Search results for: cutting cycle

Authors: Yoftahe Nigussie

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This research explores the implementation of a vapor absorption refrigeration system (VARS) in mini-bus cars to enhance air conditioning efficiency. The conventional vapor compression refrigeration system (VCRS) in vehicles relies on mechanical work from the engine, leading to increased fuel consumption. The proposed VARS aims to utilize waste heat and exhaust gas from the internal combustion engine to cool the mini-bus cabin, thereby reducing fuel consumption and atmospheric pollution. The project involves two models: Model 1, a two-fluid vapor absorption system (VAS), and Model 2, a three-fluid VAS. Model 1 uses ammonia (NH₃) and water (H₂O) as refrigerants, where water absorbs ammonia rapidly, producing a cooling effect. The absorption cycle operates on the principle that absorbing ammonia in water decreases vapor pressure. The ammonia-water solution undergoes cycles of desorption, condensation, expansion, and absorption, facilitated by a generator, condenser, expansion valve, and absorber. The objectives of this research include reducing atmospheric pollution, minimizing air conditioning maintenance costs, lowering capital costs, enhancing fuel economy, and eliminating the need for a compressor. The comparison between vapor absorption and compression systems reveals advantages such as smoother operation, fewer moving parts, and the ability to work at lower evaporator pressures without affecting the Coefficient of Performance (COP). The proposed VARS demonstrates potential benefits for mini-bus air conditioning systems, providing a sustainable and energy-efficient alternative. By utilizing waste heat and exhaust gas, this system contributes to environmental preservation while addressing economic considerations for vehicle owners. Further research and development in this area could lead to the widespread adoption of vapor absorption technology in automotive air conditioning systems.

Keywords: room, zone, space, thermal resistance

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Authors: Stavroula Stavropoulou-Tatla, Danyal Awal, Mohammad Ayaz Hossain

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The first wave of the COVID-19 pandemic saw several countries issue guidance postponing all non-urgent diagnostic evaluations and operations, leading to an estimated backlog of 28 million cases worldwide and over 4 million in the UK alone. In an attempt to regulate the resumption of elective surgical activity, the National Institute for Health and Care Excellence (NICE) introduced the ‘COVID-19 rapid guideline [NG179]’. This project aimed to increase healthcare staff knowledge of the aforementioned guideline to a targeted score of 100% in the disseminated questionnaire within 3 months at the Royal Free Hospital. A standardized online questionnaire was used to assess the knowledge of surgical and medical staff at baseline and following each 4-week-long Plan-Study-Do-Act (PDSA) cycle. During PDSA1, the A4 visual summary accompanying the guideline was visibly placed in all relevant clinical areas and the full guideline was distributed to the staff in charge together with a short briefing on the salient points. PDSA2 involved brief small-group teaching sessions. A total of 218 responses was collected. Mean percentage scores increased significantly from 51±19% at baseline to 81±16% after PDSA1 (t=10.32, p<0.0001) and further to 93±8% after PDSA2 (t=4.9, p<0.0001), with 54% of participants achieving a perfect score. In conclusion, the targeted distribution of guideline printouts and visual aids, combined with small-group teaching sessions, were simple and effective ways of educating healthcare staff about the new standards of elective surgical care at the time of COVID-19. This could facilitate the safe restoration of surgical activity, which is critical in order to mitigate the far-reaching consequences of surgical delays on an unprecedented scale during a time of great crisis and uncertainty.

Keywords: COVID-19, elective surgery, NICE guidelines, quality improvement

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Authors: Abhay Vir Singh Kanwar

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The pharmaceutical industry today is a multi-billion dollar business and yet disadvantages people in many corners of the globe who are still dying in large numbers from curable illnesses for lack of access to drugs. The astronomical prices of essential and life-saving drugs is not just an economic problem that can be settled through clever market strategies but is an ethical issue, given the accumulated wealth of today’s humanity and the sense of global justice that it increasingly comes to share. In this paper, I make a very practical argument for what I shall call ‘the ethical healthcare paradigm’, which, I propose, can replace the economistic paradigm that can still drive the healthcare sector without creating spillover effects on the market. Taking off from the ethical-philosophical argument for recognizing every individual’s right to capability to be healthy, I shall come to the focused practical proposal of the cost-rationalization and universal availability of essential, life-saving drugs through the undertaking of research and development funding for drug innovation by the business establishment as such in terms of the concept of CSR. The paper will first expose the concepts of basic and fundamental capabilities in relation to education and health, after which it will focus on the right to capability to be healthy of every person. In the third section, it will discuss the ‘ethical healthcare paradigm’ as opposed to the economistic health paradigm and will argue that the patient will have to be considered the primary stakeholder of this paradigm or the very ‘subject’ of healthcare. The next section will be on an ethical-historical critique of the pharmaceutical industry’s profit driven economism. The section after that will look at the business operation and the stages in the life cycle of a drug that comes to the market in order to understand the risks, strengths and problems of the pharmaceutical industry. Finally, the paper will discuss the concept of CSR in relation to the ethical healthcare paradigm in order to propose CSR funding in research and development for innovation on drugs so that life-saving drugs can be made available to every sick person cost-effectively.

