Search results for: genetic optimization

Authors: Masaki Ohno, Cervinia Manalo, Tetsuji Okuda, Satoshi Nakai, Wataru Nishijima

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Reverse osmosis (RO) membranes have been widely used for desalination to purify water for drinking and other purposes. Although at present most RO membranes have no resistance to chlorine, chlorine-resistant membranes are being developed. Therefore, direct chlorine treatment or chlorine washing will be an option in preventing biofouling on chlorine-resistant membranes. Furthermore, if particle accumulation control is possible by using chlorine washing, expensive pretreatment for particle removal can be removed or simplified. The objective of this study was to determine the effective hypochlorite washing condition required for controlling biofilm formation and inorganic particle accumulation on RO membrane in a continuous flow channel with RO membrane and spacer. In this study, direct chlorine washing was done by soaking fouled RO membranes in hypochlorite solution and fluorescence intensity was used to quantify biofilm on the membrane surface. After 48 h of soaking the membranes in high fouling potential waters, the fluorescence intensity decreased to 0 from 470 using the following washing conditions: 10 mg/L chlorine concentration, 2 times/d washing interval, and 30 min washing time. The chlorine concentration required to control biofilm formation decreased as the chlorine concentration (0.5–10 mg/L), the washing interval (1–4 times/d), or the washing time (1–30 min) increased. For the sample solutions used in the study, 10 mg/L chlorine concentration with 2 times/d interval, and 5 min washing time was required for biofilm control. The optimum chlorine washing conditions obtained from soaking experiments proved to be applicable also in controlling biofilm formation in continuous flow experiments. Moreover, chlorine washing employed in controlling biofilm with suspended particles resulted in lower amounts of organic (0.03 mg/cm²) and inorganic (0.14 mg/cm²) deposits on the membrane than that for sample water without chlorine washing (0.14 mg/cm² and 0.33 mg/cm², respectively). The amount of biofilm formed was 79% controlled by continuous washing with 10 mg/L of free chlorine concentration, and the inorganic accumulation amount decreased by 58% to levels similar to that of pure water with kaolin (0.17 mg/cm²) as feed water. These results confirmed the acceleration of particle accumulation due to biofilm formation, and that the inhibition of biofilm growth can almost completely reduce further particle accumulation. In addition, effective hypochlorite washing condition which can control both biofilm formation and particle accumulation could be achieved.

Keywords: reverse osmosis, washing condition optimization, hypochlorous acid, biofouling control

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Authors: Anthony F. Peressini

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The concept of race has recently come prominently back into discussion in the context of medicine and medical science, along with renewed effort to biologize racial concepts. This paper argues that this renewed effort to biologize race by way of medicine and population genetics fail on their own terms, and more importantly, that the philosophical project of biologizing race ought to be recognized for what it is—a retrograde racial project—and abandoned. There is clear agreement that standard racial categories and concepts cannot be grounded in the old way of racial naturalism, which understand race as a real, interest-independent biological/metaphysical category in which its members share “physical, moral, intellectual, and cultural characteristics.” But equally clear is the very real and pervasive presence of racial concepts in individual and collective consciousness and behavior, and so it remains a pressing area in which to seek deeper understanding. Recent philosophical work has endeavored to reconcile these two observations by developing a “thin” conception of race, grounded in scientific concepts but without the moral and metaphysical content. Such “thin,” science-based analyses take the “commonsense” or “folk” sense of race as it functions in contemporary society as the starting point for their philosophic-scientific projects to biologize racial concepts. A “philosophic-scientific analysis” is a special case of the cornerstone of analytic philosophy: a conceptual analysis. That is, a rendering of a concept into the more perspicuous concepts that constitute it. Thus a philosophic-scientific account of a concept is an attempt to work out an analysis of a concept that makes use of empirical science's insights to ground, legitimate and explicate the target concept in terms of clearer concepts informed by empirical results. The focus in this paper is on three recent philosophic-scientific cases for retaining “race” that all share this general analytic schema, but that make use of “medical necessity,” population genetics, and human genetic clustering, respectively. After arguing that each of these three approaches suffers from internal difficulties, the paper considers the general analytic schema employed by such biologizations of race. While such endeavors are inevitably prefaced with the disclaimer that the theory to follow is non-essentialist and non-racialist, the case will be made that such efforts are not neutral scientific or philosophical projects but rather are what sociologists call a racial project, that is, one of many competing efforts that conjoin a representation of what race means to specific efforts to determine social and institutional arrangements of power, resources, authority, etc. Accordingly, philosophic-scientific biologizations of race, since they begin from and condition their analyses on “folk” conceptions, cannot pretend to be “prior to” other disciplinary insights, nor to transcend the social-political dynamics involved in formulating theories of race. As a result, such traditional philosophical efforts can be seen to be disciplinarily parochial and to address only a caricature of a large and important human problem—and thereby further contributing to the unfortunate isolation of philosophical thinking about race from other disciplines.

Keywords: population genetics, ontology of race, race-based medicine, racial formation theory, racial projects, racism, social construction

Procedia PDF Downloads 247

Authors: Govind Kumar

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The concept of ‘e-governance’ that was brought about by the new wave of reforms, namely ‘LPG’ in the early 1990s, has been enabling governments across the globe to digitally transform themselves. Digital transformation is leading the governments with qualitative decisions, optimization in rational use of resources, facilitation of cost-benefit analyses, and elimination of redundancy and corruption with the help of ICT-based applications interface. ICT-based applications/technologies have enormous potential for impacting positive change in the social lives of the global citizenry. Supercomputers test and analyze millions of drug molecules for developing candidate vaccines to combat the global pandemic. Further, e-commerce portals help distribute and supply household items and medicines, while videoconferencing tools provide a visual interface between the clients and hosts. Besides, crop yields are being maximized with the help of drones and machine learning, whereas satellite data, artificial intelligence, and cloud computing help governments with the detection of illegal mining, tackling deforestation, and managing freshwater resources. Such e-applications have the potential to take governance an extra mile by achieving 5 Es (effective, efficient, easy, empower, and equity) of e-governance and six Rs (reduce, reuse, recycle, recover, redesign and remanufacture) of sustainable development. If such digital transformation gains traction within the government framework, it will replace the traditional administration with the digitalization of public administration. On the other hand, it has brought in a new set of challenges, like the digital divide, e-illiteracy, technological divide, etc., and problems like handling e-waste, technological obsolescence, cyber terrorism, e-fraud, hacking, phishing, etc. before the governments. Therefore, it would be essential to bring in a rightful mixture of technological and humanistic interventions for addressing the above issues. This is on account of the reason that technology lacks an emotional quotient, and the administration does not work like technology. Both are self-effacing unless a blend of technology and a humane face are brought in into the administration. The paper will empirically analyze the significance of the technological framework of digital transformation within the government set up for the digitalization of public administration on the basis of the synthesis of two case studies undertaken from two diverse fields of administration and present a future framework of the study.

