Search results for: toll pathway

Authors: Viral Nagori, Preeti Shroff, Prathana Dodia

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The paper presents the study on women entrepreneurship over the last decade in Indian and Global Context. This research study has its basis primarily in the literature review. The research methodology classifies the literature review paper based on different parameters of women entrepreneurship. The literature review relies on research papers in journals, articles in periodicals, and books published on women entrepreneurship. To accomplish this, the criteria included finding the most relevant, recent, and cited studies on women entrepreneurship over the last decade. It aims to evaluate the issues and challenges faced by women entrepreneurs. The finding suggested that there are several common obstacles, which hinders the pathway to success towards being a successful woman entrepreneur. The paper also describes such common obstacles like the level of education, family responsibilities, lack of business information, religious and cultural constraints, limited mobility, exposure, lack of working capital, and more. The in-depth analysis of literature review indicates that despite the numerous barriers, the arrival of social media has played a crucial role in enabling women to start and scale up their enterprises. Further, technology innovation has given them access to have relevant market information, increase reach and network with the customers. It enabled them to achieve work life balance and pursuing entrepreneur in them. The paper also describes the Government and Nongovernmental initiatives for promotion of women entrepreneurship. At the end, the study provides insights into the changing dynamics of women entrepreneurship in the current scenario and future prospects.

Keywords: changing dynamics, government initiatives, literature review, social media, technology innovation, women entrepreneurship

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Authors: Sibgha Noreen, Muhammad Salim Akhter, Seema Mahmood

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Salt stress is an abiotic stress that causes a heavy toll on growth and development and also reduces the productivity of arable and horticultural crops. Globally, a quarter of total arable land has fallen prey to this menace, and more is being encroached because of the usage of brackish water for irrigation purposes. Though barley is categorized as salt-tolerant crop, but cultivars show a wide genetic variability in response to it. In addressing salt stress, silicon nutrition would be a facile tool for enhancing salt tolerant to sustain crop production. A greenhouse study was conducted to evaluate the response of barley (Hordeum vulgare L.) cultivars to silicon nutrition under salt stress. The treatments included [(a) four barley cultivars (Jou-87, B-14002, B-14011, B-10008); (b) two salt levels (0, 200 mM, NaCl); and (c) two silicon levels (0, 200ppm, K2SiO3. nH2O), arranged in a factorial experiment in a completely randomized design with 16 treatments and repeated 4 times. Plants were harvested at 15 days after exposure to different experimental salinity and silicon foliar conditions. Results revealed that various physiological and biochemical attributes differed significantly (p<0.05) in response to different treatments and their interactive effects. Cultivar “B-10008” excelled in biological yield, chlorophyll constituents, antioxidant enzymes, and grain yield compared to other cultivars. The biological yield of shoot and root organs was reduced by 27.3 and 26.5 percent under salt stress, while it was increased by 14.5 and 18.5 percent by exogenous application of silicon over untreated check, respectively. The imposition of salt stress at 200 mM caused a reduction in total chlorophyll content, chl ‘a’ , ‘b’ and ratio a/b by 10.6,16.8,17.1 and 7.1, while spray of 200 ppm silicon improved the quantum of the constituents by 10.4,12.1,10.2,10.3 over untreated check, respectively. The quantum of free amino acids and protein content was enhanced in response to salt stress and the spray of silicon nutrients. The amounts of superoxide dismutase, catalases, peroxidases, hydrogen peroxide, and malondialdehyde contents rose to 18.1, 25.7, 28.1, 29.5, and 17.6 percent over non-saline conditions under salt stress. However, the values of these antioxidants were reduced in proportion to salt stress by 200 ppm silicon applied as rooting medium on barley crops. The salt stress caused a reduction in the number of tillers, number of grains per spike, and 100-grain weight to the amount of 29.4, 8.6, and 15.8 percent; however, these parameters were improved by 7.1, 10.3, and 9.6 percent by foliar spray of silicon over untreated crop, respectively. It is concluded that the barley cultivar “B-10008” showed greater tolerance and adaptability to saline conditions. The yield of barley crops could be potentiated by a foliar spray of 200 ppm silicon at the vegetative growth stage under salt stress.

Keywords: salt stress, silicon nutrition, chlorophyll constituents, antioxidant enzymes, barley crop

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Authors: Suhail Shersad

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Introduction In developing countries, the access to higher education for the lower socioeconomic strata is very poor at less than 0.05%. The challenges faced by prospective students in these circumstances to pursue higher education have been explored through direct interaction with them and their families in urban slums of New Delhi. This study included evaluation of the demographics, social indices, expectations and perceptions of selected communities. Results The results show that the poor life expectancy, low exposure to technology, lack of social infrastructure and poor sanitary conditions have reduced their drive for academic achievements. This is despite a good level of intelligence and critical thinking skills among these students. The perception of the community including parents shows that despite their desire to excel, there are too may roadblocks to achieving a fruitful professional life for the next generation. Discussion The prerequisites of higher education may have to be revisited to be more inclusive of socially handicapped students. The knowledge, skills and attributes required for higher education system should form the baseline for creating a roadmap for higher secondary education suited for local needs. Conventional parameters like marks and grading have to be re-looked so that life skills and vocational training form part of the core curriculum. Essential skills should be incorporated at an earlier age, providing an alternative pathway for such students to join higher education. Conclusion: There is a need to bridge the disconnect that exists between higher education planning, the needs of the concerned cohorts and the existing higher secondary education. The variables that contribute to making such a decision have to be examined further. Keywords: prerequisites of higher education, social mobility, society expectations, access to higher education

