Search results for: drug stability

Authors: Gela Gelashvili, David Gelenidze, Sulkhan Nanobashvili, Irakli Nanobashvili, George Tavkhelidze, Tsiuri Sitchinava

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Development of new highly efficient plasma arc combustion system of pulverized coal is presented. As it is well-known, coal is one of the main energy carriers by means of which electric and heat energy is produced in thermal power stations. The quality of the extracted coal decreases very rapidly. Therefore, the difficulties associated with its firing and complete combustion arise and thermo-chemical preparation of pulverized coal becomes necessary. Usually, other organic fuels (mazut-fuel oil or natural gas) are added to low-quality coal for this purpose. The fraction of additional organic fuels varies within 35-40% range. This decreases dramatically the economic efficiency of such systems. At the same time, emission of noxious substances in the environment increases. Because of all these, intense development of plasma combustion systems of pulverized coal takes place in whole world. These systems are equipped with Non-Transferred Plasma Arc Torches. They allow practically complete combustion of pulverized coal (without organic additives) in boilers, increase of energetic and financial efficiency. At the same time, emission of noxious substances in the environment decreases dramatically. But, the non-transferred plasma torches have numerous drawbacks, e.g. complicated construction, low service life (especially in the case of high power), instability of plasma arc and most important – up to 30% of energy loss due to anode cooling. Due to these reasons, intense development of new plasma technologies that are free from these shortcomings takes place. In our proposed system, pulverized coal-air mixture passes through plasma arc area that burns between to carbon electrodes directly in pulverized coal muffler burner. Consumption of the carbon electrodes is low and does not need a cooling system, but the main advantage of this method is that radiation of plasma arc directly impacts on coal-air mixture that accelerates the process of thermo-chemical preparation of coal to burn. To ensure the stability of the plasma arc in such difficult conditions, we have developed a power source that provides fixed current during fluctuations in the arc resistance automatically compensated by the voltage change as well as regulation of plasma arc length over a wide range. Our combustion system where plasma arc acts directly on pulverized coal-air mixture is simple. This should allow a significant improvement of pulverized coal combustion (especially low-quality coal) and its economic efficiency. Preliminary experiments demonstrated the successful functioning of the system.

Keywords: coal combustion, plasma arc, plasma torches, pulverized coal

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Authors: Lijuan Li

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Nitric oxide (NO) has become a fascinating entity in biological chemistry over the past few years. It is a gaseous lipophilic radical molecule that plays important roles in several physiological and pathophysiological processes in mammals, including activating the immune response, serving as a neurotransmitter, regulating the cardiovascular system, and acting as an endothelium-derived relaxing factor. NO functions in eukaryotes both as a signal molecule at nanomolar concentrations and as a cytotoxic agent at micromolar concentrations. The latter arises from the ability of NO to react readily with a variety of cellular targets leading to thiol S-nitrosation, amino acid N-nitrosation, and nitrosative DNA damage. Nitric oxide can readily bind to metals to give metal-nitrosyl (M-NO) complexes. Some of these species are known to play roles in biological NO storage and transport. These complexes have different biological, photochemical, or spectroscopic properties due to distinctive structural features. These recent discoveries have spawned a great interest in the development of transition metal complexes containing NO, particularly its iron complexes that are central to the role of nitric oxide in the body. Spectroscopic evidence would appear to implicate species of “Fe(NO)2+” type in a variety of processes ranging from polymerization, carcinogenesis, to nitric oxide stores. Our research focuses on isolation and structural studies of non-heme iron nitrosyls that mimic biologically active compounds and can potentially be used for anticancer drug therapy. We have shown that reactions between Fe(NO)2(CO)2 and a series of imidazoles generated new non-heme iron nitrosyls of the form Fe(NO)2(L)2 [L = imidazole, 1-methylimidazole, 4-methylimidazole, benzimidazole, 5,6-dimethylbenzimidazole, and L-histidine] and a tetrameric cluster of [Fe(NO)2(L)]4 (L=Im, 4-MeIm, BzIm, and Me2BzIm), resulted from the interactions of Fe(NO)2 with a series of substituted imidazoles was prepared. Recently, a series of sulfur bridged iron di nitrosyl complexes with the general formula of [Fe(µ-RS)(NO)2]2 (R = n-Pr, t-Bu, 6-methyl-2-pyridyl, and 4,6-dimethyl-2-pyrimidyl), were synthesized by the reaction of Fe(NO)2(CO)2 with thiols or thiolates. Their structures and properties were studied by IR, UV-vis, 1H-NMR, EPR, electrochemistry, X-ray diffraction analysis and DFT calculations. IR spectra of these complexes display one weak and two strong NO stretching frequencies (νNO) in solution, but only two strong νNO in solid. DFT calculations suggest that two spatial isomers of these complexes bear 3 Kcal energy difference in solution. The paramagnetic complexes [Fe2(µ-RS)2(NO)4]-, have also been investigated by EPR spectroscopy. Interestingly, the EPR spectra of complexes exhibit an isotropic signal of g = 1.998 - 2.004 without hyperfine splitting. The observations are consistent with the results of calculations, which reveal that the unpaired electron dominantly delocalize over the two sulfur and two iron atoms. The difference of the g values between the reduced form of iron-sulfur clusters and the typical monomeric di nitrosyl iron complexes is explained, for the first time, by of the difference in unpaired electron distributions between the two types of complexes, which provides the theoretical basis for the use of g value as a spectroscopic tool to differentiate these biologically active complexes.

Keywords: di nitrosyl iron complex, metal nitrosyl, non-heme iron, nitric oxide

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Authors: Dila Ram Bhandari

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Throughout the 20th century, new governments were created where identities such as ethnic, religious, linguistic, caste, communal, tribal, and others played a part in the development of constitutions and the legal system of victim and criminal justice. Acute issues with extremism, poverty, environmental degradation, cybercrimes, human rights violations, crime against, and victimization of both individuals and groups have recently plagued South Asian nations. Everyday massive number of crimes are steadfast, these frequent crimes have made the lives of common citizens restless. Crimes are one of the major threats to society and also for civilization. Crime is a bone of contention that can create a societal disturbance. The old-style crime solving practices are unable to live up to the requirement of existing crime situations. Crime analysis is one of the most important activities of the majority of intelligent and law enforcement organizations all over the world. The South Asia region lacks such a regional coordination mechanism, unlike central Asia of Asia Pacific regions, to facilitate criminal intelligence sharing and operational coordination related to organized crime, including illicit drug trafficking and money laundering. There have been numerous conversations in recent years about using data mining technology to combat crime and terrorism. The Data Detective program from Sentient as a software company, uses data mining techniques to support the police (Sentient, 2017). The goals of this internship are to test out several predictive model solutions and choose the most effective and promising one. First, extensive literature reviews on data mining, crime analysis, and crime data mining were conducted. Sentient offered a 7-year archive of crime statistics that were daily aggregated to produce a univariate dataset. Moreover, a daily incidence type aggregation was performed to produce a multivariate dataset. Each solution's forecast period lasted seven days. Statistical models and neural network models were the two main groups into which the experiments were split. For the crime data, neural networks fared better than statistical models. This study gives a general review of the applied statistics and neural network models. A detailed image of each model's performance on the available data and generalizability is provided by a comparative analysis of all the models on a comparable dataset. Obviously, the studies demonstrated that, in comparison to other models, Gated Recurrent Units (GRU) produced greater prediction. The crime records of 2005-2019 which was collected from Nepal Police headquarter and analysed by R programming. In conclusion, gated recurrent unit implementation could give benefit to police in predicting crime. Hence, time series analysis using GRU could be a prospective additional feature in Data Detective.