Keywords: digital transformation, electronic governance, public administration, knowledge framework

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Authors: Seyedeh Bahar Hashemi, Alireza Rahimi, Mehdi Arjmand

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Food is the source of energy and growth through the breakdown of its vital components and plays a vital role in human health and nutrition. Many natural compounds found in plant and animal materials play a special role in biological systems and the origin of many such compounds directly or indirectly is algae. Algae is an enormous source of polysaccharides and have gained much interest in human flourishing. In this study, algae biomass extraction is conducted using deep eutectic-based solvents (NADES) and Ultrasound-assisted extraction (UAE). The aim of this research is to extract bioactive compounds including total carotenoid, antioxidant activity, and polyphenolic contents. For this purpose, the influence of three important extraction parameters namely, biomass-to-solvent ratio, temperature, and time are studied with respect to their impact on the recovery of carotenoids, and phenolics, and on the extracts’ antioxidant activity. Here we employ the Response Surface Methodology for the process optimization. The influence of the independent parameters on each dependent is determined through Analysis of Variance. Our results show that Ultrasound-assisted extraction (UAE) for 50 min is the best extraction condition, and proline:lactic acid (1:1) and choline chloride:urea (1:2) extracts show the highest total phenolic contents (50.00 ± 0.70 mgGAE/gdw) and antioxidant activity [60.00 ± 1.70 mgTE/gdw, 70.00 ± 0.90 mgTE/gdw in 2.2-diphenyl-1-picrylhydrazyl (DPPH), and 2.2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)]. Our results confirm that the combination of UAE and NADES provides an excellent alternative to organic solvents for sustainable and green extraction and has huge potential for use in industrial applications involving the extraction of bioactive compounds from algae. This study is among the first attempts to optimize the effects of ultrasonic-assisted extraction, ultrasonic devices, and deep natural eutectic point and investigate their application in bioactive compounds extraction from algae. We also study the future perspective of ultrasound technology which helps to understand the complex mechanism of ultrasonic-assisted extraction and further guide its application in algae.

Keywords: natural deep eutectic solvents, ultrasound-assisted extraction, algae, antioxidant activity, phenolic compounds, carotenoids

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Authors: Carine Muster, Prina Howald Erika

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Today's ice rinks are important energy consumers for the production and maintenance of ice. At the same time, users demand that the other rooms should be tempered or heated. The building complex must equally provide cooled and heated zones, which does not translate as carbon-zero ice rinks. The study provides an analysis of how the civil engineering sector can significantly impact minimizing greenhouse gas emissions and optimizing synergies across an entire ice rink complex. The analysis focused on three distinct aspects: the layout, including the volumetric layout of the premises present in an ice rink; the materials chosen that can potentially use the most ecological structural approach; and the construction methods based on innovative solutions to reduce carbon footprint. The first aspect shows that the organization of the interior volumes and defining the shape of the rink play a significant role. Its layout makes the use and operation of the premises as efficient as possible, thanks to the differentiation between heated and cooled volumes while optimising heat loss between the different rooms. The sprayed concrete method, which is still little known, proves that it is possible to achieve the strength of traditional concrete for the structural aspect of the load-bearing and non-load-bearing walls of the ice rink by using materials excavated from the construction site and providing a more ecological and sustainable solution. The installation of an empty sanitary space underneath the ice floor, making it independent of the rest of the structure, provides a natural insulating layer, preventing the transfer of cold to the rest of the structure and reducing energy losses. The addition of active pipes as part of the foundation of the ice floor, coupled with a suitable system, gives warmth in the winter and storage in the summer; this is all possible thanks to the natural heat in the ground. In conclusion, this study provides construction recommendations for future ice rinks with a significantly reduced energy demand, using some simple preliminary design concepts. By optimizing the layout, materials, and construction methods of ice rinks, the civil engineering sector can play a key role in reducing greenhouse gas emissions and promoting sustainability.

Keywords: climate change, energy optimization, green building, sustainability

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Authors: Nicolas Bae, Theodore L. Karavasilis

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Increasingly, a large number of new and existing tall buildings are required to improve their resilient performance against strong winds and earthquakes to minimize direct, as well as indirect damages to society. Those advent stationary functions of tall building structures in metropolitan regions can be severely hazardous, in socio-economic terms, which also increase the requirement of advanced seismic performance. To achieve these progressive requirements, the seismic reinforcement for some old, conventional buildings have become enormously costly. The methods of increasing the buildings’ resilience against wind or earthquake loads have also become more advanced. Up to now, vibration control devices, such as the passive damper system, is still regarded as an effective and an easy-to-install option, in improving the seismic resilience of buildings at affordable prices. The main purpose of this paper is to examine 1) the optimization of the shape of visco plastic brace damper (VPBD) system which is one of hybrid damper system so that it can maximize its energy dissipation capacity in tall buildings against wind and earthquake. 2) the verification of the seismic performance of the visco plastic brace damper system in tall buildings; up to forty-storey high steel frame buildings, by comparing the results of Non-Linear Response History Analysis (NLRHA), with and without a damper system. The most significant contribution of this research is to introduce the optimized hybrid damper system that is adequate for high rise buildings. The efficiency of this visco plastic brace damper system and the advantages of its use in tall buildings can be verified since tall buildings tend to be affected by wind load at its normal state and also by earthquake load after yielding of steel plates. The modeling of the prototype tall building will be conducted using the Opensees software. Three types of modeling were used to verify the performance of the damper (MRF, MRF with visco-elastic, MRF with visco-plastic model) 22-set seismic records used and the scaling procedure was followed according to the FEMA code. It is shown that MRF with viscous, visco-elastic damper, it is superior effective to reduce inelastic deformation such as roof displacement, maximum story drift, roof velocity compared to the MRF only.