Keywords: access to higher education, prerequisites of higher education, society expectations, social mobility

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Authors: T. Aboumahboub, R. Brecha, H. B. Shrestha, U. F. Hutfilter, A. Geiges, W. Hare, M. Schaeffer, L. Welder, M. Gidden

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The proposed stringent mitigation targets require an immediate start for a drastic transformation of the whole energy system. The current Australian energy system is mainly centralized and fossil fuel-based in most states with coal and gas-fired plants dominating the total produced electricity over the recent past. On the other hand, the country is characterized by a huge, untapped renewable potential, where wind and solar energy could play a key role in the decarbonization of the Australia’s future energy system. However, integrating high shares of such variable renewable energy sources (VRES) challenges the power system considerably due to their temporal fluctuations and geographical dispersion. This raises the concerns about flexibility gap in the system to ensure the security of supply with increasing shares of such intermittent sources. One main flexibility dimension to facilitate system integration of high shares of VRES is to increase the cross-sectoral integration through coupling of electricity to other energy sectors alongside the decarbonization of the power sector and reinforcement of the transmission grid. This paper applies a multi-sectoral energy system optimization model for Australia. We investigate the cost-optimal configuration of a renewable-based Australian energy system and its transformation pathway in line with the ambitious range of proposed climate change mitigation targets. We particularly analyse the implications of linking the electricity and transport sectors in a prospective, highly renewable Australian energy system.

Keywords: decarbonization, energy system modelling, renewable energy, sector coupling

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Authors: Reni Francis

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Learning has transcended the classroom boundaries to create a learner centric, interactive, and integrative teaching learning environment. This study analysed the impact of iLearn on the teaching, learning, and evaluation among 100 teacher trainees. The objectives were to cater to the different learning styles of the teacher trainees, to incorporate innovative teaching learning activities, to assist in peer tutoring, to implement different evaluation processes. i: Identifying the learning styles among the teacher trainees through VARK Learning style checklist was followed by planning the teaching-learning process to meet the learning styles of the teacher trainees. L: Leveraging innovations in teaching- learning by planning and creating modules incorporating innovative teaching learning and hence the concept based year plan was prepared. E: Engage learning through constructivism using different teaching methodology to engage the teacher trainees in the learning process through Workshop, Round Robin, Gallery walk, Co-Operative learning, Think-Pair-Share, EDMODO, Course Networking, Concept Map, Brainstorming Sessions, Video Clippings. A: Assessing the learning through an Open Book assignment, Closed book assignment, and Multiple Choice Questions and Seminar presentation. R: Remediation through peer tutoring through Mentor-mentee approach in the tutorial groups, Group work, Library Hours. N: Norming new standards. This was done in the form of extended remediation and tutorials to understand the need of the teacher trainee and support them for further achievements in learning through Face to face interaction, Supervised Study Circle, Mobile (Device) learning. The findings of the study revealed the positive impact of iLearn towards student achievement and enhanced social skills.

Keywords: academic achievement, innovative strategy, learning styles, social skills

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Authors: Sangeeta Pilkhwal Sah, C. S. Mathela, Kanwaljit Chopra

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Valeriana wallichii DC, an ayurvedic traditional medicine, popularly named as Indian valerian exist as three chemotypes. GC-MS analysis of V. wallichii essential oil in present study showed maaliol as the major constituent followed by the presence of β-gurjunene, acoradiene, guaiol and α-santalene. The results thus confirmed it to be a maaliol chemotype. Further, the antidepressant-like effect of root essential oil (10, 20 and 40 mg/kg p.o.) was investigated in both acute and chronic treatment study using forced swim test in mice. Single administration of different doses produced an inverted U shaped curve and significantly inhibited the immobility period (39.7% and 58%) at doses 10 and 40 mg/kg respectively. Standard drug imipramine significantly decreased immobility period (59.8%). None of the doses altered locomotor activity except a significant decrease of 44.9% was observed with 40 mg/kg (p < 0.05). Similarly, daily administration of essential oil for 14 days produced a dose dependent effect with significantly reduced immobility period (70.9%) at 40 mg/kg dose only whereas imipramine produced 86% decrease (p < 0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (10%) and dopamine (23%) (p < 0.05) was found at 40 mg/kg dose, while no change was observed at 10 and 20 mg/kg doses. The antidepressant-like effect of essential oil (40 mg/kg) was prevented by pretreatment of mice with L-arginine (750 mg/kg i.p.) and sildenafil (5 mg/kg i.p). On the contrary, pretreatment of mice with L-NAME (10 mg/kg i.p.) or methylene blue (10 mg/kg i.p.) potentiated the antidepressant action of essential oil (20 mg/kg). The findings thus demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.

