Search results for: heart failure reversal therapy

Authors: Zahra Mohajer, Afsaneh Soltani

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Doping is a major issue in competitive sports and is favored by vast groups of athletes. The feeling of being higher-ranking than others and gaining fame has caused many athletes to misuse drugs. The definition of doping is to use prohibited substances and/or methods that help physical or mental performances or both. Doping counts as the illegal use of chemical substances or drugs, excessive amounts of physiological substances to increase the performance at or out of competition or even the use of inappropriate medications to treat an injury to gain the ability to participate in a competition. The International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have forbidden these substances to ensure fair and equal competition and also the health of the competitors. As of 2004 WADA has published an international list of illegal substances used for doping, which is updated annually. In the process of the Genome Project scientists have gained the ability to treat numerous diseases by gene therapy, which may result in bodily performance increase and therefore a potential opportunity to misuse by some athletes. Gene doping is defined as the non-therapeutic direct and indirect genetic modifications using genetic materials that can improve the performances in sports events. Biosynthetic drugs are a form of indirect genetic engineering. The method can be performed in three ways such as injecting the DNA directly into the muscle, inserting the genetically engineered cells, or transferring the DNA using a virus as a vector. Erythropoietin is a hormone majorly released by the kidney and in small amounts by the liver. Its function is to stimulate the erythropoiesis and therefore the more production of red blood cells (RBC) which causes an increase in Hemoglobin (Hb). During this process, the oxygen delivery to muscles will increase, which will improve athletic performance and postpone exhaustion. There are ways to increase the oxygen transferred to muscles such as blood transfusion, stimulating the production of red blood cells by using Erythropoietin (EPO), and also using allosteric effectors of Hemoglobin. EPO can either be injected as a protein or can be inserted into the cells as the gene which encodes EPO. Adeno-associated viruses have been employed to deliver the EPO gene to the cells. Employing the genes that naturally exist in the human body such as the EPO gene can reduce the risk of detecting gene doping. The first research about blood doping was conducted in 1947. The study has shown that an increase in hematocrit (HCT) up to 55% following homologous transfusion makes it more unchallenging for the body to perform the exercise at the altitude. Thereafter athletes’ attraction to blood infusion escalated. Also, a study has demonstrated that by reinfusing their own blood 4 weeks after being drawn, three men have shown a rise in Hb level which improved the oxygen uptake, and a delay in exhaustion. The list of performance-enhancing drugs is published by WADA annually and includes the following drugs: anabolic agents, hormones, Beta-2 agonists, Beta-blockers, Diuretics, Stimulants, narcotics, cannabinoids, and corticosteroids.

Keywords: doping, PEDs, sports, WADA

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Authors: Kitoholi V. Zhimo

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Unlike the cases of cases of homosexuals, haemophilic and or drug users in USA, France, Africa and other countries, in India the first case of HIV/AIDS was detected in heterosexual female sex workers (FSW) in Chennai in 1986. This image played an important role in understanding HIV/AIDS scenario in the country. Similar to popular and dominant metaphors on HIV/AIDS such as ‘gay plague’, ‘new cancer’, ‘lethal disease’, ‘slim disease’, ‘foreign disease’, ‘junkie disease’, etc. around the world, the social construction of the virus was largely attributed to women in India. It was established that women particularly sex workers are ‘carrier’ and ‘transmitter’ of virus and were categorised as High Risk Groups (HRG’s) alongside homosexuals, transgenders and injecting drug users. Recent literature reveals growing rate of HIV infection among housewives since 1997 which revolutionised public health scenario in India. This means shift from high risk group to general public through ‘bridge population’ encompassing long distance truckers and migrant labours who at the expense of their nature of work and mobility comes in contact with HRG’s and transmit the virus to the general public especially women who are confined to the domestic space. As HIV epidemic expands, married women in monogamous relationship/marriage stand highly susceptible to infection with limited control, right and access over their sexual and reproductive health and planning. In context of Nagaland, a small state in North-eastern part of India HIV/AIDS transmission through injecting drug use dominated the early scene of the epidemic. However, paradigm shift occurred with declining trend of HIV prevalence among injecting drug users (IDU’s) over the past years with the introduction of Opioid Substitution Therapy (OST) and easy access/availability of syringes and injecting needles. Reflection on statistical data reveals that out of 36 states and union territories in India, the position of Nagaland in HIV prevalence among IDU’s has significantly dropped down from 6th position in 2003 to 16th position in 2017. The present face of virus in Nagaland is defined by (hetero) sexual mode of transmission which accounts for about 91% of as reported by Nagaland state AIDS control society (NSACS) in 2016 wherein young and married woman were found to be most affected leading to feminization of HIV/AIDS epidemic in the state. Thus, not only is HIV epidemic feminised but emerged victim to domestic violence which is more often accepted as normal part of heterosexual relationship. In the backdrop of these understanding, the present paper based on ethnographic fieldwork explores the plight, lived experiences and images of HIV+ve women with regard to sexual and reproductive rights against the backdrop of patriarchal system in Nagaland.

Keywords: HIV/AIDS, monogamy, Nagaland, sex worker disease, women

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Authors: Ignitia Motjolopane

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Small and medium enterprises (SMEs) play an important role in economies by contributing to economic growth and employment. In the fourth industrial revolution, the convergence of technologies and the changing nature of work created pressures on economies globally. Generative artificial intelligence (AI) may support SMEs in exploring, exploiting, and transforming business models to align with their growth aspirations. SMEs' growth aspirations fall into four categories: subsistence, income, growth, and speculative. Subsistence-oriented firms focus on meeting basic financial obligations and show less motivation for business model innovation. SMEs focused on income, growth, and speculation are more likely to pursue business model innovation to support growth strategies. SMEs' strategic goals link to distinct business model innovation paths depending on whether SMEs are starting a new business, pursuing growth, or seeking profitability. Integrating generative artificial intelligence in start-up SME business model innovation enhances value creation, user-oriented innovation, and SMEs' ability to adapt to dynamic changes in the business environment. The existing literature may lack comprehensive frameworks and guidelines for effectively integrating generative AI in start-up reiterative business model innovation paths. This paper examines start-up business model innovation path with generative artificial intelligence. A theoretical approach is used to examine start-up-focused SME reiterative business model innovation path with generative AI. Articulating how generative AI may be used to support SMEs to systematically and cyclically build the business model covering most or all business model components and analyse and test the BM's viability throughout the process. As such, the paper explores generative AI usage in market exploration. Moreover, market exploration poses unique challenges for start-ups compared to established companies due to a lack of extensive customer data, sales history, and market knowledge. Furthermore, the paper examines the use of generative AI in developing and testing viable value propositions and business models. In addition, the paper looks into identifying and selecting partners with generative AI support. Selecting the right partners is crucial for start-ups and may significantly impact success. The paper will examine generative AI usage in choosing the right information technology, funding process, revenue model determination, and stress testing business models. Stress testing business models validate strong and weak points by applying scenarios and evaluating the robustness of individual business model components and the interrelation between components. Thus, the stress testing business model may address these uncertainties, as misalignment between an organisation and its environment has been recognised as the leading cause of company failure. Generative AI may be used to generate business model stress-testing scenarios. The paper is expected to make a theoretical and practical contribution to theory and approaches in crafting a robust business model innovation path with generative artificial intelligence in start-up SMEs.

Keywords: business models, innovation, generative AI, small medium enterprises

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Authors: Armine Vahanyan

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Humanity has been still coping with the new COVID-19 pandemic. Healthcare providers, economists, psychologists, and other specialists speak about the impact of the virus on different spheres of our life. In the list of similar discussions, the impact of pandemics on global education is of utmost importance. Ideally, providing quality education services should be crucial, and the ways education programs are being adapted will determine the success or failure of the service providers. The paper aims to summarize the research touching upon the current situation of higher education in Armenia. The research includes data from official reports, surveys among education leads, faculty, and students, as well as personal observations and consideration. Through descriptive analysis, the findings of the research are being presented from various aspects. Interim results of the research unveiled two major issues in the sector of higher education in Armenia. On the one hand, the entire compulsory digitization of instruction, assessment, and grading has evoked serious gaps related to the lack of technical competencies. There is an urgent need for professional development programs that will address most of the concerns due to the shift to the online instruction mode. On the other hand, online teaching and learning require revision and adaptation of the existing curricula. Given that the content of certain programs may not be compromised, the teaching methods, the assignments, and evaluation require profound transformation, which will still be in line with course learning outcomes and student learning outcomes. The given paper focuses on the ways the mentioned issues are being addressed in Armenia. The extent of commitment for changes and adaptability to the new situation varies from the government-funded and private universities. In particular, the paper compares and contrasts activities and measures taken at the Armenian State Pedagogical University and the American University of Armenia. Thus, the Pedagogical University focused on the use of Google Classroom as the only means for teaching and learning as well as adopted the compulsory synchronous instruction mode. The American University, on the contrary, kept practicing the academic freedom, enabling both synchronous and asynchronous instruction modes, ensuring alignment of the course learning outcomes and student learning outcomes. The State University utilized the assignments and assessment, which would work for the on-campus instruction mode, while the American university employed a variety of assignments applicable for online teaching mode. The latter has suggested the utilization of multiple apps, internet sources, and online library access for a better online instant. Discussions with faculty through online forums and/or professional development workshops also facilitate restructuring and adaptation of the courses. Finally, the paper will synthesize the results of the undertaken research and will outline the e-learning perspectives and opportunities boosted by the known devastating healthcare issue.