Keywords: tall steel building, seismic retrofit, viscous, viscoelastic damper, performance based design, resilience based design

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Authors: Lotanna Ezeonu, Jason P. Robbins, Ziyu Tang, Xiaofang Yang, Bruce E. Koel, Simon G. Podkolzin

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The interaction of organic molecules with metal surfaces is of interest in numerous technological applications, such as catalysis, bone replacement, and biosensors. Acetic acid is one of the main products of bio-oils produced from the pyrolysis of hemicellulosic feedstocks. However, their high oxygen content makes them unsuitable for use as fuels. Hydrodeoxygenation is a proven technique for catalytic deoxygenation of bio-oils. An understanding of the energetics and control of the bond-breaking sequences of biomass-derived oxygenates on metal surfaces will enable a guided optimization of existing catalysts and the development of more active/selective processes for biomass transformations to fuels. Such investigations have been carried out with the aid of ultrahigh vacuum and its concomitant techniques. The high catalytic activity of platinum in biomass-derived oxygenate transformations has sparked a lot of interest. We herein exploit infrared reflection absorption spectroscopy(IRAS), temperature-programmed desorption(TPD), and density functional theory(DFT) to study the adsorption and decomposition of acetic acid on a Pt(111) surface, which was then compared with Ni(111), a model non-noble metal. We found that acetic acid adsorbs molecularly on the Pt(111) surface, interacting through the lone pair of electrons of one oxygen atomat 90 K. At 140 K, the molecular form is still predominant, with some dissociative adsorption (in the form of acetate and hydrogen). Annealing to 193 K led to complete dehydrogenation of molecular acetic acid species leaving adsorbed acetate. At 440 K, decomposition of the acetate species occurs via decarbonylation and decarboxylation as evidenced by desorption peaks for H₂,CO, CO₂ and CHX fragments (x=1, 2) in theTPD.The assignments for the experimental IR peaks were made using visualization of the DFT-calculated vibrational modes. The results showed that acetate adsorbs in a bridged bidentate (μ²η²(O,O)) configuration. The coexistence of linear and bridge bonded CO was also predicted by the DFT results. Similar molecular acid adsorption energy was predicted in the case of Ni(111) whereas a significant difference was found for acetate adsorption.

Keywords: acetic acid, platinum, nickel, infared-absorption spectrocopy, temperature programmed desorption, density functional theory

Procedia PDF Downloads 83

Authors: Banafsheh Nikmehr, Mohsen Bahrami, Yueqiang Song, Anuradha Koduru, Ayse K. Vuruskan, Hongkun Lu, Mallory Pitts, Tolga B. Mesen, Tamer M. Yalcinkaya

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The number of people who receive in vitro fertilization (IVF) treatment has increased on a startling trajectory over the past two decades. Despite advances in this field, particularly the introduction of intracytoplasmic sperm injection (ICSI) and the preimplantation genetic screening (PGS), the IVF success remains low. A major factor contributing to IVF failure is embryonic aneuploidy (abnormal chromosome content), which often results in miscarriage and birth defects. Although PGS is often used as the standard diagnostic tool to identify aneuploid embryos, it is an invasive approach that could affect the embryo development, and yet inaccessible to many patients due its high costs. As such, there is a clear need for a non-invasive cost-effective approach to identify euploid embryos for single embryo transfer (SET). The reported differences between morphokinetic behaviors of aneuploid and euploid embryos has shown promise to address this need. However, current literature is inconclusive and further research is urgently needed to translate current findings into clinical diagnostics. In this ongoing study, we found significant differences between morphokinetic behaviors of euploid and aneuploid embryos that provides important insights and reaffirms the promise of such behaviors for developing non-invasive methodologies. Methodology—A total of 242 embryos (euploid: 149, aneuploid: 93) from 74 patients who underwent IVF treatment in Carolinas Fertility Clinics in Winston-Salem, NC, were analyzed. All embryos were incubated in an EmbryoScope incubator. The patients were randomly selected from January 2019 to June 2021 with most patients having both euploid and aneuploid embryos. All embryos reached the blastocyst stage and had known PGS outcomes. The ploidy assessment was done by a third-party testing laboratory on day 5-7 embryo biopsies. The morphokinetic variables of each embryo were measured by the EmbryoViewer software (Uniesense FertiliTech) on time-lapse images using 7 focal depths. We compared the time to: pronuclei fading (tPNf), division to 2,3,…,9 cells (t2, t3,…,t9), start of embryo compaction (tSC), Morula formation (tM), start of blastocyst formation (tSC), blastocyst formation (tB), and blastocyst expansion (tEB), as well as intervals between them (e.g., c23 = t3 – t2). We used a mixed regression method for our statistical analyses to account for the correlation between multiple embryos per patient. Major Findings— The average age of the patients was 35.04 yrs. The average patient age associated with euploid and aneuploid embryos was not different (P = 0.6454). We found a significant difference in c45 = t5-t4 (P = 0.0298). Our results indicated this interval on average lasts significantly longer for aneuploid embryos - c45(aneuploid) = 11.93hr vs c45(euploid) = 7.97hr. In a separate analysis limited to embryos from the same patients (patients = 47, total embryos=200, euploid=112, aneuploid=88), we obtained the same results (P = 0.0316). The statistical power for this analysis exceeded 87%. No other variable was different between the two groups. Conclusion— Our results demonstrate the importance of morphokinetic variables as potential biomarkers that could aid in non-invasively characterizing euploid and aneuploid embryos. We seek to study a larger population of embryos and incorporate the embryo quality in future studies.

Keywords: IVF, embryo, euploidy, aneuploidy, morphokinteic

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Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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

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

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

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Authors: Ayat-Allah Bouramdane

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Since 2010, there have been sustained decreases in the unit costs of onshore wind energy and large increases in its deployment, varying widely across regions. In fact, the onshore wind production is affected by air density— because cold air is more dense and therefore more effective at producing wind power— and by wind speed—as wind turbines cannot operate in very low or extreme stormy winds. The wind speed is essentially affected by the surface friction or the roughness and other topographic features of the land, which slow down winds significantly over the continent. Hence, the identification of the most appropriate locations of onshore wind systems is crucial to maximize their energy output and therefore minimize their Levelized Cost of Electricity (LCOE). This study focuses on the preliminary assessment of onshore wind energy potential, in several areas in Morocco with a particular focus on the Dakhla city, by analyzing the diurnal and seasonal variability of wind speed for different hub heights, the frequency distribution of wind speed, the wind rose and the wind performance indicators such as wind power density, capacity factor, and LCOE. In addition to climate criterion, other criteria (i.e., topography, location, environment) were selected fromGeographic Referenced Information (GRI), reflecting different considerations. The impact of each criterion on the suitability map of onshore wind farms was identified using the Analytic Hierarchy Process (AHP). We find that the majority of suitable zones are located along the Atlantic Ocean and the Mediterranean Sea. We discuss the sensitivity of the onshore wind site suitability to different aspects such as the methodology—by comparing the Multi-Criteria Decision-Making (MCDM)-AHP results to the Mean-Variance Portfolio optimization framework—and the potential impact of climate change on this suitability map, and provide the final recommendations to the Moroccan energy strategy by analyzing if the actual Morocco's onshore wind installations are located within areas deemed suitable. This analysis may serve as a decision-making framework for cost-effective investment in onshore wind power in Morocco and to shape the future sustainable development of the Dakhla city.

