Search results for: treatment success rate

Authors: Bhupendra G. Prajapati, Alpesh R. Patel

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The aim of this research work is to develop sustained release multi-particulates dosage form of Dexketoprofen trometamol, which is the pharmacologically active isomer of ketoprofen. The objective is to utilization of active enantiomer with minimal dose and administration frequency, extended release multi-particulates dosage form development for better patience compliance was explored. Drug loaded and sustained release coated pellets were prepared by fluidized bed coating principle by wurster coater. Microcrystalline cellulose as core pellets, povidone as binder and talc as anti-tacking agents were selected during drug loading while Kollicoat SR 30D as sustained release polymer, triethyl citrate as plasticizer and micronized talc as an anti-adherent were used in sustained release coating. Binder optimization trial in drug loading showed that there was increase in process efficiency with increase in the binder concentration. 5 and 7.5%w/w concentration of Povidone K30 with respect to drug amount gave more than 90% process efficiency while higher amount of rejects (agglomerates) were observed for drug layering trial batch taken with 7.5% binder. So for drug loading, optimum Povidone concentration was selected as 5% of drug substance quantity since this trial had good process feasibility and good adhesion of the drug onto the MCC pellets. 2% w/w concentration of talc with respect to total drug layering solid mass shows better anti-tacking property to remove unnecessary static charge as well as agglomeration generation during spraying process. Optimized drug loaded pellets were coated for sustained release coating from 16 to 28% w/w coating to get desired drug release profile and results suggested that 22% w/w coating weight gain is necessary to get the required drug release profile. Three critical process parameters of Wurster coating for sustained release were further statistically optimized for desired quality target product profile attributes like agglomerates formation, process efficiency, and drug release profile using central composite design (CCD) by Minitab software. Results show that derived design space consisting 1.0 to 1.2 bar atomization air pressure, 7.8 to 10.0 gm/min spray rate and 29-34°C product bed temperature gave pre-defined drug product quality attributes. Scanning Image microscopy study results were also dictate that optimized batch pellets had very narrow particle size distribution and smooth surface which were ideal properties for reproducible drug release profile. The study also focused on optimized dexketoprofen trometamol pellets formulation retain its quality attributes while administering with common vehicle, a liquid (water) or semisolid food (apple sauce). Conclusion: Sustained release multi-particulates were successfully developed for dexketoprofen trometamol which may be useful to improve acceptability and palatability of a dosage form for better patient compliance.

Keywords: dexketoprofen trometamol, pellets, fluid bed technology, central composite design

Procedia PDF Downloads 112

Authors: Eric Bang

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Interactions between receptors and ligands are crucial for many essential biological processes, including neurotransmission and metabolism. Ligand-receptor analyses that examine cell behavior and interactions often utilize cell type-specific RNA expressions from single-cell RNA sequencing (scRNA-seq) data. Using CellPhoneDB, a public repository consisting of ligands, receptors, and ligand-receptor interactions, the cell-cell interactions were explored in a specific scRNA-seq dataset from kidney tissue and portrayed the results with dot plots and heat maps. Depending on the type of cell, each ligand-receptor pair was aligned with the interacting cell type and calculated the positori probabilities of these associations, with corresponding P values reflecting average expression values between the triads and their significance. Using single-cell data (sample kidney cell references), genes in the dataset were cross-referenced with ones in the existing CellPhoneDB dataset. For example, a gene such as Pleiotrophin (PTN) present in the single-cell data also needed to be present in the CellPhoneDB dataset. Using the single-cell transcriptomics data via slide-seq and reference data, the CellPhoneDB program defines cell types and plots them in different formats, with the two main ones being dot plots and heat map plots. The dot plot displays derived measures of the cell to cell interaction scores and p values. For the dot plot, each row shows a ligand-receptor pair, and each column shows the two interacting cell types. CellPhoneDB defines interactions and interaction levels from the gene expression level, so since the p-value is on a -log10 scale, the larger dots represent more significant interactions. By performing an interaction analysis, a significant interaction was discovered for myeloid and T-cell ligand-receptor pairs, including those between Secreted Phosphoprotein 1 (SPP1) and Fibronectin 1 (FN1), which is consistent with previous findings. It was proposed that an effective protocol would involve a filtration step where cell types would be filtered out, depending on which ligand-receptor pair is activated in that part of the tissue, as well as the incorporation of the CellPhoneDB data in a streamlined workflow pipeline. The filtration step would be in the form of a Python script that expedites the manual process necessary for dataset filtration. Being in Python allows it to be integrated with the CellPhoneDB dataset for future workflow analysis. The manual process involves filtering cell types based on what ligand/receptor pair is activated in kidney cells. One limitation of this would be the fact that some pairings are activated in multiple cells at a time, so the manual manipulation of the data is reflected prior to analysis. Using the filtration script, accurate sorting is incorporated into the CellPhoneDB database rather than waiting until the output is produced and then subsequently applying spatial data. It was envisioned that this would reveal wherein the cell various ligands and receptors are interacting with different cell types, allowing for easier identification of which cells are being impacted and why, for the purpose of disease treatment. The hope is this new computational method utilizing spatially explicit ligand-receptor association data can be used to uncover previously unknown specific interactions within kidney tissue.

Keywords: bioinformatics, Ligands, kidney tissue, receptors, spatial transcriptome

Procedia PDF Downloads 120

Authors: Jin Yue

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Fresh produces especially fruits, vegetables, meats and aquatic products have limited shelf life and are highly susceptible to deterioration. Essential oils (EOs) extracted from plants have excellent antioxidant and broad-spectrum antibacterial activities, and they can play as natural food preservatives. But EOs are volatile, water insoluble, pungent, and easily decomposing under light and heat. Many approaches have been developed to improve the solubility and stability of EOs such as polymeric film, coating, nanoparticles, nano-emulsions and nanofibers. Construction of active packaging film which can incorporate EOs with high loading efficiency and controlled release of EOs has received great attention. It is still difficult to achieve accurate release of antibacterial compounds at specific target locations in active packaging. In this research, a relative humidity-responsive packaging material was designed, employing the electrospinning technique to fabricate a nanofibrous film loaded with a 4-terpineol/β-cyclodextrin inclusion complexes (4-TA/β-CD ICs). Functioning as an innovative food packaging material, the film demonstrated commendable attributes including pleasing appearance, thermal stability, mechanical properties, and effective barrier properties. The incorporation of inclusion complexes greatly enhanced the antioxidant and antibacterial activity of the film, particularly against Shewanella putrefaciens, with an inhibitory efficiency of up to 65%. Crucially, the film realized controlled release of 4-TA under 98% high relative humidity conditions by inducing the plasticization of polymers caused by water molecules, swelling of polymer chains, and destruction of hydrogen bonds within the cyclodextrin inclusion complex. This film with a long-term antimicrobial effect successfully extended the shelf life of Litopenaeus vannamei shrimp to 7 days at 4 °C. To further improve the loading efficiency and long-acting release of EOs, we synthesized the γ-cyclodextrin-metal organic frameworks (γ-CD-MOFs), and then efficiently anchored γ-CD-MOFs on chitosan-cellulose (CS-CEL) composite film by in situ growth method for controlled releasing of carvacrol (CAR). We found that the growth efficiency of γ-CD-MOFs was the highest when the concentration of CEL dispersion was 5%. The anchoring of γ-CD-MOFs on CS-CEL film significantly improved the surface area of CS-CEL film from 1.0294 m2/g to 43.3458 m2/g. The molecular docking and 1H NMR spectra indicated that γ-CD-MOF has better complexing and stabilizing ability for CAR molecules than γ-CD. In addition, the release of CAR reached 99.71±0.22% on the 10th day, while under 22% RH, the release pattern of CAR was a plateau with 14.71 ± 4.46%. The inhibition rate of this film against E. coli, S. aureus and B. cinerea was more than 99%, and extended the shelf life of strawberries to 7 days. By incorporating the merits of natural biopolymers and MOFs, this active packaging offers great potential as a substitute for traditional packaging materials.

