Search results for: dose calculation
Commenced in January 2007
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Edition: International
Paper Count: 2586

Search results for: dose calculation

96 Contrastive Analysis of Parameters Registered in Training Rowers and the Impact on the Olympic Performance

Authors: Gheorghe Braniste

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The management of the training process in sports is closely related to the awareness of the close connection between performance and the morphological, functional and psychological characteristics of the athlete's body. Achieving high results in Olympic sports is influenced, on the one hand, by the genetically determined characteristics of the body and, on the other hand, by the morphological, functional and motor abilities of the athlete. Taking into account the importance of properly understanding the evolutionary specificity of athletes to assess their competitive potential, this study provides a comparative analysis of the parameters that characterize the growth and development of the level of adaptation of sweeping rowers, considering the growth interval between 12 and 20 years. The study established that, in the multi-annual training process, the bodies of the targeted athletes register significant adaptive changes while analyzing parameters of the morphological, functional, psychomotor and sports-technical spheres. As a result of the influence of physical efforts, both specific and non-specific, there is an increase in the adaptability of the body, its transfer to a much higher level of functionality within the parameters, useful and economical adaptive reactions influenced by environmental factors, be they internal or external. The research was carried out for 7 years, on a group of 28 athletes, following their evolution and recording the specific parameters of each age stage. In order to determine the level of physical, morpho-functional, psychomotor development and technical training of rowers, the screening data were applied at the State University of Physical Education and Sports in the Republic of Moldova. During the research, measurements were made on the waist, in the standing and sitting position, arm span, weight, circumference and chest perimeter, vital capacity of the lungs, with the subsequent determination of the vital index (tolerance level to oxygen deficiency in venous blood in Stange and Genchi breath-taking tests that characterize the level of oxygen saturation, absolute and relative strength of the hand and back, calculation of body mass and morphological maturity indices (Kettle index), body surface area (body gait), psychomotor tests (Romberg test), test-tepping 10 s., reaction to a moving object, visual and auditory-motor reaction, recording of technical parameters of rowing on a competitive distance of 200 m. At the end of the study it was found that highly performance is sports is to be associated on the one hand with the genetically determined characteristics of the body and, on the other hand, with favorable adaptive reactions and energy saving, as well as morphofunctional changes influenced by internal and external environmental factors. The importance of the results obtained at the end of the study was positively reflected in obtaining the maximum level of training of athletes in order to demonstrate performance in large-scale competitions and mostly in the Olympic Games.

Keywords: olympics, parameters, performance, peak

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95 Comparative Evaluation of High Pure Mn3O4 Preparation Technique between the Conventional Process from Electrolytic Manganese and a Sustainable Approach Directly from Low-Grade Rhodochrosite

Authors: Fang Lian, Zefang Chenli, Laijun Ma, Lei Mao

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Up to now, electrolytic process is a popular way to prepare Mn and MnO2 (EMD) with high purity. However, the conventional preparation process of manganese oxide such as Mn3O4 with high purity from electrolytic manganese metal is characterized by long production-cycle, high-pollution discharge and high energy consumption especially initially from low-grade rhodochrosite, the main resources for exploitation and applications in China. Moreover, Mn3O4 prepared from electrolytic manganese shows large particles, single morphology beyond the control and weak chemical activity. On the other hand, hydrometallurgical method combined with thermal decomposition, hydrothermal synthesis and sol-gel processes has been widely studied because of its high efficiency, low consumption and low cost. But the key problem in direct preparation of manganese oxide series from low-grade rhodochrosite is to remove completely the multiple impurities such as iron, silicon, calcium and magnesium. It is urgent to develop a sustainable approach to high pure manganese oxide series with character of short process, high efficiency, environmentally friendly and economical benefit. In our work, the preparation technique of high pure Mn3O4 directly from low-grade rhodochrosite ore (13.86%) was studied and improved intensively, including the effective leaching process and the short purifying process. Based on the same ion effect, the repeated leaching of rhodochrosite with sulfuric acid is proposed to improve the solubility of Mn2+ and inhibit the dissolution of the impurities Ca2+ and Mg2+. Moreover, the repeated leaching process could make full use of sulfuric acid and lower the cost of the raw material. With the aid of theoretical calculation, Ba(OH)2 was chosen to adjust the pH value of manganese sulfate solution and BaF2 to remove Ca2+ and Mg2+ completely in the process of purifying. Herein, the recovery ratio of manganese and removal ratio of the impurity were evaluated via chemical titration and ICP analysis, respectively. Comparison between conventional preparation technique from electrolytic manganese and a sustainable approach directly from low-grade rhodochrosite have also been done herein. The results demonstrate that the extraction ratio and the recovery ratio of manganese reached 94.3% and 92.7%, respectively. The heavy metal impurities has been decreased to less than 1ppm, and the content of calcium, magnesium and sodium has been decreased to less than 20ppm, which meet standards of high pure reagent for energy and electronic materials. In compare with conventional technique from electrolytic manganese, the power consumption has been reduced to ≤2000 kWh/t(product) in our short-process approach. Moreover, comprehensive recovery rate of manganese increases significantly, and the wastewater generated from our short-process approach contains low content of ammonia/ nitrogen about 500 mg/t(product) and no toxic emissions. Our study contributes to the sustainable application of low-grade manganese ore. Acknowledgements: The authors are grateful to the National Science and Technology Support Program of China (No.2015BAB01B02) for financial support to the work.

Keywords: leaching, high purity, low-grade rhodochrosite, manganese oxide, purifying process, recovery ratio

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94 Groundwater Arsenic Contamination in Gangetic Jharkhand, India: Risk Implications for Human Health and Sustainable Agriculture