Keywords: Valeriana wallichii DC chemotype, essential oil, forced swim test, nitric oxide modulators, neurotransmitters

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Authors: Nabil Jallouli, Luisa M. Pastrana-Martínez, Ana R. Ribeiro, Nuno F. F. Moreira, Joaquim L. Faria, Olfa Hentati, Adrián M. T. Silva, Mohamed Ksibi

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Degradation and mineralization of ibuprofen (IBU) were investigated using Ultraviolet (UV) Light Emitting Diodes (LEDs) in TiO2 photocatalysis. Samples of ultrapure water (UP) and a secondary treated effluent of a municipal wastewater treatment plant (WWTP), both spiked with IBU, as well as a highly concentrated IBU (230 mgL-1) pharmaceutical industry wastewater (PIWW), were tested in the TiO2/UV-LED system. Three operating parameters, namely, pH, catalyst load and number of LEDs were optimized. The process efficiency was evaluated in terms of IBU removal using high performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Additionally, the mineralization was investigated by determining the dissolved organic carbon (DOC) content. The chemical structures of transformation products were proposed based on the data obtained using liquid chromatography with a high resolution mass spectrometer ion trap/time-of-flight (LC-MS-IT-TOF). A possible pathway of IBU degradation was accordingly proposed. Bioassays were performed using the marine bacterium Vibrio fischeri to evaluate the potential acute toxicity of original and treated wastewaters. TiO2 heterogeneous photocatalysis was efficient to remove IBU from UP and from PIWW, and less efficient in treating the wastewater from the municipal WWTP. The acute toxicity decreased by ca. 40% after treatment, regardless of the studied matrix.

Keywords: acute toxicity, Ibuprofen, UV-LEDs, wastewaters

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Authors: Arsalan Makinian

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Our future cities will constantly evolve the necessary technologies for tomorrow’s needs. Technologies which enable a better kind of prosperity and security. This paper reports on the precedent of a smart city from its beginning to prevalence among urbanism academic literature and reports of tech companies. The article aims to direct urban foresight studies and to build a pathway for the future of smart city concept by gathering theoretical and empirical experiences related to smart cities with both top-down and bottom-up approaches. It hopes to deliver results of different studies, pilot projects, and development strategies of some of the smart cities in order to allow a shareable knowledge to take shape and develop in terms of qualitative aspects of a smart city. Now the definition of the smart city goes beyond removing physical boundaries, changing the concept of mobility and providing electronic service for citizens, it now constitutes fields such as energy efficiency, economic competitiveness, protecting the environment and finally, it takes advantage of technology and data science to improve the quality of life. In the smart city, the role of citizens is considered as both final purpose and contributor. Emerging issues which are almost implications of advanced technologies -as the most important trends of the future- and their reflection on the society need to be foresighted. Educating and fostering knowledge of smartness is one of the targets of the smart city concept. In this regard, some of these smart cites have established research and development units to share their projects and smart city initiatives. Due to this fact, gaining experience and sharing the results of this subject is necessary for technology management and moving toward a smart urban future.

Keywords: age of urban tech, bottom-up approach, role of citizens, smart city

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Authors: Ishani Majumdar, Jaishree Paul

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Introduction: Ulcerative Colitis (UC) is an inflammatory disease of the colon resulting from an autoimmune response towards individual’s own microbiota. Excessive inflammation is characterized by hyper-activation of NFkB, a transcription factor regulating expression of various pro-inflammatory genes. The ubiquitin editing complex consisting of TNFAIP3, ITCH, RNF11 and TAX1BP1 maintains homeostatic levels of active NFkB through feedback inhibition and assembles in response to various stimuli that activate NFkB. TNFAIP3 deubiquitinates key signaling molecules involved in NFkB activation pathway. ITCH, RNF11 and TAX1BP1 provide substrate specificity, acting as adaptors for TNFAIP3 function. Aim: This study aimed to find expression of members of the ubiquitin editing complex at the transcript level in inflamed colon tissues of UC patients. Materials and Methods: Colonic biopsy samples were collected from 30 UC patients recruited at Department of Gastroenterology, AIIMS (New Delhi). Control group (n= 10) consisted of individuals undergoing examination for functional disorders. Real Time PCR was used to determine relative expression with GAPDH as housekeeping gene. Results: Expression of members of the ubiquitin editing complex was significantly altered during active disease. Expression of TNFAIP3 was upregulated while concomitant decrease in expression of ITCH, RNF11, TAX1BP1 was seen in UC patients. Discussion: This study reveals that increase in expression of TNFAIP3 was unable to control inflammation during active UC. Further, insufficient upregulation of ITCH, RNF11, TAX1BP1 may limit the formation of the ubiquitin complex and contribute to pathogenesis of UC.

Keywords: altered expression, inflammation, ubiquitin editing complex, ulcerative colitis

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Authors: Gaya Bin Noon, Thoko Hanjahanja-Phiri, Laura Xavier Fadrique, Plinio Pelegrini Morita, Hélène Vaillancourt, Jennifer Teague, Tania Donovska

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Active Assisted Living (AAL) refers to systems designed to improve the quality of life, aid in independence, and create healthier lifestyles for care recipients. As the population ages, there is a pressing need for non-intrusive, continuous, adaptable, and reliable health monitoring tools to support aging in place. AAL has great potential to support these efforts with the wide variety of solutions currently available, but insufficient efforts have been made to address concerns arising from the integration of AAL into care. The purpose of this research was to (1) explore the integration of AAL technologies and data into the clinical pathway, and (2) map data access and governance for AAL technology in order to develop standards for use by policy-makers, technology manufacturers, and developers of smart communities for seniors. This was done through four successive research phases: (1) literature search to explore existing work in this area and identify lessons learned; (2) modeling of the continuum of care; (3) adapting a framework for data governance into the AAL context; and (4) interviews with stakeholders to explore the applicability of previous work. Opportunities for standards found in these research phases included a need for greater consistency in language and technology requirements, better role definition regarding who can access and who is responsible for taking action based on the gathered data, and understanding of the privacy-utility tradeoff inherent in using AAL technologies in care settings.

