Search results for: advanced therapy medicinal products (ATMPs)

Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: Ruqayya Naheed Khan, Awais Amjad Malik, Awais Naeem, Amina Khan, Asad Parvaiz

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Introduction: Axillary nodal status in breast cancer patients is a paramount prognosticator, next to primary tumor size and grade. It has been well established that patients with negative sentinel lymph node biopsy can safely avoid axillary lymph node dissection. A positive sentinel lymph node has traditionally required subsequent axillary dissection. According to ACOSOG Z11 trial, patients who underwent axillary dissection with 3 or more positive sentinel nodes or opted for observation in case of negative sentinel lymph node, did not find any difference in Overall Survival (OS) and Disease Free Survival (DFS). The Z11 trial included patients who underwent breast conserving surgery and excluded patients with mastectomies. The purpose of this study is to determine whether Z0011 can be applied to mastectomy patients as well in 1-3 positive sentinel lymph nodes and avoid unnecessary ALND. Methods: A retrospective review was conducted at Shaukat Khanam Memorial Cancer Hospital Pakistan from Jan 2015 to Dec 2017 including patients who were treated for invasive breast cancer and required upfront mastectomy. They were clinically node negative, so sentinel lymph node biopsy was performed. Patients underwent ALND with positive sentinel lymph node. A total of 156 breast cancer patients with mastectomies were reviewed. Results: 95% of the patients were female while 3% were male. Average age was 44 years. There was no difference in race, comorbidities, histology, T stage, N stage, and overall stage, use of adjuvant chemotherapy and radiation therapy. 64 patients underwent ALND for positive lymph node while 92 patients were spared of axillary dissection due to negative sentinel lymph node biopsy. Out of 64 patients, 38 patients (59%) had only 1 lymph node positive which was the sentinel node. 18 patients (28%) had 2 lymph nodes positive including the sentinel node while only 8 patients (13%) had 3 or more positive nodes. Conclusion: Keeping in mind the complications related to ALND, above results clearly show that ALND could have been avoided in 87% of patients in the setting of adjuvant radiation, possibly avoiding the morbidity associated with axillary lymphadenectomy although a prospective randomized trial needs to confirm these results.

Keywords: mastectomy, sentinel lymph node biopsy, axillary lymph node dissection, breast cancer

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Authors: Nikolai Bertelsen, Robert A. Alphinas, Klaus B. Orskov

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The shortest possible tool stickout has been the traditional go-to approach with expectations of increased stability and productivity. However, experimental studies at Danish Advanced Manufacturing Research Center (DAMRC) have proven that for some tool stickout lengths, there exist local productivity optimums when utilizing the Stability Lobe Diagrams for chatter avoidance. This contradicts with traditional logic and the best practices taught to machinists. This paper explores the vibrational characteristics and behaviour of a milling system over the tool stickout length. The experimental investigation has been conducted by tap testing multiple endmills where the tool stickout length has been varied. For each length, the modal parameters have been recorded and mapped to visualize behavioural tendencies. Furthermore, the paper explores the correlation between the modal parameters and the Stability Lobe Diagram to outline the influence and importance of each parameter in a multi-mode system. The insights are conceptualized into a tool tuning approximation solution. It builds on an almost linear change in the natural frequencies when amending tool stickout, which results in changed positions of the Chatter-free Stability Lobes. Furthermore, if the natural frequency of two modes become too close, it will onset of the dynamic absorber effect phenomenon. This phenomenon increases the critical stable depth of cut, allowing for a more stable milling process. Validation tests on the tool tuning approximation solution have shown varying success of the solution. This outlines the need for further research on the boundary conditions of the solution to understand at which conditions the tool tuning approximation solution is applicable. If the conditions get defined, the conceptualized tool tuning approximation solution outlines an approach for quick and roughly approximating tool stickouts with the potential for increased stiffness and optimized productivity.

Keywords: milling, modal parameters, stability lobes, tap testing, tool tuning

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Authors: Menna Brown, Tania Domun

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Digital health interventions are effective across a wide array of health conditions spanning physical health, lifestyle behaviour change, and mental health and wellbeing; furthermore, they are rapidly increasing in volume within both the academic literature and society as commercial apps continue to proliferate the digital health market. However, adherence and engagement to digital health interventions remains problematic. Technology-based personalised and tailored reminder strategies can support engagement to digital health interventions. Interventions which support individuals’ mental health and wellbeing are of critical importance in the wake if the COVID-19 pandemic. Student and young person’s mental health has been negatively affected and digital resources continue to offer cost effective means to address wellbeing at a population level. Develop a databank of digital co-produced tailored messages to support engagement to a range of digital health interventions including those focused on mental health and wellbeing, and lifestyle behaviour change. Qualitative research design. Participants discussed their views of health and wellbeing, engagement and adherence to digital health interventions focused around a 12-week wellbeing intervention via a series of focus group discussions. They worked together to co-create content following a participatory design approach. Three focus group discussions were facilitated with (n=15) undergraduate students at one Welsh university to provide an empirically derived, co-produced, databank of (n=145) tailored messages. Messages were explored and categorised thematically, and the following ten themes emerged: Autonomy, Recognition, Guidance, Community, Acceptance, Responsibility, Encouragement, Compassion, Impact and Ease. The findings provide empirically derived, co-produced tailored messages. These have been made available for use, via ‘ACTivate your wellbeing’ a digital, automated, 12-week health and wellbeing intervention programme, based on acceptance and commitment therapy (ACT). The purpose of which is to support future research to evaluate the impact of thematically categorised tailored messages on engagement and adherence to digital health interventions.