Keywords: assessment, compulsory digitization of education services, online teaching, instruction mode, program restructuring

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Authors: S. Raghibdoust, E. Kamari

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Research show that reduced functional hearing has a detrimental influence on the ability of an individual to establish proper phonological representations of words, since the phonological representations are claimed to mediate the conceptual processing of written words. Word processing efficiency is expected to decrease with a decrease in functional hearing. In other words, it is predicted that hearing individuals would be more capable of word processing than individuals with hearing loss, as their functional hearing works normally. Studies also demonstrate that the quality of the functional hearing affects reading comprehension via its effect on their word processing skills. In other words, better hearing facilitates the development of phonological knowledge, and can promote enhanced strategies for the recognition of written words, which in turn positively affect higher-order processes underlying reading comprehension. The aims of this study were to investigate and compare the effect of deafness on the participants’ abilities to process written words at the lexical and sentence levels through using two online and one offline reading comprehension tests. The performance of a group of 8 deaf male students (ages 8-12) was compared with that of a control group of normal hearing male students. All the participants had normal IQ and visual status, and came from an average socioeconomic background. None were diagnosed with a particular learning or motor disability. The language spoken in the homes of all participants was Persian. Two tests of word processing were developed and presented to the participants using OpenSesame software, in order to measure the speed and accuracy of their performance at the two perceptual and conceptual levels. In the third offline test of reading comprehension which comprised of semantically plausible and semantically implausible subject relative clauses, the participants had to select the correct answer out of two choices. The data derived from the statistical analysis using SPSS software indicated that hearing and deaf participants had a similar word processing performance both in terms of speed and accuracy of their responses. The results also showed that there was no significant difference between the performance of the deaf and hearing participants in comprehending semantically plausible sentences (p > 0/05). However, a significant difference between the performances of the two groups was observed with respect to their comprehension of semantically implausible sentences (p < 0/05). In sum, the findings revealed that the seriously impoverished sentence reading ability characterizing the profound deaf subjects of the present research, exhibited their reliance on reading strategies that are based on insufficient or deviant structural knowledge, in particular in processing semantically implausible sentences, rather than a failure to efficiently process written words at the lexical level. This conclusion, of course, does not mean to say that deaf individuals may never experience deficits at the word processing level, deficits that impede their understanding of written texts. However, as stated in previous researches, it sounds reasonable to assume that the more deaf individuals get familiar with written words, the better they can recognize them, despite having a profound phonological weakness.

Keywords: deafness, reading comprehension, reading strategy, word processing, subject and object relative sentences

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Authors: Maha E. Ibrahim, Mona Abdel Aziz

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Background: Chronic low back pain (CLBP) in urban communities represents a challenge to healthcare systems worldwide. The traditional biomedical approach to back pain has been particularly inadequate. Failure of the biomedical model to explain the poor correlation between pain and disability on the one hand, and biological and physical factors that explain those symptoms on the other has led to the adoption of the biopsychosocial model, to recognize the reciprocal influence of physical, social and psychological factors implicated in CLBP, a condition that shows higher prevalence among women residing in urban areas. Urban design of the built community has been shown to exert a significant influence on physical and psychological health. However, little research has investigated the relationship between elements of the built environment, and the level of pain and disability of women with CLBP. As Egypt embarks on building a new capital city, and new settlements proliferate, better understanding of this relationship could greatly reduce the economic and human costs of this widespread medical problem for women. Methods: This study was designed as an exploratory mixed qualitative and quantitative study. Twenty-Six women with CLBP living in two neighborhoods in Cairo, different in their urban structure, but adjacent in their locations (Old Maadi and New Maadi) were interviewed using semi-structured interviews (8 from Old Maadi and 18 from New Maadi). Located in the South of Cairo, New Maadi is a neighborhood with the characteristic modern urban style (narrow streets and tall, adjacent buildings), while Old Maadi is known for being greener, quieter and more relaxed than the usual urban districts of Cairo. The interviews examined their perceptions of the built environment, including building shapes and colors and street light, as well as their sense of safety and comfort, and how it affects their physical and psychological health in general, and their back condition in particular. In addition, they were asked to rate their level of pain and to fill the Oswestry Disability Index (ODI), and the General Health Questionnaire (GHQ-12) to rate their level of disability and psychological status, respectively. Results: Women in both districts had moderate to severe pain and moderate disability with no significant differences between the two districts. However, those living in New Maadi had significantly worse scores on the GHQ-12 than those living in Old Maadi. Most women did not feel that specific elements of the built environment affected their back pain, however, they expressed distress of the elements that were ugly, distorted or damaged, especially where there were no ways of avoiding or fixing them. Furthermore, most women affirmed that the unsightly and uncomfortable elements of their neighborhoods affected their mood states and were a constant source of stress. Conclusion: This exploratory study concludes that elements of the urban built environment do not exert a direct effect on CLBP. However, the perception of women regarding these elements does affect their mood states, and their levels of stress, making them a possible indirect cause of increased suffering in these women.

Keywords: built environment, chronic back pain, disability, urban Cairo

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Authors: Lilian Nantume Wampande

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Group-based strategies in the delivery of HIV care have opened up new avenues not only for meaningful participation for HIV positive people but also platforms for deconstruction and reconstruction of knowledge about living with the virus. Yet the contributions of such strategies among patients who live in high risk areas are still not explored. This case study research assessed the impact of HIV support networks on sexual health outcomes of HIV positive out-of-school adolescents residing in fishing islands of Kalangala in Uganda. The study population was out-of-school adolescents living with HIV and their sexual partners (n=269), members of their households (n=80) and their health service providers (n=15). Data were collected via structured interviews, observations and focus group discussions between August 2016 and March 2017. Data was then analyzed inductively to extract key themes related to the approaches and outcomes of the groups’ activities. The study findings indicate that support groups unite HIV positive adolescents in a bid for social renegotiation to achieve change but individual constraints surpass the groups’ intentions. Some adolescents for example reported increased fear which led to failure to cope, sexual violence, self-harm and denial of status as a result of the high expectations placed on them as members of the support groups. Further investigations around this phenomenon show that HIV networks play a monotonous role as information sources for HIV positive out-of-school adolescents which limit their creativity to seek information elsewhere. Results still indicate that HIV adolescent groups recognize the complexity of long-term treatment and stay in care leading to improved immunity for the majority yet; there is still scattered evidence about how effective they are among adolescents at different phases in the disease trajectory. Nevertheless, the primary focus of developing adolescent self-efficacy and coping skills significantly address a range of disclosure difficulties and supports autonomy. Moreover, the peer techniques utilized in addition to the almost homogeneous group characteristics accelerates positive confidence, hope and belongingness. Adolescent HIV-support groups therefore have the capacity to both improve and/or worsen sexual health outcomes for a young adolescent who is out-of-school. Communication interventions that seek to increase awareness about ‘self’ should therefore be emphasized more than just fostering collective action. Such interventions should be sensitive to context and gender. In addition, facilitative support supervision done by close and trusted health care providers, most preferably Village Health Teams (who are often community elected volunteers) would help to follow-up, mentor, encourage and advise this young adolescent in matters involving sexuality and health outcomes. HIV/AIDS prevention programs have extended their efforts beyond individual focus to those that foster collective action, but programs should rekindle interpersonal level strategies to address the complexity of individual behavior.

