and that such collagen remodeling functionally impacts the development of COPD. This study further supports the potential of targeting collagen as a promising approach to treating respiratory diseases.

Keywords: lung, extracellular matrix, chronic obstructive pulmonary disease, matrix metalloproteinases, collagen

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Authors: Pawan Kumar Gupta, Sumana Ghosh

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Parkinson's Disease (PD) is a long-term neurodegenerative movement disorder of the central nervous system with vast symptoms related to the motor system. The common symptoms of PD are tremor, rigidity, bradykinesia/akinesia, and postural instability, but the clinical symptom includes other motor and non‐motor issues. The motor symptoms of the disease are consequence of death of the neurons in a region of the midbrain known as substantia nigra pars compacta, leading to decreased level of a neurotransmitter known as dopamine. The cause of this neuron death is not clearly known but involves formation of Lewy bodies, an abnormal aggregation or clumping of the protein alpha-synuclein in the neurons. Unfortunately, there is no cure for PD, and the management of this disease is challenging. Therefore, it is critical for a patient to be diagnosed at early stages. A limited choice of drugs is available to improve the symptoms, but those become less and less effective over time. Apart from that, with rapid growth in the field of science and technology, other methods such as multi-area brain stimulation are used to treat patients. In order to develop advanced techniques and to support drug development for treating PD patients, an accurate mathematical model is needed to explain the underlying relationship of dopamine secretion in the brain with the hand tremors. There has been a lot of effort in the past few decades on modeling PD tremors and treatment effects from a computational point of view. These models can effectively save time as well as the cost of drug development for the pharmaceutical industry and be helpful for selecting appropriate treatment mechanisms among all possible options. In this review paper, an effort is made to investigate studies on PD modeling and analysis and to highlight some of the key advances in the field over the past centuries with discussion on the current challenges.

Keywords: Parkinson's disease, deep brain stimulation, tremor, modeling

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Authors: Sergei Voychuk

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Introduction: Adaptive response (AR) is a manifestation of radiation hormesis, which deal with the radiation resistance that may be increased with the pretreatment with small doses of radiation. In the current study, we evaluated the potency of radiofrequency EMF to induce the AR mechanisms and to increase a resistance to UV light. Methods: Saccharomyces cerevisiae yeast strains, which were created to study induction of mutagenesis and recombination, were used in the study. The strains have mutations in rad2 and rad54 genes, responsible for DNA repair: nucleotide excision repair (PG-61), postreplication repair (PG-80) and mitotic (crossover) recombination (T2). An induction of mutation and recombination are revealed due to the formation of red colonies on agar plates. The PG-61 and T2 are UV sensitive strains, while PG-80 is sensitive to ionizing radiation. Extremely high frequency electromagnetic field (EHF-EMF) was used. The irradiation was performed in floating mode and frequency changed during exposure from 57 GHz to 62 GHz. The power of irradiation was 100 mkW, and duration of exposure was 10 and 30 min. Treatment was performed at RT and then cells were stored at 28° C during 1 h without any exposure but after that they were treated with UV light (254nm) for 20 sec (strain T2) and 120 sec (strain PG-61 and PG-80). Cell viability and quantity of red colonies were determined after 5 days of cultivation on agar plates. Results: It was determined that EHF-EMF caused 10-20% decrease of viability of T2 and PG-61 strains, while UV showed twice stronger effect (30-70%). EHF-EMF pretreatment increased T2 resistance to UV, and decreased it in PG-61. The PG-80 strain was insensitive to EHF-EMF and no AR effect was determined for this strain. It was not marked any induction of red colonies formation in T2 and PG-80 strain after EHF or UV exposure. The quantity of red colonies was 2 times more in PG-61 strain after EHF-EMF treatment and at least 300 times more after UV exposure. The pretreatment of PG-61 with EHF-EMF caused at least twice increase of viability and consequent decrease of amount of red colonies. Conclusion: EHF-EMF may induce AR in yeast cells and increase their viability under UV treatment.