Keywords: time series analysis, forecasting, ARIMA, machine learning

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Authors: Jung-En Kuan, Whei-Fen Wu

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In this study, a symbiotic bacteria from yellow mealworm's (Tenebrio molitor) mid-gut was isolated with characteristics of growth on minimal-tributyrin medium. After a PCR-amplification of its 16s rDNA, the resultant nucleotide sequences were then analyzed by schemes of the phylogeny trees. Accordingly, it was designated as Pseudomonas nitroreducens D-01. Next, by searching the lipolytic enzymes in its protein data bank, one of those potential lipolytic α/β hydrolases was identified, again using PCR-amplification and nucleotide-sequencing methods. To construct an expression of this lipolytic gene in plasmids, the target-gene primers were then designed, carrying the C-terminal his-tag sequences. Using the vector pET21a, a recombinant lipolytic hydrolase D gene with his-tag nucleotides was successfully cloned into it, of which the lipolytic D gene is under a control of the T7 promoter. After transformation of the resultant plasmids into Eescherichia coli BL21 (DE3), an IPTG inducer was used for the induction of the recombinant proteins. The protein products were then purified by metal-ion affinity column, and the purified proteins were found capable of forming a clear zone on tributyrin agar plate. Shortly, its enzyme activities were determined by degradation of p-nitrophenyl ester(s), and the substantial yellow end-product, p-nitrophenol, was measured at O.D.405 nm. Specifically, this lipolytic enzyme efficiently targets p-nitrophenyl butyrate. As well, it shows the most reactive activities at 40°C, pH 8 in potassium phosphate buffer. In thermal stability assays, the activities of this enzyme dramatically drop when the temperature is above 50°C. In metal ion assays, MgCl₂ and NH₄Cl induce the enzyme activities while MnSO₄, NiSO₄, CaCl₂, ZnSO₄, CoCl₂, CuSO₄, FeSO₄, and FeCl₃ reduce its activities. Besides, NaCl has no effects on its enzyme activities. Most organic solvents decrease the activities of this enzyme, such as hexane, methanol, ethanol, acetone, isopropanol, chloroform, and ethyl acetate. However, its enzyme activities increase when DMSO exists. All the surfactants like Triton X-100, Tween 80, Tween 20, and Brij35 decrease its lipolytic activities. Using Lineweaver-Burk double reciprocal methods, the function of the enzyme kinetics were determined such as Km = 0.488 (mM), Vmax = 0.0644 (mM/min), and kcat = 3.01x10³ (s⁻¹), as well the total efficiency of kcat/Km is 6.17 x10³ (mM⁻¹/s⁻¹). Afterwards, based on the phylogenetic analyses, this lipolytic protein is classified to type IV lipase by its homologous conserved region in this lipase family.

Keywords: enzyme, esterase, lipotic hydrolase, type IV

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Authors: Md. Soebur Rahman, Mahbuba Begum, Raquib Ahsan

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Composite column is a structural member that uses a combination of structural steel shapes, pipes or tubes with or without reinforcing steel bars and reinforced concrete to provide adequate load carrying capacity to sustain either axial compressive loads alone or a combination of axial loads and bending moments. Composite construction takes the advantages of the speed of construction, light weight and strength of steel, and the higher mass, stiffness, damping properties and economy of reinforced concrete. The most usual types of composite columns are the concrete filled steel tubes and the partially or fully encased steel profiles. Fully encased composite column (FEC) provides compressive strength, stability, stiffness, improved fire proofing and better corrosion protection. This paper reports experimental and numerical investigations of the behaviour of concrete encased steel composite columns subjected to short-term axial load. In this study, eleven short FEC columns with square shaped cross section were constructed and tested to examine the load-deflection behavior. The main variables in the test were considered as concrete compressive strength, cross sectional size and percentage of structural steel. A nonlinear 3-D finite element (FE) model has been developed to analyse the inelastic behaviour of steel, concrete, and longitudinal reinforcement as well as the effect of concrete confinement of the FEC columns. FE models have been validated against the current experimental study conduct in the laboratory and published experimental results under concentric load. It has been observed that FE model is able to predict the experimental behaviour of FEC columns under concentric gravity loads with good accuracy. Good agreement has been achieved between the complete experimental and the numerical load-deflection behaviour in this study. The capacities of each constituent of FEC columns such as structural steel, concrete and rebar's were also determined from the numerical study. Concrete is observed to provide around 57% of the total axial capacity of the column whereas the steel I-sections contributes to the rest of the capacity as well as ductility of the overall system. The nonlinear FE model developed in this study is also used to explore the effect of concrete strength and percentage of structural steel on the behaviour of FEC columns under concentric loads. The axial capacity of FEC columns has been found to increase significantly by increasing the strength of concrete.

Keywords: composite, columns, experimental, finite element, fully encased, strength

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Authors: Suleyman Ogul Ertugrul, Mustafa Turgut, Serkan Inandı, Mustafa Gorkem Coban, Mustafa Kıgılı, Ali Mert, Oguzhan Kesmez, Murat Ozancı, Caglar Uyulan

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In high-performance automotive engineering, the realistic simulation of suspension systems is crucial for enhancing vehicle dynamics and handling. This study focuses on the double wishbone suspension system, prevalent in racing vehicles due to its superior control and stability characteristics. Utilizing MATLAB and Adams Car simulation software, we conduct a comprehensive analysis of displacement behaviors and damper sizing under various dynamic conditions. The initial phase involves using MATLAB to simulate the entire suspension system, allowing for the preliminary determination of damper size based on the system's response under simulated conditions. Following this, manual calculations of wheel loads are performed to assess the forces acting on the front and rear suspensions during scenarios such as braking, cornering, maximum vertical loads, and acceleration. Further dynamic force analysis is carried out using MATLAB Simulink, focusing on the interactions between suspension components during key movements such as bumps and rebounds. This simulation helps in formulating precise force equations and in calculating the stiffness of the suspension springs. To enhance the accuracy of our findings, we focus on a detailed kinematic and dynamic analysis. This includes the creation of kinematic loops, derivation of relevant equations, and computation of Jacobian matrices to accurately determine damper travel and compression metrics. The calculated spring stiffness is crucial in selecting appropriate springs to ensure optimal suspension performance. To validate and refine our results, we replicate the analyses using the Adams Car software, renowned for its detailed handling of vehicular dynamics. The goal is to achieve a robust, reliable suspension setup that maximizes performance under the extreme conditions encountered in racing scenarios. This study exemplifies the integration of theoretical mechanics with advanced simulation tools to achieve a high-performance suspension setup that can significantly improve race car performance, providing a methodology that can be adapted for different types of racing vehicles.