Keywords: capability approach, healthcare, CSR, patient

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Authors: Florina Dutt, Subhajit Das, Matthew Swartz

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Lighting design and its impact on indoor comfort conditions are an integral part of good interior design. Impact of lighting in an interior space is manifold and it involves many sub components like glare, color, tone, luminance, control, energy efficiency, flexibility etc. While other components have been researched and discussed multiple times, this paper discusses the research done to understand the glare component from an artificial lighting source in an indoor space. Consequently, the paper discusses a parametric model to convey real time glare level in an interior space to the designer/ architect. Our end users are architects and likewise for them it is of utmost importance to know what impression the proposed lighting arrangement and proposed furniture layout will have on indoor comfort quality. This involves specially those furniture elements (or surfaces) which strongly reflect light around the space. Essentially, the designer needs to know the ramification of the ‘discomfortable glare’ at the early stage of design cycle, when he still can afford to make changes to his proposed design and consider different routes of solution for his client. Unfortunately, most of the lighting analysis tools that are present, offer rigorous computation and analysis on the back end eventually making it challenging for the designer to analyze and know the glare from interior light quickly. Moreover, many of them do not focus on glare aspect of the artificial light. That is why, in this paper, we explain a novel approach to approximate interior glare data. Adding to that we visualize this data in a color coded format, expressing the implications of their proposed interior design layout. We focus on making this analysis process very fluid and fast computationally, enabling complete user interaction with the capability to vary different ranges of user inputs adding more degrees of freedom for the user. We test our proposed parametric model on a case study, a Computer Lab space in our college facility.

Keywords: computational geometry, glare impact in interior space, info visualization, parametric lighting analysis

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Authors: Maureen Royce, Joshi Jariwala, Sally Kah

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Change is inevitable, but the change process is progressive. Organisational change is the process in which an organisation changes strategies, operational methods, systems, culture, and structure to affect something different in the organisation. This process can be continuous or developed over a period and driven by internal and external factors. Organisational change is essential if organisations are to survive in dynamic and uncertain environments. However, evidence from research shows that many change initiatives fail, leading to severe consequences for organisations and their resources. The complex models of third sector organisations, i.e., social enterprise, compounds the levels of change in these organisations. Interestingly, innovation is associated with a change in social enterprises due to the hybridity of product and service development. Furthermore, the creation of social intervention has offered a new process and outcomes to the lifecycle of change. Therefore, different forms of organisational innovation are developed, i.e., total, evolutionary, expansionary, and developmental, which affect the interventions of social enterprises. This raises both theoretical and business concerns on how the competing hybrid nature of social enterprises change, how change is managed, and the impact on these organisations. These perspectives present critical questions for further investigation. In this study, we investigate the impact of organisational change on employees and organisational development at DaDaFest –a disability arts organisation with a social focus based in Liverpool. The three main objectives are to explore the drivers of change and the implementation process; to examine the impact of organisational change on employees and; to identify barriers to organisation change and development. To address the preceding research objectives, qualitative research design is adopted using semi-structured interviews. Data is analysed using a six-step thematic analysis framework, which enables the study to develop themes depicting the impact of change on employees and organisational development. This study presents theoretical and practical contributions for academics and practitioners. The knowledge contributions encapsulate the evolution of change and the change cycle in a social enterprise. However, practical implications provide critical insights into the change management process and the impact of change on employees and organisational development.

Keywords: organisational change, change management, organisational change system, social enterprise

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Authors: Maciej Jedrzejczyk, Karolina Marzantowicz

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Traditional utility value chain is being transformed during last few years into unbundled markets. Increased distributed generation of energy is one of considerable challenges faced by Smart Grid networks. New sources of energy introduce volatile demand response which has a considerable impact on traditional middlemen in E&U market. The purpose of this research is to search for ways to allow near-real-time electricity markets to transact with surplus energy based on accurate time synchronous measurements. A proposed framework evaluates the use of secure peer-2-peer (P2P) communication and distributed transaction ledgers to provide flat hierarchy, and allow real-time insights into present and forecasted grid operations, as well as state and health of the network. An objective is to achieve dynamic grid operations with more efficient resource usage, higher security of supply and longer grid infrastructure life cycle. Methods used for this study are based on comparative analysis of different distributed ledger technologies in terms of scalability, transaction performance, pluggability with external data sources, data transparency, privacy, end-to-end security and adaptability to various market topologies. An intended output of this research is a design of a framework for safer, more efficient and scalable Smart Grid network which is bridging a gap between traditional components of the energy network and individual energy producers. Results of this study are ready for detailed measurement testing, a likely follow-up in separate studies. New platforms for Smart Grid achieving measurable efficiencies will allow for development of new types of Grid KPI, multi-smart grid branches, markets, and businesses.

Keywords: autonomous agents, Distributed computing, distributed ledger technologies, large scale systems, micro grids, peer-to-peer networks, Self-organization, self-stabilization, smart grids

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Authors: Tasneem Imam, Justine S. Gibson, Mohammad Foysal, Shetu B. Das, Rashed Mahmud, Suman D. Gupta, Ahasanul Hoque, Guillaume Fournie, Joerg Henning

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Commercial chicken production is an import livestock industry in Bangladesh. Antimicrobials are commonly used to control and prevent infectious diseases. It was hypothesized that inadequate biosecurity practices might promote antimicrobial usage on commercial chicken farms. A cross-sectional study was carried out to evaluate antimicrobial usage and farm biosecurity practices implemented on 57 layer and 83 broiler farms in eight sub-districts of the Chattogram district in Bangladesh. A questionnaire was used to collect data on antimicrobial usage and biosecurity practices on these farms. A causal framework was used to guide the development of a multi-level mixed-effects logistic regression analysis to evaluate the total and direct effects of practiced biosecurity management on prophylactic and therapeutic administration of antimicrobials. A total of 24 antimicrobials were administered in the current production cycle at the time of the survey. The most administered antimicrobials on layer farms were ciprofloxacin (37.0% of farms), amoxicillin (33.3%), and tiamulin (31.5%); however, on broiler farms, colistin (56.6% of farms), doxycycline (50.6%), and neomycin (38.6%) were most used. Only 15.3% of commercial farmers used antimicrobials entirely for therapeutic purposes, whereas 84.7% administered antimicrobials prophylactically. Inadequate biosecurity practices were more common among commercial broiler farmers compared to layer farmers. For example, only 2.4% of broiler farmers used footbaths before entering sheds compared to 22.2% of the layer farmers (p < 0.001). Farms that used antimicrobials only for therapeutic purposes (vs prophylactic) implemented more frequently adequate disease control measures, such as separating sick birds from healthy birds. This research highlighted that the prophylactic application of antimicrobials is often conducted to substitute poor biosecurity practices on commercial chicken farms. Awareness programs for farmers are crucial to inform them about the risk associated with antimicrobial usage and to highlight the economic benefits of implementing cost-effective biosecurity measures to control infectious poultry diseases.