Keywords: Saccharomyces cerevisiae, EHF-EMF, UV light, adaptive response

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Authors: Alokananda Nath

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Land is an important issue anywhere in the world as it is one of the fundamental elements in human settlements. Since the urban areas are considered to be the drivers of economy for any country across the world and the phenomenon of ‘urbanization’ happening everywhere, there is always a greater pressure on urban land and its management. Many states in India have realized the importance of land as a valuable resource and have implemented certain framework for managing and developing land. But in West Bengal no such statutory framework has been formulated till now and a very out dated model of land acquisition for public purpose is practiced. Due to the lop-sided character of urban growth in the entire eastern region of India, the city of Kolkata continues to bear the burden of excessive growth of population and consequent urbanization of the adjoining areas at a rapid pace. This research tries to look into these conflicts with respect to the present pattern of development in the context of Kolkata and suggest a system for land management in order to implement the planning processes. For this purpose, five case study areas were taken up within the Kolkata Metropolitan Area and subsequent analysis of their present land management and development techniques was done. The findings reveal that there is a lack of political will as well as administrative inefficiency on part of both the development authority and the local bodies. Mostly the local bodies lack the financial resources and technical expertise to work out any kind of land management framework or work out any kind of model in order to manage the development that is happening. All these place undue strain on city infrastructure systems and reduce the potential of cities to contribute as engines of economic growth. The focus of reforms, therefore, ought to be on streamlining the urban planning process, judicious and optimal land use, efficient plan implementation mechanisms, improvement of titling and registration processes.

Keywords: urbanization, land management framework, land development, policy reforms, land-use planning processes

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Authors: Ali̇ Bayram, Semih Dalkilic, Remzi Yigiter

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N-methyl-D-aspartate (NMDA) receptor is a subtype of glutamate receptor and plays a pivotal role in learning, memory, neuronal plasticity, neurotoxicity and synaptic mechanisms. Animal experiments were suggested that glutamate-induced excitotoxic injuriy and NMDA receptor blockage lead to amnesia and other neurodegenerative diseases including Alzheimer’s disease (AD), Huntington’s disease, amyotrophic lateral sclerosis. Aim of this study is to investigate association between NMDA receptor coding gene GRIN2B expression level and Alzheimer disease. The study was approved by the local ethics committees, and it was conducted according to the principles of the Declaration of Helsinki and guidelines for the Good Clinical Practice. Peripheral blood was collected 50 patients who diagnosed AD and 49 healthy control individuals. Total RNA was isolated with RNeasy midi kit (Qiagen) according to manufacturer’s instructions. After checked RNA quality and quantity with spectrophotometer, GRIN2B expression levels were detected by quantitative real time PCR (QRT-PCR). Statistical analyses were performed, variance between two groups were compared with Mann Whitney U test in GraphpadInstat algorithm with 95 % confidence interval and p < 0.05. After statistical analyses, we have determined that GRIN2B expression levels were down regulated in AD patients group with respect to control group. But expression level of this gene in each group was showed high variability. İn this study, we have determined that NMDA receptor coding gene GRIN2B expression level was down regulated in AD patients when compared with healthy control individuals. According to our results, we have speculated that GRIN2B expression level was associated with AD. But it is necessary to validate these results with bigger sample size.

Keywords: Alzheimer’s disease, N-methyl-d-aspartate receptor, NR2B, GRIN2B, mRNA expression, RT-PCR

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Authors: Chetan Gupta, Ramesh Gupta

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Unmanned aerial vehicles, of all sizes, are prime targets of the wing morphing concept as their lightweight structures demand high aerodynamic stability while traversing unsteady atmospheric conditions. In this research study, a hybrid morphing technology is developed to aid the trailing edge of the aircraft wing to alter its camber as a monolithic element rather than functioning as conventional appendages like flaps. Kinematic tailoring, actuation techniques involving shape memory alloys (SMA), piezoelectrics – individually fall short of providing a simplistic solution to the conundrum of morphing aircraft wings. On the other hand, the feature of negligible hysteresis while actuating using compliant mechanisms has shown higher levels of applicability and deliverability in morphing wings of even large aircrafts. This research paper delves into designing a wing section model with a periodic, multi-stable compliant structure requiring lower orders of topological optimization. The design is sub-divided into three smaller domains with external hyperelastic connections to achieve deflections ranging from -15° to +15° at the trailing edge of the wing. To facilitate this functioning, a hybrid actuation system by combining the larger bandwidth feature of piezoelectric macro-fibre composites and relatively higher work densities of shape memory alloy wires are used. Finite element analysis is applied to optimize piezoelectric actuation of the internal compliant structure. A coupled fluid-surface interaction analysis is conducted on the wing section during morphing to study the development of the velocity boundary layer at low Reynold’s numbers of airflow.