Keywords: FSAE, suspension system, Adams Car, kinematic

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Authors: Gautier Viaud, Paul-Henry Cournède

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Plant growth models have been used extensively for the prediction of the phenotypic performance of plants. However, they remain most often calibrated for a given genotype and therefore do not take into account genotype by environment interactions. One way of achieving such an objective is to consider Bayesian hierarchical models. Three levels can be identified in such models: The first level describes how a given growth model describes the phenotype of the plant as a function of individual parameters, the second level describes how these individual parameters are distributed within a plant population, the third level corresponds to the attribution of priors on population parameters. Thanks to the Bayesian framework, choosing appropriate priors for the population parameters permits to derive analytical expressions for the full conditional distributions of these population parameters. As plant growth models are of a nonlinear nature, individual parameters cannot be sampled explicitly, and a Metropolis step must be performed. This allows for the use of a hybrid Gibbs--Metropolis sampler. A generic approach was devised for the implementation of both general state space models and estimation algorithms within a programming platform. It was designed using the Julia language, which combines an elegant syntax, metaprogramming capabilities and exhibits high efficiency. Results were obtained for Arabidopsis thaliana on both simulated and real data. An organ-scale Greenlab model for the latter is thus presented, where the surface areas of each individual leaf can be simulated. It is assumed that the error made on the measurement of leaf areas is proportional to the leaf area itself; multiplicative normal noises for the observations are therefore used. Real data were obtained via image analysis of zenithal images of Arabidopsis thaliana over a period of 21 days using a two-step segmentation and tracking algorithm which notably takes advantage of the Arabidopsis thaliana phyllotaxy. Since the model formulation is rather flexible, there is no need that the data for a single individual be available at all times, nor that the times at which data is available be the same for all the different individuals. This allows to discard data from image analysis when it is not considered reliable enough, thereby providing low-biased data in large quantity for leaf areas. The proposed model precisely reproduces the dynamics of Arabidopsis thaliana’s growth while accounting for the variability between genotypes. In addition to the estimation of the population parameters, the level of variability is an interesting indicator of the genotypic stability of model parameters. A promising perspective is to test whether some of the latter should be considered as fixed effects.

Keywords: bayesian, genotypic differentiation, hierarchical models, plant growth models

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Authors: Iddy Iddy, Qin Jiang, Changkuan Zhang

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This paper addresses the hydraulic performance of curtain wall breakwaters as a coastal structure protection based on the particles method modelling. The hydraulic functions of curtain wall as wave barriers by reflecting large parts of incident waves through the vertical wall, a part transmitted and a particular part was dissipating the wave energies through the eddy flows formed beneath the lower end of the plate. As a Lagrangian particle, the Moving Particle Semi-implicit (MPS) method which has a robust capability for numerical representation has proven useful for design of structures application that concern free-surface hydrodynamic flow, such as wave breaking and overtopping. In this study, a vertical two-dimensional numerical model for the simulation of violent flow associated with the interaction between the curtain-wall breakwaters and progressive water waves is developed by MPS method in which a higher precision pressure gradient model and free surface particle recognition model were proposed. The wave transmission, reflection, and energy dissipation of the vertical wall were experimentally and theoretically examined. With the numerical wave flume by particle method, very detailed velocity and pressure fields around the curtain-walls under the action of waves can be computed in each calculation steps, and the effect of different wave and structural parameters on the hydrodynamic characteristics was investigated. Also, the simulated results of temporal profiles and distributions of velocity and pressure in the vicinity of curtain-wall breakwaters are compared with the experimental data. Herein, the numerical investigation of hydraulic performance of curtain wall breakwaters indicated that the incident wave is largely reflected from the structure, while the large eddies or turbulent flows occur beneath the curtain-wall resulting in big energy losses. The improved MPS method shows a good agreement between numerical results and analytical/experimental data which are compared to related researches. It is thus verified that the improved pressure gradient model and free surface particle recognition methods are useful for enhancement of stability and accuracy of MPS model for water waves and marine structures. Therefore, it is possible for particle method (MPS method) to achieve an appropriate level of correctness to be applied in engineering fields through further study.

Keywords: curtain wall breakwaters, free surface flow, hydraulic performance, improved MPS method

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Authors: Savitha Janakiraman, Shivakumar M. C

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Anidulafungin, an advanced class of antifungal agent used for the treatment of chronic fungal infections, is derived from Echinocandin B nucleus, an intermediate metabolite of Echinocandin B produced by Aspergillus nidulans. The enzyme acylase derived from the fermentation broth of Actinoplanes utahensis (NRRL 12052) plays a key role in the bioconversion of echinocandin B to echinocandin B nucleus. The membrane-bound nature of acylase and low levels of expression contributes to the rate-limiting process of enzymatic deacylation, hence low yields of ECB nucleus and anidulafungin. In the present study, this is addressed through novel genetic engineering approaches of overexpression and heterologous expression studies, immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) and Co-cultivation studies. Overexpression of the acylase gene in Actinoplanes utahensis (NRRL 12052) was done by increasing the gene copy number to increase the echinocandin B nucleus production. Echinocandin B acylase gene, under the control of a PermE* promoter, was cloned in pSET152 vector and introduced into Actinoplanes utahensis (NRRL12052) by a ɸC31-directed site-specific recombination method. The resultant recombinant strain (C2-18) showed a 3-fold increase in acylase expression, which was confirmed by HPLC analysis. Pichia pastoris is one of the most effective and versatile host systems for the production of heterologous proteins. The ECB acylase gene was cloned into pPIC9K vector with AOX1 promoter and was transformed into Pichia pastoris (GS115). The acylase expression was confirmed by protein expression and bioconversion studies. The heterologous expression of acylase in Pichia pastoris, is a milestone in the development of antifungals. Actively growing cells of Actinoplanes utahensis (NRRL 12052) were immobilized and tested for bioconversion ability which showed >90% conversion in each cycle. The stability of immobilized cell beads retained the deacylation ability up to 60 days and reusability was confirmed up to 4 cycles. The significant findings from the study have revealed that immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) could be an alternative option for bioconversion of echinocandin B to echinocandin B nucleus, which has not been reported to date. The concept of co-cultivation of Aspergillus nidulans and Actinoplanes utahensis strains for the production of the echinocandin B nucleus was also carried out in order to produce echinocandin B nucleus. The process completely reduced the ECB purification step and, therefore, could be recommended as an ingenious method to improve the yield of the ECB nucleus.