Keywords: active packaging, antibacterial activity, controlled release, essential oils, food quality control

Procedia PDF Downloads 32

Authors: Cristobal García

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The visual inspection of bolted joints in wind turbines is dangerous, expensive, and impractical due to the non-possibility to access the platform by workboat in certain sea state conditions, as well as the high costs derived from the transportation of maintenance technicians to offshore platforms located far away from the coast, especially if helicopters are involved. Consequently, the wind turbine operators have the need for simpler and less demanding techniques for the analysis of the bolts tightening. Vibration-based structural health monitoring is one of the oldest and most widely-used means for monitoring the health of onshore and offshore wind turbines. The core of this work is to find out if the modal parameters can be efficiently used as a key performance indicator (KPIs) for the assessment of joint bolts in a 1:50 scale tower of a floating offshore wind turbine (12 MW). A non-destructive vibration test is used to extract the vibration signals of the towers with different damage statuses. The procedure can be summarized in three consecutive steps. First, an artificial excitation is introduced by means of a commercial shaker mounted on the top of the tower. Second, the vibration signals of the towers are recorded for 8 s at a sampling rate of 20 kHz using an array of commercial accelerometers (Endevco, 44A16-1032). Third, the natural frequencies, damping, and overall vibration mode shapes are calculated using the software Siemens LMS 16A. Experiments show that the natural frequencies, damping, and mode shapes of the tower are directly dependent on the fixing conditions of the towers, and therefore, the variations of both parameters are a good indicator for the estimation of the static axial force acting in the bolt. Thus, this vibration-based structural method proposed can be potentially used as a diagnostic tool to evaluate the tightening torques of the bolted joints with the advantages of being an economical, straightforward, and multidisciplinary approach that can be applied for different typologies of connections by operation and maintenance technicians. In conclusion, TSI, in collaboration with the consortium of the FIBREGY project, is conducting innovative research where vibrations are utilized for the estimation of the tightening torque of a 1:50 scale steel-based tower prototype. The findings of this research carried out in the context of FIBREGY possess multiple implications for the assessment of the bolted joint integrity in multiple types of connections such as tower-to-nacelle, modular, tower-to-column, tube-to-tube, etc. This research is contextualized in the framework of the FIBREGY project. The EU-funded FIBREGY project (H2020, grant number 952966) will evaluate the feasibility of the design and construction of a new generation of marine renewable energy platforms using lightweight FRP materials in certain structural elements (e.g., tower, floating platform). The FIBREGY consortium is composed of 11 partners specialized in the offshore renewable energy sector and funded partially by the H2020 program of the European Commission with an overall budget of 8 million Euros.

Keywords: SHM, vibrations, connections, floating offshore platform

Procedia PDF Downloads 91

Authors: Sezen Aslan, N. Aydan Sat

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The society of 21st century constantly faces with complex otherness that emerges in various forms and justifications. Otherness caused by class, race or ethnicity inevitably reflects to urban areas, and in this way, cities are diversified into totally self-centered and closed-off urban enclaves. One of the most important dynamics that creates otherness in contemporary society is migration. Immigration on an international scale is one of the most important events that have reshaped the world, and the number of immigrants in the world is increasing day by day. Forced migration and refugee statements constitute the major part of countries' immigration policies and practices. Domestic problems such as racism, violence, war, censorship and silencing, attitudes contrary to human rights, different cultural or religious identities cause populations to migrate. Immigration is one of the most important reasons for the formation of urban enclaves within cities. Turkey, which was used to face a higher rate of outward migration, has begun to host immigrant groups from foreign countries. 1980s is the breaking point about the issue as a result of internal disturbances in the Middle East. After Iranian, Iraqi and Afghan immigrants, Turkey faces the largest external migration in its story with Syrian population. Turkey has been hosting approximate three million Syrian people after Syrian Civil War which started in 2011. 92% of Syrian refugees are currently living in different urban areas in Turkey instead of camps. Syrian refugees are experiencing a spontaneous spatiality due to the lack of specific settlement and housing policies of the country. This spontaneity is one of the most important factors in the creation of urban enclaves. From this point of view, the aim of this study is to clarify processes that lead the creation of urban enclaves and to explain socio-spatial effects of these urban enclaves to the other parts of the cities. Ankara, which is one of the most registered Syrian hosting Province in Turkey, is selected as a case study area. About 55% of the total Syrian population lives in the Altındağ district in Ankara. They settled specifically in two neighborhoods in Altındağ district, named as Önder and Ulubey. These neighborhoods are old slum areas, and they were evacuated due to urban renewal on the same dates with the migration of the Syrians. Before demolition of these old slums, Syrians are settled into them as tenants. In the first part of the study, a brief explanation of the concept of urban enclave, its occurrence parameters and possible socio-spatial threats, examples from previous immigrant urban enclaves caused internal migration will be given. Emergence of slums, planning history and social processes in the case study area will be described in the second part of the study. The third part will be focused on the Syrian refugees and their socio-spatial relationship in the case study area and in-depth interviews with refugees and spatial analysis will be realized. Suggestions for the future of the case study area and recommendations to prevent immigrant groups from social and spatial exclusion will be discussed in the conclusion part of the study.

Keywords: migration, immigration, Syrian refugees, urban enclaves, Ankara

Procedia PDF Downloads 182

Authors: Mehdi Soula, Yosra Mani, Estelle Saras, Antoine Drapeau, Raoudha Grami, Mahjoub Aouni, Jean-Yves Madec, Marisa Haenni, Wejdene Mansour

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Multi-resistance to antibiotics in gram-negative bacilli and particularly in enterobacteriaceae, has become frequent in hospitals in Tunisia. However, data on antibiotic resistant bacteria in aquatic products are scarce. The aims of this study are to estimate the proportion of ESBL- and carbapenemase-producing Enterobacterales in seafood (clams and fish) in Tunisia and to molecularly characterize the collected isolates. Two types of seafood were sampled in unrelated markets in four different regions in Tunisia (641 pieces of farmed fish and 1075 mediterranean clams divided into 215 pools, and each pool contained 5 pieces). Once purchased, all samples were incubated in tubes containing peptone salt broth for 24 to 48h at 37°C. After incubation, overnight cultures were isolated on selective MacConkey agar plates supplemented with either imipenem or cefotaxime, identified using API20E test strips (bioMérieux, Marcy-l’Étoile, France) and confirmed by Maldi-TOF MS. Antimicrobial susceptibility was determined by the disk diffusion method on Mueller-Hinton agar plates and results were interpreted according to CA-SFM 2021. ESBL-producing Enterobacterales were detected using the Double Disc Synergy Test (DDST). Carbapenem-resistance was detected using an ertapenem disk and was respectively confirmed using the ROSCO KPC/MBL and OXA-48 Confirm Kit (ROSCO Diagnostica, Taastrup, Denmark). DNA was extracted using a NucleoSpin Microbial DNA extraction kit (Macherey-Nagel, Hoerdt, France), according to the manufacturer’s instructions. Resistance genes were determined using the CGE online tools. The replicon content and plasmid formula were identified from the WGS data using PlasmidFinder 2.0.1 and pMLST 2.0. From farmed fishes, nine ESBL-producing strains (9/641, 1.4%) were isolated, which were identified as E. coli (n=6) and K. pneumoniae (n=3). Among the 215 pools of 5 clams analyzed, 18 ESBL-producing isolates were identified, including 14 E. coli and 4 K. pneumoniae. A low isolation rate of ESBL-producing Enterobacterales was detected 1.6% (18/1075) in clam pools. In fish, the ESBL phenotype was due to the presence of the blaCTX-M-15 gene in all nine isolates, but no carbapenemase gene was identified. In clams, the predominant ESBL phenotype was blaCTX-M-1 (n=6/18). blaCPE (NDM1, OXA48) was detected only in 3 isolates ‘K. pneumoniae isolates’. Replicon typing on the strains carring the ESBL and carbapenemase gene revelead that the major type plasmid carried ESBL were IncF (42.3%) [n=11/26]. In all, our results suggest that seafood can be a reservoir of multi-drug resistant bacteria, most probably of human origin but also by the selection pressure of antibiotic. Our findings raise concerns that seafood bought for consumption may serve as potential reservoirs of AMR genes and pose serious threat to public health.