Keywords: analytic hierarchy process (ahp), dakhla, geographic referenced information, morocco, multi-criteria decision-making, onshore wind, site suitability.

Procedia PDF Downloads 139

Authors: Nisha Sharma, Mili Kaur, Ashutosh Halder, Seema Kaushal, Manoj Kumar, Manish Jain

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Purpose: To investigate microRNAs (miRNA) as an epigenomic etiological factor in idiopathic non-obstructive azoospermia (NOA). In order to achieve the same, an association was seen between occupational exposure to radiation, thermal, and chemical factors and idiopathic cases of non-obstructive azoospermia, and later, testicular differential miRNA expression profiling was done in exposure group NOA cases. Method: It is a prospective study in which 200 apparent idiopathic male factor infertility cases, who have been advised to undergo testicular fine needle aspiration (FNA) evaluation, are recruited. A detailed occupational history was taken to understand the possible type of exposure due to the nature and duration of work. A total of 26 patients were excluded upon XY-FISH and Yq microdeletion tests due to the presence of genetic causes of infertility, 6 hypospermatogeneis (HS), six Sertoli cell-only syndrome (SCOS), and six normospermatogeneis patients testicular FNA samples were used for RNA isolation followed by small RNA sequencing and nCounter miRNA expression analysis. Differential miRNA expression profile of HS and SCOS patients was done. A web-based tool, miRNet, was used to predict the interacting compounds or chemicals using the shortlisted miRNAs with high fold change. The major limitation encountered in this study was the insufficient quantity of testicular FNA sample used for total RNA isolation, which resulted in a low yield and RNA integrity number (RIN) value. Therefore, the number of RNA samples admissible for differential miRNA expression analysis was very small in comparison to the total number of patients recruited. Results: Differential expression analysis revealed 69 down-regulated and 40 up-regulated miRNAs in HS and 66 down-regulated and 33 up-regulated miRNAs in SCOS in comparison to normospermatogenesis controls. The miRNA interaction analysis using the miRNet tool showed that the differential expression profiles of HS and SCOS patients were associated with arsenic trioxide, bisphenol-A, calcium sulphate, lithium, and cadmium. These compounds are reproductive toxins and might be responsible for miRNA-mediated epigenetic deregulation leading to NOA. The association between occupational risk factor exposure and the non-exposure group of NOA patients was not statistically significant, with ꭓ2 (3, N= 178) = 6.70, p= 0.082. The association between individual exposure groups (radiation, thermal, and chemical) and various sub-types of NOA is also not significant, with ꭓ2 (9, N= 178) = 15.06, p= 0.089. Functional analysis of HS and SCOS patients' miRNA profiles revealed some important miR-family members in terms of male fertility. The miR-181 family plays a role in the differentiation of spermatogonia and spermatocytes, as well as the transcriptional regulation of haploid germ cells. The miR-34 family is expressed in spermatocytes and round spermatids and is involved in the regulation of SSCs differentiation. Conclusion: The reproductive toxins might adopt the miRNA-mediated mechanism of disease development in idiopathic cases of NOA. Chemical compound induced; miRNA-mediated epigenetic deregulation can give a future perspective on the etiopathogenesis of the disease.

Keywords: microRNA, non-obstructive azoospermia (NOA), occupational exposure, hypospermatogenesis (HS), Sertoli cell only syndrome (SCOS)

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Authors: Moses Kolade Ogun, Ina Korner

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To improve on the sustainable resource management in the wastepaper recycling industry, studies into the valorization of wastes generated by the industry are necessary. The industry produces different residues, among which is the deinking sludge (DS). The DS is generated from the deinking process and constitutes a major fraction of the residues generated by the European pulp and paper industry. The traditional treatment of DS by incineration is capital intensive due to energy requirement for dewatering and the need for complementary fuel source due to DS low calorific value. This could be replaced by a biotechnological approach. This study, therefore, investigated the biogas potential of different DS streams (different dewatering degrees) and the influence of the high calcium carbonate content of DS on its biogas potential. Dewatered DS (solid fraction) sample from filter press and the filtrate (liquid fraction) were collected from a partner wastepaper recycling company in Germany. The solid fraction and the liquid fraction were mixed in proportion to realize DS with different water content (55–91% fresh mass). Spiked samples of DS using deionized water, cellulose and calcium carbonate were prepared to simulate DS with varying calcium carbonate content (0– 40% dry matter). Seeding sludge was collected from an existing biogas plant treating sewage sludge in Germany. Biogas potential was studied using a 1-liter batch test system under the mesophilic condition and ran for 21 days. Specific biogas potential in the range 133- 230 NL/kg-organic dry matter was observed for DS samples investigated. It was found out that an increase in the liquid fraction leads to an increase in the specific biogas potential and a reduction in the absolute biogas potential (NL-biogas/ fresh mass). By comparing the absolute biogas potential curve and the specific biogas potential curve, an optimal dewatering degree corresponding to a water content of about 70% fresh mass was identified. This degree of dewatering is a compromise when factors such as biogas yield, reactor size, energy required for dewatering and operation cost are considered. No inhibitory influence was observed in the biogas potential of DS due to the reported high calcium carbonate content of DS. This study confirms that DS is a potential bioresource for biogas production. Further optimization such as nitrogen supplementation due to DS high C/N ratio can increase biogas yield.

Keywords: biogas, calcium carbonate, deinking sludge, dewatering, water content

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Authors: Sophie Lemoussu, Jean-Charles Chaudemar, Robertus A. Vingerhoeds

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Many innovative projects exist in the field of aeronautics, each addressing specific areas so to reduce weight, increase autonomy, reduction of CO2, etc. In many cases, such innovative developments are being carried out by very small enterprises (VSE’s) or small and medium sized-enterprises (SME’s). A good example concerns airships that are being studied as a real alternative to passenger and cargo transportation. Today, no international regulations propose a precise and sufficiently detailed framework for the development and certification of airships. The absence of such a regulatory framework requires a very close contact with regulatory instances. However, VSE’s/SME’s do not always have sufficient resources and internal knowledge to handle this complexity and to discuss these issues. This poses an additional challenge for those VSE’s/SME’s, in particular those that have system integration responsibilities and that must provide all the necessary evidence to demonstrate their ability to design, produce, and operate airships with the expected level of safety and reliability. The main objective of this research is to provide a methodological framework enabling VSE’s/SME’s with limited resources to organize the development of airships while taking into account the constraints of safety, cost, time and performance. This paper proposes to provide a contribution to this problematic by proposing a Model-Based Systems Engineering approach. Through a comprehensive process modeling approach applied to the development processes, the regulatory constraints, existing best practices, etc., a good image can be obtained as to the process landscape that may influence the development of airships. To this effect, not only the necessary regulatory information is taken on board, also other international standards and norms on systems engineering and project management are being modeled and taken into account. In a next step, the model can be used for analysis of the specific situation for given developments, derive critical paths for the development, identify eventual conflicting aspects between the norms, standards, and regulatory expectations, or also identify those areas where not enough information is available. Once critical paths are known, optimization approaches can be used and decision support techniques can be applied so to better support VSE’s/SME’s in their innovative developments. This paper reports on the adopted modeling approach, the retained modeling languages, and how they all fit together.