Keywords: acylase, anidulafungin, antifungals, Aspergillus nidulans

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Authors: Ekemini M. Okon, Reuben C. Okocha, Babatunde T. Adesina, Judith O. Ehigie, Babatunde M. Falana, Boluwape T. Okikiola

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Antimicrobial resistance (AMR) has evolved to become a significant threat to global public health and food safety. The development of AMR in animals has been associated with antimicrobial overuse. In recent years, the number of antimicrobials used in food animals such as fish and poultry has escalated. It, therefore, becomes imperative to understand the patterns of AMR in fish and poultry and map out future directions for better surveillance efforts. This study used the Preferred Reporting Items for Systematic reviews and Meta-Analyses(PRISMA) to assess the trend, patterns, and spatial distribution for AMR research in Egypt, Nigeria, and South Africa. A literature search was conducted through the Scopus and Web of Science databases in which published studies on AMR between 1989 and 2021 were assessed. A total of 172 articles were relevant for this study. The result showed progressive attention on AMR studies in fish and poultry from 2018 to 2021 across the selected countries. The period between 2018 (23 studies) and 2021 (25 studies) showed a significant increase in AMR publications with a peak in 2019 (28 studies). Egypt was the leading exponent of AMR research (43%, n=74) followed by Nigeria (40%, n=69), then South Africa (17%, n=29). AMR studies in fish received relatively little attention across countries. The majority of the AMR studies were on poultry in Egypt (82%, n=61), Nigeria (87%, n=60), and South Africa (83%, n=24). Further, most of the studies were on Escherichia and Salmonella species. Antimicrobials frequently researched were ampicillin, erythromycin, tetracycline, trimethoprim, chloramphenicol, and sulfamethoxazole groups. Multiple drug resistance was prevalent, as demonstrated by antimicrobial resistance patterns. In poultry, Escherichia coli isolates were resistant to cefotaxime, streptomycin, chloramphenicol, enrofloxacin, gentamycin, ciprofloxacin, oxytetracycline, kanamycin, nalidixic acid, tetracycline, trimethoprim/sulphamethoxazole, erythromycin, and ampicillin. Salmonella enterica serovars were resistant to tetracycline, trimethoprim/sulphamethoxazole, cefotaxime, and ampicillin. Staphylococcusaureus showed high-level resistance to streptomycin, kanamycin, erythromycin, cefoxitin, trimethoprim, vancomycin, ampicillin, and tetracycline. Campylobacter isolates were resistant to ceftriaxone, erythromycin, ciprofloxacin, tetracycline, and nalidixic acid at varying degrees. In fish, Enterococcus isolates showed resistance to penicillin, ampicillin, chloramphenicol, vancomycin, and tetracycline but sensitive to ciprofloxacin, erythromycin, and rifampicin. Isolated strains of Vibrio species showed sensitivity to florfenicol and ciprofloxacin, butresistance to trimethoprim/sulphamethoxazole and erythromycin. Isolates of Aeromonas and Pseudomonas species exhibited resistance to ampicillin and amoxicillin. Specifically, Aeromonashydrophila isolates showed sensitivity to cephradine, doxycycline, erythromycin, and florfenicol. However, resistance was also exhibited against augmentinandtetracycline. The findings constitute public and environmental health threats and suggest the need to promote and advance AMR research in other countries, particularly those on the global hotspot for antimicrobial use.

Keywords: antibiotics, antimicrobial resistance, bacteria, environment, public health

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Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

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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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Authors: Lin Zhao, Hanqiao Jiang, Junjian Li

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Polymers injected into elevated-temperature reservoirs inevitably suffer from thermal degradation, resulting in severe viscosity loss and poor flooding performance. However, for polymer flooding in such reservoirs, present simulators fail to provide accurate results for lack of description on thermal degradation. In light of this, the objectives of this paper are to provide a simulation model for polymer flooding with thermal degradation and study the effect of thermal degradation on polymer flooding in elevated-temperature reservoirs. Firstly, a thermal degradation experiment was conducted to obtain the degradation law of polymer concentration and viscosity. Different types of polymers degraded in the Thermo tank with elevated temperatures. Afterward, based on the obtained law, a streamline-assistant model was proposed to simulate the degradation process under in-situ flow conditions. Model validation was performed with field data from a well group of an offshore oilfield. Finally, the effect of thermal degradation on polymer flooding was studied using the proposed model. Experimental results showed that the polymer concentration remained unchanged, while the viscosity degraded exponentially with time after degradation. The polymer viscosity was functionally dependent on the polymer degradation time (PDT), which represented the elapsed time started from the polymer particle injection. Tracing the real flow path of polymer particle was required. Therefore, the presented simulation model was streamline-assistant. Equation of PDT vs. time of flight (TOF) along streamline was built by the law of polymer particle transport. Based on the field polymer sample and dynamic data, the new model proved its accuracy. Study of degradation effect on polymer flooding indicated: (1) the viscosity loss increased with TOF exponentially in the main body of polymer-slug and remained constant in the slug front; (2) the responding time of polymer flooding was delayed, but the effective time was prolonged; (3) the breakthrough of subsequent water was eased; (4) the capacity of polymer adjusting injection profile was diminished; (5) the incremental recovery was reduced significantly. In general, the effect of thermal degradation on polymer flooding performance was rather negative. This paper provides a more comprehensive insight into polymer thermal degradation in both the physical process and field application. The proposed simulation model offers an effective means for simulating the polymer flooding process with thermal degradation. The negative effect of thermal degradation suggests that the polymer thermal stability should be given full consideration when designing polymer flooding project in elevated-temperature reservoirs.

Keywords: polymer flooding, elevated-temperature reservoir, thermal degradation, numerical simulation

Procedia PDF Downloads 120

Authors: N. C. van der Merwe, J. Oosthuizen, M. F. Makhetha, J. Adams, B. K. Dajee, S-R. Schneider

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Women representing high-risk breast cancer families, who tested negative for pathogenic mutations in BRCA1 and BRCA2, are four times more likely to develop breast cancer compared to women in the general population. Sequencing of genes involved in genomic stability and DNA repair led to the identification of novel contributors to familial breast cancer risk. These include BLM and PALB2. Bloom's syndrome is a rare homozygous autosomal recessive chromosomal instability disorder with a high incidence of various types of neoplasia and is associated with breast cancer when in a heterozygous state. PALB2, on the other hand, binds to BRCA2 and together, they partake actively in DNA damage repair. Archived DNA samples of 66 BRCA1/2 negative high-risk breast cancer patients were retrospectively selected based on the presence of an extensive family history of the disease ( > 3 affecteds per family). All coding regions and splice-site boundaries of both genes were screened using High-Resolution Melting Analysis. Samples exhibiting variation were bi-directionally automated Sanger sequenced. The clinical significance of each variant was assessed using various in silico and splice site prediction algorithms. Comprehensive screening identified a total of 11 BLM and 26 PALB2 variants. The variants detected ranged from global to rare and included three novel mutations. Three BLM and two PALB2 likely pathogenic mutations were identified that could account for the disease in these extensive breast cancer families in the absence of BRCA mutations (BLM c.11T > A, p.V4D; BLM c.2603C > T, p.P868L; BLM c.3961G > A, p.V1321I; PALB2 c.421C > T, p.Gln141Ter; PALB2 c.508A > T, p.Arg170Ter). Conclusion: The study confirmed the contribution of pathogenic mutations in BLM and PALB2 to the familial breast cancer burden in South Africa. It explained the presence of the disease in 7.5% of the BRCA1/2 negative families with an extensive family history of breast cancer. Segregation analysis will be performed to confirm the clinical impact of these mutations for each of these families. These results justify the inclusion of both these genes in a comprehensive breast and ovarian next generation sequencing cancer panel and should be screened simultaneously with BRCA1 and BRCA2 as it might explain a significant percentage of familial breast and ovarian cancer in South Africa.