Keywords: antimicrobial, biosecurity, broiler, layer

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Authors: Md. Afroz Ansari

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The Bengal basin is a spectacular example of a peripheral foreland basin formed by the convergence of the Indian plate beneath the Eurasian and Burmese plates. The basin is embraced on three sides; north, west and east by different fault-controlled tectonic features whereas released in the south where the rivers are drained into the Bay of Bengal. The Bengal basin in the eastern part of the Indian subcontinent constitutes the largest fluvio-deltaic to shallow marine sedimentary basin in the world today. This continental basin coupled with the offshore Bengal Fan under the Bay of Bengal forms the biggest sediment dispersal system. The continental basin is continuously receiving the sediments by the two major rivers Ganga and Brahmaputra (known as Jamuna in Bengal), and Meghna (emerging from the point of conflux of the Ganga and Brahmaputra) and large number of rain-fed, small tributaries originating from the eastern Indian Shield. The drained sediments are ultimately delivered into the Bengal fan. The significance of the present study is to delineate the variations in thicknesses of the sediments, different crustal structures, and the mantle lithosphere throughout the onshore-offshore Bengal basin. In the present study, the different crustal/geological units and the shallower mantle lithosphere were delineated by analyzing the Bouguer Gravity Anomaly (BGA) data along two long traverses South-North (running from Bengal fan cutting across the transition offshore-onshore of the Bengal basin and intersecting the Main Frontal Thrust of India-Himalaya collision zone in Sikkim-Bhutan Himalaya) and West-East (running from the Peninsular Indian Shield across the Bengal basin to the Chittagong–Tripura Fold Belt). The BGA map was derived from the analysis of topex data after incorporating Bouguer correction and all terrain corrections. The anomaly map was compared with the available ground gravity data in the western Bengal basin and the sub-continents of India for consistency of the data used. Initially, the anisotropy associated with the thicknesses of the different crustal units, crustal interfaces and moho boundary was estimated through spectral analysis of the gravity data with varying window size over the study area. The 2D density sections along the traverses were finalized after a number of iterations with the acceptable root mean square (RMS) errors. The estimated thicknesses of the different crustal units and dips of the Moho boundary along both the profiles are consistent with the earlier results. Further the results were encouraged by examining the earthquake database and focal mechanism solutions for better understanding the geodynamics. The earthquake data were taken from the catalogue of US Geological Survey, and the focal mechanism solutions were compiled from the Harvard Centroid Moment Tensor Catalogue. The concentrations of seismic events at different depth levels are not uncommon. The occurrences of earthquakes may be due to stress accumulation as a result of resistance from three sides.

Keywords: anisotropy, interfaces, seismicity, spectrum analysis

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Umar Saeed

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Peptidyl-prolyl cis/trans isomerases Par14 and Par17 in humans play crucial roles in diverse cellular processes, including protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have been explored to a limited extent. We first time discovered their influential roles in promoting Hepatitis B Virus replication. In this study, we observed that in the presence of HBx, either Par14 or Par17 could upregulate HBV replication. However, in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Their mechanism of action involves binding to specific motifs within HBc and HBx proteins. Notably, they target the conserved 133Arg-Pro134 (RP) motif of HBc and the 19RP20-28RP29 motifs of HBx. This interaction is fundamental for the stability of HBx, core particles, and HBc. Par14 and Par17 exhibit versatility by binding both outside and inside core particles, thereby facilitating core particle assembly through their participation in HBc dimer-dimer interactions. NAGE and immunoblotting analyses unveiled the binding of Par14/Par17 to core particles. Co-immunoprecipitation experiments further demonstrated the interaction of Par14/Par17 with core particle assembly-defective and dimer-positive HBc-Y132A. It's essential to emphasize that R133 is the key residue in the HBc RP motif that governs their interaction with Par14/Par17. Chromatin immunoprecipitation conducted on HBV-infected cells elucidated the participation of residues S19 and E46/D74 in Par14 and S44 and E71/D99 in Par17 in the recruitment of 133RP134 motif-containing HBc into cccDNA. Depleting PIN4 in liver cell lines results in a significant reduction in cccDNA levels, pgRNA, sgRNAs, HBc, core particle assembly, and HBV DNA synthesis. Notably, parvulin inhibitors like juglone and PiB have proven to be effective in substantially reducing HBV replication. These inhibitors weaken the interaction between HBV core particles and Par14/Par17, underscoring the dynamic nature of this interaction. It's also worth noting that specific Par14/Par17 inhibitors hold promise as potential therapeutic options for chronic hepatitis B.