Authors: Sukalyan Chakraborty

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Arsenic contamination in groundwater has been a matter of serious concern worldwide. Globally, arsenic contaminated water has caused serious chronic human diseases and in the last few decades the transfer of arsenic to human beings via food chain has gained much attention because food represents a further potential exposure pathway to arsenic in instances where crops are irrigated with high arsenic groundwater, grown in contaminated fields or cooked with arsenic laden water. In the present study, the groundwater of Sahibganj district of Jharkhand has been analysed to find the degree of contamination and its probable associated risk due to direct consumption or irrigation. The present study area comprising of three blocks, namely Sahibganj, Rajmahal and Udhwa in Sahibganj district of Jharkhand state, India, situated in the western bank of river Ganga has been investigated for arsenic contamination in groundwater, soil and crops predominantly growing in the region. Associated physicochemical parameters of groundwater including pH, temperature, electrical conductivity (EC), total dissolved solids (TDS), dissolved oxygen (DO), oxidation reduction potential (ORP), ammonium, nitrate and chloride were assessed to understand the mobilisation mechanism and chances of arsenic exposure from soil to crops and further into the food chain. Results suggested the groundwater to be dominantly Ca-HCO3- type with low redox potential and high total dissolved solids load. Major cations followed the order of Ca ˃ Na ˃ Mg ˃ K. The concentration of major anions was found in the order of HCO3− > Cl− > SO42− > NO3− > PO43− varied between 0.009 to 0.20 mg L-1. Fe concentrations of the groundwater samples were below WHO permissible limit varying between 54 to 344 µg L-1. Phosphate concentration was high and showed a significant positive correlation with arsenic. As concentrations ranged from 7 to 115 µg L-1 in premonsoon, between 2 and 98 µg L-1 in monsoon and 1 to 133µg L-1 in postmonsoon season. Arsenic concentration was found to be much higher than the WHO or BIS permissible limit in majority of the villages in the study area. Arsenic was also seen to be positively correlated with iron and phosphate. PCA results demonstrated the role of both geological condition and anthropogenic inputs to influence the water quality. Arsenic was also found to increase with depth up to 100 m from the surface. Calculation of carcinogenic and non-carcinogenic effects of the arsenic concentration in the communities exposed to the groundwater for drinking and other purpose indicated high risk with an average of more than 1 in a 1000 population. Health risk analysis revealed high to very high carcinogenic and non-carcinogenic risk for adults and children in the communities dependent on groundwater of the study area. Observation suggested the groundwater to be considerably polluted with arsenic and posing significant health risk for the exposed communities. The mobilisation mechanism of arsenic also could be identified from the results suggesting reductive dissolution of Fe oxyhydroxides due to high phosphate concentration from agricultural input arsenic release from the sediments along river Ganges.

Keywords: arsenic, physicochemical parameters, mobilisation, health effects

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93 Developing Effective Strategies to Reduce Hiv, Aids and Sexually Transmitted Infections, Nakuru, Kenya

Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi

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Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.

Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach

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92 Modeling Taxane-Induced Peripheral Neuropathy Ex Vivo Using Patient-Derived Neurons

Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

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91 The Derivation of a Four-Strain Optimized Mohr's Circle for Use in Experimental Reinforced Concrete Research

Authors: Edvard P. G. Bruun

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One of the best ways of improving our understanding of reinforced concrete is through large-scale experimental testing. The gathered information is critical in making inferences about structural mechanics and deriving the mathematical models that are the basis for finite element analysis programs and design codes. An effective way of measuring the strains across a region of a specimen is by using a system of surface mounted Linear Variable Differential Transformers (LVDTs). While a single LVDT can only measure the linear strain in one direction, by combining several measurements at known angles a Mohr’s circle of strain can be derived for the whole region under investigation. This paper presents a method that can be used by researchers, which improves the accuracy and removes experimental bias in the calculation of the Mohr’s circle, using four rather than three independent strain measurements. Obtaining high quality strain data is essential, since knowing the angular deviation (shear strain) and the angle of principal strain in the region are important properties in characterizing the governing structural mechanics. For example, the Modified Compression Field Theory (MCFT) developed at the University of Toronto, is a rotating crack model that requires knowing the direction of the principal stress and strain, and then calculates the average secant stiffness in this direction. But since LVDTs can only measure average strains across a plane (i.e., between discrete points), localized cracking and spalling that typically occur in reinforced concrete, can lead to unrealistic results. To build in redundancy and improve the quality of the data gathered, the typical experimental setup for a large-scale shell specimen has four independent directions (X, Y, H, and V) that are instrumented. The question now becomes, which three should be used? The most common approach is to simply discard one of the measurements. The problem is that this can produce drastically different answers, depending on the three strain values that are chosen. To overcome this experimental bias, and to avoid simply discarding valuable data, a more rigorous approach would be to somehow make use of all four measurements. This paper presents the derivation of a method to draw what is effectively a Mohr’s circle of 'best-fit', which optimizes the circle by using all four independent strain values. The four-strain optimized Mohr’s circle approach has been utilized to process data from recent large-scale shell tests at the University of Toronto (Ruggiero, Proestos, and Bruun), where analysis of the test data has shown that the traditional three-strain method can lead to widely different results. This paper presents the derivation of the method and shows its application in the context of two reinforced concrete shells tested in pure torsion. In general, the constitutive models and relationships that characterize reinforced concrete are only as good as the experimental data that is gathered – ensuring that a rigorous and unbiased approach exists for calculating the Mohr’s circle of strain during an experiment, is of utmost importance to the structural research community.

Keywords: reinforced concrete, shell tests, Mohr’s circle, experimental research

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90 Isolation and Transplantation of Hepatocytes in an Experimental Model

Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

Abstract:

Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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89 Optimizing Stormwater Sampling Design for Estimation of Pollutant Loads

Authors: Raja Umer Sajjad, Chang Hee Lee

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Stormwater runoff is the leading contributor to pollution of receiving waters. In response, an efficient stormwater monitoring program is required to quantify and eventually reduce stormwater pollution. The overall goals of stormwater monitoring programs primarily include the identification of high-risk dischargers and the development of total maximum daily loads (TMDLs). The challenge in developing better monitoring program is to reduce the variability in flux estimates due to sampling errors; however, the success of monitoring program mainly depends on the accuracy of the estimates. Apart from sampling errors, manpower and budgetary constraints also influence the quality of the estimates. This study attempted to develop optimum stormwater monitoring design considering both cost and the quality of the estimated pollutants flux. Three years stormwater monitoring data (2012 – 2014) from a mix land use located within Geumhak watershed South Korea was evaluated. The regional climate is humid and precipitation is usually well distributed through the year. The investigation of a large number of water quality parameters is time-consuming and resource intensive. In order to identify a suite of easy-to-measure parameters to act as a surrogate, Principal Component Analysis (PCA) was applied. Means, standard deviations, coefficient of variation (CV) and other simple statistics were performed using multivariate statistical analysis software SPSS 22.0. The implication of sampling time on monitoring results, number of samples required during the storm event and impact of seasonal first flush were also identified. Based on the observations derived from the PCA biplot and the correlation matrix, total suspended solids (TSS) was identified as a potential surrogate for turbidity, total phosphorus and for heavy metals like lead, chromium, and copper whereas, Chemical Oxygen Demand (COD) was identified as surrogate for organic matter. The CV among different monitored water quality parameters were found higher (ranged from 3.8 to 15.5). It suggests that use of grab sampling design to estimate the mass emission rates in the study area can lead to errors due to large variability. TSS discharge load calculation error was found only 2 % with two different sample size approaches; i.e. 17 samples per storm event and equally distributed 6 samples per storm event. Both seasonal first flush and event first flush phenomena for most water quality parameters were observed in the study area. Samples taken at the initial stage of storm event generally overestimate the mass emissions; however, it was found that collecting a grab sample after initial hour of storm event more closely approximates the mean concentration of the event. It was concluded that site and regional climate specific interventions can be made to optimize the stormwater monitoring program in order to make it more effective and economical.