Keywords: adolescent, HIV, support groups, Uganda

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Authors: Alec Chabwinja, Cannan Tawonezvi, Jerneja Vidmar, Constance Chingwaru, Walter Chingwaru

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Objective: To evaluate the potential of commercial fermented / probiotic products available in Zimbabwe or internationally, and strains of Lactobacillus plantarum (L. plantarum) as prophylaxis and therapy against diarrhoeal and sexually transmitted infections. Methods: The antimicrobial potential of cultures of lactobacilli enriched from 4 Zimbabwean commercial food/beverage products, namely Dairibord Lacto sour milk (DLSM), Probrand sour milk (PSM), Kefalos Vuka cheese (KVC) and Chibuku opaque beer (COB); three probiotic products obtainable in Europe and internationally; and four strains of L. plantarum obtained from Balkan traditional cheeses and Zimbabwean foods against clinical strains of Escherichia coli (E. coli) and non-clinical strains of Candida albicans and Rhodotorula spp. was assayed using the well diffusion method. Three commercial Agar diffusion assay and a competitive exclusion assay were carried out on Mueller-Hinton agar. Results: Crude cultures of putative lactobacillus strains obtained from Zimbabwean dairy products (Probrand sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer) exhibited significantly greater antimicrobial activities against clinical strains of E. coli than strains of L. plantarum isolated from Balkan cheeses (CLP1, CLP2 or CLP3) or crude microbial cultures from commercial paediatric probiotic products (BG, PJ and PL) of a culture of Lactobacillus rhamnosus LGG (p < 0.05). Furthermore, the following has high antifungal activities against the two yeasts: supernatant-free microbial pellet (SFMP) from an extract of M. azedarach leaves (27mm ± 2.5) > cell-free culture supernatants (CFCS) from Maaz Dairy sour milk and Mnandi sour milk (approximately 26mm ± 1.8) > CFCS and SFMP from Amansi hodzeko (25mm ± 1.5) > CFCS from Parinari curatellifolia fruit (24mm ± 1.5), SFMP from P. curatellifolia fruit (24mm ± 1.4) and SFMP from mahewu (20mm ± 1.5). These cultures also showed high tolerance to acidic conditions (~pH4). Conclusions: The putative lactobacilli from four commercial Zimbabwean dairy products (Probrand sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer), and three strains of L. plantarum from Balkan cheeses (CLP1, CLP2 or CLP3) exhibited high antibacterial activities, while Maaz Dairy sour-, Mnandi sour- and Amansi hodzeko milk products had high antifungal activities. Our selection of Zimbabwean probiotic products has potential for further development into probiotic products for use in the control diarrhea caused by pathogenic strains of E. coli or yeast infections. Studies to characterise the probiotic potential of the live cultures in the products are underway.

Keywords: lactic acid bacteria, Staphylococcus aureus, Streptococcus spp, yeast, inhibition, acid tolerance

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Authors: A. Moghadasein, M. Ghasemi, S. Fazelifar

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Aim: Chemerin is a novel adipokine that play an important role in regulating lipid metabolism and abiogenesis. Chemerin is dependent on autocrine and paracrine signals for the differentiation and maturation of fat cells; it also regulates glucose uptake in fat cells and stimulates lipolysis. It has been reported that in adipocytes, chemerin enhances the insulin-stimulated glucose and causes the phosphorylation of tyrosine in Insulin receptor substrate. According to the studies, Chemerin may increase insulin sensitivity in adipose tissue and is largely associated with Body mass index, triglycerides, and blood pressure in those with normal glucose tolerance. There is limited information available regarding the effect of exercise training on serum chemerin concentrations. The purpose of this study was to investigate the effect of endurance training on serum chemerin levels and lipids of plasma in overweight women. Methodology: This study was a quasi-experimental research with a pre-post test design. After required examination and verification of high pressure by the physician, 22 obese subjects (age: 35.64±5.55 yr, weight: 75.62±9.30 kg, body mass index: 32.4±1.6 kg/m2) were randomly assigned to aerobic training (n= 12) and control (n= 12) groups. Participants completed a questionnaire indicating the lack of sports history during the past six months, the lack of anti-hypertension drugs use, hormone therapy, cardiovascular problems, and complete stoppage of menstrual cycle. Aerobic training was performed 3 times weekly for 8 weeks. Resting levels of chemerin plasma, metabolic parameters were measured prior to and after the intervention. The control group did not participate in any training program. In this study, ethical considerations included the complete description of the objectives to the study participants, ensuring the confidentiality of their information. Kolmogorov-Smirnov and Levin test were used for determining the normal distribution of data and homogeneity of variances, respectively. Analyze of variance with repeated measure were used to investigate the changes in the intra-group and the differences in inter-group of variables. Statistical operations were performed using SPSS 16 and the significance level of the tests was considered at P < 0.05. Results: After an 8 week aerobic training, levels of chemerin plasma were significantly decreased in aerobic trained group when compared with their control groups (p < 0.05).Concurrently, levels of HDL-c were significantly decreased (p < 0.05) whereas, levels of cholesterol, TG and LDL-c, showed no significant changes (p > 0.05). No significant correlations between chemerin levels and weight loss were observed in subjects with overweight women. Conclusion: The present study demonstrated, 8 weeks aerobic training, reduced serum chemerin concentrations in overweight women. Whereas, aerobic training exercise programmers affected the lipid profile response of obese subjects differently. However further research is warranted in order to unravel the molecular mechanism for the range of responses and the role of serum chemerin.

Keywords: chemerin, aerobic training, lipid profile, obese women

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Authors: Indre Brazauskaite, Vilte Auruskeviciene

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Significance of the study is outlined through current strategic management challenges faced by SMEs. First, innovation is recognized as competitive advantage in the market, having ever changing market conditions. It is of constant interest from both practitioners and academics to capture and capitalize on business opportunities or mitigate the foreseen risks. Secondly, it is recognized that integrated system is needed for proper implementation of innovation process, especially during the period of business incubation, associated with relatively high risks of new product failure. Finally, ability to successful commercialize innovations leads to tangible business results that allow to grow organizations further. This is particularly relevant to SMEs due to limited structures, resources, or capabilities. Cooperation between scientific and business institutions could be a tool of mutual interest to observe, address, and further develop innovations during the incubation period, which is the most demanding and challenging during the innovation process. Material aims to address the following problematics: i) indicate the major barriers and challenges in innovation process that SMEs are facing, ii) outline the possibilities for these barriers and challenges to be addressed by cooperation between scientific and business institutions. Basis for this research is stage-by-stage integrated innovation management process which presents existing challenges and needed aid in operational decision making. The stage-by-stage innovation management process exploration highlights relevant research opportunities that have high practical relevance in the field. It is expected to reveal the possibility for business incubation programs that could combine interest from both – practices and academia. Methodology. Scientific meta-analysis of to-date scientific literature that explores innovation process. Research model is built on the combination of stage-gate model and lean six sigma approach. It outlines the following steps: i) pre-incubation (discovery and screening), ii) incubation (scoping, planning, development, and testing), and iii) post-incubation (launch and commercialization) periods. Empirical quantitative research is conducted to address barriers and challenges related to innovation process among SMEs that limits innovations from successful launch and commercialization and allows to identify potential areas for cooperation between scientific and business institutions. Research sample, high level decision makers representing trading SMEs, are approached with structured survey based on the research model to investigate the challenges associated with each of the innovation management step. Expected findings. First, the current business challenges in the innovation process are revealed. It will outline strengths and weaknesses of innovation management practices and systems across SMEs. Secondly, it will present material for relevant business case investigation for scholars to serve as future research directions. It will contribute to a better understanding of quality innovation management systems. Third, it will contribute to the understanding the need for business incubation systems for mutual contribution from practices and academia. It can increase relevance and adaptation of business research.

Keywords: cooperation between scientific and business institutions, innovation barriers and challenges, innovation measure, innovation process, SMEs

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Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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Authors: Tamrat Girma Biru

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Multidrug-resistant tuberculosis (MDR-TB) is defined as resistant to at least Refampicin and Isoniazed: the most two power full TB drugs. It is a leading cause of high rates of morbidity and mortality, and increasing psychosocial challenges to patients, especially when co-infected with Human Immunodeficiency Virus (HIV). Ethiopia faces the highest rates of MDR-TB infection in the world. Objectives: The main objective of this study was to identify the psychosocial challenges of MDR-TB patients, to investigate the extent of the psychosocial challenges on (self-esteem, depression, and stigma) that MDR-TB patients encounter, to examine whether there is a sex difference in experiencing psychosocial challenges and assess the counseling needs of MDR-TB patients. Methodology: A cross-sectional study was conducted at St. Peter TB Specialized Hospital, Addis Ababa on 40 patients (25 males and 15 females) who are hospitalized for treatment. The patients were identified by using purposive sampling and made fill a questionnaire measuring their level of self-esteem, depression and stigma. Besides, data were collected from 16 participants, 28 care providers and 8 guardians, using semi-structured interview. The obtained data were analyzed using SPSS statistical program, descriptive statistics, independent t-test, and qualitative description. Results and Discussion: The results of the study showed that the majority (80%) of the respondents had suffered psychological challenges and social discriminations. Thus, the significance of MDR-TB and its association with HIV/AIDS problems is considered. Besides the psychosocial challenges, various aggravating factors such as length of treatment, drug burden and insecurity in economy together highly challenges the life of patients. In addition, 60% of participants showed low level of self-esteem. The patients also reported that they experienced high self-stigma and stigma by other members of the society. The majority of the participants (75%) showed moderate and severe level of depression. In terms of sex there is no difference between the mean scores of males and females in the level of depression and stigmatization by others and by themselves. But females showed lower level of self-esteem than males. The analysis of the t-test also shows that there were no statistically significant sex difference on the level of depression and stigma. Based on the qualitative data MDR-TB patients face various challenges in their life sphere such as: Psychological (depression, low self value, lowliness, anxiety), social (stigma, isolation from social relations, self-stigmatization,) and medical (drug side effect, drug toxicity, drug burden, treatment length, hospital stays). Recommendations: Based on the findings of this study possible recommendations were forwarded: develop and extend MDR-TB disease awareness creation through by media (printing and electronic), school net TB clubs, and door to door community education. Strengthen psychological wellbeing and social relationship of MDR-TB patients using proper and consistent psychosocial support and counseling. Responsible bodies like Ministry of Health (MOH) and its stakeholders and Non Governmental Organizations (NGOs) need to assess the challenges of patients and take measures on this pressing issue.