Keywords: Par14Par17, HBx, HBc, cccDNA, HBV

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Authors: Tong Mei Yan

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Introduction: The experience of infertility could be excruciating but has not received much attention in Hong Kong. The strong Confucian culture pressures couples to continue their family lineage resulting in women facing more stress than men in the social-cultural milieu. In Vitro Fertilization (IVF) treatment is one of the common ways to deal with the problem. Abundant literature exists the psychological trajectories of people receiving IVF treatment in Europe, the USA and other east Asian societies but not in Hong Kong. Aim: This study aims to highlight the circumstances and needs of the women before, during and after IVF treatment through examining their lived experiences. It is hoped that the public, once informed of regarding their tribulations and needs , would support the adequate provision of the required psychological support . Methods: Qualitative analysis was adopted in this study. In-depth interviews were conducted with six women who have undergone at least one complete cycle of IVF treatment within the past five years. Data was analyzed through thematic analysis and narrative analysis. Results: 4 broad themes were found, including (i) emotional responses; (ii) experiences in medical consultation; (iii) impacts of the treatment; and (iv) their coping strategies. Additionally, specific events in three cases were chosen for narrative analysis to further examine their unresolved emotional distress and the ethical issues. Conclusion: IVF treatment distressed the interviewees immensely, both physically and psychologically, with the negative emotions outweighing their physical strains, a result unexpected by all of the interviewees. The pressure for lineage continuation, the demanding treatment process and the dearth of support from health professionals all contribute to their emotional pain which could linger for both successful and unsuccessful cases. Although a number of coping strategies were attempted, most of them completely failed to ease their psychological tension. The findings of this study therefore evidence the need for psychological support for this population. A service model to cater their needs of IVF treatment before, during and after treatment is therefore proposed.

Keywords: coping strategies, emotional experiences, impacts of IVF, infertility, IVF treatment, medical experiences

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Authors: Loubna Khalile, Hicham Lahlaoi, Hassan Rhinane, A. Kaoukaya, S. Fal

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Green spaces is an essential element, they contribute to improving the quality of lives of the towns around them. They are a place of relaxation, walk and rest a playground for sport and youths. According to United Nations Organization Forests cover 31% of the land. In Morocco in 2013 that cover 12.65 % of the total land area, still, a small proportion compared to the natural needs of forests as a green lung of our planet. The Benslimane Forest is a large green area It belongs to Chaouia-Ouardigha Region and Greater Casablanca Region, it is located geographically between Casablanca is considered the economic and business Capital of Morocco and Rabat the national political capital, with an area of 12261.80 Hectares. The essential problem usually encountered in suburban forests, is visitation and tourism pressure it is anthropogenic actions, as well as other ecological and environmental factors. In recent decades, Morocco has experienced a drought year that has influenced the forest with increasing human pressure and every day it suffers heavy losses, as well as over-exploitation. The Moroccan forest ecosystems are weak with intense ecological variation, domanial and imposed usage rights granted to the population; forests are experiencing a significant deterioration due to forgetfulness and immoderate use of forest resources which can influence the destruction of animal habitats, vegetation, water cycle and climate. The purpose of this study is to make a model of the degree of degradation of the forest and know the causes for prevention by using remote sensing and geographic information systems by introducing climate and ancillary data. Analytic hierarchy process was used to find out the degree of influence and the weight of each parameter, in this case, it is found that anthropogenic activities have a fairly significant impact has thus influenced the climate.

Keywords: analytic hierarchy process, degradation, forest, geographic information system

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: Jessica Achebe, Susan Tighe

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The recent Canadian infrastructure report card reveals the unhealthy state of municipal infrastructure intensified challenged faced by municipalities to maintain adequate infrastructure performance thresholds and meet user’s required service levels. For a road agency, huge funding gap issue is inflated by growing concerns of the environmental repercussion of road construction, operation and maintenance activities. As the reduction of material consumption and greenhouse gas emission when maintain and rehabilitating road networks can achieve added benefits including improved life cycle performance of pavements, reduced climate change impacts and human health effect due to less air pollution, improved productivity due to optimal allocation of resources and reduced road user cost. Incorporating environmental sustainability measure into pavement management is solution widely cited and studied. However measuring the environmental performance of road network is still a far-fetched practice in road network management, more so an ostensive agency-wide environmental sustainability or sustainable maintenance specifications is missing. To address this challenge, this present research focuses on the environmental sustainability performance of network-level pavement management. The ultimate goal is to develop a framework to incorporate environmental sustainability in pavement management systems for network-level maintenance programming. In order to achieve this goal, this study reviewed previous studies that employed environmental performance measures, as well as the suitability of environmental performance indicators for the evaluation of the sustainability of network-level pavement maintenance strategies. Through an industry practice survey, this paper provides a brief forward regarding the pavement manager motivations and barriers to making more sustainable decisions, and data needed to support the network-level environmental sustainability. The trends in network-level sustainable pavement management are also presented, existing gaps are highlighted, and ideas are proposed for sustainable network-level pavement management.

Keywords: pavement management, sustainability, network-level evaluation, environment measures

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Authors: Yong-Hui Zheng

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Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

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Authors: Theodore Panton

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As cities in the United States experience critical housing shortages, mass timber presents the opportunity to address this crisis in housing supply while taking advantage of the carbon-positive benefits of sustainably forested wood fiber. Mass timber, however, currently has a low level of adoption in residential multifamily structures due to the risk-averse nature of change within the construction financing, Architecture / Engineering / Contracting (AEC) communities, as well as various agency approval challenges. This study demonstrates how mass timber can be used within the cost and feasibility parameters of a typical multistory residential structure and ultimately address the need for dense urban housing. This study will utilize The Garden District, a mixed-use market-rate housing project in Woodinville, Washington, as a case study to illuminate the potential of mass timber in this application. The Garden District is currently in final stages of permit approval and will commence construction in 2023. It will be the tallest dowel-laminated timber (DLT) residential structure in the United States when completed. This case study includes economic, technical, and design reference points to demonstrate the relevance of the use of this system and its ability to deliver “triple bottom line” results. In terms of results, the study establishes scalable and repeatable approaches to project design and delivery of mass timber in multifamily residential uses and includes economic data, technical solutions, and a summary of end-user advantages. This study discusses the third party tested systems for satisfying acoustical requirements within dwelling units, a key to resolving the use of mass timber within multistory residential use. Lastly, the study will also compare the mass timber solution with a comparable cold formed steel (CFS) system with a similar program, which indicates a net carbon savings of over three million tons over the life cycle of the building.