Keywords: BLSE, carbapenemase, enterobacterales, tunisian seafood

Procedia PDF Downloads 78

Authors: N. Singh, G. K. Darbha

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Since the last decade, a wave of research has begun to study the prevalence and impact of ever-increasing plastic pollution in the environment. The wide application and ubiquitous distribution of plastic have become a global concern due to its persistent nature. The disposal of plastics has emerged as one of the major challenges for waste management landfills. Microplastics (MPs) have found its existence in almost every environment, from the high altitude mountain lake to the deep sea sediments, polar icebergs, coral reefs, estuaries, beaches, and river, etc. Microplastics are fragments of plastics with size less than 5 mm. Microplastics can be classified as primary microplastics and secondary microplastics. Primary microplastics includes purposefully introduced microplastics into the end products for consumers (microbeads used in facial cleansers, personal care product, etc.), pellets (used in manufacturing industries) or fibres (from textile industries) which finally enters into the environment. Secondary microplastics are formed by disintegration of larger fragments under the exposure of sunlight, mechanical abrasive forces by rain, waves, wind and/or water. A number of factors affect the quantity of microplastic present in freshwater environments. In addition to physical forces, human population density proximal to the water body, proximity to urban centres, water residence time, and size of the water body also affects plastic properties. With time, other complex processes in nature such as physical, chemical and biological break down plastics by interfering with its structural integrity. Several studies demonstrate that microplastics found in wastewater sludge being used as manure for agricultural fields, thus having the tendency to alter the soil environment condition influencing the microbial population as well. Inadequate data are available on the fate and transport of microplastics under varying environmental conditions that are required to supplement important information for further research. In addition, microplastics have the tendency to absorb heavy metals and hydrophobic organic contaminants such as PAHs and PCBs from its surroundings and thus acting as carriers for these contaminants in the environment system. In this study, three kinds of microplastics (polyethylene, polypropylene and expanded polystyrene) of different densities were chosen. Plastic samples were placed in sand with different aqueous media (distilled water, surface water, groundwater and marine water). It was incubated at varying temperatures (25, 35 and 40 °C) and agitation levels (rpm). The results show that the number of plastic fragments enhanced with increase in temperature and agitation speed. Moreover, the rate of disintegration of expanded polystyrene is high compared to other plastics. These results demonstrate that temperature, salinity, and mechanical abrasion plays a major role in degradation of plastics. Since weathered microplastics are more harmful as compared to the virgin microplastics, long-term studies involving other environmental factors are needed to have a better understanding of degradation of plastics.

Keywords: environmental contamination, fragmentation, microplastics, temperature, weathering

Procedia PDF Downloads 137

Authors: Tamar Trop

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Bike sharing systems can be important elements of smart cities as they have the potential for impact on multiple levels. These systems can add a significant alternative to other modes of mass transit in cities that are continuously looking for measures to become more livable and maintain their attractiveness for citizens, businesses and tourism. Bike-sharing began in Europe in 1965, and a viable format emerged in the mid-2000s thanks to the introduction of information technology. The rate of growth in bike-sharing schemes and fleets has been very rapid since 2008 and has probably outstripped growth in every other form of urban transport. Today, public bike-sharing systems are available on five continents, including over 700 cities, operating more than 800,000 bicycles at approximately 40,000 docking stations. Since modern bike sharing systems have become prevalent only in the last decade, the existing literature analyzing these systems and their sustainability is relatively new. The purpose of the presented study is to assess the sustainability of these newly emerging transportation systems, by using the Envision™ rating system as a methodological framework and the Israeli 'Tel -O-Fun' – bike sharing project as a case study. The assessment was conducted by project team members. Envision™ is a new guidance and rating system used to assess and improve the sustainability of all types and sizes of infrastructure projects. This tool provides a holistic framework for evaluating and rating the community, environmental, and economic benefits of infrastructure projects over the course of their life cycle. This evaluation method has 60 sustainability criteria divided into five categories: Quality of life, leadership, resource allocation, natural world, and climate and risk. 'Tel -O-Fun' project was launched in Tel Aviv-Yafo on 2011 and today provides about 1,800 bikes for rent, at 180 rental stations across the city. The system is based on a complex computer terminal that is located in the docking stations. The highest-rated sustainable features that the project scored include: (a) Improving quality of life by: offering a low cost and efficient form of public transit, improving community mobility and access, enabling the flexibility of travel within a multimodal transportation system, saving commuters time and money, enhancing public health and reducing air and noise pollution; (b) improving resource allocation by: offering inexpensive and flexible last-mile connectivity, reducing space, materials and energy consumption, reducing wear and tear on public roads, and maximizing the utility of existing infrastructure, and (c) reducing of greenhouse gas emissions from transportation. Overall, 'Tel -O-Fun' project was highly scored as an environmentally sustainable and socially equitable infrastructure. The use of this practical framework for evaluation also yielded various interesting insights on the shortcoming of the system and the characteristics of good solutions. This can contribute to the improvement of the project and may assist planners and operators of bike sharing systems to develop a sustainable, efficient and reliable transportation infrastructure within smart cities.

Keywords: bike sharing, Envision™, sustainability rating system, sustainable infrastructure

Procedia PDF Downloads 317

Authors: Josiah O. Carter, Charlotte Hayden, Elizabeth Arthurs

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Background: During the COVID-19 pandemic, hospital management policies have changed frequently and rapidly. This has created novel challenges in keeping the workforce abreast of these changes to enable them to deliver safe and effective care. Traditional communication methods, e.g. email, do not keep pace with the rapidly changing environment in the hospital, resulting in inaccurate, irrelevant, or outdated information being communicated, resulting in inefficiencies in patient care. Methods: The creation of a WhatsApp messaging group within the medical division at the Bristol Royal Infirmary has enabled senior clinicians and the hospital management team to update the medical workforce in real-time. It has two primary functions: (1) To enable dissemination of a concise, important operational summary. This comprises information on bed status and infection control procedural changes. It is fed directly from a daily critical incident briefing (2) To facilitate a monthly scheduled question and answer (Q&A) session for junior doctors to clarify issues with clinical directors, rota, and management staff. Additional ad-hoc updates are sent out for time-critical information; otherwise, it mainly functions as a broadcast-only group to prevent important information from being lost amongst other communication. All junior doctors within the medical division were invited to join the group. At present, the group comprises 131 participants, of which 10 are administrative staff (rota coordinators, management staff & clinical directors); the remaining 121 are junior clinicians working within the medical division. An electronic survey via Microsoft forms was sent out to junior doctors via the WhatsApp group and via email to assess its utilisation and effectiveness with the aim of quality improvements. Results: Of the 121 group participants, 19 completed the questionnaire (response rate 15.7%). Of these, 16/19 (84.2%) used it regularly, and 12/19 (63.2%) rated it as the most useful source for reliable updates relating to the hospital response to the COVID-19 pandemic, whereas only 2/19 (10.5%) found the trust intranet and the trust COVID-19 operational email update most useful. Respondents rated the WhatsApp group more useful as an information source (mean score 7.7/10) than as a means of providing feedback to management staff (mean score 6.3/10). Qualitative feedback suggested information around ward closures and changes to COVID cohorting, along with updates on staffing issues, were most useful. Respondents also noted the Q&A sessions were an efficient way of relaying feedback about management decisions but that it would be preferable if these sessions could be delivered more frequently. Discussion: During the current global COVID-19 pandemic, there is an increased need for rapid dissemination of critical information within NHS trusts; this includes communication between junior doctors, managers, and senior clinicians. The versatility of WhatsApp permits a variety of functions allowing for regular updates, the dissemination of time-critical information, and enables conversing and feedback. The project has demonstrated that reserved and well-managed use of a WhatsApp group is a welcome, efficient and practical means of communication between the senior management team and the junior medical workforce.

Keywords: communication, COVID-19, hospital management, WhatsApp

Procedia PDF Downloads 87

Authors: Kenechukwu Ikebuaku

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Entrepreneurship has long been offered as the panacea for poor economic growth and high rate of unemployment. Business incubation is considered an effective means for enhancing entrepreneurial actitivities while engendering socio-economic development. Information Technology Developers Entrepreneurship Accelerator (iDEA), is a software business incubation programme established by the Nigerian government as a means of boosting digital entrepreneurship activities and reducing unemployment in the country. This study assessed the contribution of iDEA Nigeria’s entrepreneurship programmes towards enhancing the capabilities of its tenants. Using the capability approach and the sustainable livelihoods approach, the study analysed iDEA programmes’ contribution towards the expansion of participants’ entrepreneurial capabilities. Apart from identifying a set of entrepreneurial capabilities from both the literature and empirical analysis, the study went further to ascertain how iDEA incubation has helped to enhance those capabilities for its tenants. It also examined digital entrepreneurship as a valued functioning and as an intermediate functioning leading to other valuable functioning. Furthermore, the study examined gender as a conversion factor in digital entrepreneurship. Both qualitative and quantitative research methods were used for the study, and measurement of key variables was made. While the entire population was utilised to collect data for the quantitative research, purposive sampling was used to select respondents for semi-structured interviews in the qualitative research. However, only 40 beneficiaries agreed to take part in the survey while 10 respondents were interviewed for the study. Responses collected from questionnaires administered were subjected to statistical analysis using SPSS. The study developed indexes to measure the perception of the respondents, on how iDEA programmes have enhanced their entrepreneurial capabilities. The Capabilities Enhancement Perception Index (CEPI) computed indicated that the respondents believed that iDEA programmes enhanced their entrepreneurial capabilities. While access to power supply and reliable internet have the highest positive deviations around mean, negotiation skills and access to customers/clients have the highest negative deviation. These were well supported by the findings of the qualitative analysis in which the participants unequivocally narrated how the resources provided by iDEA aid them in their entrepreneurial endeavours. It was also found that iDEA programmes have a significant effect on the tenants’ access to networking opportunities, both with other emerging entrepreneurs and established entrepreneurs. While assessing gender as a conversion factor, it was discovered that there was very low female participation within the digital entrepreneurship ecosystem. The root cause of this gender disparity was found in unquestioned cultural beliefs and social norms which relegate women to a subservient position and household duties. The findings also showed that many of the entrepreneurs could be considered opportunity-based entrepreneurs rather than necessity entrepreneurs, and that digital entrepreneurship is a valued functioning for iDEA tenants. With regards to challenges facing digital entrepreneurship in Nigeria, infrastructural/institutional inadequacies, lack of funding opportunities, and unfavourable government policies, were considered inimical to entrepreneurial capabilities in the country.