Keywords: psychosocial challenges, counseling, multi-drug resistant tuberculosis (MDR-TB), tuberculosis therapy

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Authors: Monika Patel, Kazuaki Matsumura

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Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

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Authors: Tomofumi Kubota, Mitsuhiro Okayasu

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In recent years, environmental problems and energy problems typified by global warming are intensifying, and transportation devices are required to reduce the weight of structural materials from the viewpoint of strengthening fuel efficiency regulations and energy saving. Carbon fiber reinforced plastic (CFRP) used in this research is attracting attention as a structural material to replace metallic materials. Among them, thermoplastic CFRP is expected to expand its application range in terms of recyclability and cost. High formability and weldability of the unidirectional CFRP sheets conducted by a proposed hot stamping process were proposed, in which the carbon fiber reinforced plastic sheets are heated by a designed technique. In this case, the CFRP sheets are heated by the high electric voltage applied through carbon fibers. In addition, the electric voltage was controlled by the area ratio of exposed carbon fiber on the sample surfaces. The lower exposed carbon fiber on the sample surface makes high electric resistance leading to the high sample temperature. In this case, the CFRP sheets can be heated to more than 150 °C. With the sample heating, the stamping and welding technologies can be carried out. By changing the sample temperature, the suitable stamping condition can be detected. Moreover, the proper welding connection of the CFRP sheets was proposed. In this study, we propose a fusion bonding technique using thermoplasticity, high current flow, and heating caused by electrical resistance. This technology uses the principle of resistance spot welding. In particular, the relationship between the carbon fiber exposure rate and the electrical resistance value that affect the bonding strength is investigated. In this approach, the mechanical connection using rivet is also conducted to make a comparison of the severity of welding. The change of connecting strength is reflected by the fracture mechanism. The low and high connecting strength are obtained for the separation of two CFRP sheets and fractured inside the CFRP sheet, respectively. In addition to the two fracture modes, micro-cracks in CFRP are also detected. This approach also includes mechanical connections using rivets to compare the severity of the welds. The change in bond strength is reflected by the destruction mechanism. Low and high bond strengths were obtained to separate the two CFRP sheets, each broken inside the CFRP sheets. In addition to the two failure modes, micro cracks in CFRP are also detected. In this research, from the relationship between the surface carbon fiber ratio and the electrical resistance value, it was found that different carbon fiber ratios had similar electrical resistance values. Therefore, we investigated which of carbon fiber and resin is more influential to bonding strength. As a result, the lower the carbon fiber ratio, the higher the bonding strength. And this is 50% better than the conventional average strength. This can be evaluated by observing whether the fracture mode is interface fracture or internal fracture.

Keywords: CFRP, hot stamping, weliding, deforamtion, mechanical property

Procedia PDF Downloads 105

Authors: Abdulkadir Sarauta

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Almost every type of industrial process involves the release of trace quantity of toxic organic and inorganic compound that up in receiving water bodies, this study was aimed at assessing the Persistent Organic Pollutant Level in Challawa River Basin of Kano State, Nigeria. And the research formed the basis of identifying the presence of PCBs and PAHs in receiving water bodies in the study area, assessing the PCBs and PAHs concentration in receiving water body of Challawa system, evaluate the concentration level of PCBs and PAHs in fishes in the study area, determine the concentration level of PCBs and PAHs in crops irrigated in the study area as well as compare the concentration of PCBs and PAHs with the acceptable limit set by Nigerian, EU, U.S and WHO standard. Data were collected using reconnaissance survey, site inspection, field survey, laboratory experiment as well as secondary data source. A total of 78 samples were collected through stratified systematic random sampling (i.e., 26 samples for each of water, crops and fish) three sampling points were chosen and designated A, B and C along the stretch of the river (i.e. up, middle, and downstream) from Yan Danko Bridge to Tambirawa bridge. The result shows that the Polychlorinated biphenyls (PCBs) was not detected while, polycyclic aromatic hydrocarbons (PAHs) was detected in the whole samples analysed at the trench of Challawa River basin in order to assess the contribution of human activities to global environmental pollution. The total concentrations of ΣPAH and ΣPCB ranges between 0.001 to 0.087mg/l and 0.00 to 0.00mg/l of water samples While, crops samples ranges between 2.0ppb to 8.1ppb and fish samples ranges from 2.0 to 6.7ppb.The whole samples are polluted because most of the parameters analyzed exceed the threshold limits set by WHO, Nigerian, U.S and EU standard. The analytical results revealed that some chemicals are present in water, crops and fishes are significantly very high at Zamawa village which is very close to Challawa industrial estate and also is main effluent discharge point and drinking water around study area is not potable for consumption. Analysis of Variance was obtained by Bartlett’s test performance. There is only significant difference in water because the P < 0.05 level of significant, But there is no difference in crops concentration they have the same performance, likes wise in the fishes. It is said to be of concern to health hazard which will increase incidence of tumor related diseases such as skin, lungs, bladder, gastrointestinal cancer, this show there is high failure of pollution abatement measures in the area. In conclusion, it can be said that industrial activities and effluent has impact on Challawa River basin and its environs especially those that are living in the immediate surroundings. Arising from the findings of this research some recommendations were made the industries should treat their liquid properly by installing modern treatment plants.

Keywords: Challawa River Basin, organic, persistent, pollutant

Procedia PDF Downloads 557

Authors: Anja I. Petrov, Milica B. Veljković, Marija M. Ćorović, Ana D. Milivojević, Milica B. Simović, Katarina M. Banjanac, Dejan I. Bezbradica

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One of the fundamental requirements for overall human well-being is a stable and balanced microbiome. Aside from the microorganisms that reside within the body, a large number of microorganisms, especially bacteria, swarming the human skin is in homeostasis with the host and represents a skin microbiota. Even though the immune system of the skin is capable of distinguishing between commensal and potentially harmful transient bacteria, the cutaneous microbial balance can be disrupted under certain circumstances. In that case, a reduction in the skin microbiota diversity, as well as changes in metabolic activity, results in dermal infections and inflammation. Probiotics and prebiotics have the potential to play a significant role in the treatment of these skin disorders. The most common resident bacteria found on the skin, Staphylococcus epidermidis, can act as a potential skin probiotic, contributing to the protection of healthy skin from pathogen colonization, such as Staphylococcus aureus, which is related to atopic dermatitis exacerbation. However, as it is difficult to meet regulations in cosmetic products, another therapy approach could be topical prebiotic supplementation of the skin microbiota. In recent research, polyphenols are attracting scientists' interest as biomolecules with possible prebiotic effects on the skin microbiota. This research aimed to determine how herbal extracts rich in different polyphenolic compounds (lemon balm, St. John's wort, coltsfoot, pine needle, and yarrow) affected the growth of S. epidermidis and S. aureus. The first part of the study involved screening plants to determine if they could be regarded as probable candidates to be skin prebiotics. The effect of each plant on bacterial growth was examined by supplementing the nutrient medium with their extracts and comparing it with control samples (without extract). The results obtained after 24 h of incubation showed that all tested extracts influenced the growth of the examined bacteria to some extent. Since lemon balm and St. John's wort extracts displayed bactericidal activity against S. epidermidis, whereas coltsfoot inhibited both bacteria equally, they were not explored further. On the other hand, pine needles and yarrow extract led to an increase in S. epidermidis/S. aureus ratio, making them prospective candidates to be used as skin prebiotics. By examining the prebiotic effect of two extracts at different concentrations, it was revealed that, in the case of yarrow, 0.1% of extract dry matter in the fermentation medium was optimal, while for the pine needle extract, a concentration of 0.05% was preferred, since it selectively stimulated S. epidermidis growth and inhibited S. aureus proliferation. Additionally, the total polyphenols and flavonoid content of the two extracts were determined, revealing different concentrations and polyphenol profiles. Since yarrow and pine extracts affected the growth of skin bacteria in a dose-dependent manner, by carefully selecting the quantities of these extracts, and thus polyphenols content, it is possible to achieve desirable alterations of skin microbiota composition, which may be suitable for the treatment of atopic dermatitis.