Keywords: active assisted living, aging in place, internet of things, standards

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Authors: Yongde Xia, Laicong Deng, Zhuxian Yang

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Developing cost-effective electrocatalysts for oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is vital in energy conversion and storage applications. Herein, we report a simple method for the synthesis of graphene-reinforced cobalt sulfide/carbon nanocomposites and the evaluation of their electrocatalytic performance for typical electrocatalytic reactions. Nanocomposites of cobalt sulfide embedded in N, S co-doped porous carbon and graphene (CoS@C/Graphene) were generated via simultaneous sulfurization and carbonization of one-pot synthesized graphite oxide-ZIF-67 precursors. The obtained CoS@C/Graphene nanocomposite was characterized by X-ray diffraction, Raman spectroscopy, Thermogravimetric analysis-Mass spectroscopy, Scanning electronic microscopy, Transmission electronic microscopy, X-ray photoelectron spectroscopy and gas sorption. It was found that cobalt sulfide nanoparticles were homogenously dispersed in the in-situ formed N, S co-doped porous carbon/Graphene matrix. The CoS@C/10Graphene composite not only shows excellent electrocatalytic activity toward ORR with high onset potential of 0.89 V, four-electron pathway and superior durability of maintaining 98% current after continuously running for around 5 hours, but also exhibits good performance for OER and HER, due to the improved electrical conductivity, increased catalytic active sites and connectivity between the electrocatalytic active cobalt sulfide and the carbon matrix. This work offers a new approach for the development of novel multifunctional nanocomposites for the next generation of energy conversion and storage applications.

Keywords: MOF derivative, graphene, electrocatalyst, oxygen reduction reaction, oxygen evolution reaction, hydrogen evolution reaction

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Authors: Jose G. Tshikuka, Goabaone Rankgoane-Pono, Mgaywa G. M. D. Magafu, Julius C. Mwita, Tiny Masupe, Fortunat M. Kandanda, Shimeles G. Hamda, Roy Tapera, Mooketsi Molefi, John T. Tlhakanelo

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Background: Factors associated with overweight and obesity among antiretroviral therapy (ART) recipients have not been sufficiently studied in Botswana. We aimed to study (i) the prevalence and trends in overweight/obesity by duration of exposure to ART among recipients, (ii) changes in body mass index (BMI) categories among recipients before ART initiation (BMI-1) and after ART initiation (BMI-2), (iii) associations between ART and overweight/obesity and (iv) factors associated with BMI changes among ART recipients. Methods: A 12 years retrospective record-based review was conducted. Factors potentially associated with BMI change among patients after at least three years of ART exposure were examined using multiple regression model. Adjusted odds ratios (AOR) and their 95% confidence intervals (CIs) were computed. ART regimens, duration of exposure to ART, and recipients’ demographic and biomedical characteristics including the presence or absence of diabetes mellitus related comorbidities (DRC) were investigated as potential factors associated with overweight/obesity. Results: Twenty-nine percent of recipients were overweight, 16.6% had obesity of whom 2.4% were morbidly-obese at the last clinic visit. Overweight/obesity recipients were more likely to be female, to have DRC and less likely to have nadir CD4 count or CD4 count between 201 – 249 cells/mm³. Neither the first-line nor the second-, third-line ART regimens predicted overweight/obesity more than the other and neither did the duration of exposure to ART. No significant linear trends were observed in the prevalence of overweight/obesity by the duration of exposure to ART. Conclusions: These results indicate that overweight/obesity seen among ART recipients is not directly induced by ART. ART used CD4 and/or DRC pathway to induce overweight/obesity seen among recipients; suggesting that, weight gain documented herein is likely a reflection of improved health status that mirrors trends in the general population or a DRC related effect. Weight management programs may be important components of HIV care.

Keywords: overweight/obesity, recipients of antiretroviral therapy, HIV/AIDS, Botswana

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Authors: Khalda Amr, Noha Eltaweel, Sherif Ismail, Hala Raslan

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Introduction: Osteoarthritis is the most common form of arthritis that involves the wearing away of the cartilage that caps the bones in the joints. While rheumatoid arthritis is an autoimmune disease in which the immune system attacks the joints, beginning with the lining of joints. In this study, we aimed to study the top deregulated miRNAs that might be the cause of pathogenesis in both diseases. Methods: Eight cases were recruited in this study: 4 rheumatoid arthritis (RA), 2 osteoarthritis (OA) patients, as well as 2 healthy controls. Total RNA was isolated from plasma to be subjected to miRNA profiling by NGS. Sequencing libraries were constructed and generated using the NEBNextR UltraTM small RNA Sample Prep Kit for Illumina R (NEB, USA), according to the manufacturer’s instructions. The quality of samples were checked using fastqc and multiQC. Results were compared RA vs Controls and OA vs. Controls. Target gene prediction and functional annotation of the deregulated miRNAs were done using Mienturnet. The top deregulated miRNAs in each disease were selected for further validation using qRT-PCR. Results: The average number of sequencing reads per sample exceeded 2.2 million, of which approximately 57% were mapped to the human reference genome. The top DEMs in RA vs controls were miR-6724-5p, miR-1469, miR-194-3p (up), miR-1468-5p, miR-486-3p (down). In comparison, the top DEMs in OA vs controls were miR-1908-3p, miR-122b-3p, miR-3960 (up), miR-1468-5p, miR-15b-3p (down). The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Six of the deregulated miRNAs (miR-15b, -128, -194, -328, -542 and -3180) had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis. Conclusion: Six of our studied deregulated miRNAs (miR-15b, -128, -194, -328, -542 and -3180) might be highly involved in the disease pathogenesis. Further functional studies are crucial to assess their functions and actual target genes.