Keywords: digital health, engagement, wellbeing, participatory design, positive psychology, co-production

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Authors: Deepak Nathiya1, Ramesh Roop Rai, Pratima Singh1, Preeti Raj1, Supriya Suman, Balvir Singh Tomar

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Background: Sarcopenia is a catabolic state in liver cirrhosis (LC), accelerated with a breakdown of skeletal muscle to release amino acids which adversely affects survival, health-related quality of life, and response to any underlying disease. The primary objective of the study was to investigate the long-term effect of branched-chain amino acids (BCAA) supplementations on parameters associated with improved prognosis in sarcopenic patients with LC, as well as to evaluate its impact on cirrhotic-related events. Methods: We carried out a 24 week, single-center, randomized, open-label, controlled, two cohort parallel-group intervention trial comparing the efficacy of BCAA against lactoalbumin (L-ALB) on 106 sarcopenic liver cirrhotics. The BCAA (intervention) group was treated with 7.2 g BCAA per whereas, the lactoalbumin group was also given 6.3 g of L-Albumin. The primary outcome was to assess the impact of BCAA on parameters of sarcopenia: muscle mass, muscle strength, and physical performance. The secondary outcomes were to study combined survival and maintenance of liver function changes in laboratory and clinical markers in the duration of six months. Results: Treatment with BCAA leads to significant improvement in sarcopenic parameters: muscle strength, muscle function, and muscle mass. The total cirrhotic-related complications and cumulative event-free survival occurred fewer in the BCAA group than in the L-ALB group. Prognostic markers also improved significantly in the study. Conclusion: The current clinical trial demonstrated that long-term BCAAs supplementation improved sarcopenia and prognostic markers in patients with advanced liver cirrhosis.

Keywords: sarcopenia, liver cirrhosis, BCAA, quality of life

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Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

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Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

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Authors: Irfan Ahmad, Raza Ghafoor, Hammad Raza Ahmad, Muhammad Asif, Farrakh Nawaz, M. Tahir Siddiqui

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Due to the exploding population of Pakistan the pressure on natural forests is increasing to meet the demands of wood and wood based products. Agroforestry is being practiced throughout the world on scientific basis but unfortunately the farmers of Pakistan are reluctant in its adoption. The presents study was designed to assess the adoption of agroforestry practices in Faisalabad with respect to land holdings of farmers and future suitability by using Geographic information system (GIS). Faisalabad is the third largest city of the country and is famous due to the textile industry. A comprehensive survey from target villages of the Lyallpur town of Faisalabad district was carried out. Out of total 65 villages, 40 were selected for study. From each selected village, one farmer who was actively engaged in farming activities was selected. It was observed that medium sized farmers having 10-20 acre were more in number as compared to small and large farmers. Number of trees was found maximum in large farm lands, ratio of diseased trees was almost similar in all categories with maximum in small farmlands (24.1%). Regarding the future prospects 35% farmer were interested in agroforestry practices 65% were not interested in the promotion of trees due to the non-availability of technical guidance and proper markets. Geographic images of the study site can further help the researchers and policy makers in the promotion of agroforestry.

Keywords: agroforestry trends, adoption, Faisalabad, geographic information system (GIS)

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Authors: M. Baratieri, M. Beccali, S. Corradino, B. Di Pietra, C. La Grassa, F. Monteleone, G. Morosinotto, G. Puglisi

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The energy renovation of existing buildings represents an important opportunity to increase the decarbonization and the sustainability of urban environments. In this context, the work carried out has the objective of demonstrating the technical and economic feasibility of an energy renovate of a public building destined for offices located on the island of Lampedusa in the Mediterranean Sea. By applying the Italian transpositions of European Directives 2010/31/EU and 2009/28/EC, the building has been renovated from the current energy requirements of 111.7 kWh/m² to 16.4 kWh/m². The result achieved classifies the building as nZEB (nearly Zero Energy Building) according to the Italian national definition. The analysis was carried out using in parallel a quasi-stationary software, normally used in the professional field, and a dynamic simulation model often used in the academic world. The proposed interventions cover the components of the building’s envelope, the heating-cooling system and the supply of energy from renewable sources. In these latter points, the analysis has focused more on assessing two aspects that affect the supply of renewable energy. The first concerns the use of advanced logic control systems for air conditioning units in order to increase photovoltaic self-consumption. With these adjustments, a considerable increase in photovoltaic self-consumption and a decrease in the electricity exported to the Island's electricity grid have been obtained. The second point concerned the evaluation of the building's energy classification considering the real efficiency of the heating-cooling plant. Normally the energy plants have lower operational efficiency than the designed one due to multiple reasons; the decrease in the energy classification of the building for this factor has been quantified. This study represents an important example for the evaluation of the best interventions for the energy renovation of buildings in the Mediterranean Climate and a good description of the correct methodology to evaluate the resulting improvements.