Keywords: compliant mechanism, hybrid morphing, piezoelectrics, shape memory alloys

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Authors: C. Sánchez de Rojas Candela, A. Riquelme, P. Rodrigo, M. D. Escalera-Rodríguez, B. Torres, J. Rams

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Selective laser melting is one of the most commonly used AM techniques. In it, a thin layer of metallic powder is deposited, and a laser is used to melt selected zones. The accumulation of layers, each one molten in the preselected zones, gives rise to the formation of a 3D sample with a nearly arbitrary design. To ensure that the properties of the final parts match those of the powder, all the process is carried out in an inert atmosphere, preferentially Ar, although this gas could be substituted. Ti6Al4V alloy is widely used in multiple industrial applications such as aerospace, maritime transport and biomedical, due to its properties. However, due to the demanding requirements of these applications, greater hardness and wear resistance are necessary, together with a better machining capacity, which currently limits its commercialization. To improve these properties, in this study, Selective Laser Melting (SLM) is used to manufacture Ti/TiN metal matrix composites with in-situ and ex-situ titanium nitride reinforcement where the scanning speed is modified (from 28.5 up to 65 mm/s) to study the influence of the processing parameters in SLM. A one-step method of nitriding the Ti6Al4V alloy is carried out to create in-situ TiN reinforcement in a reactive atmosphere and it is compared with ex-situ composites manufactured by previous mixture of both the titanium alloy powder and the ceramic reinforcement particles. The microstructure and mechanical properties of the different Ti/TiN composite materials have been analyzed. As a result, the existence of a similar matrix has been confirmed in in-situ and ex-situ fabrications and the growth mechanisms of the nitrides have been studied. An increase in the mechanical properties with respect to the initial alloy has been observed in both cases and related to changes in their microstructure. Specifically, a greater improvement (around 30.65%) has been identified in those manufactured by the in-situ method at low speeds although other properties such as porosity must be improved for their future industrial applicability.

Keywords: in-situ reinforcement, nitriding reaction, selective laser melting, titanium nitride

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Authors: Robin V. Cupido

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Online dispute resolution has been identified in many countries as a viable alternative for resolving conflicts which have arisen in the so-called digital age. This system of dispute resolution is developing alongside the Internet, and as new types of transactions are made possible by our increased connectivity, new ways of resolving disputes must be explored. Developed nations, such as the United States of America and the European Union, have been involved in creating these online dispute resolution mechanisms from the outset, and currently have sophisticated systems in place to deal with conflicts arising in a number of different fields, such as e-commerce, domain name disputes, labour disputes and conflicts arising from family law. Specifically, in the field of e-commerce, the Internet’s borderless nature has served as a way to promote cross-border trade, and has created a global marketplace. Participation in this marketplace boosts a country’s economy, as new markets are now available, and consumers can transact from anywhere in the world. It would be especially advantageous for developing nations to be a part of this global marketplace, as it could stimulate much-needed investment in these nations, and encourage international co-operation and trade. However, for these types of transactions to proliferate, an effective system for resolving the inevitable disputes arising from such an increase in e-commerce is needed. Online dispute resolution scholarship and practice is flourishing in developed nations, and it is clear that the gap is widening between developed and developing nations in this regard. The potential for implementing online dispute resolution in developing countries has been discussed, but there are a number of obstacles that have thus far prevented its continued development. This paper aims to evaluate the various political, infrastructural and socio-economic challenges faced in developing nations, and to question how these have impacted the acceptance and development of online dispute resolution, scholarship and training of online dispute resolution practitioners and, ultimately, developing nations’ readiness to participate in cross-border e-commerce.

Keywords: developing countries, feasibility, online dispute resolution, progress

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Authors: Monica Enculescu, A. Evanghelidis, I. Enculescu