Keywords: next generation sequencing, mirnas, rheumatoid arthritis, osteoarthritis

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Authors: Lina Vyas

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Gender gap, unfortunately, is still prevalent in the workplace around the world. In most countries, women are less likely than men to participate in the workplace. They earn considerably less than men for doing the same work and are generally expected to prioritize family obligations over work responsibilities. Women often face more conflicts while balancing the increasingly normalized roles of both worker and mother. True gender equality in the workplace is still a long way off. In Hong Kong, no less is this true. Despite the fact that female students are outnumbered by males at universities, only 55% of women are active participants in the labour market, and for those in the workforce, the gender pay gap is 22%. This structural inequality also exacerbates the issues of confronting biases at work for choosing to be employed as a mother, as well as reinforces the societal expectation of women to be the primary caregiver at home. These pressures are likely to add up for women and contribute to increased levels of work-life conflict, which may be a further barrier for the inclusion of women into the workplace. Family-friendly policies have long been thought to be an alleviator of work-life conflict through helping employees balance the demands in both work and family. Particularly, for women, this could be a facilitator of their integration into the workplace. However, little research has looked at how family-friendly policies may also have a gender differential in effect, as opposed to traditional notions of having universal efficacy. This study investigates both how and how much the gender dimension impacts work-family conflict. In addition to disentangling the reasons for gender gaps existing in work-life conflict for women, this study highlights what can be done at an organizational level to alleviate these conflicts. Most importantly, the policies recommendations derived from this study serve as an avenue for more active participation for women in the workplace and can be considered as a pathway for promoting greater gender egalitarianism and fairness in a traditionally gender-segregated society.

Keywords: family-friendly policies, Hong Kong, work-family conflict, workplace

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Authors: Vadim Makarov, Stewart T.Cole

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PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

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Authors: Seyed Ali Hossein Zahraei, Iman Dianat

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The role of midwives and healthcare providers in applying pain relief methods to female patients is very important. different therapies like hydropathy, flavorer remedies, and respiratory techniques for pain relief do not work properly as what we expected. Lack of recognition of the physiological property of birth, despite findings that coming will attenuate the consequences of hurting, suggests the necessity for bigger awareness among expectant oldsters, educators, and health professionals of the potential of coming as a way of pain relief. Method: In our method we have 5 steps to achieve activation of oxytocin and dopamine pathways in order to reduce pain in all possible fields and reasons instead of using other treatments such as chemical painkillers. Step 1: First of all the patient should start by rubbing the clitoris up and down till occurring first clitoral orgasm. Step 2: Without stop rubing clitoris the patient must continue stimulate the clitoris in different way like circular motion in clock pathway until occurring second clitoral orgasm. Step 3: Immedietly the patient can change the position from clitoris to urethral opening where vestibular glands located. In this step the patient nock the urethral area very slowly without pressure and just like touching the area till feeling want to pee. But because of activation of sympathic nerves the gi tract is inactive. Step 4: In this step the patient should apply more pressure and change the motion to circular on urethral area in which the pee sensation increase but actually it is vestibular gland fluid. The patient should release it in small amount in this step. Step 5: The last step is combination of clitoral and urethral stimulation in up and down motion that cause more pee feeling and after clitoral orgasm occurred the amount of released fluid can be about 400ml.

Keywords: female, natural, method, pain

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Authors: Muhammad Adeel Arshad, Faiz-Ul Hassan, Yanfen Cheng

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According to FAO, enteric methane (CH4) production is about 44% of all greenhouse gas emissions from the livestock sector. Ruminants produce CH4 as a result of fermentation of feed in the rumen especially from roughages which yield more CH4 per unit of biomass ingested as compared to concentrates. Efficient ruminal fermentation is not possible without abating CO2 and CH4. Methane abatement strategies are required to curb the predicted rise in emissions associated with greater ruminant production in future to meet ever increasing animal protein requirements. Ecology of ruminal methanogenesis and avenues for its mitigation can be identified through various genomic and transcriptomic techniques. Programs such as Hungate1000 and the Global Rumen Census have been launched to enhance our understanding about global ruminal microbial communities. Through Hungate1000 project, a comprehensive reference set of rumen microbial genome sequences has been developed from cultivated rumen bacteria and methanogenic archaea along with representative rumen anaerobic fungi and ciliate protozoa cultures. But still many species of rumen microbes are underrepresented especially uncultivable microbes. Lack of sequence information specific to the rumen's microbial community has inhibited efforts to use genomic data to identify specific set of species and their target genes involved in methanogenesis. Metagenomic and metatranscriptomic study of entire microbial rumen populations offer new perspectives to understand interaction of methanogens with other rumen microbes and their potential association with total gas and methane production. Deep understanding of methanogenic pathway will help to devise potentially effective strategies to abate methane production while increasing feed efficiency in ruminants.