Keywords: first flush, pollutant load, stormwater monitoring, surrogate parameters

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88 Oncoplastic Augmentation Mastopexy: Aesthetic Revisional Surgery in Breast Conserving Therapy

Authors: Bar Y. Ainuz, Harry M. Salinas, Aleeza Ali, Eli B. Levitt, Austin J. Pourmoussa, Antoun Bouz, Miguel A. Medina

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Introduction: Breast conservation therapy remains the mainstay surgical treatment for early breast cancer. Oncoplastic techniques, in conjunction with lumpectomy and adjuvant radiotherapy, have been demonstrated to achieve good aesthetic results without adversely affecting cancer outcomes in the treatment of patients with macromastia or significant ptosis. In our patient population, many women present for breast conservation with pre-existing cosmetic implants or with breast volumes too small for soft tissue, only oncoplastic techniques. Our study evaluated a consecutive series of patients presenting for breast conservation undergoing concomitant oncoplastic-augmentation-mastopexy (OAM) with a contralateral augmentation-mastopexy for symmetry. Methods: OAM surgical technique involves simultaneous lumpectomy with exchange or placement of implants, oncoplastic mastopexy, and concomitant contralateral augmentation mastopexy for symmetry. Patients undergoing lumpectomy for breast conservation as outpatients were identified via retrospective chart review at a high volume private academic affiliated community-based cancer center. Patients with ptosis and either pre-existing breast implants or insufficient breast volume undergoing oncoplastic implant placement (or exchange) and mastopexy were included in the study. Operative details, aesthetic outcomes, and complications were assessed. Results: Over a continuous three-year period, with a two-surgeon cohort, 30 consecutive patients (56 breasts, 4 unilateral procedures) were identified. Patients had an average age of 52.5 years and an average BMI of 27.5, with 40% smokers or former smokers. The average operative time was 2.5 hours, the average implant size removed was 352 cc, and the average implant size placed was 300 cc. All new implants were smooth silicone, with the majority (92%) placed in a retropectoral fashion. 40% of patients received chemotherapy, and 80% of patients received whole breast adjuvant photon radiotherapy with a total radiation dose of either 42.56 or 52.56 Gy. The average and median length of follow-up were both 8.2 months. Of the 24 patients that received radiotherapy, 21% had asymmetry due to capsular contracture. A total of 7 patients (29.2%) underwent revisions for either positive margins (12.5%), capsular contracture (8.3%), implant loss (4.2%), or cosmetic concerns (4.2%). One patient developed a pulmonary embolism in the acute postoperative period and was treated with anticoagulant therapy. Conclusion: Oncoplastic augmentation mastopexy is a safe technique with good aesthetic outcomes and acceptable complication rates for ptotic patients with breast cancer and a paucity of breast volume or pre-existing implants who wish to pursue breast-conserving therapy. The revision rates compare favorably with single-stage cosmetic augmentation procedures as well as other oncoplastic techniques described in the literature. The short-term capsular contracture rates seem lower than the rates in patients undergoing radiation after mastectomy and implant-based reconstruction. Long term capsular contractures and revision rates are too early to know in this cohort.

Keywords: breast conserving therapy, oncoplastic augmentation mastopexy, capsular contracture, breast reconstruction

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87 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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86 Research on the Spatial Evolution of Tourism-Oriented Rural Settlements: Take the Xiaochanfangyu Village, Dongshuichang Village, Maojiayu Village in Jixian County, Tianjin City as Examples

Authors: Yu Zhang, Jie Wu, Li Dong

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Rural tourism is the service industry which regards the agricultural production, rural life, rural nature and cultural landscape as the tourist attraction. It aims to meet the needs of the city tourists such as country sightseeing, vacation, and leisure. According to the difference of the tourist resources, the rural settlements can be divided into different types: The type of tourism resources, scenic spot, and peri-urban. In the past ten years, the rural tourism has promoted the industrial transformation and economic growth in rural areas of China. And it is conducive to the coordinated development of urban and rural areas and has greatly improved the ecological environment and the standard of living for farmers in rural areas. At the same time, a large number of buildings and sites are built in the countryside in order to enhance the tourist attraction and the ability of tourist reception and also to increase the travel comfort and convenience, which has significant influence on the spatial evolution of the village settlement. This article takes the XiangYing Subdistrict, which is in JinPu District of Dalian in China as the exemplification and uses the technology of Remote Sensing (RS), Geographic Information System (GIS) and the technology of Landscape Spatial Analysis to study the influence of the rural tourism development in the rural settlement spaces in four steps. First, acquiring the remote sensing image data at different times of 8 administrative villages in the XiangYing Subdistrict, by using the remote sensing application EDRAS8.6; second, vectoring basic maps of XiangYing Subdistrict including its land-use map with the application of ArcGIS 9.3, associating with social and economic attribute data of rural settlements and analyzing on the rural evolution visually; third, quantifying the comparison of these patches in rural settlements by using the landscape spatial calculation application Fragstats 3.3 and analyzing on the evolution of the spatial structure of settlement in macro and medium scale; finally, summarizing the evolution characteristics and internal reasons of tourism-oriented rural settlements. The main findings of this article include: first of all, there is difference in the evolution of the spatial structure between the developing rural settlements and undeveloped rural settlements among the eight administrative villages; secondly, the villages relying on the surrounding tourist attractions, the villages developing agricultural ecological garden and the villages with natural or historical and cultural resources have different laws of development; then, the rural settlements whose tourism development in germination period, development period and mature period have different characteristics of spatial evolution; finally, the different evolution modes of the tourism-oriented rural settlement space have different influences on the protection and inheritance of the village scene. The development of tourism has a significant impact on the spatial evolution of rural settlement. The intensive use of rural land and natural resources is the fundamental principle to protect the rural cultural landscape and ecological environment as well as the critical way to improve the attraction of rural tourism and promote the sustainable development of countryside.

Keywords: landscape pattern, rural settlement, spatial evolution, tourism-oriented, Xiangying Subdistrict

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85 Pharmacognostical, Phytochemical and Biological Studies of Leaves and Stems of Hippophae Salicifolia

Authors: Bhupendra Kumar Poudel, Sadhana Amatya, Tirtha Maiya Shrestha, Bharatmani Pokhrel, Mohan Prasad Amatya