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Among the numerous methods for obtaining polymer nanofibers, the electrospinning technique distinguishes itself due to the more growing interest induced by its proved utility leading to developing and improving of the method and the appearance of novel materials. In particular, production of polymeric nanofibers in which different dopants are introduced was intensively studied in the last years because of the increased interest for the obtaining of functional electrospun nanofibers. Electrospinning is a facile method of obtaining polymer nanofibers with diameters from tens of nanometers to micrometrical sizes that are cheap, flexible, scalable, functional and biocompatible. Besides the multiple applications in medicine, polymeric nanofibers obtained by electrospinning permit manipulation of light at nanometric dimensions when doped with organic dyes or different nanoparticles. It is a simple technique that uses an electrical field to draw fine polymer nanofibers from solutions and does not require complicated devices or high temperatures. Different morphologies of the electrospun nanofibers can be obtained for the same polymeric host when different parameters of the electrospinning process are used. Consequently, we can obtain tuneable optical properties of the electrospun nanofibers (e.g. changing the wavelength of the emission peak) by varying the parameters of the fabrication method. We focus on obtaining doped polymer nanofibers with enhanced optical properties using the electrospinning technique. The aim of the paper is to produce dye-doped polymer nanofibers’ mats incorporating uniformly dispersed dyes. Transmission and fluorescence of the fibers will be evaluated by spectroscopy methods. The morphological properties of the electrospun dye-doped polymer fibers will be evaluated using scanning electron microscopy (SEM). We will tailor the luminescent properties of the material by doping the polymer (polyvinylpyrrolidone or polymethylmetacrilate) with different dyes (coumarins, rhodamines and sulforhodamines). The tailoring will be made taking into consideration the possibility of changing the luminescent properties of electrospun polymeric nanofibers that are doped with different dyes by using different parameters for the electrospinning technique (electric voltage, distance between electrodes, flow rate of the solution, etc.). Furthermore, we can evaluated the influence of the concentration of the dyes on the emissive properties of dye-doped polymer nanofibers using different concentrations. The advantages offered by the electrospinning technique when producing polymeric fibers are given by the simplicity of the method, the tunability of the morphology allowed by the possibility of controlling all the process parameters (temperature, viscosity of polymeric solution, applied voltage, distance between electrodes, etc.), and by the absence of necessity of using harsh and supplementary chemicals such as the ones used in the traditional nanofabrication techniques. Acknowledgments: The authors acknowledge the financial support received through IFA CEA Project No. C5-08/2016.

Keywords: electrospinning, luminescence, polymer nanofibers, scanning electron microscopy

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Authors: Christine Fräulin, Daniela Schurr, Hamed Shahidi Rad, Gerrit Waters, Günter Rinke, Roland Dittmeyer, Michael Nilles

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The reaction mechanisms of many liquid-phase reactions in organic chemistry have not yet been sufficiently clarified. Process conditions of several hundred degrees celsius and pressures to ten megapascals complicate the sampling and the determination of kinetic data. Space resolved in-situ measurements promises new insights. A non-invasive in-situ measurement technique has the advantages that no sample preparation is necessary, there is no change in sample mixture before analysis and the sampling do no lead to interventions in the flow. Thus, the goal of our research was the development of a contact-free spatially resolved measurement technique for kinetic studies of liquid phase reaction under process conditions. Therefore we used laser Raman spectroscopy combined with an optical transparent microchannel reactor. To show the performance of the system we choose the oxidation of cyclohexane as sample reaction. Cyclohexane oxidation is an economically important process. The products are intermediates for caprolactam and adipic acid, which are starting materials for polyamide 6 and 6.6 production. To maintain high selectivities of 70 to 90 %, the reaction is performed in industry at a low conversion of about six percent. As Raman spectroscopy is usually very selective but not very sensitive the detection of the small product concentration in cyclohexane oxidation is quite challenging. To meet these requirements, an optical experimental setup was optimized to determine the concentrations by laser Raman spectroscopy with respect to good detection sensitivity. With this measurement technique space resolved kinetic studies of uncatalysed and homogeneous catalyzed cyclohexane oxidation were carried out to obtain details about the reaction mechanism.

Keywords: in-situ laser raman spectroscopy, space resolved kinetic measurements, homogeneous catalysis, chemistry