Keywords: Genome sequences, Hungate1000, methanogens, ruminal fermentation

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Authors: Abazar Ghorbani, W. M. Wishwajith W. Kandegama, Seyed Mehdi Razavi, Moxian Chen

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The roles of hydrogen sulfide (H₂S) and melatonin (MT) as gasotransmitters in plants are widely recognised. Nevertheless, the precise nature of their involvement in defensive reactions remains uncertain. This study investigates the impact of the ML-H2S interaction on tomato plants exposed to vanadium (V) toxicity, focusing on synthesising secondary metabolites and V metal sequestration. The treatments applied in this study included a control (T1), V stress (T2), MT+V (T3), MT+H2S+V (T4), MT+hypotaurine (HT)+V (T5), and MT+H2S+HT+V (T6). These treatments were administered: MT (150 µM) as a foliar spray pre-treatment (3X), HT treatment (0.1 mM, an H2S scavenger) as root immersion for 12 hours as pre-treatments, and H2S (NaHS, 0.2 mM) and V (40 mg/L) treatments added to the Hoagland solution for 2 weeks. Results demonstrate that ML and H2S+ML treatments alleviate V toxicity by promoting the transcription of key genes (ANS, F3H, CHS, DFR, PAL, and CHI) involved in phenolic and anthocyanin biosynthesis. Moreover, they decreased V uptake and accumulation and enhanced the transcription of genes involved in glutathione and phytochelatin synthesis (GSH1, PCS, and ABC1), leading to V sequestration in roots and protection against V-induced damage. Additionally, ML and H2S+ML treatments optimize chlorophyll metabolism, and increase internal H2S levels, thereby promoting tomato growth under V stress. The combined treatment of ML+H2S shows superior effects compared to ML alone, suggesting synergistic/interactive effects between these two substances. Furthermore, inhibition of the beneficial impact of ML+H2S and ML treatments by HT, an H2S scavenger, underscores the significant involvement of H₂S in the signaling pathway activated by ML during V toxicity. Overall, these findings suggest that ML requires the presence of endogenous H₂S to mitigate V-induced adverse effects on tomato seedlings.

Keywords: vanadium toxicity, secondary metabolites, vanadium sequestration, h2s-melatonin crosstalk

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Authors: Radoslav Stojchevski, Leonid Poretsky, Dimiter Avtanski

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Proinflammatory cytokines play an important role in cancer initiation and progression by mediating the intracellular communication between the cancer cells and tumor microenvironment. Increased tumor growth causing reduced oxygen concentration and oxygen pressure commonly result in hypoxia. Mechanistically, hypoxia is characterized by stabilization and nuclear translocation of hypoxia-inducible factor 1 alpha (HIF-1α) followed by propagation of molecular pathway cascade involving multiple downstream targets. Cobalt(II) chloride (CoCl₂) is commonly used to mimic hypoxia in experimental conditions since it directly induces the expression of HIF-1α. The aim of the present study was to investigate the in vitro effects and the molecular mechanisms by which hypoxia regulates the cytokine secretory profile of breast cancer cells. As a model for this study, we used several breast cancer cell lines bearing various molecular characteristics and metastatic potential (MDA-MB-231 (clauding low, ER-/PR-/HER²⁻), MCF-7 (luminal A, ER⁺/PR⁺/HER²⁻), and BT-474 (liminal B, ER⁺/PR⁺/HER²⁺)). We demonstrated that breast cancer cells secrete numerous cytokines and cytokine ligands, including interleukins, chemokines, and growth factors. Treatment with CoCl₂significantly modulated the breast cancer cells' cytokine expression in a concentration- and time-dependent manner. These effects were mediated via activation of several signaling pathways (JNK/SAPK1, NF-κB, STAT5A/B, and Erk/MAPK1/2). Taken together, the present data define some of the molecular mechanisms by which hypoxia affects the breast cancer cells' cytokine secretory profile, thus contributing to the development of novel therapies for metastatic breast cancer.

Keywords: breast cancer, cytokines, cobalt(II) chloride (CoCl₂), hypoxia

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Authors: Azaz Zaman, Imtiaz Uddin Chowdhury, Mohammad Shariful Islam

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Corporate governance has become a crucial issue in both the business and academic world as a result of world-wide financial scandals and lack of trust in corporate practices. There is no doubt that in order to thrive and attain growth in the market, a company must earn the trust of its stakeholders by consistently delivering on its commitments. Directors of the companies thus comprehend the importance of upfront communication with relevant stakeholders to increase their confidence. The authors of this article argue that practicing good corporate governance is not enough in this highly competitive market place; corporate leaders need to market their good corporate governance practices in order to make the company more attractive to investors. This article also contends that the strength of corporate governance relies wholly upon the extent to which it is communicated simply, effectively and unceasingly to its stakeholders. The main objective of this study, therefore, is to explore the importance of branding good corporate governance in order to increase corporate brand equity, attract investors, and capture market share. A structured questionnaire comprising three sections and a total of 34 questions was prepared and surveyed by the authors among respondents residing in Bangladesh and who also have an academic and corporate background, to investigate the potential impact of branding good corporate governance in the market place. High mean values for individual questions and overall section depict that communicating and branding good corporate governance to the stakeholders will not only boost the investors’ confidence but also increase the corporate brand equity, yielding both profitable and sustainable business environment.