Keywords: Bloom Syndrome, familial breast cancer, PALB2, South Africa

Procedia PDF Downloads 212

Authors: Siti Nur Syazni Mohd Zuki, Tan Ling Ling, Nina Suhaity Azmi, Chong Kwok Feng, Lee Yook Heng

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Nitrite (NO2-) ion is used prevalently as a preservative in processed meat. Elevated levels of nitrite also found in edible bird’s nests (EBNs). Consumption of NO2- ion at levels above the health-based risk may cause cancer in humans. Spectrophotometric Griess test is the simplest established standard method for NO2- ion detection, however, it requires careful control of pH of each reaction step and susceptible to strong oxidants and dyeing interferences. Other traditional methods rely on the use of laboratory-scale instruments such as GC-MS, HPLC and ion chromatography, which cannot give real-time response. Therefore, it is of significant need for devices capable of measuring nitrite concentration in-situ, rapidly and without reagents, sample pretreatment or extraction step. Herein, we constructed a microspheres-based microbial optode for visual quantitation of NO2- ion. Raoutella planticola, the bacterium expressing NAD(P)H nitrite reductase (NiR) enzyme has been successfully extracted by microbial technique from EBN collected from local birdhouse. The whole cells and the lipophilic Nile Blue chromoionophore were physically absorbed on the photocurable poly(n-butyl acrylate-N-acryloxysuccinimide) [poly (nBA-NAS)] microspheres, whilst the reduced coenzyme NAD(P)H was covalently immobilized on the succinimide-functionalized acrylic microspheres to produce a reagentless biosensing system. Upon the NiR enzyme catalyzes the oxidation of NAD(P)H to NAD(P)+, NO2- ion is reduced to ammonium hydroxide, and that a colour change from blue to pink of the immobilized Nile Blue chromoionophore is perceived as a result of deprotonation reaction increasing the local pH in the microspheres membrane. The microspheres-based optosensor was optimized with a reflectance spectrophotometer at 639 nm and pH 8. The resulting microbial bio-optode membrane could quantify NO2- ion at 0.1 ppm and had a linear response up to 400 ppm. Due to the large surface area to mass ratio of the acrylic microspheres, it allows efficient solid state diffusional mass transfer of the substrate to the bio-recognition phase, and achieve the steady state response as fast as 5 min. The proposed optical microbial biosensor requires no sample pre-treatment step and possesses high stability as the whole cell biocatalyst provides protection to the enzymes from interfering substances, hence it is suitable for measurements in contaminated samples.

Keywords: acrylic microspheres, microbial bio-optode, nitrite ion, reflectometric

Procedia PDF Downloads 418

Authors: Gulden Aykinbaeva, Assem Umirzakova, Assel Makhadiyeva

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The problem of studying of young married couples in connection with a change of social institute of a family and marriage is represented very actual for family consultation, considering a family role in the development of modern society. Results of numerous researchs say that one of difficult in formation and stabilization of a matrimony is the period of a young family. This period is characterized by various processes of integration, adaptation and emotional compatibility of spouses. The young family in it the period endures the first standard crisis which postpones a print for the further development of the family scenario. Emergence new, earlier not existing, systems of values render a huge value on the process of formation of a young family and each of spouses separately. Possibly to solve the set family tasks at the development of the uniform system of the family relations in which socially mature persons capable to consider a family as the creativity of each other act as subjects. Due to the research objective in work the following techniques were used: a questionnaire of satisfaction with V. V. Stolin's marriage and A. N. Volkova's technique directed on detection of coherence of family values and role installations in a married couple, and also content – the analysis. Development of an internal basis of a family on mutual clearing of values is important during the work with married couples. 'The mature view' of the partner in the marriage union provides coherence between the expected and real behavior of the partner that is important for the realization of the purposes of adaptation in a family. For research of communication of the data obtained by means of A. N. Volkova's techniques, V. V. Stolina and content – the analysis, the correlation analysis, with the application of the criterion of Spirmen was used. The analysis of results of the conducted research allowed us to determine the number of consistent patterns: 1. Nature of change of satisfaction with marriage at spouses testifies that the matrimonial relations undergo high-quality changes at different stages of formation of a young family. 2. The matrimonial relations in the course of their development, formation and functioning in young marriage undergo considerable changes on psychological, social and psychological and insignificant — at the psychophysiological and sociocultural levels. The material received by us allows to plan ways of further detailed researches of the development of the matrimonial relations not only in the young marriage but also at further stages of development of a matrimony. We believe that the results received in this research can be almost applied at creation of algorithms of selection of marriage partners, at diagnostics of character and the maintenance of matrimonial disharmonies, at the forecast of stability of marriage and a family.

Keywords: married couples, formation of the young family, psychological consultation, matrimony

Procedia PDF Downloads 373

Authors: Parker Murray, Marci Johnson, Tyson S. Burnham, Alina K. Fong, Mark D. Allen, Bruce McIff

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Purpose: Pathological dysregulation of Neurovascular Coupling (NVC) caused by mild traumatic brain injury (mTBI) is the predominant source of chronic post-concussion syndrome (PCS) symptomology. fNCI has the ability to localize dysregulation in NVC by measuring blood-oxygen-level-dependent (BOLD) signaling during the performance of fMRI-adapted neuropsychological evaluations. With fNCI, 57 brain areas consistently affected by concussion were identified as PCS neural markers, which were validated on large samples of concussion patients and healthy controls. These neuromarkers provide the basis for a computation of PCS severity which is referred to as the Severity Index Score (SIS). The SIS has proven valuable in making pre-treatment decisions, monitoring treatment efficiency, and assessing long-term stability of outcomes. Methods and Materials: After being scanned while performing various cognitive tasks, 476 concussed patients received an SIS score based on the neural dysregulation of the 57 previously identified brain regions. These scans provide an objective measurement of attentional, subcortical, visual processing, language processing, and executive functioning abilities, which were used as biomarkers for post-concussive neural dysregulation. Initial SIS scores were used to develop individualized therapy incorporating cognitive, occupational, and neuromuscular modalities. These scores were also used to establish pre-treatment benchmarks and measure post-treatment improvement. Results: Changes in SIS were calculated in percent change from pre- to post-treatment. Patients showed a mean improvement of 76.5 percent (σ= 23.3), and 75.7 percent of patients showed at least 60 percent improvement. Longitudinal reassessment of 24 of the patients, measured an average of 7.6 months post-treatment, shows that SIS improvement is maintained and improved, with an average of 90.6 percent improvement from their original scan. Conclusions: fNCI provides a reliable measurement of NVC allowing for identification of concussion pathology. Additionally, fNCI derived SIS scores direct tailored therapy to restore NVC, subsequently resolving chronic PCS resulting from mTBI.