Keywords: aeronautics, certification, process modeling, project management, regulation, SME, systems engineering, VSE

Procedia PDF Downloads 139

Authors: Lucie Matricon, Anne Roubaud, Geert Haarlemmer, Christophe Geantet

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

Keywords: microalgae, biofuels, hydrothermal liquefaction, biomass

Procedia PDF Downloads 112

Authors: Magdalena Igras, Joanna Grzybowska, Mariusz Ziółko

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The study of emotions expressed in emergency phone call is presented, covering both statistical analysis of emotions configurations and an attempt to automatically classify emotions. An emergency call is a situation usually accompanied by intense, authentic emotions. They influence (and may inhibit) the communication between caller and responder. In order to support responders in their responsible and psychically exhaustive work, we studied when and in which combinations emotions appeared in calls. A corpus of 45 hours of conversations (about 3300 calls) from emergency call center was collected. Each recording was manually tagged with labels of emotions valence (positive, negative or neutral), type (sadness, tiredness, anxiety, surprise, stress, anger, fury, calm, relief, compassion, satisfaction, amusement, joy) and arousal (weak, typical, varying, high) on the basis of perceptual judgment of two annotators. As we concluded, basic emotions tend to appear in specific configurations depending on the overall situational context and attitude of speaker. After performing statistical analysis we distinguished four main types of emotional behavior of callers: worry/helplessness (sadness, tiredness, compassion), alarm (anxiety, intense stress), mistake or neutral request for information (calm, surprise, sometimes with amusement) and pretension/insisting (anger, fury). The frequency of profiles was respectively: 51%, 21%, 18% and 8% of recordings. A model of presenting the complex emotional profiles on the two-dimensional (tension-insecurity) plane was introduced. In the stage of acoustic analysis, a set of prosodic parameters, as well as Mel-Frequency Cepstral Coefficients (MFCC) were used. Using these parameters, complex emotional states were modeled with machine learning techniques including Gaussian mixture models, decision trees and discriminant analysis. Results of classification with several methods will be presented and compared with the state of the art results obtained for classification of basic emotions. Future work will include optimization of the algorithm to perform in real time in order to track changes of emotions during a conversation.

Keywords: acoustic analysis, complex emotions, emotion recognition, machine learning

Procedia PDF Downloads 373

Authors: Adel A. Ghobbar, Varun Raman

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The Corrective maintenance of components and systems is a problem plaguing almost every industry in the world today. Train operators’ and the maintenance repair and overhaul subsidiary of the Dutch railway company is also facing this problem. A considerable portion of the maintenance activities carried out by the company are unscheduled. This, in turn, severely stresses and stretches the workforce and resources available. One possible solution is to have a robust preventive maintenance plan. The other possible solution is to plan maintenance based on real-time data obtained from sensor-based ‘Health and Usage Monitoring Systems.’ The former has been investigated in this paper. The preventive maintenance model developed for train operator will subsequently be extended, to tackle the unscheduled maintenance problem also affecting the aerospace industry. The extension of the model to the aerospace sector will be dealt with in the second part of the research, and it would, in turn, validate the soundness of the model developed. Thus, there are distinct areas that will be addressed in this paper, including the mathematical modelling of preventive maintenance and optimization based on cost and system availability. The results of this research will help an organization to choose the right maintenance strategy, allowing it to save considerable sums of money as opposed to overspending under the guise of maintaining high asset availability. The concept of delay time modelling was used to address the practical problem of unscheduled maintenance in this paper. The delay time modelling can be used to help with support planning for a given asset. The model was run using MATLAB, and the results are shown that the ideal inspection intervals computed using the extended from a minimal cost perspective were 29 days, and from a minimum downtime, perspective was 14 days. Risk matrix integration was constructed to represent the risk in terms of the probability of a fault leading to breakdown maintenance and its consequences in terms of maintenance cost. Thus, the choice of an optimal inspection interval of 29 days, resulted in a cost of approximately 50 Euros and the corresponding value of b(T) was 0.011. These values ensure that the risk associated with component X being maintained at an inspection interval of 29 days is more than acceptable. Thus, a switch in maintenance frequency from 90 days to 29 days would be optimal from the point of view of cost, downtime and risk.

Keywords: delay time modelling, unscheduled maintenance, reliability, maintainability, availability

Procedia PDF Downloads 113

Authors: Joseph Fitoussi, Mohammadali Shirinbayan, Abbas Tcharkhtchi

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Due to material flow during processing, short fiber reinforced composites structures obtained by injection or compression molding generally present strong spatial microstructure variation. On the other hand, quasi-static, dynamic, and fatigue behavior of these materials are highly dependent on microstructure parameters such as fiber orientation distribution. Indeed, because of complex damage mechanisms, SFRC structures design is a key challenge for safety and reliability. In this paper, we propose a micromechanical model allowing prediction of damage behavior of real structures as a function of microstructure spatial distribution. To this aim, a statistical damage criterion including strain rate and fatigue effect at the local scale is introduced into a Mori and Tanaka model. A critical local damage state is identified, allowing fatigue life prediction. Moreover, the multi-scale model is coupled with an experimental intrinsic link between damage under monotonic loading and fatigue life in order to build an abacus giving Tsai-Wu failure criterion parameters as a function of microstructure and targeted fatigue life. On the other hand, the micromechanical damage model gives access to the evolution of the anisotropic stiffness tensor of SFRC submitted to complex thermomechanical loading, including quasi-static, dynamic, and cyclic loading with temperature and amplitude variations. Then, the latter is used to fill out microstructure dependent material cards in finite element analysis for design optimization in the case of complex loading history. The proposed methodology is illustrated in the case of a real automotive component made of sheet molding compound (PSA 3008 tailgate). The obtained results emphasize how the proposed micromechanical methodology opens a new path for the automotive industry to lighten vehicle bodies and thereby save energy and reduce gas emission.