Keywords: brand equity, investors’ preference, good corporate governance, sustainable business environment

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Authors: Kamyar Moradi

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Background: Acute mesenteric ischemia is known as a life-threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury, which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold. Methods: Male rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg, and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 minutes followed by 120 minutes of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also, protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method. Results: Histopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α. Conclusion: Single dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. Still, more studies would clarify existing causality in this phenomenon.

Keywords: albendazole, ischemia reperfusion injury, inflammation, mesenteric ischemia

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Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

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In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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Authors: S. M. M. Syairah, M. H. Rajikin, A. R. Sharaniza

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Several embryonic cellular mechanism including cell cycle, growth and apoptosis are regulated by phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The goal of present study is to determine the effects of annatto (Bixa orellana)-derived δ-tocotrienol (δ-TCT) on the regulations of PI3K/Akt genes in murine morula. Twenty four 6-8 week old (23-25g) female balb/c mice were randomly divided into four groups (G1-G4; n=6). Those groups were subjected to the following treatments for 7 consecutive days: G1 (control) received tocopherol stripped corn oil, G2 was given 60 mg/kg/day of δ-TCT mixture (contains 90% delta & 10% gamma isomers), G3 was given 60 mg/kg/day of pure δ-TCT (>98% purity) and G4 received 60 mg/kg/day α-TOC. On Day 8, females were superovulated with 5 IU Pregnant Mare’s Serum Gonadotropin (PMSG) for 48 hours followed with 5 IU human Chorionic Gonadotropin (hCG) before mated with males at the ratio of 1:1. Females were sacrificed by cervical dislocation for embryo collection 48 hours post-coitum. About fifty morula from each group were used in the gene expression analyses using Affymetrix QuantiGene Plex 2.0 Assay. Present data showed a significant increase (p<0.05) in the average number (mean + SEM) of morula produced in G2 (26.0 + 0.45), G3 (23.0 + 0.63) and G4 (25.0 + 0.73) compared to control group (G1 – 16.0 + 0.63). This is parallel with the high expression of PDK1 gene with increase of 2.75-fold (G2), 3.07-fold (G3) and 3.59-fold (G4) compared to G1 (1.78-fold). From the present data, it can be concluded that supplementation with δ-TCT(s) and α-TOC induced high expression of PDK1 in G2-G4 which enhanced the PI3K/Akt signaling activity, resulting in the increased number of morula.

Keywords: delta-tocotrienol, embryonic development, nicotine, vitamin E

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Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

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Authors: Rashmi Ranade, Neelu Joshi

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Barleria prionitis L. is a well explored Indian medicinal plant valued for its stem and leaf which forms an important ingredient of many Ayurvedic formulations. It is used for the treatment of various disorders like toothache, bleeding gums, strengthening gums, whooping cough, inflammation, arthritis, enlargement of scrotum and sciatica etc. The plant is propagated vegetatively through stem cuttings. Frequent harvesting of this plant has led to the shortage of planting material, and it has acquired the status of vulnerable plant species. Plant tissue culture technology offers a very good alternative for propagation and conservation of such plant species. The present investigation was undertaken to develop in vitro regeneration protocol for B. prionitis L. via callus organogenesis pathway. Stem and leaf explants were used for this purpose. Different media and plant growth regulators were optimized to develop the protocol. The problem of phenol secretion and browning and in vitro cultures at the establishment phase was successfully curbed with the usage of antibrowning agents such as ascorbic acid and activated charcoal. Optimum shoot multiplication was achieved by the use of liquid media and incorporation of silver nitrate and TIBA (triiodobenzoic acid) into the media. High percent rooting (76%) was observed on WPM media supplemented with IBA (2.0 mg/l), IAA (0.5 mg/l), GA3(0.5) and activated charcoal(500 mg/l). The rooted plantlets were subjected to in vitro hardening on sterile potting mix (soil:farmyard manure:compost; 1:2:1) and acclimatized under greenhouse conditions. Around 85% survival of plantlets was recorded upon acclimatization. This lab scale protocol would be tested for in vitro scaling up production of B. prionitis L.

Keywords: explant browning, liquid culture, micropropagation, shoot multiplication, phenolic secretion

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Authors: Ishan Naidu, Jessica Ryvlin, Devin Videlefsky