Keywords: concussion, functional magnetic resonance imaging (fMRI), neurovascular coupling (NVC), post-concussion syndrome (PCS)

Procedia PDF Downloads 323

Authors: S. Srinivasan, E. Cretu

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The information flow (e.g. block-diagram or signal flow graph) paradigm for the design and simulation of Microelectromechanical (MEMS)-based systems allows to model MEMS devices using causal transfer functions easily, and interface them with electronic subsystems for fast system-level explorations of design alternatives and optimization. Nevertheless, the physical bi-directional coupling between different energy domains is not easily captured in causal signal flow modeling. Moreover, models of fundamental components acting as building blocks (e.g. gap-varying MEMS capacitor structures) depend not only on the component, but also on the specific excitation mode (e.g. voltage or charge-actuation). In contrast, the energy flow modeling paradigm in terms of generalized across-through variables offers an acausal perspective, separating clearly the physical model from the boundary conditions. This promotes reusability and the use of primitive physical models for assembling MEMS devices from primitive structures, based on the interconnection topology in generalized circuits. The physical modeling capabilities of Simscape have been used in the present work in order to develop a MEMS library containing parameterized fundamental building blocks (area and gap-varying MEMS capacitors, nonlinear springs, displacement stoppers, etc.) for the design, simulation and optimization of MEMS inertial sensors. The models capture both the nonlinear electromechanical interactions and geometrical nonlinearities and can be used for both small and large signal analyses, including the numerical computation of pull-in voltages (stability loss). Simscape behavioral modeling language was used for the implementation of reduced-order macro models, that present the advantage of a seamless interface with Simulink blocks, for creating hybrid information/energy flow system models. Test bench simulations of the library models compare favorably with both analytical results and with more in-depth finite element simulations performed in ANSYS. Separate MEMS-electronic integration tests were done on closed-loop MEMS accelerometers, where Simscape was used for modeling the MEMS device and Simulink for the electronic subsystem.

Keywords: across-through variables, electromechanical coupling, energy flow, information flow, Matlab/Simulink, MEMS, nonlinear, pull-in instability, reduced order macro models, Simscape

Procedia PDF Downloads 116

Authors: Phakamani Xaba, Robert Huberts, Bilainu Oboirien

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It has been over 200 years since margarine was discovered and manufactured using liquid oil, liquified hardstock oils and other oil phase & aqueous phase ingredients. Henry W. Bradley first used vegetable oils in liquid state and around 1871, since then; spreads have been traditionally manufactured using liquified oils. The main objective of this study was to develop a process method to produce spreads using spray dried hardstock fat powders as a structing fats in place of current liquid structuring fats. A high shear mixing system was used to condition the fat phase and the aqueous phase was prepared separately. Using a single scraped surface heat exchanger and pin stirrer, margarine was produced. The process method was developed for to produce spreads with 40%, 50% and 60% fat . The developed method was divided into three steps. In the first step, fat powders were conditioned by melting and dissolving them into liquid oils. The liquified portion of the oils were at 65 °C, whilst the spray dried fat powder was at 25 °C. The two were mixed using a mixing vessel at 900 rpm for 4 minutes. The rest of the ingredients i.e., lecithin, colorant, vitamins & flavours were added at ambient conditions to complete the fat/ oil phase. The water phase was prepared separately by mixing salt, water, preservative, acidifier in the mixing tank. Milk was also separately prepared by pasteurizing it at 79°C prior to feeding it into the aqueous phase. All the water phase contents were chilled to 8 °C. The oil phase and water phase were mixed in a tank, then fed into a single scraped surface heat exchanger. After the scraped surface heat exchanger, the emulsion was fed in a pin stirrer to work the formed crystals and produce margarine. The margarine produced using the developed process had fat levels of 40%, 50% and 60%. The margarine passed all the qualitative, stability, and taste assessments. The scores were 6/10, 7/10 & 7.5/10 for the 40%, 50% & 60% fat spreads, respectively. The success of the trials brought about differentiated knowledge on how to manufacture spreads using non micronized spray dried fat powders as hardstock. Manufacturers do not need to store structuring fats at 80-90°C and even high in winter, instead, they can adapt their processes to use fat powders which need to be stored at 25 °C. The developed process method used one scrape surface heat exchanger instead of the four to five currently used in votator based plants. The use of a single scraped surface heat exchanger translated to about 61% energy savings i.e., 23 kW per ton of product. Furthermore, it was found that the energy saved by implementing separate pasteurization was calculated to be 6.5 kW per ton of product produced.

Keywords: margarine emulsion, votator technology, margarine processing, scraped sur, fat powders

Procedia PDF Downloads 72

Authors: Ifeoma Anozie, Teka Apalata, Dominic Abaver

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Introduction: Despite use of Anti-retroviral therapy to reduce the incidence of opportunistic infections among HIV/AIDS patients, rapid episodes of re-infection after deworming are still common occurrences because pharmaceutical intervention alone does not prevent reinfection. Unsafe water and inadequate personal hygiene and parasitic infections are widely expected to accelerate the progression of HIV infection. This is because the chronic immunosuppression of HIV infection encourages susceptibility to opportunistic (including parasitic) infections which is linked to CD4+ cell count of <200 cells/μl. Intestinal parasites such as G. intestinalis and Entamoeba spp are ubiquitous protozoa that remain infectious over a long time in an environment and show resistance to standard disinfection. To control re-infection, the social factors that underpin the prevention need to be controlled. This study aims at prevention of intestinal parasites in people living with HIV/AIDS by using a treatment, hygiene education and sanitation (THEdS) bundle approach. Methods: This study was conducted in four clinics (Ngangelizwe health centre, Tsolo gateway clinic, Idutywa health centre and Nqamakwe health centre) across the seven districts in Eastern cape, South Africa. The four clinics were divided in two: experimental and control, for the purpose of intervention. Data was collected from March 2019 to February 2020. Six hundred participants were screened for intestinal parasitic infections. Stool samples were collected and analysed twice: before (Pre-test infection screening) and after (Post-test re-infection) THEdS bundle intervention. The experimental clinics received full intervention package, which include therapeutic treatment, health education on personal hygiene and sanitation training, while the control clinics received only therapeutic treatment for those found with intestinal parasitic infections. Results: Baseline prevalence of Intestinal Parasites isolated shows 12 intestinal parasites with overall frequency of 65, with Ascaris lumbricoides having most frequency (44.6%). The intervention had a cure rate of 60%, with odd ratio of 1.42, which indicates that the intervention group is 1.42 times more likely of parasite clearing as compared to the control group. The relative risk ratio of 1.17 signifies that there is 1.17 times more likelihood to clear intestinal parasite if there no intervention. Discussion and conclusion: Infection with multiple parasites can cause health defects, especially among HIV/AIDS patients. Efficiency of some HIV vaccines in HIV/AIDS patients is affected because treatment of re-infection amplifies drug resistance, affects the efficacy of the front-line drugs, and still permits transmission. In South Africa, treatment of intestinal parasites is usually offered to clinic attending HIV/AIDS patients upon suspicion but not as a mandate for patients being initiated into Antiretroviral (ART) program. The effectiveness of THEdS bundle advocates for inclusiveness of mandatory screening for intestinal parasitic infections among attendees of HIV/Aids clinics on regular basis.