Keywords: heat pumps, HVAC systems, nZEB renovation, renewable energy sources

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Authors: Ratna Dewi Kusumaningtyas, Riris Pristiyani, Heny Dewajani

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Biodiesel is commonly produced via the two main routes, i.e. the transesterification of triglycerides and the esterification of free fatty acid (FFA) using short-chain alcohols. Both the two routes have drawback in term of the side product yielded during the reaction. Transesterification reaction of triglyceride results in glycerol as side product. On the other hand, FFA esterification brings in water as side product. Both glycerol and water in the biodiesel production are managed as waste. Hence, a separation process is necessary to obtain a high purity biodiesel. Meanwhile, separation processes is generally the most capital and energy intensive part in industrial process. Therefore, to reduce the separation process, it is essential to produce biodiesel via an alternative route eliminating glycerol or water side-products. In this work, biodiesel synthesis was performed using a glycerol-free process through chemical interesterification of jatropha oil with ethyl acetate in the presence on sodium acetate catalyst. By using this method, triacetine, which is known as fuel bio-additive, is yielded instead of glycerol. This research studied the effects of catalyst concentration on the jatropha oil interesterification process in the range of 0.5 – 1.25% w/w oil. The reaction temperature and molar ratio of oil to ethyl acetate were varied at 50, 60, and 70°C, and 1:6, 1:9, 1:15, 1:30, and 1:60, respectively. The reaction time was evaluated from 0 to 8 hours. It was revealed that the best yield was obtained with the catalyst concentration of 0.5%, reaction temperature of 70 °C, molar ratio of oil to ethyl acetate at 1:60, at 6 hours reaction time.

Keywords: biodiesel, interesterification, glycerol-free, triacetine, jatropha oil

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Authors: Ahmed Y. Kutbi, C. Russell. J. Baird, M. McNaughtan, Francis Wayman

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Wastewaters from antibiotic production facilities are characterized with high concentrations of dissolved organic substances. Subsequently, it challenges wastewater treatment plant operator to achieve successful biological treatment and to meet regulatory emission levels. Of the dissolved organic substances, this research is investigating the fate of organic nitrogenous compounds (i.e., Chitin) in an antibiotic production wastewater treatment plant located in Irvine, Scotland and its impact on the WWTP removal performance. Dissolved organic nitrogen (DON) in WWTP effluents are of significance because 1) its potential to cause eutrophication in receiving waters, 2) the formation of nitrogenous disinfection by products in drinking waters and 3) limits WWTPs ability to achieve very low total nitrogen (TN) emissions limits (5 – 25 mg/l). The latter point is where the knowledge gap lays between the operator and the regulator in setting viable TN emission levels. The samples collected from Irvine site at the different stages of the treatment were analyzed for TN and DON. Results showed that the average TN in the WWTP influents and effluents are 798 and 261 mg/l respectively, in other words, the plant achieved 67 % removal of TN. DON Represented 51% of the influents TN, while the effluents accounted 26 % of the TN concentrations. Therefore, an ongoing investigation is carried out to identify DON constituents in WWTP effluent and evaluate its impact on the WWTP performance and its potential bioavailability for algae in receiving waters, which is, in this case, Irvine Bay.

Keywords: biological wastewater treatment plant, dissolved organic nitrogen, bio-availability, Irvine Bay

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Authors: Tami A. Ulhiza, Noor I. M. Puad, Azlin S. Azmi, Mohd. I. A. Malek

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High amount of chemical oxygen demand (COD) in starchy waste can be harmful to the environment. In common practice, starch processing wastewater is discharged to the river without proper treatment. However, starchy waste still contains complex sugars and organic acids. By the right pretreatment method, the complex sugar can be hydrolyzed into more readily digestible sugars which can be utilized to be converted into more valuable products. At the same time, the global demand of energy is inevitable. The continuous usage of fossil fuel as the main source of energy can lead to energy scarcity. Hydrogen is a renewable form of energy which can be an alternative energy in the future. Moreover, hydrogen is clean and carries the highest energy compared to other fuels. Biohydrogen produced from waste has significant advantages over chemical methods. One of the major problems in biohydrogen production is the raw material cost. The carbohydrate-rich starchy wastes such as tapioca, maize, wheat, potato, and sago wastes is a promising candidate to be used as a substrate in producing biohydrogen. The utilization of those wastes for biohydrogen production can provide cheap energy generation with simultaneous waste treatment. Therefore this paper aims to review variety source of starchy wastes that has been widely used to synthesize biohydrogen. The scope includes the source of waste, the performance in yielding hydrogen, the pretreatment method and the type of culture that is suitable for starchy waste.

Keywords: biohydrogen, dark fermentation, renewable energy, starchy waste

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Authors: Fatimah Alhomaid

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The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of colon cancer in Saudi patients. Our results were carried out on 48 patients colon cancer. We obtained our data from laboratory in King Khalid university hospital. The specimens were taken (48) patients with colon cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as I in tow patients (male and female) and grade 2 in 42 patients (29 male and 13 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining , immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients of adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscularis layer. With advancing the disease, there were haemorge in blood and increase in lymphocytes and increase number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20,PCNA,P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for pcan and the grades. In our sections, there were strong reactions in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of colon cancer.