Keywords: entrepreneurial capabilities, unemployment, business incubators, development

Procedia PDF Downloads 211

Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

Procedia PDF Downloads 478

Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Marie Guittonny-LarchevêQue

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In boreal Canada, industrial activities such as forestry, peat extraction and metal mines often occur nearby. At closure, mine waste storage facilities have to be reclaimed. On tailings storage facilities, tree plantations can achieve rapid restoration of forested landscapes. However, trees poorly grow in mine tailings and organic amendments like peat are required to improve tailings’ structure and nutrients. Canada is a well-known producer of horticultural quality peat, but some lower quality peats coming from areas adjacent to the reclaimed mines could allow successful revegetation. In particular, hemic peat coming from the bottom of peat-bogs is more decomposed than fibric peat and is less valued for horticulture. Moreover, forest peat is sometimes excavated and piled by the forest industry after cuttings to stimulate tree regeneration on the exposed mineral soil. The objective of this project was to compare the ability of peats of differing quality and origin to improve tailings structure, nutrients and tree development. A greenhouse experiment was conducted along one growing season in 2016 with a complete randomized block design combining 8 repetitions (blocks) x 2 tree species (Populus tremuloides and Pinus banksiana) x 6 substrates (tailings, commercial horticultural peat, and mixtures of tailings with commercial peat, forest peat, local fibric peat, or local hemic peat) x 2 fertilization levels (with or without mineral fertilization). The used tailings came from a gold mine and were low in sulfur and trace metals. The commercial peat had a slightly acidic pH (around 6) while other peats had a clearly acidic pH (around 3). However, mixing peat with slightly alkaline tailings resulted in a pH close to 7 whatever the tested peats. The macroporosity of mixtures was intermediate between the low values of tailings (4%) and the high values of commercial peat alone (34%). Seedling survival was lower on tailings for poplar compared to all other treatments, with or without fertilization. Survival and growth were similar among all treatments for pine. Fertilization had no impact on the maximal height and diameter of poplar seedlings but changed the relative performance of the substrates. When not fertilized, poplar seedlings grown in commercial peat were the highest and largest, and the smallest and slenderest in tailings, with intermediate values in mixtures. When fertilized, poplar seedlings grown in commercial peat were smaller and slender compared to all other substrates. However for this species, foliar, shoot, and root biomass production was the greatest in commercial peat and the lowest in tailings compared to all mixtures, whether fertilized or not. The mixture with local fibric peat provided the seedlings with the lowest foliar N concentrations compared to all other substrates whatever the species or the fertilization treatment. At the short-term, the performance of all the tested peats were close when mixed to tailings, showing that peats of lower quality could be valorized instead of using horticultural peat. These results demonstrate that intersectorial synergies in accordance with the principles of circular economy may be developed in boreal Canada between local industries around the reclamation of mine waste dumps.

Keywords: boreal trees, mine spoil, mine revegetation, intersectorial synergies

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Authors: Omolola Ojetayo, Emmanuel Garuba, Obinna Ajunwa, Abiodun A. Onilude

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Introduction: Biofilm is a functional community of microorganisms that are associated with a surface or an interface. These adherent cells become embedded within an extracellular matrix composed of polymeric substances, i.e., biofilms refer to biological deposits consisting of both microbes and their extracellular products on biotic and abiotic surfaces. Despite their detrimental effects in medicine, biofilms as natural cell immobilization have found several applications in biotechnology, such as in the treatment of wastewater, bioremediation and biodegradation, desulfurization of gas, and conversion of agro-derived materials into alcohols and organic acids. The means of enhancing immobilized cells have been chemical-inductive, and this affects the medium composition and final product. Physical factors including electrical, magnetic, and electromagnetic flux have shown potential for enhancing biofilms depending on the bacterial species, nature, and intensity of emitted signals, the duration of exposure, and substratum used. However, the concept of cell immobilisation by electrical and magnetic induction is still underexplored. Methods: To assess the effects of physical factors on biofilm formation, six American typed culture collection (Acetobacter aceti ATCC15973, Pseudomonas aeruginosa ATCC9027, Serratia marcescens ATCC14756, Gluconobacter oxydans ATCC19357, Rhodobacter sphaeroides ATCC17023, and Bacillus subtilis ATCC6633) were used. Standard culture techniques for bacterial cells were adopted. Natural autoimmobilisation potentials of test bacteria were carried out by simple biofilms ring formation on tubes, while crystal violet binding assay techniques were adopted in the characterisation of biofilm quantity. Electroinduction of bacterial cells by direct current (DC) application in cell broth, static magnetic field exposure, and electromagnetic flux were carried out, and autoimmobilisation of cells in a biofilm pattern was determined on various substrata tested, including wood, glass, steel, polyvinylchloride (PVC) and polyethylene terephthalate. Biot Savart law was used in quantifying magnetic field intensity, and statistical analyses of data obtained were carried out using the analyses of variance (ANOVA) as well as other statistical tools. Results: Biofilm formation by the selected test bacteria was enhanced by the physical factors applied. Electromagnetic induction had the greatest effect on biofilm formation, with magnetic induction producing the least effect across all substrata used. Microbial cell-cell communication could be a possible means via which physical signals affected the cells in a polarisable manner. Conclusion: The enhancement of biofilm formation by bacteria using physical factors has shown that their inherent capability as a cell immobilization method can be further optimised for industrial applications. A possible relationship between the presence of voltage-dependent channels, mechanosensitive channels, and bacterial biofilms could shed more light on this phenomenon.

Keywords: bacteria, biofilm, cell immobilization, electromagnetic induction, substrata

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Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

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Authors: Esther Gumboh

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The police play a critical role in society and are an integral aspect of the rule of law. Equally, respect for human rights is an integral part of professional policing. In view of the vast powers that the police enjoy and the attendant risk of abuse and resulting human rights violations, the need for police accountability and civilian police oversight is internationally and regionally recognised. Policing oversight springs from the duty to investigate human rights violations. Those implicated in perpetrating or covering up violations must be disciplined or prosecuted to ensure effective accountability. Police accountability is particularly important in Malawi given the dark history of policing in the country during the 30-year dictatorial era under President Kamuzu Banda. Described as one of the most repressive regimes in Africa, the Banda administration was characterised by gross state-sponsored violence, repressive policing and human rights violations. Indeed, the police were involved in various forms of human rights abuse including arbitrary arrests and unlawful detentions, torture, and excessive use of force in conducting arrests and public order policing. This situation flourished within a culture of police impunity bolstered in part by the absence of clear oversight mechanisms for police accountability. In turn, there was immense public mistrust of the police. Unsurprisingly, the criminal justice system was one of the priority areas for reform when Malawi adopted its first democratic Constitution in 1994. Section 153 of the Constitution envisions a police service that is, for all intents and purposes, there to provide for the protection of public safety and the rights of persons in Malawi according to the prescriptions of the Constitution and any other law. This position reflects the view that the duty to protect and promote human rights is not incompatible with effective policing. Despite this, the police continue to engage in questionable behaviour in public order policing, excessive use of force, deaths in police custody, ill-treatment, torture and other forms of abuse including sexual abuse. Perpetrators of abuses are occasionally punished, but investigations are often delayed, abandoned, or remain inconclusive. Police accountability remains largely elusive. Commendably, the law does subject the police to significant oversight both internally and externally. However, until 2010, Malawi lacked a wholly independent civilian oversight mechanism specifically mandated to monitor the activities of the Malawi Police Service and held it accountable. This void has since been filled by the Independent Complaints Commission established under the Police Act. This is a positive development that reiterates Malawi’s commitment to the investigation of human rights violations by the police and to ending police impunity. This contribution examines the legal framework for this Commission to project the effectiveness of the Commission. While the framework looks promising on various fronts, there are potential challenges that lie ahead. Malawi must pre-emptively deal with these challenges carefully if the Commission is to have any practical significance in transforming police accountability in the country. Drawing on lessons from other jurisdictions like South Africa, the paper makes recommendations for legislative reform to strengthen the Commission’s framework.