Keywords: DLT, dowell laminated timber, mass timber, market rate multifamily

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Authors: Chun-Fang Hsueh, Chen-Kang Chang

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Introduction: Branched-chain amino acids (BCAA) could reduce cerebral uptake of tryptophan, leading to decreased synthesis of serotonin in the brain. Arginine and citrulline could reduce exercise-induced hyperammonemia by increasing nitric oxide synthesis and the urea cycle. The combination of these supplements could reduce exercise-induced central fatigue. The purpose of this study was to examine the effect of BCAA, arginine, and citrulline supplementation on repeated swimming performance in teenage athletes. Methods: Eight male and eight female high school swimmers ingested 0.085 g/kg BCAA, 0.05 g/kg arginine and 0.05 g/kg citrulline (AA trial) or placebo (PL trial) in a randomized cross-over design. One hour after the ingestion, the subjects performed a 50 m sprint with their best style every 2 min for 8 times in an indoor 25 m pool. The subjects were asked to swim with their maximal effort each time. The time, stroke frequency and stroke length in each sprint were recorded. Venous blood samples were collected before and after the exercise. The time for each sprint was analyzed by 2-way analysis of variance with repeated measurement. Results: When all subjects were pooled together, total time for the AA trial was significantly faster than the PL trial (AA: 244.02 ± 22.94 s; PL: 247.55 ± 24.17 s, p < .001). Individual sprint time showed significant trial (p= .001) and trial x time (p= .004) effects. The post-hoc analysis revealed that the AA trial was significantly faster than the PL trial in the 2nd, 5th, and 6th sprint. In female subjects, there is a significant trial effect (p= .004) with the AA trial being faster in the 1st, 2nd, and 5th sprint. On the other hand, the trial effect was not significant (p= .072) in male subjects. Conclusions: The combined supplementation could improve 8 x 50 m performance in high school swimmers. The blood parameters including BCAA, tryptophan, NH₃, nitric oxide, and urea, as well as the stroke frequency and length in each sprint, are being analyzed. The results will be presented in the conference.

Keywords: central fatigue, hyperammonemia, tryptophan, urea

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Authors: Henry Kelly, Helena Shaw

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This paper will seek how innovative methods from Health Economics and, to a lesser extent, wellbeing analysis can be applied in the Cost-Benefit Analysis (CBA) of transport infrastructure and policy interventions. The context for this will focus on the framework articulated by the UK Treasury (finance department) and the English Department for Transport. Both have well-established methods for undertaking CBA, but there is increased policy interest, particularly at a regional level of exploring broader strategic goals beyond those traditionally associated with transport user benefits, productivity gains, and labour market access. Links to different CBA approaches internationally, such as New Zealand, France, and Wales will be referenced. By exploring a complementary method of accessing the impacts of policies through the quantification of health impacts is a fruitful line to explore. In a previous piece of work, 14 impact pathways were identified, mapping the relationship between transport and health. These are wide-ranging, from improved employment prospects, the stress of unreliable journey times, and air quality to isolation and loneliness. Importantly, we will consider these different measures of health from an intersectional point of view to ensure that the basis that remains in the health industry does not get translated across to this work. The objective is to explore how a CBA based on these pathways may, through quantifying forecast impacts in terms of Quality-Adjusted Life Years may, produce different findings than a standard approach. Of particular interest is how a health-based approach may have different distributional impacts on socio-economic groups and may favour distinct types of interventions. Consideration will be given to the degree this approach may double-count impacts or if it is possible to identify additional benefits to the established CBA approach. The investigation will explore a range of schemes, from a high-speed rail link, highway improvements, rural mobility hubs, and coach services to cycle lanes. The conclusions should aid the progression of methods concerning the assessment of publicly funded infrastructure projects.

Keywords: cost-benefit analysis, health, QALYs transport

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Authors: G. Disciglio, G. Gatta, F. Lops, A. Libutti, A. Tarantino, E. Tarantino

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The experimental trial was carried out in open field at Foggia district (Apulia Region, Southern Italy), during the spring-summer season 2014, in order to evaluate the effect of four biostimulant products (RadiconÒ, Viormon plusÒ, LysodinÒ and SiaptonÒ 10L), compared with a control (no biostimulant), on the infestation of processing tomato crop (cv Dres) by the chlorophyll-lacking root parasite Phelipanche ramosa. Biostimulants consist in different categories of products (microbial inoculants, humic and fulvic acids, hydrolyzed proteins and aminoacids, seaweed extracts) which play various roles in plant growing, including the improvement of crop resistance and quali-quantitative characteristics of yield. The experimental trial was arranged according to a complete randomized block design with five treatments, each of one replicated three times. The processing tomato seedlings were transplanted on 5 May 2014. Throughout the crop cycle, P. ramosa infestation was assessed according to the number of emerged shoots (branched plants) counted in each plot, at 66, 78 and 92 day after transplanting. The tomato fruits were harvested at full-stage of maturity on 8 August 2014. From each plot, the marketable yield was measured and the quali-quantitative yield parameters (mean weight, dry matter content, colour coordinate, colour index and soluble solids content of the fruits) were determined. The whole dataset was tested according to the basic assumptions for the analysis of variance (ANOVA) and the differences between the means were determined using Tukey’s tests at the 5% probability level. The results of the study showed that none of the applied biostimulants provided a whole control of Phelipanche, although some positive effects were obtained from their application. To this respect, the RadiconÒ appeared to be the most effective in reducing the infestation of this root-parasite in tomato crop. This treatment also gave the higher tomato yield.