Keywords: DNA-CK20, PCNA, P53, colon cancer

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Authors: Min-Pei Ling

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Aflatoxin is a fungal secondary metabolite with high toxicity capable of contaminating various types of food crops. It has been identified as a Group 1 human carcinogen by the International Agency for Research on Cancer. Chronic aflatoxin exposure has caused a worldwide public food safety concern. Peanuts and peanut products are the major sources of aflatoxin exposure. Therefore, some reduction interventions have been developed to minimize contamination through the peanut production chain. The purpose of this study is to estimate the efficacy of interventions in reducing the health impact of hepatocellular carcinoma caused by aflatoxin contamination in peanuts. The estimated total disability-adjusted life-years (DALYs) was calculated using FDA-iRISK online software. Six aflatoxin reduction strategies were evaluated, including good agricultural practice (GAP), biocontrol, Purdue Improved Crop Storage packaging, basic processing, ozonolysis, and ultraviolet irradiation. The results indicated that basic processing could prevent huge public health loss of 4,079.7–21,833 total DALYs per year, which accounted for 39.6% of all decreased total DALYs. GAP and biocontrol were both effective strategies in the farm field, while the other three interventions were limited in reducing total DALYs. In conclusion, this study could help farmers, processing plants, and government policymakers to alleviate aflatoxin contamination issues in the peanut production chain.

Keywords: aflatoxin, health burden, disability-adjusted life-years, peanuts

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Authors: Sung-Jun Yoo, Kazuhide Ito

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In this study, a comprehensive computer simulated person (CSP) that integrates computational human model (virtual manikin) and respiratory tract model (virtual airway), was applied for estimation of indoor environmental quality. Moreover, an inclusive prediction method was established by integrating computational fluid dynamics (CFD) analysis with advanced CSP which is combined with physiologically-based pharmacokinetic (PBPK) model, unsteady thermoregulation model for analysis targeting micro-climate around human body and respiratory area with high accuracy. This comprehensive method can estimate not only the contaminant inhalation but also constant interaction in the contaminant transfer between indoor spaces, i.e., a target area for indoor air quality (IAQ) assessment, and respiratory zone for health risk assessment. This study focused on the usage of the CSP as an air/thermal quality sensor in indoors, which means the application of comprehensive model for assessment of IAQ and thermal environmental quality. Demonstrative analysis was performed in order to examine the applicability of the comprehensive model to the heating, ventilation, air conditioning (HVAC) control scheme. CSP was located at the center of the simple model room which has dimension of 3m×3m×3m. Formaldehyde which is generated from floor material was assumed as a target contaminant, and flow field, sensible/latent heat and contaminant transfer analysis in indoor space were conducted by using CFD simulation coupled with CSP. In this analysis, thermal comfort was evaluated by thermoregulatory analysis, and respiratory exposure risks represented by adsorption flux/concentration at airway wall surface were estimated by PBPK-CFD hybrid analysis. These Analysis results concerning IAQ and thermal comfort will be fed back to the HVAC control and could be used to find a suitable ventilation rate and energy requirement for air conditioning system.

Keywords: CFD simulation, computer simulated person, HVAC control, indoor environmental quality

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Authors: Timmis W., Simms M., Thomas C.

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This case discusses the management of two floors of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk and second primary cancer development.

Keywords: alcohol dependence, biopsy, oral carcinoma, tobacco

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Authors: Samantha Burns, Melissa Brown, Judith Rankin

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Background: As a specialised intervention, NEWPIP provides a service which supports both parents and their babies from conception to two years, who are experiencing issues which may affect the quality of their relationship and development of the infant. This evaluation of the NEWPIP approach was undertaken in response to the need for rich, in-depth data to understand the lived experiences of the parents who experienced the service to improve the service. NEWPIP is currently one of 34 specialised parent–infant relationship teams across England. This evaluation contributes to increasing understanding of the impact and effectiveness of this specialised service to inform future practice. Aim: The aim of this evaluation was to explore the perspectives and experiences of parents or caregivers (service users), to assess the impact of the NEWPIP service on the parents themselves and the relationship with their baby. Methods: The exploratory nature of the aim and focus on service users’ experience and perspectives provided scope for a qualitative approach for this evaluation. This consisted of 10 semi-structured interviews with parents who had received the service within the last two years. Recruitment involved both purposive and convenience sampling. The interviews took place between February 2021 – March 2021, lasting between 30-90 minutes and were guided by open-ended questions from a topic guide. The interviews adopted a narrative approach to enable the parents to share their lived experiences. The researchers transcribed the interviews and analysed the data thematically by using a coding method which is grounded in the data. Results: The analysis and findings from the data gathered illuminated an approach which supports parents to build a better bond with their baby and provides a safe space for parents to heal through their relationships. While the parents shared their experiences, the interviews were intended to receive feedback, so questions were asked about what could be improved and what recommendations could be offered to Children North East. Guided by the voice of the parents, this evaluation provides recommendations to support the future of the NEWPIP approach. Conclusions: The NEWPIP approach appears to successfully provide early and flexible support for new parents, increasing a parent’s confidence in their ability to not only cope but thrive as a new parent.

Keywords: maternal health, mental health, parent infant relationship, therapy

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Authors: Maha Azzam, Mahmoud Gabr, Mahmoud Zakaria, Ayman Refaie, Amani Ismail, Sherry Khater, Sylvia Ashamallah, Mohamed Ghoniem