Keywords: civilian policing oversight, Malawi, police, police accountability, policing, policing oversight

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Authors: Harriet Bothwell, Lowri Evans, Kevin Jones

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Background: The University of Bristol provides all medical students the opportunity to undertake student selected components (SSCs) at multiple stages of the undergraduate programme. SSCs enable students to explore areas of interest that are not necessarily covered by the curriculum. Students are required to produce a written report and most use SSCs as an opportunity to undertake an audit or small research project. In 2013 Swindon Academy, based at the Great Western Hospital, offered eight students the opportunity of a global health SSC which included a two week trip to rural hospital in Uganda. This SSC has since expanded and in 2017 a total of 20 students had the opportunity to undertake small research projects at two hospitals in rural Uganda. 'Tomorrows Doctors' highlights the importance of understanding healthcare from a 'global perspective' and student feedback from previous SSCs suggests that self-assessed knowledge of global health increases as a result of this SSC. Through the most recent version of this SSC students had the opportunity to undertake projects in a wide range of specialties including paediatrics, palliative care, surgery and medical education. Methods: An anonymous online questionnaire was made available to students following the SSC. There was a response rate of 80% representing 16 out of the 20 students. This questionnaire surveyed students’ satisfaction and experience of the SSC including the level of academic, project and spiritual support provided as well as perceived challenges in completing the project and barriers to healthcare delivery in the low resource setting. This survey had multiple open questions allowing the collection of qualitative data. Further qualitative data was collected from the students’ project report. The suggested format included a reflection and all students completed these. All qualitative data underwent thematic analysis. Results: All respondents rated the overall experience of the SSC as 'good' or 'excellent'. Preliminary data suggest that students’ confidence in their knowledge of global health, diagnosis of tropical diseases and management of tropical diseases improved after completing this SSC. Thematic analysis of students' reflection is ongoing but suggests that students gain far more than improved knowledge of tropical diseases. Students reflect positively on having the opportunity to research in a low resource setting and feel that by completing these projects they will be 'useful' to the hospital. Several students reflect the stark contrast to healthcare delivery in the UK and recognise the 'privilege' of having a healthcare system that is free at the point of access. Some students noted the different approaches that clinicians in Uganda had to train in 'taking ownership' of their own learning. Conclusions: Students completing this SSC report increased knowledge of global health and tropical medicine. However, their reflections reveal much broader learning outcomes and demonstrate considerable insight in multiple topics including conducting research in the low resource setting, training and healthcare inequality.

Keywords: global health, medical education, student feedback, undergraduate

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Authors: Michel Patiño-Sáenz, Martín Haissiner, Jorge Martínez-Cotrina, Daniel Pastor, Hernando Santamaría-García, Maria-Alejandra Tangarife, Agustin Ibáñez, Sandra Baez

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It has been shown that gruesome descriptions of harm can increase the punishment given to a transgressor. This biasing effect is mediated by negative emotions, which are elicited upon the presentation of gruesome descriptions. However, there is a lack of studies inquiring the influence of such descriptions on moral decision-making in people involved in the criminal justice system. Such populations are of special interest since they have experience dealing with gruesome evidence, but also formal education on how to assess evidence and gauge the appropriate punishment according to the law. Likewise, they are expected to be objective and rational when performing their duty, because their decisions can impact profoundly people`s lives. Considering these antecedents, the objective of this study was to explore the influence gruesome written descriptions on moral decision-making in this group of people. To that end, we recruited attorneys, judges and public prosecutors (Criminal justice group, CJ, n=30) whose field of specialty is criminal law. In addition, we included a control group of people who did not have a formal education in law (n=30), but who were paired in age and years of education with the CJ group. All participants completed an online, Spanish-adapted version of a moral decision-making task, which was previously reported in the literature and also standardized and validated in the Latin-American context. A series of text-based stories describing two characters, one inflicting harm on the other, were presented to participants. Transgressor's intentionality (accidental vs. intentional harm) and language (gruesome vs. plain) used to describe harm were manipulated employing a within-subjects and a between-subjects design, respectively. After reading each story, participants were asked to rate (a) the harmful action's moral adequacy, (b) the amount of punishment deserving the transgressor and (c) how damaging was his behavior. Results showed main effects of group, intentionality and type of language on all dependent measures. In both groups, intentional harmful actions were rated as significantly less morally adequate, were punished more severely and were deemed as more damaging. Moreover, control subjects deemed more damaging and punished more severely any type of action than the CJ group. In addition, there was an interaction between intentionality and group. People in the control group rated harmful actions as less morally adequate than the CJ group, but only when the action was accidental. Also, there was an interaction between intentionality and language on punishment ratings. Controls punished more when harm was described using gruesome language. However, that was not the case of people in the CJ group, who assigned the same amount of punishment in both conditions. In conclusion, participants with job experience in the criminal justice system or criminal law differ in the way they make moral decisions. Particularly, it seems that they are less sensitive to the biasing effect of gruesome evidence, which is probably explained by their formal education or their experience in dealing with such evidence. Nonetheless, more studies are needed to determine the impact this phenomenon has on the fulfillment of their duty.

Keywords: criminal justice system, emotions, gruesome descriptions, intentionality, moral decision-making

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Authors: Charlotte Bach, Albrecht Jahn, Mahnaz Motamedi, Maryam Karimi-Ghahfarokhi

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Background: Maternal and infant deaths are most prevalent in the first month after birth, emphasizing the critical need for quality healthcare services during this period. Immigrant women, who are more susceptible to adverse pregnancy outcomes, often face neglect in accessing proper healthcare. The lack of adequate postpartum care significantly contributes to mortality rates. Therefore, utilizing maternal health care services and implementing postpartum care is crucial in reducing maternal and child mortality. Aims: This study aims to evaluate the assessment of pre- and postnatal care among women with and without migration background. In addition, the study explores the impact of COVID-19 procedures on women's experiences during pregnancy, birth, and the postpartum period. Methods: This research employs a cross-sectional Mixed-Method design. Data collection was facilitated through structured questionnaires administered to participants, alongside the utilization of patient bases, including Maternity and child medical records. Following the assumption that the investigator aimed to gain comprehensive insights, qualitative sampling focused on individuals with substantial experiences related to COVID-19, regarded as rich cases. Results: our study highlighted the influence of educational level, marital status, and consensual partnerships on the likelihood of Cesarean deliveries. Regarding breastfeeding practices, migrant women exhibited higher rates of breastfeeding initiation and continuation. Contraception utilization revealed interesting patterns, with non-migrants displaying higher odds of contraceptive use. The qualitative component of our research adds depth to the exploration of women's experiences during the COVID-19 pandemic, revealing nuanced challenges related to anxiety, hospital restrictions, breastfeeding support, and postnatal ward routines. Conclusion: Dissimilarity among studies toward cesarean rate between migrants and non-migrants underscores the importance of targeted interventions considering the diverse needs of distinct population groups. It also acknowledges potential cultural, contextual, and healthcare system influences on the association between mode of delivery and infant feeding practices. Studies acknowledge the influence of contextual variables on contraceptive preferences among migrants and non-migrants, emphasizing the need for tailored healthcare policies. The findings contribute to existing research, highlighting the need for a nuanced understanding of the impact of birth preparation courses on maternal and infant outcomes. Furthermore, they emphasize the universality of certain maternity care experiences, regardless of pandemic contexts, reinforcing the importance of patient-centred approaches in healthcare delivery.