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Background: H. salicifolia is a dense, branched, multipurpose, deciduous, nitrogen fixing, thorny willow-like small to moderate tree, restricted to the Himalaya. Among the two species of Nepal (Hippophae salicifolia and H. tibetana), it has been traditionally used as food additive, anticancer (bark), and treating toothache, tooth inflammation (anti-inflammatory) and radiation injury; while people of Western Nepal have largely undermined its veiled treasure by using it for fuel, wood and soil stabilization only. Therefore, the main objective of this study was to explore biological properties (analgesic, antidiabetic, cytotoxic and anti-inflammatory properties of this plant. Methodology: The transverse section of leaves and stems were viewed under microscope. Extracts obtained from soxhlation subjected to tests for phytochemical and biological studies. Rats (used to study antidiabetic and anti-inflammatory properties) and mice (used to study analgesic, CNS depressant, muscle relaxant and locomotor properties) were assumed to be normally distributed; then ANOVA and post hoc tukey test was used to find significance. The data obtained were analyzed by SPSS 17 and Excel 2007. Results and Conclusion: Pharmacognostical analysis revealed the presence of long stellate trichomes, double layered vascular bundle 5-6 in number and double layered compact sclerenchyma. The preliminary phytochemical screening of the extracts was found to exhibit the positive reaction tests for glycoside, steroid, tannin, flavonoid, saponin, coumarin and reducing sugar. The brine shrimp lethality bioassay tested in 1000, 100 and 10 ppm revealed cytotoxic activity inherent in methanol, water, chloroform and ethyl acetate extracts with LC50 (μg/ml) values of 61.42, 99.77, 292.72 and 277.84 respectively. The cytotoxic activity may be due to presence of tannins in the constituents. Antimicrobial screening of the extracts by cup diffusion method using Staphylococcus aereus, Escherichia coli and Pseudomonas aeruginosa against standard antibiotics (oxacillin, gentamycin and amikacin respectively) portrayed no activity against the microorganisms tested. The methanol extract of the stems and leaves showed various pharmacological properties: and antidiabetic, anti-inflammatory, analgesic [chemical writhing method], CNS depressant, muscle relaxant and locomotor activities in a dose-dependent fashion, indicating the possibility of the presence of different constituents in the stems and leaves responsible for these biological activities. All the effects when analyzed by post hoc tukey test were found to be significant at 95% confidence level. The antidiabetic activity was presumed to be due to flavonoids present in extract. Therefore, it can be concluded that this plant’s secondary metabolites possessed strong antidiabetic, anti-inflammatory and cytotoxic activity which could be isolated for further investigation.

Keywords: Hippophae salicifolia, constituents, antidiabetic, inflammatory, brine shrimp

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84 Oat Bran Associated with Nutritional Counseling in Treating Obesity and Other Risk Factors for Cardiovascular Disease

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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83 Preparation and Characterization of Anti-Acne Dermal Products Based on Erythromycin β-Cyclodextrin Lactide Complex

Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

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82 Design and Synthesis of an Organic Material with High Open Circuit Voltage of 1.0 V

Authors: Javed Iqbal

Abstract:

The growing need for energy by the human society and depletion of conventional energy sources demands a renewable, safe, infinite, low-cost and omnipresent energy source. One of the most suitable ways to solve the foreseeable world’s energy crisis is to use the power of the sun. Photovoltaic devices are especially of wide interest as they can convert solar energy to electricity. Recently the best performing solar cells are silicon-based cells. However, silicon cells are expensive, rigid in structure and have a large timeline for the payback of cost and electricity. Organic photovoltaic cells are cheap, flexible and can be manufactured in a continuous process. Therefore, organic photovoltaic cells are an extremely favorable replacement. Organic photovoltaic cells utilize sunlight as energy and convert it into electricity through the use of conductive polymers/ small molecules to separate electrons and electron holes. A major challenge for these new organic photovoltaic cells is the efficiency, which is low compared with the traditional silicon solar cells. To overcome this challenge, usually two straightforward strategies have been considered: (1) reducing the band-gap of molecular donors to broaden the absorption range, which results in higher short circuit current density (JSC) of devices, and (2) lowering the highest occupied molecular orbital (HOMO) energy of molecular donors so as to increase the open-circuit voltage (VOC) of applications devices.8 Keeping in mind the cost of chemicals it is hard to try many materials on test basis. The best way is to find the suitable material in the bulk. For this purpose, we use computational approach to design molecules based on our organic chemistry knowledge and determine their physical and electronic properties. In this study, we did DFT calculations with different options to get high open circuit voltage and after getting suitable data from calculation we finally did synthesis of a novel D–π–A–π–D type low band-gap small molecular donor material (ZOPTAN-TPA). The Aarylene vinylene based bis(arylhalide) unit containing a cyanostilbene unit acts as a low-band- gap electron-accepting block, and is coupled with triphenylamine as electron-donating blocks groups. The motivation for choosing triphenylamine (TPA) as capped donor was attributed to its important role in stabilizing the separated hole from an exciton and thus improving the hole-transporting properties of the hole carrier.3 A π-bridge (thiophene) is inserted between the donor and acceptor unit to reduce the steric hindrance between the donor and acceptor units and to improve the planarity of the molecule. The ZOPTAN-TPA molecule features a low HOMO level of 5.2 eV and an optical energy gap of 2.1 eV. Champion OSCs based on a solution-processed and non-annealed active-material blend of [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) and ZOPTAN-TPA in a mass ratio of 2:1 exhibits a power conversion efficiency of 1.9 % and a high open-circuit voltage of over 1.0 V.

Keywords: high open circuit voltage, donor, triphenylamine, organic solar cells

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81 Membrane Technologies for Obtaining Bioactive Fractions from Blood Main Protein: An Exploratory Study for Industrial Application

Authors: Fatima Arrutia, Francisco Amador Riera

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The meat industry generates large volumes of blood as a result of meat processing. Several industrial procedures have been implemented in order to treat this by-product, but are focused on the production of low-value products, and in many cases, blood is simply discarded as waste. Besides, in addition to economic interests, there is an environmental concern due to bloodborne pathogens and other chemical contaminants found in blood. Consequently, there is a dire need to find extensive uses for blood that can be both applicable to industrial scale and able to yield high value-added products. Blood has been recognized as an important source of protein. The main blood serum protein in mammals is serum albumin. One of the top trends in food market is functional foods. Among them, bioactive peptides can be obtained from protein sources by microbiological fermentation or enzymatic and chemical hydrolysis. Bioactive peptides are short amino acid sequences that can have a positive impact on health when administered. The main drawback for bioactive peptide production is the high cost of the isolation, purification and characterization techniques (such as chromatography and mass spectrometry) that make unaffordable the scale-up. On the other hand, membrane technologies are very suitable to apply to the industry because they offer a very easy scale-up and are low-cost technologies, compared to other traditional separation methods. In this work, the possibility of obtaining bioactive peptide fractions from serum albumin by means of a simple procedure of only 2 steps (hydrolysis and membrane filtration) was evaluated, as an exploratory study for possible industrial application. The methodology used in this work was, firstly, a tryptic hydrolysis of serum albumin in order to release the peptides from the protein. The protein was previously subjected to a thermal treatment in order to enhance the enzyme cleavage and thus the peptide yield. Then, the obtained hydrolysate was filtered through a nanofiltration/ultrafiltration flat rig at three different pH values with two different membrane materials, so as to compare membrane performance. The corresponding permeates were analyzed by liquid chromatography-tandem mass spectrometry technology in order to obtain the peptide sequences present in each permeate. Finally, different concentrations of every permeate were evaluated for their in vitro antihypertensive and antioxidant activities though ACE-inhibition and DPPH radical scavenging tests. The hydrolysis process with the previous thermal treatment allowed achieving a degree of hydrolysis of the 49.66% of the maximum possible. It was found that peptides were best transmitted to the permeate stream at pH values that corresponded to their isoelectric points. Best selectivity between peptide groups was achieved at basic pH values. Differences in peptide content were found between membranes and also between pH values for the same membrane. The antioxidant activity of all permeates was high compared with the control only for the highest dose. However, antihypertensive activity was best for intermediate concentrations, rather than higher or lower doses. Therefore, although differences between them, all permeates were promising regarding antihypertensive and antioxidant properties.