Keywords: herbal extracts, polyphenols, skin microbiota, skin prebiotics

Procedia PDF Downloads 150

Authors: Maryam Nazari

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COVID-19 is a respiratory disease triggered by the novel coronavirus, SARS-CoV-2, that has reached pandemic status today. Acute inflammation and immune cells infiltration into lung injuries result in multi-organ failure. The presence of other non-communicable diseases (NCDs) with systemic inflammation derived from COVID-19 may exacerbate the patient's situation and increase the risk for adverse effects and mortality. This pandemic is a novel situation and the scientific community at this time is looking for vaccines or drugs to treat the pathology. One of the biggest challenges is focused on reducing inflammation without compromising the correct immune response of the patient. In this regard, addressing the nutritional factors should not be overlooked not only as a matter of avoiding the presence of NCDs with severe infections but also as an adjunctive way to modulate the inflammatory status of the patients. Despite the pivotal role of nutrition in modifying immune response, due to the novelty of the COVID-19 disease, information about the effects of specific dietary agents is limited in this area. From the macronutrients point of view, protein deficiency (quantity or quality) has negative effects on the number of functional immunoglobulins and gut-associated lymphoid tissue (GALT). High biological value proteins or some amino acids like arginine and glutamine are well known for their ability to augment the immune system. Among lipids, fish oil has the ability to inactivate enveloped viruses, suppress pro-inflammatory prostaglandin production and block platelet-activating factors and their receptors. In addition, protectin D1, which is an Omega-3 PUFAs derivation, is a novel antiviral drug. So it seems that these fatty acids can reduce the severity and/or improve recovery of patients with COVID-19. Carbohydrates with lower glycemic index and fibers are associated with lower levels of inflammatory cytokines (CRP, TNF-α, and IL-6). Short-Chain Fatty acids not only exert a direct anti-inflammatory effect but also provide appropriate gut microbial, which is important in gastrointestinal issues related to COVID-19. From the micronutrients point of view, Vitamins A, C, D, E, iron, magnesium, zinc, selenium and copper play a vital role in the maintenance of immune function. Inadequate status in these nutrients may result in decreased resistance against COVID-19 infection. There are specific bioactive compounds in the diet that interact with the ACE2 receptor, which is the gateway for SARS and SARS-CoV-2, and thus controls the viral infection. Regarding this, the potential benefits of probiotics, resveratrol (a polyphenol found in grape), oleoylethanolamide (derived from oleic acid), and natural peroxisome proliferator-activated receptor γ agonists in foodstuffs (like curcumin, pomegranate, hot pepper) are suggested. Yet, it should be pointed out that most of these results have been reported in animal models and further human studies are needed to be verified.

Keywords: Covid-19, inflammation, nutrition, dietary agents

Procedia PDF Downloads 153

Authors: Francesco Saverio Angiò

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The Islamic State of Iraq and the Levant / Syria (ISIL/S), Al-Qaeda in the Islamic Maghreb (AQIM) and People Committed to the Propagation of the Prophet's Teachings and Jihad, also known as ‘Boko Haram’ (BH), have fought successfully against Syria and Iraq, Mali, Nigeria’s government, respectively. According to Napoleoni, the ‘shell-state’ concept can explain the economic dimension and the financing model of the ISIL insurgency. However, she argues that AQIM and BH did not properly plan their financial model. Consequently, her idea would not be suitable to these groups. Nevertheless, AQIM and BH’s economic performances and their (short) territorialisation suggest that their financing models respond to a well-defined strategy, which they were able to adapt to new circumstances. Therefore, Napoleoni’s idea of ‘shell-state’ can be applied to the three jihadist armed groups. In the last five years, together with other similar entities, ISIL/S, AQIM and BH have been fighting against governments with insurgent tactics and terrorism acts, conquering and ruling a quasi-state; a physical space they presented as legitimate territorial entity, thanks to a puritan version of the Islamic law. In these territories, they have exploited the traditional local economic networks. In addition, they have contributed to the development of legal and illegal transnational business activities. They have also established a justice system and created an administrative structure to supply services. Napoleoni’s ‘shell-state’ can describe the evolution of ISIL/S, AQIM and BH, which has switched from an insurgency to a proto or a quasi-state entity, enjoying a significant share of power over territories and populations. Napoleoni first developed and applied the ‘Shell-state’ concept to describe the nature of groups such as the Palestine Liberation Organisation (PLO), before using it to explain the expansion of ISIL. However, her original conceptualisation emphasises on the economic dimension of the rise of the insurgency, focusing on the ‘business’ model and the insurgents’ financing management skills, which permits them to turn into an organisation. However, the idea of groups which use, coordinate and grab some territorial economic activities (at the same time, encouraging new criminal ones), can also be applied to administrative, social, infrastructural, legal and military levels of their insurgency, since they contribute to transform the insurgency to the same extent the economic dimension does. In addition, according to Napoleoni’s view, the ‘shell-state’ prism is valid to understand the ISIL/S phenomenon, because the group has carefully planned their financial steps. Napoleoni affirmed that ISIL/S carries out activities in order to promote their conversion from a group relying on external sponsors to an entity that can penetrate and condition local economies. On the contrary, ‘shell-state’ could not be applied to AQIM or BH, which are acting more like smugglers. Nevertheless, despite its failure to control territories, as ISIL has been able to do, AQIM and BH have responded strategically to their economic circumstances and have defined specific dynamics to ensure a flow of stable funds. Therefore, Napoleoni’s theory is applicable.

Keywords: shell-state, jihadist insurgency, proto or quasi-state entity economic planning, strategic financing

Procedia PDF Downloads 326

Authors: Shyamani Hettiarachchi, Thilini Lokubalasuriya, Shakeela Saleem, Dinusha Nonis, Isuru Dharmaratne, Lakshika Udugama

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Introduction: Late identification of language difficulties in children could result in long-term negative consequences for communication, literacy and self-esteem. This highlights the need for early identification and intervention for speech, language and communication difficulties. Speech and language therapy is a relatively new profession in Sri Lanka and at present, there are no formal standardized screening tools to assess language skills in Sinhala-speaking children. The development and validation of a short, accurate screening tool to enable the identification of children with syntactic difficulties in Sinhala is a current need. Aims: 1) To develop test items for a Sinhala Syntactic Structures (S3 Short Form) test on children aged between 3;0 to 5;0 years 2) To validate the test of Sinhala Syntactic Structures (S3 Short Form) on children aged between 3; 0 to 5; 0 years Methods: The Sinhala Syntactic Structures (S3 Short Form) was devised based on the Renfrew Action Picture Test. As Sinhala contains post-positions in contrast to English, the principles of the Renfrew Action Picture Test were followed to gain an information score and a grammar score but the test devised reflected the linguistic-specificity and complexity of Sinhala and the pictures were in keeping with the culture of the country. This included the dative case marker ‘to give something to her’ (/ejɑ:ʈə/ meaning ‘to her’), the instrumental case marker ‘to get something from’ (/ejɑ:gən/ meaning ‘from him’ or /gɑhən/ meaning ‘from the tree’), possessive noun (/ɑmmɑge:/ meaning ‘mother’s’ or /gɑhe:/ meaning ‘of the tree’ or /male:/ meaning ‘of the flower’) and plural markers (/bɑllɑ:/ bɑllo:/ meaning ‘dog/dogs’, /mɑlə/mɑl/ meaning ‘flower/flowers’, /gɑsə/gɑs/ meaning ‘tree/trees’ and /wɑlɑ:kulə/wɑlɑ:kulu/ meaning ‘cloud/clouds’). The picture targets included socio-culturally appropriate scenes of the Sri Lankan New Year celebration, elephant procession and the Buddhist ‘Wesak’ ceremony. The test was piloted with a group of 60 participants and necessary changes made. In phase 1, the test was administered to 100 Sinhala-speaking children aged between 3; 0 and 5; 0 years in one district. In this presentation on phase 2, the test was administered to another 100 Sinhala-speaking children aged between 3; 0 to 5; 0 in three districts. In phase 2, the selection of the test items was assessed via measures of content validity, test-retest reliability and inter-rater reliability. The age of acquisition of each syntactic structure was determined using content and grammar scores which were statistically analysed using t-tests and one-way ANOVAs. Results: High percentage agreement was found on test-retest reliability on content validity and Pearson correlation measures and on inter-rater reliability. As predicted, there was a statistically significant influence of age on the production of syntactic structures at p<0.05. Conclusions: As the target test items included generated the information and the syntactic structures expected, the test could be used as a quick syntactic screening tool with preschool children.