Keywords: short fiber reinforced composite, structural design, damage, micromechanical modelling, fatigue, strain rate effect

Procedia PDF Downloads 88

Authors: Ishani Maheshika

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The intermediary role performed by freight forwarders in exportation has become significant in fulfilling businesses’ supply chain needs in this dynamic world. Since the success of exporter’s business is at present, highly reliant on supply chain optimization, cost efficiency, profitability, consistent service and responsiveness, the decision of selecting the most beneficial freight forwarder has become crucial for exporters. Although there are similar foreign researches, prior researches covering Sri Lankan setting are not in existence. Moreover, results vary with time, nature of industry and business environment factors. Therefore, a study from the perspective of Sri Lankan exporters was identified as a requisite to be researched. In order to identify and prioritize key factors which have affected the exporter’s decision in selecting freight forwarders in Sri Lankan context, Sri Lankan export industry was stratified into 22 sectors based on commodity using stratified sampling technique. One exporter from each sector was then selected using judgmental sampling to have a sample of 22. Factors which were identified through a pilot survey, was organized under 6 main criteria. A questionnaire was basically developed as pairwise comparisons using 9-point semantic differential scale and comparisons were done within main criteria and subcriteria. After a pre-testing, interviews and e-mail questionnaire survey were conducted. Data were analyzed using Analytic Hierarchy Process to determine priority vectors of criteria. Customer service was found to be the most important main criterion for Sri Lankan exporters. It was followed by reliability and operational efficiency respectively. The criterion of the least importance is company background and reputation. Whereas small sized exporters pay more attention to rate, reliability is the major concern among medium and large scale exporters. Irrespective of seniority of the exporter, reliability is given the prominence. Responsiveness is the most important sub criterion among Sri Lankan exporters. Consistency of judgments with respect to main criteria was verified through consistency ratio, which was less than 10%. Being more competitive, freight forwarders should come up with customized marketing strategies based on each target group’s requirements and expectations in offering services to retain existing exporters and attract new exporters.

Keywords: analytic hierarchy process, freight forwarders, main criteria, Sri Lankan exporters, subcriteria

Procedia PDF Downloads 386

Authors: Amal G. Kurian

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The use of mathematical modeling has seen a considerable boost in recent times with the development of many advanced algorithms and mathematical modeling capabilities. The advantages this method has over other methods are that they are much closer to standard physics theories and thus represent a better theoretical model. They take lesser solving time and have the ability to change various parameters for optimization, which is a big advantage, especially in automotive industry. This thesis work focuses on a thorough investigation of the effects of vehicle speed and road roughness on a heavy commercial vehicle ride and structural dynamic responses. Since commercial vehicles are kept in operation continuously for longer periods of time, it is important to study effects of various physical conditions on the vehicle and its user. For this purpose, various experimental as well as simulation methodologies, are adopted ranging from experimental transfer path analysis to various road scenario simulations. To effectively investigate and eliminate several causes of unwanted responses, an efficient and robust technique is needed. Carrying forward this motivation, the present work focuses on the development of a mathematical model of a 4-axle configuration heavy commercial vehicle (HCV) capable of calculating responses of the vehicle on different road PSD inputs and vehicle speeds. Outputs from the model will include response transfer functions and PSDs and wheel forces experienced. A MATLAB code will be developed to implement the objectives in a robust and flexible manner which can be exploited further in a study of responses due to various suspension parameters, loading conditions as well as vehicle dimensions. The thesis work resulted in quantifying the effect of various physical conditions on ride comfort of the vehicle. An increase in discomfort is seen with velocity increase; also the effect of road profiles has a considerable effect on comfort of the driver. Details of dominant modes at each frequency are analysed and mentioned in work. The reduction in ride height or deflection of tire and suspension with loading along with load on each axle is analysed and it is seen that the front axle supports a greater portion of vehicle weight while more of payload weight comes on fourth and third axles. The deflection of the vehicle is seen to be well inside acceptable limits.

Keywords: mathematical modeling, HCV, suspension, ride analysis

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Authors: Hanjun Hu, Jinxiang Zhang

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With the decline of "growthism", China's urbanization process has shifted from the stage of spatial expansion to the stage of optimization of built-up spaces, and urban renewal has gradually become a new wave of China's urban movement in recent years. The ongoing urban renewal movement in China not only needs to generate new motivation for urban development but also solve the backlog of social problems caused by rapid urbanization, which provides an opportunity for the transformation of China's urban governance model. Unlike previous approaches that focused on physical space and functional renewal, such as urban reconstruction, redevelopment, and reuse, the key challenge of urban renewal in the post-growth era lies in coordinating the complex interest relationships between multiple stakeholders. The traditional theoretical frameworks that focus on the structural relations between social groups are insufficient to explain the behavior logic and mutual cooperation mechanism of various groups and individuals in the current urban renewal practices. Therefore, based on the long-term tracking of the urban renewal practices in the Old City of Nanjing (OCN), this paper introduces the "collective action" theory to deeply analyze changes in the urban renewal governance model in OCN and tries to summarize the governance strategies that promote the formation of collective action within recent practices from a micro-scale. The study found that the practice in OCN experienced three different stages "government-led", "growth coalition" and "asymmetric game". With the transformation of government governance concepts, the rise of residents' consciousness of rights, and the wider participation of social organizations in recent years, the urban renewal in OCN is entering a new stage of "collective renewal action". Through the establishment of the renewal organization model, incentive policies, and dynamic negotiation mechanism, urban renewal in OCN not only achieves a relative balance between individual interests and collective interests but also makes the willingness of residents the dominant factor in formulating urban renewal policies. However, the presentation of "collective renewal action" in OCN is still mainly based on typical cases. Although the government is no longer the dominant role, a large number of resident-led collective actions have not yet emerged, which puts forward new research needs for a sustainable governance policy innovation in this action.