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Evidence was provided that human bone marrow-derived mesenhymal stem cells (HBM-MSCs) could be differentiated to form insulin-producing cells (IPCs). Transplantation of these cells was able to cure chemically-induced diabetes in nude mice. The efficacy of these cells to control diabetes in large animals was carried out to evaluate the sufficient number of cells needed/Kg body weight and to determine the functional longevity in vivo. Materials/Methods: Ten male mongrel dogs weighing 15-20 Kg were used in this study. Diabetes was chemically-induced in 7 dogs by a mixture of alloxan and streptozotocin. Three non-diabetic served as normal controls. Differentiated HBM-MSCs (5 million/Kg) were encapsulated in theracyte capsules and transplanted beneath the rectus sheath. Each dog received 2 capsules. One dog died 4 days postoperative from inhalation pneumonia. The remaining 6 dogs were followed up for 6-18 months. Results: Four dogs became normoglycemic within 6-8 weeks with normal glucose tolerance curves providing evidence that the transplanted cells were glucose-sensitive and insulin-responsive. In the remaining 2 dogs, fasting blood glucose was reduced but did not reach euglycemic levels. The sera of all transplanted dogs contained human insulin and c-peptide but negligible levels of canine insulin. When the HBM-MSCs loaded capsules were removed, rapid return of diabetic state was noted. The harvested capsules were examined by immunofluorescence. IPCs were seen and co-expression of with c-peptide was confirmed. Furthermore, all the pancreatic endocrine genes were expressed by the transplanted cells. Conclusions: This study provided evidence that theracyte capsules could protect the xenogenic HBM-MSCs from the host immune response. This is an important issue when clinical stem cell therapy is considered for definitive treatment for T1DM.

Keywords: diabetes, mesenchymal stem cells, dogs, Insulin-producing cells

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Authors: Hagos Gebrehiwet Bahta

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Asmara, the capital city of Eritrea, is facing a sanitation challenge because the city discharges its wastewater to the environment without any kind of treatment. The aim of this research is to conduct a pre-feasibility study of using constructed wetlands in the peri-urban areas of Asmara for wastewater treatment and reuse. It was found that around 15,000 m³ of wastewater is used daily for agricultural activities, and products are sold in the city's markets, which are claimed to cause some health effects. In this study, three potential sites were investigated around Mai-Bela and an optimum location was selected on the basis of land availability, topography, and geotechnical information. Some types of local microphytes that can be used in constructed wetlands have been identified and documented for further studies. It was found that subsurface constructed wetlands can provide a sufficient pollutant removal with careful planning and design. Following the feasibility study, a preliminary design of screening, grit chamber and subsurface constructed wetland was prepared and cost estimation was done. In the cost estimation part, the filter media was found to be the most expensive part and consists of around 30% percent of the overall cost. The city wastewater drainage runs in two directions and the selected site is located in the southern sub-system, which only carries sewage (separate system). The wastewater analysis conducted particularly around this area (Sembel) indicates high heavy metal levels and organic concentrations, which reveals that there is a high level of industrial pollution in addition to the domestic sewage.

Keywords: agriculture, constructed wetland, Mai-Bela, wastewater reuse

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Authors: Bahareh Mostofian

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Foreign Direct Investment (FDI) has long been recognized as a crucial driver of economic growth and development in less-developed countries and their integration into Global Production Networks (GPNs). FDI not only brings capital from the core countries but also technology, innovation, and know-how knowledge that can upgrade the capabilities of host automotive industries. On the other hand, FDI can also have negative impacts on host countries if it leads to significant import dependency. In the case of the Iranian automotive sector, the industry greatly benefited from FDI, with Western carmakers dominating the market. Over time, various types of know-how knowledge, including joint ventures (JVs), trade licenses, and technical assistance, have been provided, helping Iran upgrade its automotive industry. While after the severe geopolitical obstacles imposed by both the EU and the U.S., the industry became over-reliant on the car and spare parts imports, and the lack of emphasis on knowledge transfer further affected the growth and development of the Iranian automotive sector. To address these challenges, current research has adopted a descriptive-analytical methodology to illustrate the gradual changes accrued with foreign suppliers through FDI. The research finding shows that after the two-phase imposed sanctions, the detrimental linkages created by overreliance on the car and spare parts imports without any industrial upgrading negatively affected the growth and development of the national and assembled products of the Iranian automotive sector.

Keywords: less-developed country, FDI, GPNs, automotive industry, Iran

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Authors: Sipho Mbatha, Anne Mastament-Mason

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South African manufacturing global competitiveness was ranked 22nd (out of 38 countries), dropped to 24th in 2013 and is expected to drop further to 25th by 2018. These impacts negatively on the industrialisation project of South Africa. For industrialization to be achieved through labour intensive industries like the Apparel Manufacturing Industries of South Africa (AMISA), South Africa needs to identify and respond to factors negatively impacting on the development of competitive advantage This paper applied factor conditions from Porter’s Diamond Model (1990) to understand the various challenges facing the AMISA. Factor conditions highlighted in Porter’s model are grouped into two groups namely, basic and advance factors. Two AMISA associations representing over 10 000 employees were interviewed. The largest Clothing, Textiles and Leather (CTL) apparel retail group was also interviewed with a government department implementing the industrialisation policy were interviewed The paper points out that while AMISA have basic factor conditions necessary for competitive advantage in the clothing and textiles industries, Advance factor coordination has proven to be a challenging task for the AMISA, Higher Education Institutions (HEIs) and government. Poor infrastructural maintenance has contributed to high manufacturing costs and poor quick response as a result of lack of advanced technologies. The use of Porter’s Factor Conditions as a tool to analyse the sector’s competitive advantage challenges and opportunities has increased knowledge regarding factors that limit the AMISA’s competitiveness. It is therefore argued that other studies on Porter’s Diamond model factors like Demand conditions, Firm strategy, structure and rivalry and Related and supporting industries can be used to analyse the situation of the AMISA for the purposes of improving competitive advantage.