Keywords: biostimulant, control methods, Phelipanche ramosa, tomato crop

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Authors: Disciglio G., Lops F., Carlucci A., Gatta G., Tarantino A., Frabboni L, Tarantino E.

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The Phelipanche ramosa is considered the most damaging obligate flowering parasitic weed on a wide species of cultivated plants. The semiarid regions of the world are considered the main center of this parasitic weed, where heavy infestation are due to the ability to produce high numbers of seeds (up to 200,000), that remain viable for extended period (more than 19 years). In this paper 13 treatments of parasitic weed control, as physical, chemical, biological and agronomic methods, including the use of the resistant plants, have been carried out. In 2014 a trial was performed on processing tomato (cv Docet), grown in pots filled with soil taken from a plot heavily infested by Phelipanche ramosa, at the Department of Agriculture, Food and Environment, University of Foggia (southern Italy). Tomato seedlings were transplanted on August 8, 2014 on a clay soil (USDA) 100 kg ha-1 of N; 60 kg ha-1 of P2O5 and 20 kg ha-1 of S. Afterwards, top dressing was performed with 70 kg ha-1 of N. The randomized block design with 3 replicates was adopted. During the growing cycle of the tomato, at 70-75-81 and 88 days after transplantation the number of parasitic shoots emerged in each pot was detected. Also values of leaf chlorophyll Meter SPAD of tomato plants were measured. All data were subjected to analysis of variance (ANOVA) using the JMP software (SAS Institute Inc., Cary, NC, USA), and for comparison of means was used Tukey's test. The results show lower values of the color index SPAD in tomato plants parasitized compared to those healthy. In addition, each treatment studied did not provide complete control against Phelipanche ramosa. However the virulence of the attacks was mitigated by some treatments: radicon product, compost activated with Fusarium, mineral fertilizer nitrogen, sulfur, enzone and resistant tomato genotype. It is assumed that these effects can be improved by combining some of these treatments each other, especially for a gradual and continuing reduction of the “seed bank” of the parasite in the soil.

Keywords: control methods, Phelipanche ramose, tomato crop

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Authors: Hamza Ikhlaq, Stephen Franks

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Background: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. The aetiology behind PCOS is poorly understood but influencing ethnic, environmental, and genetic factors have been recognised. However, literature examining the impact of ethnicity is scarce. We hypothesised Body Mass Index (BMI) and ethnicity influence the clinical, metabolic, and biochemical presentations of PCOS, with an interaction between these factors. Methods: A database of 1081 women with PCOS and a control group of 72 women were analysed. BMIs were grouped using the World Health Organisation classification into normal weight, overweight and obese groups. Ethnicities were classified into European, South Asian, and Afro-Caribbean groups. Biochemical and clinical presentations were compared amongst these groups, and statistical analyses were performed to assess significance. Results: This study revealed ethnicity significantly influences biochemical and clinical presentations of PCOS. A greater proportion of South Asian women are impacted by menstrual cycle disturbances and hirsutism than European and Afro-Caribbean women. South Asian and Afro-Caribbean women show greater measures of insulin resistance and weight gain when compared to their European peers. Women with increased BMI are shown to have an increased prevalence of PCOS phenotypes alongside increased levels of insulin resistance and testosterone. Furthermore, significantly different relationships between the waist-hip ratio and measures of insulin and glucose control for Afro-Caribbean women were identified compared to other ethnic groups. Conclusions: The findings of this study show ethnicity significantly influence the phenotypic and biochemical presentations of PCOS, with an interaction between body habitus and ethnicity found. Furthermore, we provide further data on the influences of BMI on the manifestations of PCOS. Therefore, we highlight the need to consider these factors when reviewing diagnostic criteria and delivering clinical care for these groups.

Keywords: PCOS, ethnicity, BMI, clinical

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Authors: Ana Maria Reis D'Azevedo Breda, Catarina Maria Neto da Cruz

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The Japanese art of origami provides a rich context for designing exploratory mathematical activities for children and young people. By folding a simple sheet of paper, fascinating and surprising planar and spatial configurations emerge. Equally surprising is the unfolding process, which also produces striking patterns. The procedure of folding, unfolding, and folding again allows the exploration of interesting geometric patterns. When adequately and systematically done, we may deduce some of the mathematical rules ruling origami. As the child/youth folds the sheet of paper repeatedly, he can physically observe how the forms he obtains are transformed and how they relate to the pattern of the corresponding unfolding, creating space for the understanding/discovery of mathematical principles regulating the folding-unfolding process. As part of a 2023 Summer Academy organized by a Portuguese university, a session entitled “Folding, Thinking and Generalizing” took place. Twenty-three students attended the session, all enrolled in the 2nd cycle of Portuguese Basic Education and aged between 10 and 12 years old. The main focus of this session was to foster the development of critical cognitive and socio-emotional skills among these young learners using origami. These skills included creativity, critical analysis, mathematical reasoning, collaboration, and communication. Employing a qualitative, descriptive, and interpretative analysis of data collected during the session through field notes and students’ written productions, our findings reveal that structured origami-based activities not only promote student engagement with mathematical concepts in a playful and interactive but also facilitate the development of socio-emotional skills, which include collaboration and effective communication between participants. This research highlights the value of integrating origami into educational practices, highlighting its role in supporting comprehensive cognitive and emotional learning experiences.