Keywords: urban renewal, collective action theory, governance, cooperation mechanism, China

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Authors: Yena Lee, Vassilis M. Charitopoulos, Karthik Thyagarajan, Ian Morris, Jose M. Pinto, Lazaros G. Papageorgiou

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With globalisation, the need to have better coordination of production and distribution decisions has become increasingly important for industrial gas companies in order to remain competitive in the marketplace. In this work, we investigate a problem that integrates production, inventory, and routing decisions in a liquid oxygen supply chain. The oxygen supply chain consists of production facilities, external third-party suppliers, and multiple customers, including hospitals and industrial customers. The product produced by the plants or sourced from the competitors, i.e., third-party suppliers, is distributed by a fleet of heterogenous vehicles to satisfy customer demands. The objective is to minimise the total operating cost involving production, third-party, and transportation costs. The key decisions for production include production and inventory levels and product amount from third-party suppliers. In contrast, the distribution decisions involve customer allocation, delivery timing, delivery amount, and vehicle routing. The optimisation of the coordinated production, inventory, and routing decisions is a challenging problem, especially when dealing with large-size problems. Thus, we present a two-stage procedure to solve the integrated problem efficiently. First, the problem is formulated as a mixed-integer linear programming (MILP) model by simplifying the routing component. The solution from the first-stage MILP model yields the optimal customer allocation, production and inventory levels, and delivery timing and amount. Then, we fix the previous decisions and solve a detailed routing. In the second stage, we propose a column generation scheme to address the computational complexity of the resulting detailed routing problem. A case study considering a real-life oxygen supply chain in the UK is presented to illustrate the capability of the proposed models and solution method. Furthermore, a comparison of the solutions from the proposed approach with the corresponding solutions provided by existing metaheuristic techniques (e.g., guided local search and tabu search algorithms) is presented to evaluate the efficiency.

Keywords: production planning, inventory routing, column generation, mixed-integer linear programming

Procedia PDF Downloads 95

Authors: Peter O. Osifo, Hein W. J. P. Neomagus, Hein V. D. Merwe

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Chitosan materials from different sources of raw materials were characterized in order to determine optimal preparation conditions and parameters for membrane production. The membrane parameters such as molecular weight, viscosity, and degree of deacetylation were used to evaluate the membrane performance for zinc ion adsorption. The molecular weight of the chitosan was found to influence the viscosity of the chitosan/acetic acid solution. An increase in molecular weight (60000-400000 kg.kmol-1) of the chitosan resulted in a higher viscosity (0.05-0.65 Pa.s) of the chitosan/acetic acid solution. The effect of the degree of deacetylation on the viscosity is not significant. The effect of the membrane production parameters (chitosan- and acetic acid concentration) on the viscosity is mainly determined by the chitosan concentration. For higher chitosan concentrations, a membrane with a better adsorption capacity was obtained. The membrane adsorption capacity increases from 20-130 mg Zn per gram of wet membrane for an increase in chitosan concentration from 2-7 mass %. Chitosan concentrations below 2 and above 7.5 mass % produced membranes that lack good mechanical properties. The optimum manufacturing conditions including chitosan concentration, acetic acid concentration, sodium hydroxide concentration and crosslinking for chitosan membranes within the workable range were defined by the criteria of adsorption capacity and flux. The adsorption increases (50-120 mg.g-1) as the acetic acid concentration increases (1-7 mass %). The sodium hydroxide concentration seems not to have a large effect on the adsorption characteristics of the membrane however, a maximum was reached at a concentration of 5 mass %. The adsorption capacity per gram of wet membrane strongly increases with the chitosan concentration in the acetic acid solution but remains constant per gram of dry chitosan. The optimum solution for membrane production consists of 7 mass % chitosan and 4 mass % acetic acid in de-ionised water. The sodium hydroxide concentration for phase inversion is at optimum at 5 mass %. The optimum cross-linking time was determined to be 6 hours (Percentage crosslinking of 18%). As the cross-linking time increases the adsorption of the zinc decreases (150-50 mg.g-1) in the time range of 0 to 12 hours. After a crosslinking time of 12 hours, the adsorption capacity remains constant. This trend is comparable to the effect on flux through the membrane. The flux decreases (10-3 L.m-2.hr-1) with an increase in crosslinking time range of 0 to 12 hours and reaches a constant minimum after 12 hours.

Keywords: chitosan, membrane, waste water, heavy metal ions, adsorption

Procedia PDF Downloads 359

Authors: Suehyun Cho, Darrell Harrington, Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Alex Kiselyov, Michael Shpigelmacher

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The Dandy-Walker malformation (DWM) represents a clinical syndrome manifesting as a combination of posterior fossa cyst, hypoplasia of the cerebellar vermis, and obstructive hydrocephalus. Anatomic hallmarks include hypoplasia of the cerebellar vermis, enlargement of the posterior fossa, and cystic dilatation of the fourth ventricle. Current treatments of DWM, including shunting of the cerebral spinal fluid ventricular system and endoscopic third ventriculostomy (ETV), are frequently clinically insufficient, require additional surgical interventions, and carry risks of infections and neurological deficits. Bionaut Labs develops an alternative way to treat Dandy-Walker Malformation (DWM) associated with non-communicating hydrocephalus. We utilize our discreet microsurgical Bionaut™ particles that are controlled externally and remotely to perform safe, accurate, effective fenestration of the Dandy-Walker cyst, specifically in the posterior fossa of the brain, to directly normalize intracranial pressure. Bionaut™ allows for complex non-linear trajectories not feasible by any conventional surgical techniques. The microsurgical particle safely reaches targets in the lower occipital section of the brain. Bionaut™ offers a minimally invasive surgical alternative to highly involved posterior craniotomy or shunts via direct fenestration of the fourth ventricular cyst at the locus defined by the individual anatomy. Our approach offers significant advantages over the current standards of care in patients exhibiting anatomical challenge(s) as a manifestation of DWM, and therefore, is intended to replace conventional therapeutic strategies. Current progress, including platform optimization, Bionaut™ control, and real-time imaging and in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of ovine models, will be discussed.

Keywords: Bionaut™, cerebral spinal fluid, CSF, cyst, Dandy-Walker, fenestration, hydrocephalus, micro-robot

Procedia PDF Downloads 198

Authors: Ella Tyuryumina, Alexey Neznanov

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Finding algorithms to predict the growth of tumors has piqued the interest of researchers ever since the early days of cancer research. A number of studies were carried out as an attempt to obtain reliable data on the natural history of breast cancer growth. Mathematical modeling can play a very important role in the prognosis of tumor process of breast cancer. However, mathematical models describe primary tumor growth and metastases growth separately. Consequently, we propose a mathematical growth model for primary tumor and primary metastases which may help to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoM-IV and corresponding software. We are interested in: 1) modelling the whole natural history of primary tumor and primary metastases; 2) developing adequate and precise CoM-IV which reflects relations between PT and MTS; 3) analyzing the CoM-IV scope of application; 4) implementing the model as a software tool. The CoM-IV is based on exponential tumor growth model and consists of a system of determinate nonlinear and linear equations; corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and primary metastases: 1) ‘non-visible period’ for primary tumor; 2) ‘non-visible period’ for primary metastases; 3) ‘visible period’ for primary metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. Thus, the CoM-IV model and predictive software: a) detect different growth periods of primary tumor and primary metastases; b) make forecast of the period of primary metastases appearance; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of BC and facilitate optimization of diagnostic tests. The following are calculated by CoM-IV: the number of doublings for ‘nonvisible’ and ‘visible’ growth period of primary metastases; tumor volume doubling time (days) for ‘nonvisible’ and ‘visible’ growth period of primary metastases. The CoM-IV enables, for the first time, to predict the whole natural history of primary tumor and primary metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-IV describes correctly primary tumor and primary distant metastases growth of IV (T1-4N0-3M1) stage with (N1-3) or without regional metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and manifestation of primary metastases.