Keywords: migration background, pregnancy outcome, covid-19, postpartum

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Authors: Leigha C. Crout

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This paper will investigate the categorical disregard of the People’s Republic of China (PRC) in establishing and maintaining a baseline standard of civil guarantees for economic migrant women and their dependents. In light of the relative forward strides in terms of policy facilitating the ascension of female workers in China, this oft-invisible subgroup of women remains neglected from the modern-day “iron rice bowl” of the self-identified communist state. This study is being undertaken to rectify the absence of data on this subject and provide a baseline for future studies on the matter, as the human rights of migrants has become an established facet of transnational dialogue and debate. The basic methodology of this research will consist of the evaluation of China’s compliance with its own national guidelines, and the eight international human rights law treaties it has ratified. Data will be extracted and cross-checked from a number of relevant sources to monitor the extent of compliance, including but by no means limited to the United Nations Human Rights Council (UNHRC) Universal Periodic Review (UPR) reports and responses, submissions and responses of international human rights treaty bodies, local and international nongovernmental organizations (NGOs) and their annual reports, and articles and commentaries authored by specialists on the modern state and implementation of Chinese law. Together, these data will illuminate the vast network of compliance that has forced many migrant women to work within situations of extreme economic precarity. The structure will proceed as follows: first, an outline of the current status of migrant workers and the enforcement of stipulated protections will be provided; next, the analysis of the oft-debated regulations directing and the outline of mandatory services guaranteed to external and internal migrants; and finally, a conclusion incorporating various recommendations to improve transparency and gradually decrease the amount of migrant work turned forced labor that typifies the economic migrant experience, especially in the case of women. The internal and international migrant workers in China are bound by different and uncomplimentary systems. The first, which governs Chinese citizens moving to different regions or provinces to find more sustainable employment (internal migrants), is called the hukou (or huji) residency system. This law enforces strict regulation of the movement of peoples, while ensuring that residents of urban areas receive preferential benefits to those received by their so-called “agricultural” resident counterparts. Given the overwhelming presence of the Communist Party of China throughout the vast state, the management of internal migrants and the disregard for foreign domestic workers is, at minimum, a surprising oversight. This paper endeavors to provide a much-needed foundation for future commentary and discussion on the treatment of female migrant workers and their families in the People’s Republic of China.

Keywords: female migrant worker’s rights, the People’s Republic of China, forced labor, Hukou residency system

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Authors: Irfan Anjum Manarvi, Fawzi Aljassir

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Human bones have been a keen area of research over a long time in the field of biomechanical engineering. Medical professionals, as well as engineering academics and researchers, have investigated various bones by using medical, mechanical, and materials approaches to discover the available body of knowledge. Their major focus has been to establish properties of these and ultimately develop processes and tools either to prevent fracture or recover its damage. Literature shows that mechanical professionals conducted a variety of tests for hardness, deformation, and strain field measurement to arrive at their findings. However, they considered these results accuracy to be insufficient due to various limitations of tools, test equipment, difficulties in the availability of human bones. They proposed the need for further studies to first overcome inaccuracies in measurement methods, testing machines, and experimental errors and then carry out experimental or theoretical studies. Finite Element analysis is a technique which was developed for the aerospace industry due to the complexity of design and materials. But over a period of time, it has found its applications in many other industries due to accuracy and flexibility in selection of materials and types of loading that could be theoretically applied to an object under study. In the past few decades, the field of biomechanical engineering has also started to see its applicability. However, the work done in the area of Tarsals, metatarsals and phalanges using this technique is very limited. Therefore, present research has been focused on using this technique for analysis of these critical bones of the human body. This technique requires a 3-dimensional geometric computer model of the object to be analyzed. In the present research, a 3d laser scanner was used for accurate geometric scans of individual tarsals, metatarsals, and phalanges from a typical human foot to make these computer geometric models. These were then imported into a Finite Element Analysis software and a length refining process was carried out prior to analysis to ensure the computer models were true representatives of actual bone. This was followed by analysis of each bone individually. A number of constraints and load conditions were applied to observe the stress and strain distributions in these bones under the conditions of compression and tensile loads or their combination. Results were collected for deformations in various axis, and stress and strain distributions were observed to identify critical locations where fracture could occur. A comparative analysis of failure properties of all the three types of bones was carried out to establish which of these could fail earlier which is presented in this research. Results of this investigation could be used for further experimental studies by the academics and researchers, as well as industrial engineers, for development of various foot protection devices or tools for surgical operations and recovery treatment of these bones. Researchers could build up on these models to carryout analysis of a complete human foot through Finite Element analysis under various loading conditions such as walking, marching, running, and landing after a jump etc.

Keywords: tarsals, metatarsals, phalanges, 3D scanning, finite element analysis

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Authors: Timur S. Zaripov, Artur K. Gilfanov, Sergei S. Sazhin, Steven M. Begg, Morgan R. Heikal

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The calculation of the concentration of inertial droplets in complex flows is encountered in the modelling of numerous engineering and environmental phenomena; for example, fuel droplets in internal combustion engines and airborne pollutant particles. The results of recent research, focused on the development of methods for calculating concentration and their implementation in the commercial CFD code, ANSYS Fluent, is presented here. The study is motivated by the investigation of the mixture preparation processes in internal combustion engines with direct injection of fuel sprays. Two methods are used in our analysis; the Fully Lagrangian method (also known as the Osiptsov method) and the Eulerian approach. The Osiptsov method predicts droplet concentrations along path lines by solving the equations for the components of the Jacobian of the Eulerian-Lagrangian transformation. This method significantly decreases the computational requirements as it does not require counting of large numbers of tracked droplets as in the case of the conventional Lagrangian approach. In the Eulerian approach the average droplet velocity is expressed as a function of the carrier phase velocity as an expansion over the droplet response time and transport equation can be solved in the Eulerian form. The advantage of the method is that droplet velocity can be found without solving additional partial differential equations for the droplet velocity field. The predictions from the two approaches were compared in the analysis of the problem of a dilute gas-droplet flow around an infinitely long, circular cylinder. The concentrations of inertial droplets, with Stokes numbers of 0.05, 0.1, 0.2, in steady-state and transient laminar flow conditions, were determined at various Reynolds numbers. In the steady-state case, flows with Reynolds numbers of 1, 10, and 100 were investigated. It has been shown that the results predicted using both methods are almost identical at small Reynolds and Stokes numbers. For larger values of these numbers (Stokes — 0.1, 0.2; Reynolds — 10, 100) the Eulerian approach predicted a wider spread in concentration in the perturbations caused by the cylinder that can be attributed to the averaged droplet velocity field. The transient droplet flow case was investigated for a Reynolds number of 200. Both methods predicted a high droplet concentration in the zones of high strain rate and low concentrations in zones of high vorticity. The maxima of droplet concentration predicted by the Osiptsov method was up to two orders of magnitude greater than that predicted by the Eulerian method; a significant variation for an approach widely used in engineering applications. Based on the results of these comparisons, the Osiptsov method has resulted in a more precise description of the local properties of the inertial droplet flow. The method has been applied to the analysis of the results of experimental observations of a liquid gasoline spray at representative fuel injection pressure conditions. The preliminary results show good qualitative agreement between the predictions of the model and experimental data.

Keywords: internal combustion engines, Eulerian approach, fully Lagrangian approach, gasoline fuel sprays, droplets and particle concentrations

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Authors: Simone Raimondi De Souza, Glaucia Maria Moraes De Oliveira, Ronir Raggio Luiz, Glorimar Rosa

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Introduction: Obesity is among the main risk factors for cardiovascular disease (CVD). Genesis is multifactorial, including genetic, hormonal and environmental factors disorders, among which inadequate feeding pattern, for which nutritional counseling strategies have proven effective. The consumption of beta-glucans (soluble fibers that reportedly promote satiety) present in oat bran can be an effective strategy for preventing and treating obesity. Other benefits have been observed with oat bran consumption, such as reduction of hypercholesterolemia and hyperglycemia, two other risk factors for CVD. Objectives: To analyze the effect of oat bran consumption associated with nutritional counseling in reducing body mass index (BMI), blood cholesterol, glucose profile, waist and neck circumference in obese individuals, and to evaluate the change in eating pattern. Methods: clinical trial, randomized, double-blind, placebo-controlled, lasting 90 days with adults of both genders, with BMI ≥30kg/m2. The study was approved by the Ethics in Research involving human beings in a public institute of cardiology, in Rio de Janeiro, Brazil. Individuals were invited to participate and accepted formally by signing the Terms of Consent. Participants were randomized into oat bran group (gOB) or placebo group (gPCB) and received, respectively: morning prepared consisting of 40g oat bran, 30g of skimmed milk powder and 1g sweetener sucralose; refined flour 40g rice, 30g of milk powder and 1g sweetener sucralose. The Ten Steps to Healthy Eating, of Brazilian Ministry of Health were used to support the nutritional counseling. Variables analyzed: gender; age; BMI, waist circumference (WC) neck circumference (NC); systolic blood pressure (SBP); diastolic blood pressure (DBP); food consumption, total cholesterol (TC), LDL-cholesterol (LDL-c), HDL-cholesterol (HDL-c), non-HDL cholesterol (nHDLc), triglycerides (TG), fasting glucose (FG), fasting insulin (FI) and HOMA-IR. Dietary intake was assessed by 24-hour dietary recall. The Diet Quality Index revised for the Brazilian population (IQD-R) assessed quality of feeding pattern. Statistical analyzes were performed using SPSS version 21, considering statistically significant p-value less than 0.05. Results: A total of 38 participants were included, age = 50 ± 7,6years, 63% women. 19 subjects were placed in gOB and 19 in gPCB. After intervention, statistically significant reductions were observed in the following parameters: in gOB: IQD-R, TC, LDL-c, nHDL-c, FI, SBP, DBP, BMI, WC, NC; in gPCB: IQD-R, LDL-c, SBP, DBP, BMI, WC, NC. No statistically significant differences were observed in the results between groups. Conclusion: Our results reinforce nutritional counseling as important strategy for prevention and treatment of obesity and suggest that inclusion of oat bran in daily diet can bring additional benefits controlling risk factors for CVD. More studies are needed to establish all benefits of oat bran to human health as well as the ideal daily dose for consumption.