Keywords: compliance rule, apparel manufacturing industry, factor conditions, advance skills and South African industrial policy

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Authors: Sunho Seo, Younghwan Shin, Jong-Hong Park, Sooeun Song, Junsung Kim, Jusik Yun, Yongkyun Kim, Jong-Moon Chung

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In order to effectively cope with large and complex disasters, disaster response training is needed. Recently, disaster response training led by the ROK (Republic of Korea) government is being implemented through a 4 year R&D project, which has several similar functions as the HSEEP (Homeland Security Exercise and Evaluation Program) of the United States, but also has several different features as well. Due to the unpredictiveness and diversity of disasters, existing training methods have many limitations in providing experience in the efficient use of disaster incident response and recovery resources. Always, the challenge is to be as efficient and effective as possible using the limited human and material/physical resources available based on the given time and environmental circumstances. To enable repeated training under diverse scenarios, an AR (Augmented Reality) and VR (Virtual Reality) combined simulator is under development. Unlike existing disaster response training, simulator based training (that allows remote login simultaneous multi-user training) enables freedom from limitations in time and space constraints, and can be repeatedly trained with different combinations of functions and disaster situations. There are related systems such as ADMS (Advanced Disaster Management Simulator) developed by ETC simulation and HLS2 (Homeland Security Simulation System) developed by ELBIT system. However, the ROK government needs a simulator custom made to the country's environment and disaster types, and also combines the latest information and communication technologies, which include AR, VR, and MPEG-DASH (Moving Picture Experts Group - Dynamic Adaptive Streaming over HTTP) technology. In this paper, a new disaster response training simulator is proposed to overcome the limitation of existing training systems, and adapted to actual disaster situations in the ROK, where several technical features are described.

Keywords: augmented reality, emergency response training simulator, MPEG-DASH, virtual reality

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Authors: Rashima Mahajan, Dipali Bansal, Shweta Singh

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Real time non-invasive Brain Computer Interfaces have a significant progressive role in restoring or maintaining a quality life for medically challenged people. This manuscript provides a comprehensive review of emerging research in the field of cognitive/affective computing in context of human neural responses. The perspectives of different emotion assessment modalities like face expressions, speech, text, gestures, and human physiological responses have also been discussed. Focus has been paid to explore the ability of EEG (Electroencephalogram) signals to portray thoughts, feelings, and unspoken words. An automated workflow-based protocol to design an EEG-based real time Brain Computer Interface system for analysis and classification of human emotions elicited by external audio/visual stimuli has been proposed. The front end hardware includes a cost effective and portable Emotive EEG Neuroheadset unit, a personal computer and a set of external stimulators. Primary signal analysis and processing of real time acquired EEG shall be performed using MATLAB based advanced brain mapping toolbox EEGLab/BCILab. This shall be followed by the development of MATLAB based self-defined algorithm to capture and characterize temporal and spectral variations in EEG under emotional stimulations. The extracted hybrid feature set shall be used to classify emotional states using artificial intelligence tools like Artificial Neural Network. The final system would result in an inexpensive, portable and more intuitive Brain Computer Interface in real time scenario to control prosthetic devices by translating different brain states into operative control signals.

Keywords: brain computer interface, electroencephalogram, EEGLab, BCILab, emotive, emotions, interval features, spectral features, artificial neural network, control applications

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Authors: Meichen He, Xuan Yang

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Background: In the field of psychotherapy, the role of the family of origin is of utmost importance. Over the past few decades, both individual-oriented and family-oriented approaches to child therapy have shown moderate success in reducing children's psychological and behavioral issues. Objective: However, in exploring how the family of origin influences individuals, it has been noted that there is a lack of comprehensive measurement indicators and an absence of an exact model to assess the impact of the family of origin on individual development. Therefore, this study aims to develop a model based on a literature review regarding the influence of the family of origin on children. Specifically, it will examine the effects of factors such as education level, economic status, maternal age, family integration, family violence, marital conflict, parental substance abuse, and alcohol consumption on children's self-confidence and life satisfaction. Through this research, we aim to further investigate the impact of the family of origin on children and provide directions for future research in positive psychology and psychotherapy. Methods: This study will employ a literature review methodology to gather and analyze relevant research articles on the influence of the family of origin on children. Subsequently, we will conduct quantitative analyses to establish a comprehensive model explaining how family of origin factors affect children's psychological and behavioral outcomes. Findings: the research has revealed that family of origin factors, including education level, economic status, maternal age, family integration, family violence, marital conflict, parental drug and alcohol consumption, have an impact on children's self-confidence and life satisfaction. These factors can affect children's psychological well-being and happiness through various pathways. Implications: The results of this study will contribute to a better understanding of the influence of the family of origin on children and provide valuable directions for future research in positive psychology and psychotherapy. This research will enhance awareness of children's psychological well-being and lay the foundation for improving psychotherapeutic methods.

Keywords: family of origion, positive psychology, developmental psychology, family education, social psychology, educational psychology

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Authors: Arielle Ferdinand

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A plant-based diet focuses on foods from plant sources, limiting or altogether omitting animal products. Some of the most common chronic illnesses seen in primary care are hypertension, hyperlipidemia, and diabetes type II. These common chronic illnesses can often be debilitating, costly, time-consuming, and, when left untreated, can lead to an early death. Treatment and maintenance of care are also labor intensive for the patient. They are often required to have at least four blood pressure checks yearly and a hemoglobin A1C checked quarterly. Though preventative interventions and prevention education should be included in patient visits in the primary care setting, education about dietary interventions, such as a plant-based diet, also yields positive outcomes for patients who already have hypertension, hyperlipidemia, and diabetes mellitus type 2. Evidence will show that incorporating a plant-based diet results in decreased blood pressure, as well as decreased levels of LDL-C, improved post-prandial glucose levels, and a reduction in HbA1C. It is cost-effective for the patient by generally lower grocery costs, and it can either reduce or prevent the need to pay for more office visits and pharmacotherapy. Incorporating this method of dietary changes is an easy intervention during a primary care office visit that would greatly benefit the patient in many ways.