Keywords: bioactive peptides, bovine serum albumin, hydrolysis, membrane filtration

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80 Effect of Radioprotectors on DNA Repair Enzyme and Survival of Gamma-Irradiated Cell Division Cycle Mutants of Saccharomyces pombe

Authors: Purva Nemavarkar, Badri Narain Pandey, Jitendra Kumar

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Introduction: The objective was to understand the effect of various radioprotectors on DNA damage repair enzyme and survival in gamma-irradiated wild and cdc mutants of S. pombe (fission yeast) cultured under permissive and restrictive conditions. DNA repair process, as influenced by radioprotectors, was measured by activity of DNA polymerase in the cells. The use of single cell gel electrophoresis assay (SCGE) or Comet Assay to follow gamma-irradiation induced DNA damage and effect of radioprotectors was employed. In addition, studying the effect of caffeine at different concentrations on S-phase of cell cycle was also delineated. Materials and Methods: S. pombe cells grown at permissive temperature (250C) and/or restrictive temperature (360C) were followed by gamma-radiation. Percentage survival and activity of DNA Polymerase (yPol II) were determined after post-irradiation incubation (5 h) with radioprotectors such as Caffeine, Curcumin, Disulphiram, and Ellagic acid (the dose depending on individual D 37 values). The gamma-irradiated yeast cells (with and without the radioprotectors) were spheroplasted by enzyme glusulase and subjected to electrophoresis. Radio-resistant cells were obtained by arresting cells in S-phase using transient treatment of hydroxyurea (HU) and studying the effect of caffeine at different concentrations on S-phase of cell cycle. Results: The mutants of S. pombe showed insignificant difference in survival when grown under permissive conditions. However, growth of these cells under restrictive temperature leads to arrest in specific phases of cell cycle in different cdc mutants (cdc10: G1 arrest, cdc22: early S arrest, cdc17: late S arrest, cdc25: G2 arrest). All the cdc mutants showed decrease in survival after gamma radiation when grown at permissive and restrictive temperatures. Inclusion of the radioprotectors at respective concentrations during post irradiation incubation showed increase in survival of cells. Activity of DNA polymerase enzyme (yPol II) was increased significantly in cdc mutant cells exposed to gamma-radiation. Following SCGE, a linear relationship was observed between doses of irradiation and the tail moments of comets. The radioprotection of the fission yeast by radioprotectors can be seen by the reduced tail moments of the yeast comets. Caffeine also exhibited its radio-protective ability in radio-resistant S-phase cells obtained after HU treatment. Conclusions: The radioprotectors offered notable radioprotection in cdc mutants when added during irradiation. The present study showed activation of DNA damage repair enzyme (yPol II) and an increase in survival after treatment of radioprotectors in gamma irradiated wild type and cdc mutants of S. pombe cells. Results presented here showed feasibility of applying SCGE in fission yeast to follow DNA damage and radioprotection at high doses, which are not feasible with other eukaryotes. Inclusion of caffeine at 1mM concentration to S phase cells offered protection and did not decrease the cell viability. It can be proved that at minimal concentration, caffeine offered marked radioprotection.

Keywords: radiation protection, cell cycle, fission yeast, comet assay, s-phase, DNA repair, radioprotectors, caffeine, curcumin, SCGE

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79 Optimal-Based Structural Vibration Attenuation Using Nonlinear Tuned Vibration Absorbers

Authors: Pawel Martynowicz

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Vibrations are a crucial problem for slender structures such as towers, masts, chimneys, wind turbines, bridges, high buildings, etc., that is why most of them are equipped with vibration attenuation or fatigue reduction solutions. In this work, a slender structure (i.e., wind turbine tower-nacelle model) equipped with nonlinear, semiactive tuned vibration absorber(s) is analyzed. For this study purposes, magnetorheological (MR) dampers are used as semiactive actuators. Several optimal-based approaches to structural vibration attenuation are investigated against the standard ‘ground-hook’ law and passive tuned vibration absorber(s) implementations. The common approach to optimal control of nonlinear systems is offline computation of the optimal solution, however, so determined open loop control suffers from lack of robustness to uncertainties (e.g., unmodelled dynamics, perturbations of external forces or initial conditions), and thus perturbation control techniques are often used. However, proper linearization may be an issue for highly nonlinear systems with implicit relations between state, co-state, and control. The main contribution of the author is the development as well as numerical and experimental verification of the Pontriagin maximum-principle-based vibration control concepts that produce directly actuator control input (not the demanded force), thus force tracking algorithm that results in control inaccuracy is entirely omitted. These concepts, including one-step optimal control, quasi-optimal control, and optimal-based modified ‘ground-hook’ law, can be directly implemented in online and real-time feedback control for periodic (or semi-periodic) disturbances with invariant or time-varying parameters, as well as for non-periodic, transient or random disturbances, what is a limitation for some other known solutions. No offline calculation, excitations/disturbances assumption or vibration frequency determination is necessary, moreover, all of the nonlinear actuator (MR damper) force constraints, i.e., no active forces, lower and upper saturation limits, hysteresis-type dynamics, etc., are embedded in the control technique, thus the solution is optimal or suboptimal for the assumed actuator, respecting its limitations. Depending on the selected method variant, a moderate or decisive reduction in the computational load is possible compared to other methods of nonlinear optimal control, while assuring the quality and robustness of the vibration reduction system, as well as considering multi-pronged operational aspects, such as possible minimization of the amplitude of the deflection and acceleration of the vibrating structure, its potential and/or kinetic energy, required actuator force, control input (e.g. electric current in the MR damper coil) and/or stroke amplitude. The developed solutions are characterized by high vibration reduction efficiency – the obtained maximum values of the dynamic amplification factor are close to 2.0, while for the best of the passive systems, these values exceed 3.5.