Keywords: Sinhala, screening, syntax, language

Procedia PDF Downloads 323

Authors: Hamid Reza Mahdipoor, Mehdi Bahrami, Mohammad Bodaghi, Seyed Ali Akbar Mansoori

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Nowadays, with stricter limitations to reduce emissions, considerable penalties are imposed if pollution limits are exceeded. Therefore, refineries, along with focusing on improving the quality of their products, are also focused on producing products with the least environmental impact. The duty of the sulfur recovery unit (SRU) is to convert H₂S gas coming from the upstream units to elemental sulfur and minimize the burning of sulfur compounds to SO₂. The Claus process is a common process for converting H₂S to sulfur, including a reaction furnace followed by catalytic reactors and sulfur condensers. In addition to a Claus section, SRUs usually consist of a tail gas treatment (TGT) section to decrease the concentration of SO₂ in the flue gas below the emission limits. To operate an SRU properly, the flow rate of combustion air to the reaction furnace must be adjusted so that the Claus reaction is performed according to stoichiometry. Accurate control of the air demand leads to an optimum recovery of sulfur during the flow and composition fluctuations in the acid gas feed. Therefore, the major control system in the SRU is the air demand control loop, which includes a feed-forward control system based on predetermined feed flow rates and a feed-back control system based on the signal from the tail gas online analyzer. The use of online analyzers requires compliance with the installation and operation instructions. Unfortunately, most of these analyzers in Iran are out of service for different reasons, like the low importance of environmental issues and a lack of access to after-sales services due to sanctions. In this paper, an SRU in Iran was simulated and calibrated using industrial experimental data. Afterward, the effect of the malfunction of the online analyzer on the performance of SRU was investigated using the calibrated simulation. The results showed that an increase in the SO₂ concentration in the tail gas led to an increase in the temperature of the reduction reactor in the TGT section. This increase in temperature caused the failure of TGT and increased the concentration of SO₂ from 750 ppm to 35,000 ppm. In addition, the lack of a control system for the adjustment of the combustion air caused further increases in SO₂ emissions. In some processes, the major variable cannot be controlled directly due to difficulty in measurement or a long delay in the sampling system. In these cases, a secondary variable, which can be measured more easily, is considered to be controlled. With the correct selection of this variable, the main variable is also controlled along with the secondary variable. This strategy for controlling a process system is referred to as inferential control" and is considered in this paper. Therefore, a sensitivity analysis was performed to investigate the sensitivity of other measurable parameters to input disturbances. The results revealed that the output temperature of the first Claus reactor could be used for inferential control of the combustion air. Applying this method to the operation led to maximizing the sulfur recovery in the Claus section.

Keywords: sulfur recovery, online analyzer, inferential control, SO₂ emission

Procedia PDF Downloads 53

Authors: Sean Griffiths

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Introduction: This paper examines the expression of ‘objectivity’ in architecture in the context of the post-war rejection of this concept. It aims to re-examine the question in light of the assault on truth characterizing contemporary culture and of the unassailable truth of the climate emergency. The paper analyses the search for objective truth as it was prosecuted in the Modern Movement in the early 20th century, looking at the extent to which this quest was successful in contributing to the development of a radically new, politically-informed architecture and the extent to which its particular interpretation of objectivity, limited that development. The paper studies the influence of the Vienna Circle philosophers Rudolph Carnap and Otto Neurath on the pedagogy of the Bauhaus and the architecture of the Neue Sachlichkeit in Germany. Their logical positivism sought to determine objective truths through empirical analysis, expressed in an austere formal language as part of a ‘scientific world conception’ which would overcome metaphysics and unverifiable mystification. These ideas, and the concurrent prioritizing of measurement as the determinant of environmental quality, became key influences in the socially-driven architecture constructed in the 1920s and 30s by Bauhaus architects in numerous German Cities. Methodology: The paper reviews the history of the early Modern Movement and summarizes accounts of the relationship between the Vienna Circle and the Bauhaus. It looks at key differences in the approaches Neurath and Carnap took to the achievement of their shared philosophical and political aims. It analyses how the adoption of Carnap’s foundationalism influenced the architectural language of modern architecture and compares, through a close reading of the structure of Neurath’s ‘protocol sentences,’ the latter’s alternative approach, speculating on the possibility that its adoption offered a different direction of travel for Modern Architecture. Findings: The paper finds that the adoption of Carnap’s foundationalism, while helping Modern Architecture forge a new visual language, ultimately limited its development and is implicated in its failure to escape the very metaphysics against which it had set itself. It speculates that Neurath’s relational language-based approach to the issue of establishing objectivity has its architectural corollary in the process of revision and renovation that offers new ways an ‘objective’ language of architecture might be developed in a manner that is more responsive to our present-day crisis. Conclusion: The philosophical principles of the Vienna Circle and the architects of the Modern Movement had much in common. Both contributed to radical historical departures which sought to instantiate a world scientific conception in their respective fields, which would attempt to banish mystification and metaphysics and would align itself with socialism. However, in adopting Carnap’s foundationalism as the theoretical basis for the new architecture, Modern Architecture not only failed to escape metaphysics but arguably closed off new avenues of development to itself. The adoption of Neurath’s more open-ended and interactive approach to objectivity offers possibilities for new conceptions of the expression of objectivity in architecture that might be more tailored to the multiple crises we face today.

Keywords: Bauhaus, logical positivism, Neue Sachlichkeit, rationalism, Vienna Circle

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Authors: George Zhou, Yunchan Chen, Candace Chien

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Kidney replacement therapy is the current standard of care for end-stage renal diseases. In-center or home hemodialysis remains an integral component of the therapeutic regimen. Arteriovenous fistulas (AVF) make up the vascular circuit through which blood is filtered and returned. Naturally, AVF patency determines whether adequate clearance and filtration can be achieved and directly influences clinical outcomes. Our aim was to build a deep learning model for automated AVF stenosis screening based on the sound of blood flow through the AVF. A total of 311 patients with AVF were enrolled in this study. Blood flow sounds were collected using a digital stethoscope. For each patient, blood flow sounds were collected at 6 different locations along the patient’s AVF. The 6 locations are artery, anastomosis, distal vein, middle vein, proximal vein, and venous arch. A total of 1866 sounds were collected. The blood flow sounds are labeled as “patent” (normal) or “stenotic” (abnormal). The labels are validated from concurrent ultrasound. Our dataset included 1527 “patent” and 339 “stenotic” sounds. We show that blood flow sounds vary significantly along the AVF. For example, the blood flow sound is loudest at the anastomosis site and softest at the cephalic arch. Contextualizing the sound with location metadata significantly improves classification performance. How to encode and incorporate categorical metadata is an active area of research1. Herein, we study ordinal (i.e., integer) encoding schemes. The numerical representation is concatenated to the flattened feature vector. We train a vision transformer (ViT) on spectrogram image representations of the sound and demonstrate that using scalar multiples of our integer encodings improves classification performance. Models are evaluated using a 10-fold cross-validation procedure. The baseline performance of our ViT without any location metadata achieves an AuROC and AuPRC of 0.68 ± 0.05 and 0.28 ± 0.09, respectively. Using the following encodings of Artery:0; Arch: 1; Proximal: 2; Middle: 3; Distal 4: Anastomosis: 5, the ViT achieves an AuROC and AuPRC of 0.69 ± 0.06 and 0.30 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 10; Proximal: 20; Middle: 30; Distal 40: Anastomosis: 50, the ViT achieves an AuROC and AuPRC of 0.74 ± 0.06 and 0.38 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 100; Proximal: 200; Middle: 300; Distal 400: Anastomosis: 500, the ViT achieves an AuROC and AuPRC of 0.78 ± 0.06 and 0.43 ± 0.11. respectively. Interestingly, we see that using increasing scalar multiples of our integer encoding scheme (i.e., encoding “venous arch” as 1,10,100) results in progressively improved performance. In theory, the integer values do not matter since we are optimizing the same loss function; the model can learn to increase or decrease the weights associated with location encodings and converge on the same solution. However, in the setting of limited data and computation resources, increasing the importance at initialization either leads to faster convergence or helps the model escape a local minimum.