Keywords: plant-based, nutrition, diabetes, hyperlipidemia

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Authors: Xin Li, Ji-Yang Yu, Yue-Hua Niu, Lu-Yuan Wang

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As an inevitable chain of the space data acquirement system, space-borne storage system based on Nand Flash has gradually been implemented in spacecraft. In face of massive, parallel and varied data on board, efficient data management become an important issue of storage research. Face to the requirements of high-performance and reliability in Nand Flash storage system, a combination of hardware and file system design can drastically increase system dependability, even for missions with a very long duration. More sophisticated flash storage concepts with advanced operating systems have been researched to improve the reliability of Nand Flash storage system on satellites. In this paper, architecture of file system with multi-channel data acquisition and storage on board is proposed, which obtains large-capacity and high-performance with the combine of intra-channel pipeline and device partition in Nand Flash. Multi-channel data in different rate are stored as independent files with parallel-storage system in device partition, which assures the high-effective and reliable throughput of file treatments. For massive and high-speed data storage, an efficiency assessment model is established to calculate the bandwidth formula of intra-channel pipeline. Information tables designed in Magnetoresistive RAM (MRAM) hold the management of bad block in Nand Flash and the arrangement of file system address for the high-reliability of data storage. During the full-load test, the throughput of 3D PLUS Module 160Gb Nand Flash can reach 120Mbps for store and reach 120Mbps for playback, which efficiently satisfies the requirement of multi-channel data acquisition in Satellite. Compared with previous literature, the results of experiments verify the advantages of the proposed system.

Keywords: device partition architecture, intra-channel pipelining, nand flash, parallel storage

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Authors: Saman Shafei

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Tourism has improved for several reasons, with the main objective of producing economic benefits, including foreign exchange earnings, income generation, employment, rising government incomes, and contributing to the financing of tourism infrastructure, which also has public consumption. Although today the interests of the tourism industry are not overlooked by anyone, the expansion and development of tourism services and products can make it competitive, and in this competition, those who bring creativity and diversity are ahead of other competitors. Developing creative tourism as third-generation tourism can help to attract visitors, increasing demand and diversifying it, achieving new markets and boosting growth. Creative tourism is a journey aimed at achieving a brand –new experience and is along with collaborative learning of arts, cultural heritage, or specific features of a place, and provides useful communication with the inhabitants of the tourism destination who is creators of the living culture of that place. The present study aims to identify and introduce the capabilities of the city of Isfahan in IRAN for the development of creative tourism and the role of creative tourism on the destination and the local community of this city. The research method is descriptive-analytical and field method, interviewing tool and questionnaire have been applied to obtain research findings. The results indicate that the city of Isfahan has the potential to develop creative tourism in the field of traditional handicrafts and traditional foods, and developing this kind of tourism will lead to the development of sustainable tourism in this destination and will bring numerous benefits for the local community.

Keywords: creative tourism, tourism, Isfahan city, sustainable tourism development

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Authors: Piyakajornkul T., Noppiboon S., Hochareon L., Kitsubun P.

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Nowadays, DNA vaccines become an interesting subject in the third vaccine generation. The platform of DNA vaccines production has been developed and its downstream process becomes challenging due to the quality of the products in terms of purity and percentage of supercoiled DNA. To overcome these challenges, tangential flow filtration (TFF), which is involved in the purification process, could be used since it provides effective separation of impurity prior to performing further purification steps. However, operating conditions of TFF is varied based on several factors such as sizes of target particle and impurities, a concentration of solution as well as a concentration polarization on the membrane surface. In this study, pVAX1/lacZ was used as a model of TFF optimization in order to prevent a concentration polarization that can lead to the membrane fouling and also minimize a diafiltration volume while maintaining the maximum permeate flux resulting in proper operating times and buffer volume. By using trans membrane pressure (TMP) excursion method, feed flow rates and TMP were varied. The results showed a correlation of permeate flux with TMP where the maximum volume concentration factor reached 2.5 times of the initial volume when feed flow rate and TMP were 7 liters/m²/min and 1 bar, respectively. It was optimal operating conditions before TFF system undergone pressure independent regime. In addition, the diafiltration volume was 14 times of the concentrated volume prior to performing a further anion chromatography process.