Keywords: cure rate, , HIV/AIDS patients, intestinal parasites, intervention studies, reinfection rate

Procedia PDF Downloads 55

Authors: Devi Eka Septiyani Arifin, Jrjeng Ruan

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As an approach to manipulate the performance of polymer thin film, epitaxy crystallization within polymer blends of poly(vinylidene fluoride) (PVDF) and its copolymer poly(vinylidene fluoride-trifluoroethylene) P(VDF-TrFE) was studied in this research, which involves the competition between phase separation and crystal growth of constitutive semicrystalline polymers. The unique piezoelectric feature of poly(vinylidene fluoride) crystalline phase is derived from the packing of molecular chains in all-trans conformation, which spatially arranges all the substituted fluorene atoms on one side of the molecular chain and hydrogen atoms on the other side. Therefore, the net dipole moment is induced across the lateral packing of molecular chains. Nevertheless, due to the mutual repulsion among fluorene atoms, this all-trans molecular conformation is not stable, and ready to change above curie temperature, where thermal energy is sufficient to cause segmental rotation. This research attempts to explore whether the epitaxial interactions between piezoelectric crystals and crystal lattice of hexamethylbenzene (HMB) crystalline platelet is able to stabilize this metastable all-trans molecular conformation or not. As an aromatic crystalline compound, the melt of HMB was surprisingly found able to dissolve the poly(vinylidene fluoride), resulting in homogeneous eutectic solution. Thus, after quenching this binary eutectic mixture to room temperature, subsequent heating or annealing processes were designed to explore the involve phase separation and crystallization behavior. The phase transition behaviors were observed in-situ by X-ray diffraction and differential scanning calorimetry (DSC). The molecular packing was observed via transmission electron microscope (TEM) and the principles of electron diffraction were brought to study the internal crystal structure epitaxially developed within thin films. Obtained results clearly indicated the occurrence of heteroepitaxy of PVDF/PVDF-TrFE on HMB crystalline platelet. Both the concentration of poly(vinylidene fluoride) and the mixing ratios of these two constitutive polymers have been adopted as the influential factors for studying the competition between the epitaxial crystallization of PVDF and P(VDF-TrFE) on HMB crystalline. Furthermore, the involved epitaxial relationship is to be deciphered and studied as a potential factor capable of guiding the wide spread of piezoelectric crystalline form.

Keywords: epitaxy, crystallization, crystalline platelet, thin film and mixing ratio

Procedia PDF Downloads 204

Authors: Ece Cigdem Mutlu, Burak Alakent

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Maintaining the quality of manufactured products at a desired level depends on the stability of process dispersion and location parameters and detection of perturbations in these parameters as promptly as possible. Shewhart control chart is the most widely used technique in statistical process monitoring to monitor the quality of products and control process mean and variability. In the application of Xbar control charts, sample standard deviation and sample mean are known to be the most efficient conventional estimators in determining process dispersion and location parameters, respectively, based on the assumption of independent and normally distributed datasets. On the other hand, there is no guarantee that the real-world data would be normally distributed. In the cases of estimated process parameters from Phase I data clouded with outliers, efficiency of traditional estimators is significantly reduced, and performance of Xbar charts are undesirably low, e.g. occasional outliers in the rational subgroups in Phase I data set may considerably affect the sample mean and standard deviation, resulting a serious delay in detection of inferior products in Phase II. For more efficient application of control charts, it is required to use robust estimators against contaminations, which may exist in Phase I. In the current study, we present a simple approach to construct robust Xbar control charts using average distance to the median, Qn-estimator of scale, M-estimator of scale with logistic psi-function in the estimation of process dispersion parameter, and Harrell-Davis qth quantile estimator, Hodge-Lehmann estimator and M-estimator of location with Huber psi-function and logistic psi-function in the estimation of process location parameter. Phase I efficiency of proposed estimators and Phase II performance of Xbar charts constructed from these estimators are compared with the conventional mean and standard deviation statistics both under normality and against diffuse-localized and symmetric-asymmetric contaminations using 50,000 Monte Carlo simulations on MATLAB. Consequently, it is found that robust estimators yield parameter estimates with higher efficiency against all types of contaminations, and Xbar charts constructed using robust estimators have higher power in detecting disturbances, compared to conventional methods. Additionally, utilizing individuals charts to screen outlier subgroups and employing different combination of dispersion and location estimators on subgroups and individual observations are found to improve the performance of Xbar charts.

Keywords: average run length, M-estimators, quality control, robust estimators

Procedia PDF Downloads 171

Authors: Homyr L. Garcia, Jr., Anne Margaret A. Rendon, Carla Michaela B. Taguinod

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Nothing is constant in this world but change. This is the reality wherein a lot of people fail to recognize and maybe, it is because of the fact that some see things that are happening with little value or no value at all until it’s gone. For the past years, Egypt was known for its stable government. It was able to withstand a lot of problems and crisis which challenged their country in ways which can never be imagined. In the present time, it seems like in just a snap of a finger, the said stability vanished and it was immediately replaced by a crisis which resulted to a failure in some parts of their government. In addition, this problem continued to worsen and the current situation of Egypt is just a reflection or a result of it. On the other hand, as the researchers continued to study the reasons why the government of Egypt is unstable, they concluded that there might be a possibility that they will be able to produce ways in which their country could be helped or improved. The instability of the government of Egypt is the product of combining all the problems which affects the lives of the people. Some of the reasons that the researchers found are the following: 1) unending doubts of the people regarding the ruling capacity of elected presidents, 2) removal of President Mohamed Morsi in position, 3) economic crisis, 4) a lot of protests and revolution happened, 5) resignation of the long term President Hosni Mubarak and 6) the office of the President is most likely available only to the chosen successor. Also, according to previous researches, there are two plausible scenarios for the instability of Egypt: 1) a military intervention specifically the Supreme Council of the Armed Forces or SCAF, resulting from a contested succession and 2) an Islamist push for political power which highlights the claim that religion is a hindrance towards the development of their country and government. From the eight possible reasons, the researchers decided that they will be focusing on economic crisis since the instability is more clearly seen in the country’s economy which directly affects the people and the government itself. In addition, they made a hypothesis which states that stable economy is a prerequisite towards a stable government. If they will be able to show how this claim is true by using the Social Autopsy Research Design for the qualitative method and Pearson’s correlation coefficient for the quantitative method, the researchers might be able to produce a proposal on how Egypt can stabilize their government and avoid such problems. Also, the hypothesis will be based from the Rational Action Theory which is a theory for understanding and modeling social and economy as well as individual behavior.