Keywords: arteriovenous fistula, blood flow sounds, metadata encoding, deep learning

Procedia PDF Downloads 62

Authors: Ngoc Thao Linh Dang

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Urban waterfront redevelopment is a global phenomenon, and thousands of schemes are being carried out in large metropoles, medium-sized cities, and even small towns all over the world. This opportunity brings the city back to the river and rediscovers waterfront revitalization as a unique opportunity for cities to reconnect with their unique historical and cultural image. The redevelopment can encourage economic investments, serve as a social platform for public interactions, and allow dwellers to express their rights to the city. Many coastal cities have effectively transformed the perception of their waterfront area through years of redevelopment initiatives, having been neglected for over a century. However, this process has never been easy due to the particular complexity of the space: local culture, history, and market-led development. Moreover, municipal governments work out the balance of diverse stakeholder interests, especially when repurposing high-profile and redundant spaces that form the core of urban economic investment while also accommodating the present and future generations in sustainable environments. Urban critics consistently grapple with the effectiveness of the planning process on the new waterfront, where public spaces are criticized for presenting a lack of opportunities for actual public participation due to privatization and authoritarian governance while no longer doing what they are ‘meant to’: all arise in reaction to the perceived failure of these places to meet expectations. The planning culture and the decision-making context determine the level of public involvement in the planning process; however, in the context of competing market forces and commercial interests dominating cities’ planning agendas, planning for public space in urban waterfronts tends to be for economic gain rather than supporting residents' social needs. These newly pleasing settings satisfied the cluster of middle-class individuals, new communities living along the waterfront, and tourists. A trend of public participatory exclusion is primarily determined by the nature of the planning being undertaken and the decision-making context in which it is embedded. Starting from this context, the research investigates the influence of planning on waterfront regeneration and the role of participation in this process. The research aims to look specifically at the characteristics of the planning process of the waterfront in Da Nang and its impact on the regeneration of the place to regain the city’s historical value and enhance local cultural identity and images. Vietnam runs a top-down planning system where municipal governments have control or power over what happens in their city following the approved planning from the national government. The community has never been excluded from development; however, their participation is still marginalized. In order to ensure social equality, a proposed approach called "bottom-up" should be considered and implemented alongside the traditional "top-down" process and provide a balance of perspectives, as it allows for the voices of the most underprivileged social group involved in a planning project to be heard, rather than ignored. The research provides new insights into the influence of the planning process on the waterfront regeneration in the context of Da Nang.

Keywords: planning process, public participation, top-down planning, waterfront regeneration

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Authors: Abderrhamane Jarou, Dominique Sauter, Christophe Aubrun

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Over the past decade, the growing demand for energy efficiency in buildings has attracted the attention of the control community. Failures in HVAC (heating, ventilation and air conditioning) systems in buildings can have a significant impact on the desired and expected energy performance of buildings and on the user's comfort as well. FTC is a recent technology area that studies the adaptation of control algorithms to faulty operating conditions of a system. The application of Fault-Tolerant Control (FTC) in HVAC systems has gained attention in the last two decades. The objective is to maintain the variations in system performance due to faults within an acceptable range with respect to the desired nominal behavior. This paper considers the so-called active approach, which is based on fault and identification scheme combined with a control reconfiguration algorithm that consists in determining a new set of control parameters so that the reconfigured performance is "as close as possible, "in some sense, to the nominal performance. Thermal models of buildings and their HVAC systems are described by non-linear (usually bi-linear) equations. Most of the works carried out so far in FDI (fault diagnosis and isolation) or FTC consider a linearized model of the studied system. However, this model is only valid in a reduced range of variation. This study presents a new fault diagnosis (FD) algorithm based on a bilinear observer for the detection and accurate estimation of the magnitude of the HVAC system failure. The main contribution of the proposed FD algorithm is that instead of using specific linearized models, the algorithm inherits the structure of the actual bilinear model of the building thermal dynamics. As an immediate consequence, the algorithm is applicable to a wide range of unpredictable operating conditions, i.e., weather dynamics, outdoor air temperature, zone occupancy profile. A bilinear fault detection observer is proposed for a bilinear system with unknown inputs. The residual vector in the observer design is decoupled from the unknown inputs and, under certain conditions, is made sensitive to all faults. Sufficient conditions are given for the existence of the observer and results are given for the explicit computation of observer design matrices. Dedicated observer schemes (DOS) are considered for sensor FDI while unknown input bilinear observers are considered for actuator or system components FDI. The proposed strategy for FTC works as follows: At a first level, FDI algorithms are implemented, making it also possible to estimate the magnitude of the fault. Once the fault is detected, the fault estimation is then used to feed the second level and reconfigure the control low so that that expected performances are recovered. This paper is organized as follows. A general structure for fault-tolerant control of buildings is first presented and the building model under consideration is introduced. Then, the observer-based design for Fault Diagnosis of bilinear systems is studied. The FTC approach is developed in Section IV. Finally, a simulation example is given in Section V to illustrate the proposed method.

Keywords: bilinear systems, fault diagnosis, fault-tolerant control, multi-zones building

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Authors: Arindam Roy

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Public policy is an intriguing terrain, which involves complex interplay of administrative, social political and economic components. There is hardly any fit-for all formulation of public policy as Lindbloom has aptly categorized it as a science of muddling through. In fact, policies are both temporally and contextually determined as one the proponents of policy sciences Harold D Lasswell has underscored it in his ‘contextual-configurative analysis’ as early as 1950s. Though, a lot of theoretical efforts have been made to make sense of this intricate dynamics of policy making, at the end of the day the applied area of public policy negates any such uniform, planned and systematic formulation. However, our policy makers seem to have learnt very little of that. Until recently, policy making was deemed as an absolutely specialized exercise to be conducted by a cadre of professionally trained seasoned mandarin. Attributes like homogeneity, impartiality, efficiency, and neutrality were considered as the watchwords of delivering common goods. Citizen or clientele was conceptualized as universal political or economic construct, to be taken care of uniformly. Moreover, policy makers usually have the proclivity to put anything into straightjacket, and to ignore the nuances therein. Hence, least attention has been given to the ground level reality, especially the socio-cultural milieu where the policy is supposed to be applied. Consequently, a substantial amount of public money goes in vain as the intended beneficiaries remain indifferent to the delivery of public policies. The present paper in the light of Reproductive Health Care policy in rural West Bengal has tried to underscore the criticality of socio-cultural factors in public health delivery. Indian health sector has traversed a long way. From a near non-existent at the time of independence, the Indian state has gradually built a country-wide network of health infrastructure. Yet it has to make a major breakthrough in terms of coverage and penetration of the health services in the rural areas. Several factors are held responsible for such state of things. These include lack of proper infrastructure, medicine, communication, ambulatory services, doctors, nursing services and trained birth attendants. Policy makers have underlined the importance of supply side in policy formulation and implementation. The successive policy documents concerning health delivery bear the testimony of it. The present paper seeks to interrogate the supply-side oriented explanations for the failure of the delivery of health services. Instead, it identified demand side to find out the answer. The state-led and bureaucratically engineered public health measures fail to engender demands as these measures mostly ignore socio-cultural nuances of health and well-being. Hence, the hiatus between supply side and demand side leads to huge wastage of revenue as health infrastructure, medicine and instruments remain unutilized in most cases. Therefore, taking proper cognizance of these factors could have streamlined the delivery of public health.

Keywords: context, policy, socio-cultural factor, uniformity

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Authors: Gianmarco Taveri, Ivo Dlouhy

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Geopolymers are well-suited materials to abate CO2 emission coming from the Portland cement production, and then replace them, in the near future, in building and other applications. The cost of production of geopolymers may be seen the only weakness, but the use of wastes as raw materials could provide a valid solution to this problem, as demonstrated by the successful incorporation of fly-ash, a by-product of thermal power plants, and waste glasses. Recycled glass in waste-derived geopolymers was lately employed as a further silica source. In this work we present, for the first time, the introduction of recycled borosilicate glass (BSG). BSG is actually a waste glass, since it derives from dismantled pharmaceutical vials and cannot be reused in the manufacturing of the original articles. Owing to the specific chemical composition (BSG is an ‘alumino-boro-silicate’), it was conceived to provide the key components of zeolitic networks, such as amorphous silica and alumina, as well as boria (B2O3), which may replace Al2O3 and contribute to the polycondensation process. The solid–state MAS NMR spectroscopy was used to assess the extent of boron oxide incorporation in the structure of geopolymers, and to define the degree of networking. FTIR spectroscopy was utilized to define the degree of polymerization and to detect boron bond vibration into the structure. Mechanical performance was tested by means of 3 point bending (flexural strength), chevron notch test (fracture toughness), compression test (compressive strength), micro-indentation test (Vicker’s hardness). Spectroscopy (SEM and Confocal spectroscopy) was performed on the specimens conducted to failure. FTIR showed a characteristic absorption band attributed to the stretching modes of tetrahedral boron ions, whose tetrahedral configuration is compatible to the reaction product of geopolymerization. 27Al NMR and 29Si NMR spectra were instrumental in understanding the extent of the reaction. 11B NMR spectroscopies evidenced a change of the trigonal boron (BO3) inside the BSG in favor of a quasi-total tetrahedral boron configuration (BO4). Thanks to these results, it was inferred that boron is part of the geopolymeric structure, replacing the Si in the network, similarly to the aluminum, and therefore improving the quality of the microstructure, in favor of a more cross-linked network. As expected, the material gained as much as 25% in compressive strength (45 MPa) compared to the literature, whereas no improvements were detected in flexural strength (~ 5 MPa) and superficial hardness (~ 78 HV). The material also exhibited a low fracture toughness (0.35 MPa*m1/2), with a tangible brittleness. SEM micrographies corroborated this behavior, showing a ragged surface, along with several cracks, due to the high presence of porosity and impurities, acting as preferential points for crack initiation. The 3D pattern of the surface fracture, following the confocal spectroscopy, evidenced an irregular crack propagation, whose proclivity was mainly, but not always, to follow the porosity. Hence, the crack initiation and propagation are largely unpredictable.