Keywords: magnetorheological damper, nonlinear tuned vibration absorber, optimal control, real-time structural vibration attenuation, wind turbines

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78 Concentration of Droplets in a Transient Gas Flow

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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77 A Designing 3D Model: Castle of the Mall-Dern

Authors: Nanadcha Sinjindawong

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This article discusses the design process of a community mall called Castle of The Mall-dern. The concept behind this mall is to combine elements of a medieval castle with modern architecture. The author aims to create a building that fits into the surroundings while also providing users with the vibes of the ancient era. The total area used for the mall is 4,000 square meters, with three floors. The first floor is 1,500 square meters, the second floor is 1,750 square meters, and the third floor is 750 square meters. Research Aim: The aim of this research is to design a community mall that sells ancient clothes and accessories, and to combine sustainable architectural design with the ideas of ancient architecture in an urban area with convenient transportation. Methodology: The research utilizes qualitative research methods in architectural design. The process begins with calculating the given area and dividing it into different zones. The author then sketches and draws the plan of each floor, adding the necessary rooms based on the floor areas mentioned earlier. The program "SketchUp" is used to create an online 3D model of the community mall, and a physical model is built for presentation purposes on A1 paper, explaining all the details. Findings: The result of this research is a community mall with various amenities. The first floor includes retail shops, clothing stores, a food center, and a service zone. Additionally, there is an indoor garden with a fountain and a tree for relaxation. The second and third floors feature a void in the middle, with a few stores, cafes, restaurants, and studios on the second floor. The third floor is home to the administration and security control room, as well as a community gathering area designed as a public library with a café inside. Theoretical Importance: This research contributes to the field of sustainable architectural design by combining ancient architectural ideas with modern elements. It showcases the potential for creating buildings that blend historical aesthetics with contemporary functionality. Data Collection and Analysis Procedures: The data for this research is collected through a combination of area calculation, sketching, and building a 3D model. The analysis involves evaluating the design based on the allocated area, zoning, and functional requirements for a community mall. Question Addressed: The research addresses the question of how to design a community mall with a theme of ancient Medieval and Victorian eras. It explores how to combine sustainable architectural design principles with historical aesthetics to create a functional and visually appealing space. Conclusion: In conclusion, this research successfully designs a community mall called “Castle of The Mall-dern” that incorporates elements of Medieval and Victorian architecture. The building encompasses various zones, including retail shops, restaurants, community gathering areas, and service zones. It also features an interior garden and a public library within the mall. The research contributes to the field of sustainable architectural design by showcasing the potential for combining ancient architectural ideas with modern elements in an urban setting.

Keywords: 3D model, community mall, modern architecture, medieval architecture

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76 Associated Factors the Safety of the Patient in Hemodialysis Clinics of a Brazilian Municipality: Cross-Sectional Study

Authors: Magda Milleyde de Sousa Lima, Letícia Lima Aguiar, Marina Guerra Martins, Erika Veríssimo Dias Sousa, Lizandra Sampaio de Oliveira, Lívia Moreira Barros, Joselany Áfio Caetano

Abstract:

Patients with chronic kidney disease are vulnerable to episodes which make the safety of their health vulnerable, mainly due to the treatment process that exposes them to high rates of interventions during hemodialysis sessions. Some factors associated with health care contribute to the risk of death and complications. However, there are a small number of scientific studies evaluating the level of safety of hemodialysis clinics, and the sociodemographic characteristics of patients and professionals associated with this safety. Therefore, the present study aims to examine the level of patient safety in hemodialysis clinics in the Brazilian capital, to identify the sociodemographic and clinical factors of patients and nursing staff associated with the level of safety. This is an observational, descriptive and quantitative research conducted in three hemodialysis clinics placed in the city of Fortaleza-CE, Brazil, from September to November 2019. The sample was formed after a sample calculation for finite inhabitants of correlation with 200 chronic renal patients, 30 nursing technicians and seven nurses. Conventional sampling was used based on the inclusion criteria: being present at the hemodialysis session on the day the researcher performed the data collection and being 18 years of age or older. Participants who presented communication difficulties to listen to and/or answer the sociodemographic and clinical questionnaire were excluded. Two instruments were applied: sociodemographic and clinical characterization form and Chronic Renal Patient Safety Assessment Scale on Hemodialysis (EASPRCH). The data were analyzed using the Kruskal Walls Test for categorical variables and Spearman correlation coefficient for non-categorical variables, using the Statistical Package SPSS version 20.0. The present study respected the ethical and legal principles determined by resolution 466/2012 of the National Health Council, under the approval of the Ethics and Research Committee with an opinion number: 3,255,635. The results showed that a hemodialysis clinic presented unsafe care practices of 32 points in the EASPRCH (p=0.001). A statistical association was identified between the level of safety and the variables of the patients: level of education (p=0.018), family income (p=0.049), type of employment (p=0.012), venous access site (p=0.009), use of medication during the session (p=0.008) and time of hemodialysis (p=0.002). When evaluating the profile of nurses, a statistical association was evidenced between the level of safety with the variables: marital status (p=0.000), race (p=0.017), schooling (p= 0.000), income (p=0.013), age (p=0.000), clinic workload (p=0.000), time working with hemodialysis (p=0.000), time working in the clinic (p= 0.007) and clinic sizing (p=0.000). In order, the sociodemographic factors of nursing technicians associated with the level of patient safety were: race (p= 0.001) and weekly workload at (p=0.010). Therefore, it is concluded that there is a non-conformity in the level of patient safety in one of the clinics studied and, that sociodemographic and clinical factors of patients and health professionals corroborate the level of safety of the health unit.

Keywords: hemodialysis, nursing, patient safety, quality improvement

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75 Rainwater Harvesting is an Effective Tool for City’s Storm Water Management and People’s Willingness to Install Rainwater Harvesting System in Buildings: A Case Study in Kazipara, Dhaka, Bangladesh

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

Abstract:

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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74 Hypothalamic Para-Ventricular and Supra-Optic Nucleus Histo-Morphological Alterations in the Streptozotocin-Diabetic Gerbils (Gerbillus Gerbillus)

Authors: Soumia Hammadi, Imane Nouacer, Lamine Hamida, Younes A. Hammadi, Rachid Chaibi