Keywords: skills, origami rules, active learning, hands-on activities

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Authors: Alessandro Suardi, Rodolfo Picchio, Domenico Coaloa, Maria Bonaventura Forleo, Nadia Palmieri, Luigi Pari

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The reconversion process of the Italian sugar supply chain to bio-energy supply chains, as a result of the 2006 Sugar CMO reform, have involved research to define the best logistics, the most adapted energy crops for the Italian territory and their sustainability. Rapeseed (Brassica napus L.), Giant reed (Arundo donax L.) and Poplar (Poplar ssp.) are energy crops considered strategic for the development of Italian energy supply-chains. This study analyzed the environmental and the economic impacts on the farm level of these three energy crops. The environmental assessment included six farming units, two per crop, which were extracted from a sample of 251 rapeseed farm units (2751 ha), 7 giant reed farm units (7.8 ha), and 91 poplar farm units (440 ha) using a statistical multivariate analysis. Life Cycle Assessment (LCA) research method has been used to evaluate and compare the sustainability of the agricultural phases of the crops studied. The impact analyses have been performed at mid-point and end-point levels. The results of the analysis shown that the fertilization, is the major source of environmental impact of the agricultural phase due to the production of the fertilizers and the soil emissions of GHG following the treatment. The perennial energy crops studied (Arundo donax L., Poplar ssp.) were environmentally more sustainable if compared with the annual crop (Brassica napus L.) for all the impact categories at mid-point and end-point levels analyzed. The most relevant impact category influenced by the agricultural process result the fossil depletion, mainly due to the fossil fuels consumed during the mineral fertilizers production (urea). Human health was the most affected damage category at the end point level. Poplar result the energy crop with the best environmental performance for the Italian territory, in the distribution areas most suitable for its cultivation.

Keywords: LCA, energy crops, rapeseed, giant reed, poplar

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Authors: Sara Parker, Kay Standing

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This paper will share insights into how menstruators bodies in Nepal are viewed and controlled in Nepal due to the deeply held stigmas and taboos that exist that frame menstrual blood as impure and polluting. It draws on a British Academy Global Challenges Research (BA/GCRF) funded project, ‘Dignity Without Danger,’ that ran from December 2019 to 2022. In Nepal, beliefs and myths around menstrual related practices prevail and vary in accordance to time, generation, caste and class. Physical seclusion and/or restrictions include the consumption of certain foods, the ability to touch certain people and objects, and restricted access to water sources. These restrictions not only put women at risk of poor health outcomes, but they also promote discrimination and challenge fundamental human rights. Despite the pandemic, a wealth of field research and creative outputs have been generated to help break the silence that surrounds menstruation and also highlights the complexity of addressing the harms associated with the exclusion from sacred and profane spaces that menstruators face. Working with locally recruited female research assistants, NGOS and brining together academics from the UK and Nepal, we explore the intersecting factors that impact on menstrual experiences and how they vary throughout Nepal. WE concur with Tamang that there is no such thing as a ‘Nepali Woman’, and there is no one narrative that captures the experiences of menstruators in Nepal. These deeply held beliefs and practices mean that menstruators are denied their right to a dignified menstruation. By being excluded from public and private spaces, such as temples and religious sites, as well as from kitchens and your own bedroom in your own home, these beliefs impact on individuals in complex and interesting ways. Existing research in Nepal by academics and activists demonstrates current programmes and initiatives do not fully address the misconceptions that underpin the exclusionary practices impacting on sexual and reproductive health, a sense of well being and highlight more work is needed in this area. Research has been conducted in all 7 provinces and through exploring and connecting disparate stories, artefacts and narratives, we will deepen understanding of the complexity of menstrual practices enabling local stakeholders to challenge exclusionary practices. By using creative methods to engage with stakeholders and share our research findings as well as highlighting the wealth of activism in Nepal. We highlight the importance of working with local communities, leaders and cutting across disciplines and agencies to promote menstrual justice and dignity. Our research findings and creative outputs that we share on social media channels such as Dignity Without Danger Facebook, Instagram and you tube stress the value of employing a collaborative action research approach to generate material which helps local people take control of their own narrative and change social relations that lead to harmful practices.

Keywords: menstruation, Nepal, stigma, social norms

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Authors: Dyah Larasati, Karishma Alize Huda, Sri Kusumastuti Rahayu, Martin Daniel Siyaranamual

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Indonesia continues to reform its social protection system to provide the needed protection for its citizen. Indonesia Social Protection consisted of social assistance programs (non-contributory/tax-financed) specifically targeted for the poor and at-risk and social security/insurance program (contributory system). The social assistance programs have mostly been implemented since 1998. The national health insurance has been implemented since 2014 and the employment social insurance since 2015. One major reform implemented has been improving the targeting performance of its major social assistance portfolios including (1) Food Assistance for the poor families (Rastra and BPNT/noncash foods assistance); (2) Education Assistance for poor children; (3) Conditional Cash Transfer for poor families (PKH); and (4) Subsidized beneficiaries of National Health Insurance (JKN-PBI) for the poor and at-risk individuals. For the Social Insurance (through BPJS Employment program), several initiatives have been implemented to expand the program contributing members, although it mostly benefits the formal sector workers. However, major gaps still exist especially for the emerging middle-income groups who typically work at the informal sectors. They have yet to get the protection needed to sustain their social and economic growth. Since 2017, TNP2K (the National Team for Poverty Reduction) under the Vice President office has led the social protection discourse as the government understands the need to address vulnerabilities across the lifecycle and prioritize support to the most at-risk population particularly the elderly, young children and people with disabilities. Discussion and advocacy to recommend for more investment is continuing in order for the government to establish a comprehensive social protection system in the near future (2020-2024) that protects children through an inclusive child benefit program; build a system to benefit more working-age adults (including individuals with disabilities) and a three-tier elderly protection as they reach 65 years.