Keywords: borosilicate glass, characterization, fly-ash, geopolymerization

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Authors: Isaac Martin, Abigail Lark, Sandra Morales, Eric W. Alton, Jane C. Davies

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Objectives: The cystic fibrosis (CF) lung is a unique microbiological niche, wherein harmful bacteria persist for many years despite antibiotic therapy. Pseudomonas aeruginosa (Pa), the major culprit leading to lung decline and increased mortality, thrives in the lungs of patients with CF due to several factors that have been linked with poor antibiotic performance. Our group is investigating alternative therapies including bacteriophage cocktails with which we have previously demonstrated efficacy against planktonic organisms. In this study, we explored the effects of a 4-phage cocktail on Pa grown in two different conditions, intended to mirror the CF lung: a) alongside standard antibiotic treatment in pre-formed biofilms (structures formed by Pa-secreted exopolysaccharides which provide both physical and cell division barriers to antimicrobials and host defenses and b) in an acidic environment postulated to be present in the CF airway due both to the primary defect in bicarbonate secretion and secondary effects of inflammation. Methods: 16 Pa strains from CF patients at the Royal Brompton Hospital were selected based on sensitivity to a) ceftazidime/ tobramycin and b) the phage cocktail in a conventional plaque assay. To assess efficacy of phage in biofilms, 96 well plates with Pa (5x10⁷ CFU/ ml) were incubated in static conditions, allowing adherent bacterial colonies to form for 24 hr. Ceftazidime and tobramycin (both at 2 × MIC) were added, +/- bacteriophage (4x10⁸ PFU/mL) for a further 24 hr. Cell viability and biomass were estimated using fluorescent resazurin and crystal violet assays, respectively. To evaluate the effect of pH, strains were grown planktonically in shaking 96 well plates at pH 6.0, 6.6, 7.0 and 7.5 with tobramycin or phage, at varying concentrations. Cell viability was quantified by fluorescent resazurin assay. Results: For the biofilm assay, treatment groups were compared with untreated controls and expressed as percent reduction in cell viability and biomass. Addition of the 4-phage cocktail resulted in a 1.3-fold reduction in cell viability and 1.7-fold reduction in biomass (p < 0.001) when compared to standard antibiotic treatment alone. Notably, there was a 50 ± 15% reduction in cell viability and 60 ± 12% reduction in biomass (95% CI) for the 4 biofilms demonstrating the most resistance to antibiotic treatment. 83% of strains tested (n=6) showed decreased bacterial killing by tobramycin at acidic pHs (p < 0.01). However, 25% of strains (n=12) showed improved phage killing at acidic pHs (p < 0.05), with none showing the pattern of reduced efficacy at acidic pH demonstrated by tobramycin. Conclusion: The 4-phage anti-Pa cocktail tested against Pa performs well in pre-formed biofilms and in acidic environments; two conditions intended to mimic the CF lung. To our knowledge, these are the first data looking at the effects of subtle pH changes on phage-mediated bacterial killing in the context of Pa infection. These findings contribute to a growing body of evidence supporting the use of nebulised lytic bacteriophage as a treatment in the context of lung infection.

Keywords: biofilm, cystic fibrosis, pH, Pseudomonas aeruginosa, lytic bacteriophage

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Authors: Bhakti Chitale

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Mumbai city, which is the business capital of India and one of the most crowded cities in the world, holds the biggest slum in Asia. The Mumbai Metropolitan Region (MMR) occupies an area of 4035 sq.km. with a population of 22.8 million people. This population is mostly urban with 91% of this population living in areas of Municipal Corporations and Councils. Another 3% live in Census Towns. The region has 9 Municipal Corporations, 8 Municipal councils, and around 1000 villages. On the one hand MMR reflects the highest contribution to the Nations overall economy and on the other hand it shows the horrible and intolerable picture of about 2 million people, who are living in slums/without even slum with totally unhygienic conditions and with total loss of hope. The generations are about to get affected adversely if the solution is not worked out. This study is an attempt towards working out the solution. Mumbai Metropolitan Region Development Authority (MMRDA) is state government's authority, specially formed to govern the development of MMR. MMRDA is engaged in long term planning, promotion of new growth centres, implementation of strategic projects and financing infrastructure development. While preparing the master plan for MMR for next 20 years MMRDA conducted a detail study regarding Housing scenario in MMR and possible options for improvement. The author was the in charge officer for the said assignment. This paper puts light on the interesting outcomes of the research study, which ranges from the adverse effects of government policies, automatic responses of housing market, effects on planning processes, and overall changing needs of housing patterns in the world due to changes in the social mechanism. It alarms the urban planners who usually focus on smart infrastructure development, about allied future dangers. This housing study will explain the complexities, realities and needs of innovations in the housing policies all over the world. The paper will explain further few success stories and failure stories of government initiatives with reasons. It gives the clear idea about the differences in needs of housing for people from different economic groups and direct and indirect market pressures on low cost housing. Magical phenomenon came in front like a large percentage of vacant houses is present in spite of the huge need. Housing market gets affected by the developments or any other physical and financial changes taking place in the nearby areas or cities, also by changes in cities which are located far from the region and also by the international investments or policy changes. Instead of just depending on governments actions in case of generation of affordable housing, it becomes equally important to make the housing markets automatically generate such stock and still make them sustainable is the aim of all the movement. In summary, we may say that the paper will sequentially elaborate the complete dynamics of housing in one of the most crowded urban area in the world that is Mumbai Metropolitan Region, with a lot of data, analysis, case studies, and recommendations.

Keywords: Mumbai India, slum housing, region planning, market recommendations

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Authors: Lijuan Li

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Nitric oxide (NO) has become a fascinating entity in biological chemistry over the past few years. It is a gaseous lipophilic radical molecule that plays important roles in several physiological and pathophysiological processes in mammals, including activating the immune response, serving as a neurotransmitter, regulating the cardiovascular system, and acting as an endothelium-derived relaxing factor. NO functions in eukaryotes both as a signal molecule at nanomolar concentrations and as a cytotoxic agent at micromolar concentrations. The latter arises from the ability of NO to react readily with a variety of cellular targets leading to thiol S-nitrosation, amino acid N-nitrosation, and nitrosative DNA damage. Nitric oxide can readily bind to metals to give metal-nitrosyl (M-NO) complexes. Some of these species are known to play roles in biological NO storage and transport. These complexes have different biological, photochemical, or spectroscopic properties due to distinctive structural features. These recent discoveries have spawned a great interest in the development of transition metal complexes containing NO, particularly its iron complexes that are central to the role of nitric oxide in the body. Spectroscopic evidence would appear to implicate species of “Fe(NO)2+” type in a variety of processes ranging from polymerization, carcinogenesis, to nitric oxide stores. Our research focuses on isolation and structural studies of non-heme iron nitrosyls that mimic biologically active compounds and can potentially be used for anticancer drug therapy. We have shown that reactions between Fe(NO)2(CO)2 and a series of imidazoles generated new non-heme iron nitrosyls of the form Fe(NO)2(L)2 [L = imidazole, 1-methylimidazole, 4-methylimidazole, benzimidazole, 5,6-dimethylbenzimidazole, and L-histidine] and a tetrameric cluster of [Fe(NO)2(L)]4 (L=Im, 4-MeIm, BzIm, and Me2BzIm), resulted from the interactions of Fe(NO)2 with a series of substituted imidazoles was prepared. Recently, a series of sulfur bridged iron di nitrosyl complexes with the general formula of [Fe(µ-RS)(NO)2]2 (R = n-Pr, t-Bu, 6-methyl-2-pyridyl, and 4,6-dimethyl-2-pyrimidyl), were synthesized by the reaction of Fe(NO)2(CO)2 with thiols or thiolates. Their structures and properties were studied by IR, UV-vis, 1H-NMR, EPR, electrochemistry, X-ray diffraction analysis and DFT calculations. IR spectra of these complexes display one weak and two strong NO stretching frequencies (νNO) in solution, but only two strong νNO in solid. DFT calculations suggest that two spatial isomers of these complexes bear 3 Kcal energy difference in solution. The paramagnetic complexes [Fe2(µ-RS)2(NO)4]-, have also been investigated by EPR spectroscopy. Interestingly, the EPR spectra of complexes exhibit an isotropic signal of g = 1.998 - 2.004 without hyperfine splitting. The observations are consistent with the results of calculations, which reveal that the unpaired electron dominantly delocalize over the two sulfur and two iron atoms. The difference of the g values between the reduced form of iron-sulfur clusters and the typical monomeric di nitrosyl iron complexes is explained, for the first time, by of the difference in unpaired electron distributions between the two types of complexes, which provides the theoretical basis for the use of g value as a spectroscopic tool to differentiate these biologically active complexes.

Keywords: di nitrosyl iron complex, metal nitrosyl, non-heme iron, nitric oxide

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Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

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Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

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