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Authors: Rosario Carmona

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This article aims to discuss the importance of indigenous people participation in climate change mitigation and adaptation. Specifically, it analyses different understandings of climate vulnerability among diverse actors involved in climate change policies in Chile: indigenous people, state officials, and academics. These data were collected through participant observation and interviews conducted during October 2017 and January 2019 in Chile. Following Karen O’Brien, there are two types of vulnerability, outcome vulnerability and contextual vulnerability. How vulnerability to climate change is understood determines the approach, which actors are involved and which knowledge is considered to address it. Because climate change is a very complex phenomenon, it is necessary to transform the institutions and their responses. To do so, it is fundamental to consider these two perspectives and different types of knowledge, particularly those of the most vulnerable, such as indigenous people. For centuries and thanks to a long coexistence with the environment, indigenous societies have elaborated coping strategies, and some of them are already adapting to climate change. Indigenous people from Chile are not an exception. But, indigenous people tend to be excluded from decision-making processes. And indigenous knowledge is frequently seen as subjective and arbitrary in relation to science. Nevertheless, last years indigenous knowledge has gained particular relevance in the academic world, and indigenous actors are getting prominence in international negotiations. There are some mechanisms that promote their participation (e.g., Cancun safeguards, World Bank operational policies, REDD+), which are not absent from difficulties. And since 2016 parties are working on a Local Communities and Indigenous Peoples Platform. This paper also explores the incidence of this process in Chile. Although there is progress in the participation of indigenous people, this participation responds to the operational policies of the funding agencies and not to a real commitment of the state with this sector. The State of Chile omits a review of the structure that promotes inequality and the exclusion of indigenous people. In this way, climate change policies could be configured as a new mechanism of coloniality that validates a single type of knowledge and leads to new territorial control strategies, which increases vulnerability.

Keywords: indigenous knowledge, climate change, vulnerability, Chile

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Authors: Xin Li, Yan-Rong Guo, Jin-Fang Lin, Yi Feng, Håkan Billig, Ruijin Shao

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Background: Young women with polycystic ovary syndrome (PCOS) have a high risk of developing endometrial carcinoma. There is a need for the development of new medical therapies that can reduce the need for surgical intervention so as to preserve the fertility of these patients. The aim of the study was to describe and discuss cases of PCOS and insulin resistance (IR) women with early endometrial carcinoma while being co-treated with Diane-35 and metformin. Methods: Five PCOS-IR women who were scheduled for diagnosis and therapy for early endometrial carcinoma were recruited. The hospital records and endometrial pathology reports were reviewed. All patients were co-treated with Diane-35 and metformin for 6 months to reverse the endometrial carcinoma and preserve their fertility. Before, during, and after treatment, endometrial biopsies and blood samples were obtained and oral glucose tolerance tests were performed. Endometrial pathology was evaluated. Body weight (BW), body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), insulin area under curve (IAUC), and homeostasis model assessment of insulin resistance (HOMA-IR) were determined. Results: Clinical stage 1a, low grade endometrial carcinoma was confirmed before treatment. After 6 months of co-treatment, all patients showed normal epithelia. No evidence of atypical hyperplasia or endometrial carcinoma was found. Co-treatment resulted in significant decreases in BW, BMI, TT, FAI, IAUC, and HOMA-IR in parallel with a significant increase in SHBG. There were no differences in the FSH and LH levels after co-treatment. Conclusions: Combined treatment with Diane-35 and metformin has the potential to revert the endometrial carcinoma into normal endometrial cells in PCOS-IR women. The cellular and molecular mechanisms behind this effect merit further investigation.

Keywords: PCOS, progesterone resistance, insulin resistance, steroid hormone receptors, endometrial carcinoma

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Authors: Yusif Habib

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The Volta River Basin (VRB) is a transboundary resource shared by Six (6) the West African States. It’s utilization spans across irrigation, hydropower generation, domestic/household water use, transportation, industrial processing, among others. Simultaneously, mineral resources such as gold are mined within the VRB catchment. Typically, the extraction/mining operation is earth-surface excavation; known as Artisanal and Small-scale mining. We developed a conceptual framework in the context of Water-Energy-Food (WEF) Nexus to delineate the trade-offs and synergies between the mineral extractive operation’s impact on Agricultural systems, specifically, cereal crops (e.g. Maize, Millet, and Rice) and the environment (water and soil quality, deforestation, etc.) on the VRB. Thus, the study examined the trade-offs and synergies through the WEF nexus lens to explore the extent of an eventual overarching mining preference for gold exploration with high economic returns as opposed to the presumably low yearly harvest and household income from food crops production to inform intervention prioritization. Field survey (household, expert, and stakeholder consultation), bibliometric analysis/literature review, scenario, and simulation models, including land-use land cover (LULC) analyses, were conducted. The selected study area(s) in Ghana was the location where the mineral extractive operation’s presence and impact are widespread co-exist with the Agricultural systems. Overall, the study proposes mechanisms of the virtuous cycle through FEW Nexus instead of the presumably existing vicious cycle to inform decision making and policy implementation.

Keywords: agriculture, environmental sustainability, gold Mining, synergies, trade-off, water-energy-food nexus

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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