Keywords: concentration polarization, DNA vaccines, optimization, permeate flux, pressure dependent, tangential flow filtration (TFF), trans membrane pressure (TMP)

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Authors: Reza Eslami-Farsani, Hamed Khosravi, Saba Fayazzadeh

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Lightweight and efficient structures have the aim to enhance the efficiency of the components in various industries. Toward this end, composites are one of the most widely used materials because of durability, high strength and modulus, and low weight. One type of the advanced composites is grid-stiffened composite (GSC) structures which have been extensively considered in aerospace, automotive, and aircraft industries. They are one of the top candidates for replacing some of the traditional components which are used here. Although there are a good number of published surveys on the design aspects and fabrication of GSC structures, little systematic work has been reported on their material modification to improve their properties, to our knowledge. Matrix modification using nanoparticles is an effective method to enhance the flexural properties of the fibrous composites. In the present study, a silane coupling agent (3-glycidoxypropyltrimethoxysilane/3-GPTS) was introduced onto the silica (SiO2) nanoparticle surface and its effects on the three-point flexural response of isogrid E-glass/epoxy composites were assessed. Based on the fourier transform infrared spectrometer (FTIR) spectra, it was inferred that the 3-GPTS coupling agent was successfully grafted onto the surface of SiO2 nanoparticles after modification. Flexural test revealed an improvement of 16%, 14%, and 36% in stiffness, maximum load and energy absorption of the isogrid specimen filled with 3 wt.% 3-GPTS/SiO2 compared to the neat one. It would be worth mentioning that in these structures, a considerable energy absorption was observed after the primary failure related to the load peak. Also, 3-GPTMS functionalization had a positive effect on the flexural behavior of the multiscale isogrid composites. In conclusion, this study suggests that the addition of modified silica nanoparticles is a promising method to improve the flexural properties of the grid-stiffened fibrous composite structures.

Keywords: isogrid-stiffened composite panels, silica nanoparticles, surface modification, flexural properties, energy absorption

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Authors: M. Varin, A. M. Dubois, R. Gadbois-Langevin, B. Chalghaf

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Good knowledge of the physical environment is essential for an integrated forest planning. This information enables better forecasting of operating costs, determination of cutting volumes, and preservation of ecologically sensitive areas. The use of satellite images in stereoscopic pairs gives the capacity to generate high precision 3D models, which are scale-adapted for harvesting operations. These models could represent an alternative to 3D LiDAR data, thanks to their advantageous cost of acquisition. The objective of the study was to assess the quality of stereo-derived canopy height models (CHM) in comparison to a traditional LiDAR CHM and ground tree-height samples. Two study sites harboring two different forest stand types (broadleaf and conifer) were analyzed using stereo pairs and tri-stereo images from the WorldView-3 satellite to calculate CHM. Acquisition of multispectral images from an Unmanned Aerial Vehicle (UAV) was also realized on a smaller part of the broadleaf study site. Different algorithms using two softwares (PCI Geomatica and Correlator3D) with various spatial resolutions and band selections were tested to select the 3D modeling technique, which offered the best performance when compared with LiDAR. In the conifer study site, the CHM produced with Corelator3D using only the 50-cm resolution panchromatic band was the one with the smallest Root-mean-square deviation (RMSE: 1.31 m). In the broadleaf study site, the tri-stereo model provided slightly better performance, with an RMSE of 1.2 m. The tri-stereo model was also compared to the UAV, which resulted in an RMSE of 1.3 m. At individual tree level, when ground samples were compared to satellite, lidar, and UAV CHM, RMSE were 2.8, 2.0, and 2.0 m, respectively. Advanced analysis was done for all of these cases, and it has been noted that RMSE is reduced when the canopy cover is higher when shadow and slopes are lower and when clouds are distant from the analyzed site.

Keywords: very high spatial resolution, satellite imagery, WorlView-3, canopy height models, CHM, LiDAR, unmanned aerial vehicle, UAV

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Authors: Elisa K. Schoenell, Cristiano De Oliveira, Luiz R. H. Dos Santos, Alexandre Giacobbo, Andréa M. Bernardes, Marco A. S. Rodrigues

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Water is an indispensable natural resource, which must be preserved to human activities as well the ecosystems. However, the sewage discharge has been contaminating water resources. Conventional treatment, such as physicochemical treatment followed by biological processes, has not been efficient to the complete degradation of persistent organic compounds, such as medicines and hormones. Therefore, the use of advanced technologies to sewage treatment has become urgent and necessary. The aim of this study was to apply Reverse Osmosis (RO) on sewage tertiary treatment from a Waste Water Treatment Plant (WWTP) in south Brazil. It was collected 200 L of sewage pre-treated by wetland with aquatic macrophytes. The sewage was treated in a RO pilot plant, using a polyamide membrane BW30-4040 model (DOW FILMTEC), with 7.2 m² membrane area. In order to avoid damage to the equipment, this system contains a pleated polyester filter with 5 µm pore size. It was applied 8 bar until achieve 5 times of concentration, obtaining 80% of recovery of permeate, with 10 L.min-1 of concentrate flow rate. Samples of sewage pre-treated on WWTP, permeate and concentrate generated on RO was analyzed for physicochemical parameters and by gas chromatography (GC) to qualitative analysis of organic compounds. The results proved that the sewage treated on WWTP does not comply with the limit of phosphorus and nitrogen of Brazilian legislation. Besides this, it was found many organic compounds in this sewage, such as benzene, which is carcinogenic. Analyzing permeate results, it was verified that the RO as sewage tertiary treatment was efficient to remove of physicochemical parameters, achieving 100% of iron, copper, zinc and phosphorus removal, 98% of color removal, 91% of BOD and 62% of ammoniacal nitrogen. RO was capable of removing organic compounds, however, it was verified the presence of some organic compounds on de RO permeate, showing that RO did not have the capacity of removal all organic compounds of sewage. It has to be considered that permeate showed lower intensity of peaks in chromatogram in comparison to the sewage of WWTP. It is important to note that the concentrate generate on RO needs a treatment before its disposal in environment.

Keywords: organic compounds, reverse osmosis, sewage treatment, tertiary treatment

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