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Introduction: Back pain is a leading cause of years lived with disability and economic burden, exceeding over $20 billion in healthcare costs not including indirect costs such as absence from work and caregiving. The multifactorial nature of back pain leads to treatment modalities administered by a variety of specialists, which are often disjointed. Multiple studies have found that patients receiving delayed physical therapy for lower back pain had higher medical-related costs from increased health service utilization as well as a reduced improvement in pain severity compared to early management. Uncoordinated health care delivery can exacerbate the physical and economic toll of the chronic condition, thus improvements in interdisciplinary, shared decision-making may improve outcomes. Objective: To assess whether a multidisciplinary spine clinic (MSC), consisting of orthopedic surgery, neurosurgery, pain medicine, and physiatry, alters interventional and non-interventional planning and treatment compared to a traditional unidisciplinary spine clinic (USC) including only orthopedic surgery. Methods: We conducted a retrospective cohort study with patients initially presenting for spine care to orthopedic surgeons between July 1, 2018 to June 30, 2019. Time to treatment recommendation, time to treatment and rates of treatment recommendations were assessed, including physical therapy, injections and surgery. Treatment rates were compared between MSC and USC using Pearson’s chi-square test logistic regression. Time to treatment recommendation and time to treatment were compared using log-rank test and Cox proportional hazard regression. All analyses were repeated for the propensity score (PS) matched subsample. Results: This study included 1,764 patients, with 692 at MSC and 1,072 at USC. Patients in MSC were more likely to be recommended injection when compared to USC (8.5% vs. 5.4%, p=0.01). When adjusted for confounders, the likelihood of injection recommendation remained greater in MSC than USC (Odds ratio [OR]=2.22, 95% CI: (1.39, 3.53), p=0.001). MSC was also associated with a shorter time to receiving injection recommendation versus USC (median: 21 vs. 32 days, log-rank: p<0.001; hazard ratio [HR]=1.90, 95% CI: (1.25, 2.90), p=0.003). MSC was associated with a higher likelihood of injection treatment (OR=2.27, 95% CI: (1.39, 3.73), p=0.001) and shorter lead time (HR=1.98, 95% CI: (1.27, 3.09), p=0.003). PS-matched analyses yielded similar conclusions. Conclusions: Care delivered at a multidisciplinary spine clinic was associated with a higher likelihood of recommending injection and a shorter lead time to injection administration when compared to a traditional unidisciplinary spine surgery clinic. Multidisciplinary clinics may facilitate coordinated care amongst different specialties resulting in increased utilization of less invasive treatment modalities while also improving care efficiency. The multidisciplinary clinic model is an important advancement in care delivery and communication, which can be used as a powerful method of improving patient outcomes as treatment guidelines evolve.

Keywords: coordinated care, epidural steroid injection, multi-disciplinary, non-invasive

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Authors: L. K. Nivedha, V. Maruthapandian, R. Kothandaraman

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Rechargeable zinc-air batteries (ZAB) are gaining significant research attention owing to their high energy density and copious zinc resources worldwide. However, the unsolved obstacles such as dendrites, passivation, depth of discharge and the lack of an efficient cathode catalyst restrict their practical application1. By and large, non-noble transition metal-based catalysts are well-reputed materials for catalysing oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) with greater stability in alkaline medium2. Herein, we report the synthesis and application of Mn₃O4-NiFeLDH/Carbon composite as a cathode catalyst for rechargeable ZAB. The synergetic effects of the mixed transition metals (Mn/Ni/Fe) have aided in catalysing ORR and OER in alkaline electrolyte with a shallow potential gap of 0.7 V. The composite, by its distinctive physicochemical characteristics, shows an excellent OER activity with a current density of 1.5 mA cm⁻² at a potential of 1.6 V and a superior ORR activity with an onset potential of 0.8 V when compared with their counterparts. Nevertheless, the catalyst prefers a two-electron pathway for the electrochemical reduction of oxygen which results in a limiting current density of 2.5 mA cm⁻². The bifunctional activity of the Mn₃O₄-NiFeLDH/Carbon composite was utilized in developing rechargeable ZAB. The fully fabricated ZAB delivers an open circuit voltage of 1.4 V, a peak power density of 70 mW cm⁻², and a specific capacity of 800 mAh g⁻¹ at a current density of 20 mA cm⁻² with an average discharge voltage of 1 V and the cell is operable upto 50 mA cm-2. Rechargeable ZAB demonstrated over 110 h at 10 mA cm⁻². Further, the cause for the diminished charge-discharge performance experienced beyond the 100th cycle was investigated, and carbon corrosion was testified using Infrared spectroscopy.

Keywords: rechargeable zinc-air battery, oxygen evolution reaction, bifunctional catalyst, alkaline medium

Procedia PDF Downloads 51

Authors: A. A. Adebayo, A. O. Ogunkeyede, A. O. Adeigbe

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Digital globalisation and yarn of Nigeria society to overcome the digital divide have resulted in contamination of soil by heavy metals (HMs) from e-waste activities at Alaba international market, Lagos, Nigeria. The aim of this research was to determine the concentration of various metals {Cadmium (Cd), Chromium (Cr), Copper (Cu), and Lead (Pb)} and identify their ecological and health risks for the people within the study area. A total of 60 soil samples were collected at Alaba market study area. Two types of samples were collected from each sampling points: topsoil (0-15 cm), subsoil (15 -30 cm). The metal concentration results showed that the soils were heavily contaminated by HMs at topsoil and subsoil. The geoaccummulation and ecological risk indices revealed high pollution level from all studied site. The health risk assessment results suggested that there is high possibility of carcinogenic risk to humans because the carcinogenic risk via corresponding exposure pathways exceeded the safety limit of 10-6 (the acceptable level of carcinogenic risk for human). Furthermore, inhalation of soil particles is the main exposure pathway for Cr to enter the human body for all ages. Children in the vicinity are exposed more to ingestion of Pb since they tend to eat earth (pica) and repeatedly suck their fingers. This study provides basic information to create awareness for a need to introduce pollution control measures and the need to protect the ecosystem and human health within the study area at Alaba international market.

Keywords: contaminated soil, ecological risk, hazard index, risk factor, exposure pathways, heavy metals

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Authors: Liang Ning, Chung Hau Yin

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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

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Authors: Devadrita Dey Sarkar

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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

Procedia PDF Downloads 324