Keywords: breast cancer, exponential growth model, mathematical modelling, primary metastases, primary tumor, survival

Procedia PDF Downloads 317

Authors: Mariam Khaled, Noha Farag, Ghada Mohamed Abdel Salam, Khaled Abu-Aisha, Mohamed El-Azizi

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Gastric and colorectal cancers are among the most frequent causes of cancer-associated mortalities in Africa. They have been considered as a global public health concern, as nearly one million new cases are reported per year. IL-1β is a pro-inflammatory cytokine-produced by activated macrophages and monocytes- and a member of the IL-1 family. The inactive IL-1β precursor is cleaved and activated by caspase-1 enzyme, which itself is activated by the assembly of intracellular structures defined as NLRP3 (Nod Like receptor P3) inflammasomes. Activated IL-1β stimulates the Interleukin-1 receptor type-1 (IL-1R1), which is responsible for the initiation of a signal transduction pathway leading to cell proliferation. It has been proven that the IL-1β gene is a highly polymorphic gene in which single nucleotide polymorphisms (SNPs) may affect its expression. It has been previously reported that SNPs including base transitions between C and T at positions, -511 (C-T; dbSNP: rs16944) and -31 (C-T; dbSNP: rs1143627), from the transcriptional start site, contribute to the pathogenesis of gastric and colorectal cancers by affecting IL-1β levels. Altered production of IL-1β due to such polymorphisms is suspected to stimulate an amplified inflammatory response and promote Epithelial Mesenchymal Transition leading to malignancy. Allele frequency distribution of the IL-1β-31 and -511 SNPs, in different populations, and their correlation to the incidence of gastric and colorectal cancers, has been intriguing to researchers worldwide. The current study aims to investigate allele distributions of the IL-1β SNPs among gastric and colorectal cancers Egyptian patients. In order to achieve to that, 89 Biopsy and surgical specimens from the antrum and corpus mucosa of chronic gastritis subjects and gastric and colorectal carcinoma patients was collected for DNA extraction followed by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). The amplified PCR products of IL-1β-31C > T and IL-1β-511T > C were digested by incubation with the restriction endonuclease enzymes ALu1 and Ava1. Statistical analysis was carried out to determine the allele frequency distribution in the three studied groups. Also, the effect of the IL-1β -31 and -511 SNPs on nuclear factor binding was analyzed using Fluorescence Electrophoretic Mobility Shift Assay (EMSA), preceded by nuclear factor extraction from gastric and colorectal tissue samples and LPS stimulated monocytes. The results of this study showed that a significantly higher percentage of Egyptian gastric cancer patients have a homozygous CC genotype at the IL-1β-31 position and a heterozygous TC genotype at the IL-1β-511 position. Moreover, a significantly higher percentage of the colorectal cancer patients have a homozygous CC genotype at the IL-1β-31 and -511 positions as compared to the control group. In addition, the EMSA results showed that IL-1β-31C/T and IL-1β-511T/C SNPs do not affect nuclear factor binding. Results of this study suggest that the IL-1β-31 C/T and IL-1β-511 T/C may be correlated to the incidence of gastric cancer in Egyptian patients; however, similar findings couldn’t be proven in the colorectal cancer patients group for the IL-1β-511 T/C SNP. This is the first study to investigate IL-1β -31 and -511 SNPs in the Egyptian population.

Keywords: colorectal cancer, Egyptian patients, gastric cancer, interleukin-1β, single nucleotide polymorphisms

Procedia PDF Downloads 121

Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

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Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

Procedia PDF Downloads 88

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

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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

Procedia PDF Downloads 72

Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

Abstract:

The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

Procedia PDF Downloads 94

Authors: Fernando M. Soto, Gaetano Di Mino

Abstract:

The design of an unmodified bituminous mixture and three rubber-aggregate mixtures containing rubber-aggregate by a dry process (RUMAC) was evaluated, using an empirical-analytical approach based on experimental findings obtained in the laboratory with the volumetric mix design by gyratory compaction. A reference dense-graded bituminous sub-ballast mixture (3% of air voids and a bitumen 4% over the total weight of the mix), and three rubberized mixtures by dry process (1,5 to 3% of rubber by total weight and 5-7% of binder) were used applying the Superpave mix-design for a level 3 (high-traffic) design rail lines. The railway trackbed section analyzed was a granular layer of 19 cm compacted, while for the sub-ballast a thickness of 12 cm has been used. In order to evaluate the effect of increasing the specimen density (as a percent of its theoretical maximum specific gravity), in this article, are illustrated the results obtained after different comparative analysis into the influence of varying the binder-rubber percentages under the sub-ballast layer mix-design. This work demonstrates that rubberized blends containing crumb and ground rubber in bituminous asphalt mixtures behave at least similar or better than conventional asphalt materials. By using the same methodology of volumetric compaction, the densification curves resulting from each mixture have been studied. The purpose is to obtain an optimum empirical parameter multiplier of the number of gyrations necessary to reach the same compaction energy as in conventional mixtures. It has provided some experimental parameters adopting an empirical-analytical method, evaluating the results obtained from the gyratory-compaction of bituminous mixtures with an HMA and rubber-aggregate blends. An extensive integrated research has been carried out to assess the suitability of rubber-modified hot mix asphalt mixtures as a sub-ballast layer in railway underlayment trackbed. Design optimization of the mixture was conducted for each mixture and the volumetric properties analyzed. Also, an improved and complete manufacturing process, compaction and curing of these blends are provided. By adopting this increase-parameters of compaction, called 'beta' factor, mixtures modified with rubber with uniform densification and workability are obtained that in the conventional mixtures. It is found that considering the usual bearing capacity requirements in rail track, the optimal rubber content is 2% (by weight) or 3.95% (by volumetric substitution) and a binder content of 6%.

Keywords: empirical approach, rubber-asphalt, sub-ballast, superpave mix-design

Procedia PDF Downloads 342