Keywords: poverty reduction, social assistance, social insurance, social protection

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Authors: Manal Elgallal, Louise Fletcher, Barbara Evans

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Water scarcity is a growing concern in many arid and semi-arid countries. The increase of water scarcity threatens economic development and sustainability of human livelihoods as well as environment especially in developing countries. Globally, agriculture is the largest water consumption sector, accounting for approximately 70% of all freshwater extraction. Growing competition between the agricultural and higher economic value in urban and industrial uses of high-quality freshwater supplies, especially in regions where water scarcity major problems, will increase the pressure on this precious resource. In this circumstance, wastewater may provide reliable source of water for agriculture and enable freshwater to be exchanged for more economically valuable purposes. Concern regarding the risks from microbial and toxic components to human health and environment quality is a serious obstacle for wastewater reuse particularly in agriculture. Although powerful approaches and tools for microbial risk assessment and management for safe use of wastewater are now available, few studies have attempted to provide any mechanism to quantitatively assess and manage the environmental risks resulting from reusing wastewater. In seeking pragmatic solutions to sustainable wastewater reuse, there remains a lack of research incorporating both health and environmental risk assessment and management with economic analysis in order to quantitatively combine cost, benefits and risks to rank alternative reuse options. This study seeks to enhance effective reuse of wastewater for irrigation in arid and semi-arid areas, the outcome of the study is an evaluation approach that can be used to assess different reuse strategies and to determine the suitable scale at which treatment alternatives and interventions are possible, feasible and cost effective in order to optimise the trade-offs between risks to protect public health and the environment and preserving the substantial benefits.

Keywords: environmental risks, management, life cycle costs, waste water irrigation

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Authors: Nadia Belu, Laurenţiu Mihai Ionescu, Agnieszka Misztal

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The automotive industry is one of the most important industries in the world that concerns not only the economy, but also the world culture. In the present financial and economic context, this field faces new challenges posed by the current crisis, companies must maintain product quality, deliver on time and at a competitive price in order to achieve customer satisfaction. Two of the most recommended techniques of quality management by specific standards of the automotive industry, in the product development, are Failure Mode and Effects Analysis (FMEA) and Control Plan. FMEA is a methodology for risk management and quality improvement aimed at identifying potential causes of failure of products and processes, their quantification by risk assessment, ranking of the problems identified according to their importance, to the determination and implementation of corrective actions related. The companies use Control Plans realized using the results from FMEA to evaluate a process or product for strengths and weaknesses and to prevent problems before they occur. The Control Plans represent written descriptions of the systems used to control and minimize product and process variation. In addition Control Plans specify the process monitoring and control methods (for example Special Controls) used to control Special Characteristics. In this paper we propose a computer-aided solution with Genetic Algorithms in order to reduce the drafting of reports: FMEA analysis and Control Plan required in the manufacture of the product launch and improved knowledge development teams for future projects. The solution allows to the design team to introduce data entry required to FMEA. The actual analysis is performed using Genetic Algorithms to find optimum between RPN risk factor and cost of production. A feature of Genetic Algorithms is that they are used as a means of finding solutions for multi criteria optimization problems. In our case, along with three specific FMEA risk factors is considered and reduce production cost. Analysis tool will generate final reports for all FMEA processes. The data obtained in FMEA reports are automatically integrated with other entered parameters in Control Plan. Implementation of the solution is in the form of an application running in an intranet on two servers: one containing analysis and plan generation engine and the other containing the database where the initial parameters and results are stored. The results can then be used as starting solutions in the synthesis of other projects. The solution was applied to welding processes, laser cutting and bending to manufacture chassis for buses. Advantages of the solution are efficient elaboration of documents in the current project by automatically generating reports FMEA and Control Plan using multiple criteria optimization of production and build a solid knowledge base for future projects. The solution which we propose is a cheap alternative to other solutions on the market using Open Source tools in implementation.

Keywords: automotive industry, FMEA, control plan, automotive technology

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Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Roxane A. Legaie, Kjiana E. Schwab, Caroline E. Gargett

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Studies looking at the changes in gene expression from RNAseq data often make use of linear models. It is also common practice to focus on a subset of data for a comparison of interest, leaving aside the samples not involved in this particular comparison. This work shows the importance of including all observations in the modeling process to better estimate variance parameters, even when the samples included are not directly used in the comparison under test. The human endometrium is a dynamic tissue, which undergoes cycles of growth and regression with each menstrual cycle. The mesenchymal stem cells (MSCs) present in the endometrium are likely responsible for this remarkable regenerative capacity. However recent studies suggest that MSCs also plays a role in the pathogenesis of endometriosis, one of the most common medical conditions affecting the lower abdomen in women in which the endometrial tissue grows outside the womb. In this study we compared gene expression profiles between MSCs and non-stem cell counterparts (‘non-MSC’) obtained from women with (‘E’) or without (‘noE’) endometriosis from RNAseq. Raw read counts were used for differential expression analysis using a linear model with the limma-voom R package, including either all samples in the study or only the samples belonging to the subset of interest (e.g. for the comparison ‘E vs noE in MSC cells’, including only MSC samples from E and noE patients but not the non-MSC ones). Using the full dataset we identified about 100 differentially expressed (DE) genes between E and noE samples in MSC samples (adj.p-val < 0.05 and |logFC|>1) while only 9 DE genes were identified when using only the subset of data (MSC samples only). Important genes known to be involved in endometriosis such as KLF9 and RND3 were missed in the latter case. When looking at the MSC vs non-MSC cells comparison, the linear model including all samples identified 260 genes for noE samples (including the stem cell marker SUSD2) while the subset analysis did not identify any DE genes. When looking at E samples, 12 genes were identified with the first approach and only 1 with the subset approach. Although the stem cell marker RGS5 was found in both cases, the subset test missed important genes involved in stem cell differentiation such as NOTCH3 and other potentially related genes to be used for further investigation and pathway analysis.

Keywords: differential expression, endometriosis, linear model, RNAseq

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