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Aims and objective: In the present work, we investigate the impact of both acute and chronic diabetes mellitus induced by streptozotocin (STZ) on the hypothalamus of the small gerbil (Gerbillus gerbillus). In this purpose, we aimed to study the histologic structure of the gerbil’s hypothalamic supraoptic (NSO) and paraventricular nucleus (NPV) at two distinct time points: two days and 30 days after diabetes onset. Methods: We conducted our investigation using 19 adult male gerbils weighing 25 to 28 g, divided into three groups as follow: Group I: Control gerbils (n=6) received an intraperitoneal injection of citrate buffer. Group II: STZ-diabetic gerbils (n=8) received a single intraperitoneal injection of STZ at a dose of 165 mg/kg of body weight. Diabetes onset (D0) is considered with the first hyperglycemia level exceeding 2,5 g/L. This group was further divided into two subgroups: Group II-1: Experimental Gerbils, at acute state of diabetes (n=8) sacrificed after 02 days of diabetes onset, Group II-2: Experimental Gerbils at chronic state of diabetes (n=7) sacrificed after 30 days of diabetes onset. Two and 30 days after diabetes onset, gerbils had blood drawn from the retro-orbital sinus into EDTA tubes. After centrifugation at -4°C, plasma was frozen at -80°C for later measurement of Cortisol, ACTH, and insulin. Afterward, animals were decapitated; their brain was removed, weighed, fixed in aqueous bouin, and processed and stained with Toluidine Bleu stain for histo-stereological analysis. A comparison was done with control gerbils treated with citrate buffer. Results: Compared to control gerbils, at 02 Days post diabetes onset, the neuronal somata of the paraventricular (NPV) and supraoptic nuclei (NSO) expressed numerous vacuoles of various sizes, we distinct also a neuronal juxtaposition and several unidentifiable vacuolated profiles were also seen in the neuropile. At the same time, we revealed the presence of à shrunken and condensed nuclei, which seem to touch the parvocellular neurons ( NPV); this leads us to suggest the presence of an apoptotic process in the early stage of diabetes. At 30 days of diabetes mellitus, the NPV manifests a few neurons with a distant appearance, in addition the magnocellular neurons in both NPV and NSO were hypertrophied with a rich euchromatin nucleus, a well-defined nucleolus, and a granular cytoplasm. Despite the neuronal degeneration at this stage, unexpectedly, ACTH registers a continuous significant high level compared to the early stage of diabetes mellitus and to control gerbils. Conclusion: The results suggest that the induction of diabetes mellitus using STZ in the small gerbils lead to alterations in the structure and morphology of the hypothalamus and hyper-secretion of ACTH and cortisol, possibly indicating hyperactivity of the hypothalamo-pituitary adrenal axis (HPA) during both the early and later stages of the disease. The subsequent quantitative evaluation of CRH, immunehistochemical evaluation of apoptosis, and oxidative stress assessment could corroborate our results.

Keywords: diabetes type 1., streptozotocin., small gerbil., hypothalamus., paraventricular nucleus., supraoptic nucleus.

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73 The Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2)-derived Oncolytic Protein Reprograms Tumor-Associated Macrophages

Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

Abstract:

Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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72 High-Fidelity Materials Screening with a Multi-Fidelity Graph Neural Network and Semi-Supervised Learning

Authors: Akeel A. Shah, Tong Zhang

Abstract:

Computational approaches to learning the properties of materials are commonplace, motivated by the need to screen or design materials for a given application, e.g., semiconductors and energy storage. Experimental approaches can be both time consuming and costly. Unfortunately, computational approaches such as ab-initio electronic structure calculations and classical or ab-initio molecular dynamics are themselves can be too slow for the rapid evaluation of materials, often involving thousands to hundreds of thousands of candidates. Machine learning assisted approaches have been developed to overcome the time limitations of purely physics-based approaches. These approaches, on the other hand, require large volumes of data for training (hundreds of thousands on many standard data sets such as QM7b). This means that they are limited by how quickly such a large data set of physics-based simulations can be established. At high fidelity, such as configuration interaction, composite methods such as G4, and coupled cluster theory, gathering such a large data set can become infeasible, which can compromise the accuracy of the predictions - many applications require high accuracy, for example band structures and energy levels in semiconductor materials and the energetics of charge transfer in energy storage materials. In order to circumvent this problem, multi-fidelity approaches can be adopted, for example the Δ-ML method, which learns a high-fidelity output from a low-fidelity result such as Hartree-Fock or density functional theory (DFT). The general strategy is to learn a map between the low and high fidelity outputs, so that the high-fidelity output is obtained a simple sum of the physics-based low-fidelity and correction, Although this requires a low-fidelity calculation, it typically requires far fewer high-fidelity results to learn the correction map, and furthermore, the low-fidelity result, such as Hartree-Fock or semi-empirical ZINDO, is typically quick to obtain, For high-fidelity outputs the result can be an order of magnitude or more in speed up. In this work, a new multi-fidelity approach is developed, based on a graph convolutional network (GCN) combined with semi-supervised learning. The GCN allows for the material or molecule to be represented as a graph, which is known to improve accuracy, for example SchNet and MEGNET. The graph incorporates information regarding the numbers of, types and properties of atoms; the types of bonds; and bond angles. They key to the accuracy in multi-fidelity methods, however, is the incorporation of low-fidelity output to learn the high-fidelity equivalent, in this case by learning their difference. Semi-supervised learning is employed to allow for different numbers of low and high-fidelity training points, by using an additional GCN-based low-fidelity map to predict high fidelity outputs. It is shown on 4 different data sets that a significant (at least one order of magnitude) increase in accuracy is obtained, using one to two orders of magnitude fewer low and high fidelity training points. One of the data sets is developed in this work, pertaining to 1000 simulations of quinone molecules (up to 24 atoms) at 5 different levels of fidelity, furnishing the energy, dipole moment and HOMO/LUMO.

Keywords: .materials screening, computational materials, machine learning, multi-fidelity, graph convolutional network, semi-supervised learning

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71 Dimethyl fumarate Alleviates Valproic Acid-Induced Autism in Wistar Rats via Activating NRF-2 and Inhibiting NF-κB Pathways

Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar

Abstract:

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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70 Assessing Brain Targeting Efficiency of Ionisable Lipid Nanoparticles Encapsulating Cas9 mRNA/gGFP Following Different Routes of Administration in Mice

Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

Abstract:

Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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69 Confidence Envelopes for Parametric Model Selection Inference and Post-Model Selection Inference

Authors: I. M. L. Nadeesha Jayaweera, Adao Alex Trindade

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In choosing a candidate model in likelihood-based modeling via an information criterion, the practitioner is often faced with the difficult task of deciding just how far up the ranked list to look. Motivated by this pragmatic necessity, we construct an uncertainty band for a generalized (model selection) information criterion (GIC), defined as a criterion for which the limit in probability is identical to that of the normalized log-likelihood. This includes common special cases such as AIC & BIC. The method starts from the asymptotic normality of the GIC for the joint distribution of the candidate models in an independent and identically distributed (IID) data framework and proceeds by deriving the (asymptotically) exact distribution of the minimum. The calculation of an upper quantile for its distribution then involves the computation of multivariate Gaussian integrals, which is amenable to efficient implementation via the R package "mvtnorm". The performance of the methodology is tested on simulated data by checking the coverage probability of nominal upper quantiles and compared to the bootstrap. Both methods give coverages close to nominal for large samples, but the bootstrap is two orders of magnitude slower. The methodology is subsequently extended to two other commonly used model structures: regression and time series. In the regression case, we derive the corresponding asymptotically exact distribution of the minimum GIC invoking Lindeberg-Feller type conditions for triangular arrays and are thus able to similarly calculate upper quantiles for its distribution via multivariate Gaussian integration. The bootstrap once again provides a default competing procedure, and we find that similar comparison performance metrics hold as for the IID case. The time series case is complicated by far more intricate asymptotic regime for the joint distribution of the model GIC statistics. Under a Gaussian likelihood, the default in most packages, one needs to derive the limiting distribution of a normalized quadratic form for a realization from a stationary series. Under conditions on the process satisfied by ARMA models, a multivariate normal limit is once again achieved. The bootstrap can, however, be employed for its computation, whence we are once again in the multivariate Gaussian integration paradigm for upper quantile evaluation. Comparisons of this bootstrap-aided semi-exact method with the full-blown bootstrap once again reveal a similar performance but faster computation speeds. One of the most difficult problems in contemporary statistical methodological research is to be able to account for the extra variability introduced by model selection uncertainty, the so-called post-model selection inference (PMSI). We explore ways in which the GIC uncertainty band can be inverted to make inferences on the parameters. This is being attempted in the IID case by pivoting the CDF of the asymptotically exact distribution of the minimum GIC. For inference one parameter at a time and a small number of candidate models, this works well, whence the attained PMSI confidence intervals are wider than the MLE-based Wald, as expected.