Keywords: oat bran, cardiovascular disease, nutritional counseling, obesity

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Authors: V. Vsevolozhskaia

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Since 1990, energy-efficient development concepts have constituted both a turning point in civil engineering and a challenge for an environmentally friendly future. Energy and water currently play an essential role in the sustainable economic growth of the world in general and Russia in particular: the efficiency of the water supply system is the second most important parameter for energy consumption according to the British assessment method, while the water-energy nexus has been identified as a focus for accelerating sustainable growth and developing effective, innovative solutions. The activities considered in this study were aimed at organizing and executing the renovation of the property in residential buildings located in St. Petersburg, specifically buildings with local or federal historical heritage status under the control of the St. Petersburg Committee for the State Inspection and Protection of Historic and Cultural Monuments (KGIOP) and UNESCO. Even after reconstruction, these buildings still fall into energy efficiency class D. Russian Government Resolution No. 87 on the structure and required content of project documentation contains a section entitled ‘Measures to ensure compliance with energy efficiency and equipment requirements for buildings, structures, and constructions with energy metering devices’. Mention is made of the need to install collectors and meters, which only calculate energy, neglecting the main purpose: to make buildings more energy-efficient, potentially even energy efficiency class A. The least-explored aspects of energy-efficient technology in the Russian Federation remain the water balance and the possibility of implementing rain and meltwater collection systems. These modern technologies are used exclusively for new buildings due to a lack of government directive to create project documentation during the planning of major renovations and reconstruction that would include the collection and reuse of rainwater. Energy-efficient technology for rain and meltwater collection is currently applied only to new buildings, even though research has proved that using rainwater is safe and offers a huge step forward in terms of eco-efficiency analysis and water innovation. Where conservation is mandatory, making changes to protected sites is prohibited. In most cases, the protected site is the cultural heritage building itself, including the main walls and roof. However, the installation of a second water supply system and collection of rainwater would not affect the protected building itself. Water efficiency in St. Petersburg is currently considered only from the point of view of the installation that regulates the flow of the pipeline shutoff valves. The development of technical guidelines for the use of grey- and/or rainwater to meet the needs of residential buildings during reconstruction or renovation is not yet complete. The ideas for water treatment, collection and distribution systems presented in this study should be taken into consideration during the reconstruction or renovation of residential cultural heritage buildings under the protection of KGIOP and UNESCO. The methodology applied also has the potential to be extended to other cultural heritage sites in northern countries and lands with an average annual rainfall of over 600 mm to cover average toilet-flush needs.

Keywords: cultural heritage, energy efficiency, renovation, rainwater collection, reconstruction, water management, water supply

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Authors: K. S. Poutanen, P. Dussort, A. Erkner, S. Fiszman, K. Karnik, M. Kristensen, C. F. M. Marsaux, S. Miquel-Kergoat, S. Pentikäinen, P. Putz, R. E. Steinert, J. Slavin, D. J. Mela

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Dietary fiber (DF) intake has been associated with lower body weight or less weight gain. These effects are generally attributed to putative effects of DF on appetite. Many intervention studies have tested the effect of DFs on appetite-related measures, with inconsistent results. However, DF includes a wide category of different compounds with diverse chemical and physical characteristics, and correspondingly diverse effects in human digestion. Thus, inconsistent results between DF consumption and appetite are not surprising. The specific contribution of different compounds with varying physico-chemical properties to appetite control and the mediating mechanisms are not well characterized. This systematic review aimed to assess the influence of specific DF characteristics, including viscosity, gel forming capacity, fermentability, and molecular weight, on appetite-related outcomes in healthy humans. Medline and FSTA databases were searched for controlled human intervention trials, testing the effects of well-characterized DFs on subjective satiety/appetite or energy intake outcomes. Studies were included only if they reported: 1) fiber name and origin, and 2) data on viscosity, gelling properties, fermentability, or molecular weight of the DF materials tested. The search generated 3001 unique records, 322 of which were selected for further consideration from title and abstract screening. Of these, 149 were excluded due to insufficient fiber characterization and 124 for other reasons (not original article, not randomized controlled trial, or no appetite related outcome), leaving 49 papers meeting all the inclusion criteria, most of which reported results from acute testing (<1 day). The eligible 49 papers described 90 comparisons of DFs in foods, beverages or supplements. DF-containing material of interest was efficacious for at least one appetite-related outcome in 51/90 comparisons. Gel-forming DF sources were most consistently efficacious but there were no clear associations between viscosity, MW or fermentability and appetite-related outcomes. A considerable number of papers had to be excluded from the review due to shortcomings in fiber characterization. To build understanding about the impact of DF on satiety/appetite specifically there should be clear hypotheses about the mechanisms behind the proposed beneficial effect of DF material on appetite, and sufficient data about the DF properties relevant for the hypothesized mechanisms to justify clinical testing. The hypothesized mechanisms should also guide the decision about relevant duration of exposure in studies, i.e. are the effects expected to occur during acute time frame (related to stomach emptying, digestion rate, etc.) or develop from sustained exposure (gut fermentation mediated mechanisms). More consistent measurement methods and reporting of fiber specifications and characterization are needed to establish reliable structure-function relationships for DF and health outcomes.

Keywords: appetite, dietary fiber, physico-chemical properties, satiety

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Authors: Grzegorz Raniszewski, Zbigniew Kolacinski, Lukasz Szymanski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza

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One of the most promising area for carbon nanotubes (CNTs) application is medicine. One of the most devastating diseases is cancer. Carbon nanotubes may be used as carriers of a slowly released drug. It is possible to use of electromagnetic waves to destroy cancer cells by the carbon nanotubes (CNTs). In our research we focused on thermal ablation by ferromagnetic carbon nanotubes (Fe-CNTs). In the cancer cell hyperthermia functionalized carbon nanotubes are exposed to radio frequency electromagnetic field. Properly functionalized Fe-CNTs join the cancer cells. Heat generated in nanoparticles connected to nanotubes warm up nanotubes and then the target tissue. When the temperature in tumor tissue exceeds 316 K the necrosis of cancer cells may be observed. Several techniques can be used for Fe-CNTs synthesis. In our work, we use high-temperature methods where arc-discharge is applied. Low-temperature systems are microwave plasma with assisted chemical vapor deposition (MPCVD) and hybrid physical-chemical vapor deposition (HPCVD). In the arc discharge system, the plasma reactor works with a pressure of He up to 0,5 atm. The electric arc burns between two graphite rods. Vapors of carbon move from the anode, through a short arc column and forms CNTs which can be collected either from the reactor walls or cathode deposit. This method is suitable for the production of multi-wall and single-wall CNTs. A disadvantage of high-temperature methods is a low purification, short length, random size and multi-directional distribution. In MPCVD system plasma is generated in waveguide connected to the microwave generator. Then containing carbon and ferromagnetic elements plasma flux go to the quartz tube. The additional resistance heating can be applied to increase the reaction effectiveness and efficiency. CNTs nucleation occurs on the quartz tube walls. It is also possible to use substrates to improve carbon nanotubes growth. HPCVD system involves both chemical decomposition of carbon containing gases and vaporization of a solid or liquid source of catalyst. In this system, a tube furnace is applied. A mixture of working and carbon-containing gases go through the quartz tube placed inside the furnace. As a catalyst ferrocene vapors can be used. Fe-CNTs may be collected then either from the quartz tube walls or on the substrates. Low-temperature methods are characterized by higher purity product. Moreover, carbon nanotubes from tested CVD systems were partially filled with the iron. Regardless of the method of Fe-CNTs synthesis the final product always needs to be purified for applications in medicine. The simplest method of purification is an oxidation of the amorphous carbon. Carbon nanotubes dedicated for cancer cell thermal ablation need to be additionally treated by acids for defects amplification on the CNTs surface what facilitates biofunctionalization. Application of ferromagnetic nanotubes for cancer treatment is a promising method of fighting with cancer for the next decade. Acknowledgment: The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013