Keywords: model selection inference, generalized information criteria, post model selection, Asymptotic Theory

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68 The Association between Gene Polymorphisms of GPX, SEPP1, and SEP15, Plasma Selenium Levels, Urinary Total Arsenic Concentrations, and Prostate Cancer

Authors: Yu-Mei Hsueh, Wei-Jen Chen, Yung-Kai Huang, Cheng-Shiuan Tsai, Kuo-Cheng Yeh

Abstract:

Prostate cancer occurs in men over the age of 50, and rank sixth of the top ten cancers in Taiwan, and the incidence increased gradually over the past decade in Taiwan. Arsenic is confirmed as a carcinogen by International Agency for Research on (IARC). Arsenic induces oxidative stress may be a risk factor for prostate cancer, but the mechanism is not clear. Selenium is an important antioxidant element. Whether the association between plasma selenium levels and risk of prostate cancer are modified by different genotype of selenoprotein is still unknown. Glutathione peroxidase, selenoprotein P (SEPP1) and 15 kDa selenoprotein (SEP 15) are selenoprotein and regulates selenium transport and the oxidation and reduction reaction. However, the association between gene polymorphisms of selenoprotein and prostate cancer is not yet clear. The aim of this study is to determine the relationship between plasma selenium, polymorphism of selenoprotein, urinary total arsenic concentration and prostate cancer. This study is a hospital-based case-control study. Three hundred twenty-two cases of prostate cancer and age (±5 years) 1:1 matched 322 control group were recruited from National Taiwan University Hospital, Taipei Medical University Hospital, and Wan Fang Hospital. Well-trained personnel carried out standardized personal interviews based on a structured questionnaire. Information collected included demographic and socioeconomic characteristics, lifestyle and disease history. Blood and urine samples were also collected at the same time. The Research Ethics Committee of National Taiwan University Hospital, Taipei, Taiwan, approved the study. All patients provided informed consent forms before sample and data collection. Buffy coat was to extract DNA, and the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) was used to measure the genotypes of SEPP1 rs3797310, SEP15 rs5859, GPX1 rs1050450, GPX2 rs4902346, GPX3 rs4958872, and GPX4 rs2075710. Plasma concentrations of selenium were determined by inductively coupled plasma mass spectrometry (ICP-MS).Urinary arsenic species concentrations were measured by high-performance liquid chromatography links hydride generator and atomic absorption spectrometer (HPLC-HG-AAS). Subject with high education level compared to those with low educational level had a lower prostate cancer odds ratio (OR) Mainland Chinese and aboriginal people had a lower OR of prostate cancer compared to Fukien Taiwanese. After adjustment for age, educational level, subjects with GPX1 rs1050450 CT and TT genotype compared to the CC genotype have lower, OR of prostate cancer, the OR and 95% confidence interval (Cl) was 0.53 (0.31-0.90). SEPP1 rs3797310 CT+TT genotype compared to those with CC genotype had a marginally significantly lower OR of PC. The low levels of plasma selenium and the high urinary total arsenic concentrations had the high OR of prostate cancer in a significant dose-response manner, and SEPP1 rs3797310 genotype modified this joint association.

Keywords: prostate cancer, plasma selenium concentration, urinary total arsenic concentrations, glutathione peroxidase, selenoprotein P, selenoprotein 15, gene polymorphism

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67 Numerical Investigation on Design Method of Timber Structures Exposed to Parametric Fire

Authors: Robert Pečenko, Karin Tomažič, Igor Planinc, Sabina Huč, Tomaž Hozjan

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Timber is favourable structural material due to high strength to weight ratio, recycling possibilities, and green credentials. Despite being flammable material, it has relatively high fire resistance. Everyday engineering practice around the word is based on an outdated design of timber structures considering standard fire exposure, while modern principles of performance-based design enable use of advanced non-standard fire curves. In Europe, standard for fire design of timber structures EN 1995-1-2 (Eurocode 5) gives two methods, reduced material properties method and reduced cross-section method. In the latter, fire resistance of structural elements depends on the effective cross-section that is a residual cross-section of uncharred timber reduced additionally by so called zero strength layer. In case of standard fire exposure, Eurocode 5 gives a fixed value of zero strength layer, i.e. 7 mm, while for non-standard parametric fires no additional comments or recommendations for zero strength layer are given. Thus designers often implement adopted 7 mm rule also for parametric fire exposure. Since the latest scientific evidence suggests that proposed value of zero strength layer can be on unsafe side for standard fire exposure, its use in the case of a parametric fire is also highly questionable and more numerical and experimental research in this field is needed. Therefore, the purpose of the presented study is to use advanced calculation methods to investigate the thickness of zero strength layer and parametric charring rates used in effective cross-section method in case of parametric fire. Parametric studies are carried out on a simple solid timber beam that is exposed to a larger number of parametric fire curves Zero strength layer and charring rates are determined based on the numerical simulations which are performed by the recently developed advanced two step computational model. The first step comprises of hygro-thermal model which predicts the temperature, moisture and char depth development and takes into account different initial moisture states of timber. In the second step, the response of timber beam simultaneously exposed to mechanical and fire load is determined. The mechanical model is based on the Reissner’s kinematically exact beam model and accounts for the membrane, shear and flexural deformations of the beam. Further on, material non-linear and temperature dependent behaviour is considered. In the two step model, the char front temperature is, according to Eurocode 5, assumed to have a fixed temperature of around 300°C. Based on performed study and observations, improved levels of charring rates and new thickness of zero strength layer in case of parametric fires are determined. Thus, the reduced cross section method is substantially improved to offer practical recommendations for designing fire resistance of timber structures. Furthermore, correlations between zero strength layer thickness and key input parameters of the parametric fire curve (for instance, opening factor, fire load, etc.) are given, representing a guideline for a more detailed numerical and also experimental research in the future.

Keywords: advanced numerical modelling, parametric fire exposure, timber structures, zero strength layer

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