Keywords: arc discharge, cancer, carbon nanotubes, CVD, thermal ablation

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Authors: Yulia V. Krasavtseva, Tatiana V. Kornilova

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Risk-taking behaviors are not only dictated by cognitive components but also involve emotional aspects. Anticipatory emotions, involving both cognitive and affective mechanisms, are involved in decision-making in general, and risk-taking in particular. Affective reactions are prompted when an expectation or prediction is either validated or invalidated in the achieved result. This study aimed to combine predictions, anticipatory emotions, affective reactions, and personality traits in the context of risk-taking behaviors. An experimental online method Emotion and Prediction In a Casino (EPIC) was used, based on a casino-like roulette game. In a series of choices, the participant is presented with progressively riskier roulette combinations, where the potential sums of wins and losses increase with each choice and the participant is given a choice: to 'walk away' with the current sum of money or to 'play' the displayed roulette, thus accepting the implicit risk. Before and after the result is displayed, participants also rate their emotions, using the Self-Assessment Mannequin [Bradley, Lang, 1994], picking a picture, representing the intensity of pleasure, arousal, and dominance. The following personality measures were used: 1) Personal Decision-Making Factors [Kornilova, 2003] assessing risk and rationality; 2) I7 – Impulsivity Questionnaire [Kornilova, 1995] assessing impulsiveness, risk readiness, and empathy and 3) Subjective Risk Intelligence Scale [Craparo et al., 2018] assessing negative attitude toward uncertainty, emotional stress vulnerability, imaginative capability, and problem-solving self-efficacy. Two groups of participants took part in the study: 1) 98 university students (Mage=19.71, SD=3.25; 72% female) and 2) 94 online participants (Mage=28.25, SD=8.25; 89% female). Online participants were recruited via social media. Students with high rationality rated their pleasure and dominance before and after choices as lower (ρ from -2.6 to -2.7, p < 0.05). Those with high levels of impulsivity rated their arousal lower before finding out their result (ρ from 2.5 - 3.7, p < 0.05), while also rating their dominance as low (ρ from -3 to -3.7, p < 0.05). Students prone to risk-rated their pleasure and arousal before and after higher (ρ from 2.5 - 3.6, p < 0.05). High empathy was positively correlated with arousal after learning the result. High emotional stress vulnerability positively correlates with arousal and pleasure after the choice (ρ from 3.9 - 5.7, p < 0.05). Negative attitude to uncertainty is correlated with high anticipatory and reactive arousal (ρ from 2.7 - 5.7, p < 0.05). High imaginative capability correlates negatively with anticipatory and reactive dominance (ρ from - 3.4 to - 4.3, p < 0.05). Pleasure (.492), arousal (.590), and dominance (.551) before and after the result were positively correlated. Higher predictions positively correlated with reactive pleasure and arousal. In a riskier scenario (6/8 chances to win), anticipatory arousal was negatively correlated with the pleasure emotion (-.326) and vice versa (-.265). Correlations occur regardless of the roulette outcome. In conclusion, risk-taking behaviors are linked not only to personality traits but also to anticipatory emotions and affect in a modeled casino setting. Acknowledgment: The study was supported by the Russian Foundation for Basic Research, project 19-29-07069.

Keywords: anticipatory emotions, casino game, risk taking, impulsiveness

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Authors: M. Abu Hanif, Anika Tabassum, Fuad Hasan Ovi, Ishrat Islam

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Water is essential for life. Enormous quantities of water are cycled each year through hydrologic cycle but only a fraction of circulated water is available each year for human use. Dhaka, the capital of Bangladesh is the 19th mega city in the world with a population of over 14 million (World City Information, 2011). As a result the growth of urban population is increasing rapidly; the city is not able to manage with altering situations due to resource limitations and management capacity. Water crisis has become an acute problem faced by the inhabitants of Dhaka city. It is found that total water demand in Dhaka city is 2,240 million liter per day (MLD) whereas supply is 2,150 (MLD). According to Dhaka Water Supply and Sewerage Authority about 87 percent of this supply comes from groundwater resources and rest 13 percent from surface water. According to Dhaka Water Supply and Sewerage Authority it has been found that the current groundwater depletion rate is 3.52 meter per year. Such a fast depletion of the water table will result in intrusion of southern saline water into the groundwater reservoir, depriving this mega city of pure drinking water. This study mainly focus on the potential of Rainwater Harvesting System(RWHS) in Kazipara area of Dhaka city, determine the perception level of local people in installation of rainwater harvesting system in their building and identify the factors regarding willingness of owner in installing rainwater harvesting system. As most of the residential area of Dhaka city is unplanned with small plots, Kazipara area has been chosen as study area which depicts similar characteristics. In this study only roof top area is considered as catchment area and potential of rainwater harvesting has been calculated. From the calculation it is found that harvested rainwater can serve the 66% of demand of water for toilet flushing and cleaning purposes for the people of Kazipara. It is also observed that if only rooftop rainwater harvesting applied to all the structures of the study area then two third of surface runoff would be reduced than present surface runoff. In determining the perception of local people only owners of the buildings were. surveyed. From the questionnaire survey it is found that around 75% people have no idea about the rainwater harvesting system. About 83% people are not willing to install rainwater harvesting system in their dwelling. The reasons behind the unwillingness are high cost of installation, inadequate space, ignorance about the system, etc. Among 16% of the willing respondents who are interested in installing RWHS system, it was found that higher income, bigger size of buildings are important factors in willingness of installing rainwater harvesting system. Majority of the respondents demanded for both technical and economical support to install the system in their buildings. Government of Bangladesh has taken some initiatives to promote rainwater harvesting in urban areas. It is very much necessary to incorporate rainwater harvesting device and artificial recharge system in every building of Dhaka city to make Dhaka city self sufficient in water supply management and to solve water crisis problem of megacity like as Dhaka city.

Keywords: rainwater harvesting, water table, willingness, storm water

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Beihai Xiong, Dengke Hua, Wouter Hendriks, Wilbert Pellikaan

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To improve the energy status of dairy cows in the early lactation, lots of jobs have been done on adjusting the starch to fiber ratio in the diet. As a complex ecosystem, the rumen contains a large population of microorganisms which plays a crucial role in feed degradation. Further study on the microbiota alterations and metabolic changes under different dietary energy sources is essential and valuable to better understand the function of the ruminal microorganisms and thereby to optimize the rumen function and enlarge feed efficiency. The present study will focus on the effects of two glucogenic diets (G: ground corn and corn silage; S: steam-flaked corn and corn silage) and a lipogenic diet (L: sugar beet pulp and alfalfa silage) on rumen fermentation, gas production, the ruminal microbiota and metabolome, and also their correlations in vitro. The gas production was recorded consistently, and the gas volume and producing rate at times 6, 12, 24, 48 h were calculated separately. The fermentation end-products were measured after fermenting for 48 h. The ruminal bacteria and archaea communities were determined by 16S RNA sequencing technique, the metabolome profile was tested through LC-MS methods. Compared to the diet G and S, the L diet had a lower dry matter digestibility, propionate production, and ammonia-nitrogen concentration. The two glucogenic diets performed worse in controlling methane and lactic acid production compared to the L diet. The S diet produced the greatest cumulative gas volume at any time points during incubation compared to the G and L diet. The metabolic analysis revealed that the lipid digestion was up-regulated by the diet L than other diets. On the subclass level, most metabolites belonging to the fatty acids and conjugates were higher, but most metabolites belonging to the amino acid, peptides, and analogs were lower in diet L than others. Differences in rumen fermentation characteristics were associated with (or resulting from) changes in the relative abundance of bacterial and archaeal genera. Most highly abundant bacteria were stable or slightly influenced by diets, while several amylolytic and cellulolytic bacteria were sensitive to the dietary changes. The L diet had a significantly higher number of cellulolytic bacteria, including the genera of Ruminococcus, Butyrivibrio, Eubacterium, Lachnospira, unclassified Lachnospiraceae, and unclassified Ruminococcaceae. The relative abundances of amylolytic bacteria genera including Selenomonas_1, Ruminobacter, and Succinivibrionaceae_UCG-002 were higher in diet G and S. These affected bacteria was also proved to have high associations with certain metabolites. The Selenomonas_1 and Succinivibrionaceae_UCG-002 may contribute to the higher propionate production in the diet G and S through enhancing the succinate pathway. The results indicated that the two glucogenic diets had a greater extent of gas production, a higher dry matter digestibility, and produced more propionate than diet L. The steam-flaked corn did not show a better performance on fermentation end-products than ground corn. This study has offered a deeper understanding of ruminal microbial functions which could assistant the improvement in rumen functions and thereby in the ruminant production.

Keywords: gas production, metabolome, microbiota, rumen fermentation

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