Keywords: Pearson’s correlation coefficient, rational action theory, social autopsy research design, supreme council of the armed forces (SCAF)

Procedia PDF Downloads 388

Authors: Alberto Mínguez-Martínez, Jesús de Vicente y Oliva

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Modern manufacturing processes have led to the miniaturization of systems and, as a result, parts at the micro-and nanoscale are produced. This trend seems to become increasingly important in the near future. Besides, as a requirement of Industry 4.0, the digitalization of the models of production and processes makes it very important to ensure that the dimensions of newly manufactured parts meet the specifications of the models. Therefore, it is possible to reduce the scrap and the cost of non-conformities, ensuring the stability of the production at the same time. To ensure the quality of manufactured parts, it becomes necessary to carry out traceable measurements at scales lower than one millimeter. Providing adequate traceability to the SI unit of length (the meter) to 2D and 3D measurements at this scale is a problem that does not have a unique solution in industrial environments. Researchers in the field of dimensional metrology all around the world are working on this issue. A solution for industrial environments, even if it is not complete, will enable working with some traceability. At this point, we believe that the study of the surfaces could provide us with a first approximation to a solution. Among the different options proposed in the literature, the areal topography methods may be the most relevant because they could be compared to those measurements performed using Coordinate Measuring Machines (CMM’s). These measuring methods give (x, y, z) coordinates for each point, expressing it in two different ways, either expressing the z coordinate as a function of x, denoting it as z(x), for each Y-axis coordinate, or as a function of the x and y coordinates, denoting it as z (x, y). Between others, optical measuring instruments, mainly microscopes, are extensively used to carry out measurements at scales lower than one millimeter because it is a non-destructive measuring method. In this paper, the authors propose a calibration procedure for the scales of optical measuring instruments, particularizing for a confocal microscope, using material standards easy to find and calibrate in metrology and quality laboratories in industrial environments. Confocal microscopes are measuring instruments capable of filtering the out-of-focus reflected light so that when it reaches the detector, it is possible to take pictures of the part of the surface that is focused. Varying and taking pictures at different Z levels of the focus, a specialized software interpolates between the different planes, and it could reconstruct the surface geometry into a 3D model. As it is easy to deduce, it is necessary to give traceability to each axis. As a complementary result, the roughness Ra parameter will be traced to the reference. Although the solution is designed for a confocal microscope, it may be used for the calibration of other optical measuring instruments by applying minor changes.

Keywords: industrial environment, confocal microscope, optical measuring instrument, traceability

Procedia PDF Downloads 128

Authors: Z. Terzopoulou, I. Koliakou, D. Bikiaris

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Tissue engineering offers a new approach to regenerate diseased or damaged tissues such as bone. Great effort is devoted to eliminating the need of removing non-degradable implants at the end of their life span, with biodegradable polymers playing a major part. Poly(ε-caprolactone) (PCL) is one of the best candidates for this purpose due to its high permeability, good biodegradability and exceptional biocompatibility, which has stimulated extensive research into its potential application in the biomedical fields. However, PCL degrades much slower than other known biodegradable polymers and has a total degradation of 2-4 years depending on the initial molecular weight of the device. This is due to its relatively hydrophobic character and high crystallinity. Consequently, much attention has been given to the tunable degradation of PCL to meet the diverse requirements of biomedicine. Poly(ε-caprolactone) (PCL) is a biodegradable polyester that lacks bioactivity, so when used in bone tissue engineering, new bone tissue cannot bond tightly on the polymeric surface. Therefore, it is important to incorporate reinforcing fillers into PCL matrix in order to result in a promising combination of bioactivity, biodegradability, and strength. Natural clay halloysite nanotubes (HNTs) were incorporated into PCL polymeric matrix, via in situ ring-opening polymerization of caprolactone, in concentrations 0.5, 1 and 2.5 wt%. Both unmodified and modified with aminopropyltrimethoxysilane (APTES) HNTs were used in this study. The effect of nanofiller concentration and functionalization with end-amino groups on the physicochemical properties of the prepared nanocomposites was studied. Mechanical properties were found enhanced after the incorporation of nanofillers, while the modification increased further the values of tensile and impact strength. Thermal stability of PCL was not affected by the presence of nanofillers, while the crystallization rate that was studied by Differential Scanning Calorimetry (DSC) and Polarized Light Optical Microscopy (POM) increased. All materials were subjected to enzymatic hydrolysis in phosphate buffer in the presence of lipases. Due to the hydrophilic nature of HNTs, the biodegradation rate of nanocomposites was higher compared to neat PCL. In order to confirm the effect of hydrophilicity, contact angle measurements were also performed. In vitro biomineralization test confirmed that all samples were bioactive as mineral deposits were detected by X-ray diffractometry after incubation in SBF. All scaffolds were tested in relevant cell culture using osteoblast-like cells (MG-63) to demonstrate their biocompatibility

Keywords: biomaterials, nanocomposites, scaffolds, tissue engineering

Procedia PDF Downloads 293

Authors: Yusuf Hesham Mohamed

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Introduction: Three-dimensional printing technology includes multiple procedures that fabricate three-dimensional objects through consecutively layering two-dimensional cross-sections on top of each other. 3D bioprinting is a promising field of 3D printing, which fabricates tissues and organs by accurately controlling the proper arrangement of diverse biological components. 3D bioprinting uses software and prints biological materials and their supporting components layer-by-layer on a substrate or in a tissue culture plate to produce complex live tissues and organs. 3D food printing is an emerging field of 3D bioprinting in which the 3D printed products are food products that are cheap, require less effort to produce, and have more desirable traits. The Aim of the Study is the development of an affordable 3D bioprinter by altering a locally made CNC instrument with an open-source platform to suit the 3D bio-printer purposes. Later, we went through applying the prototype in several applications regarding food technology and drug testing, including the organ-On-Chip. Materials and Methods: An off-the-shelf 3D printer was modified by designing and fabricating the syringe unit, which was designed on the basis of the Milli-fluidics system. Sodium alginate and gelatin hydrogels were prepared, followed by leaf cell suspension preparation from narrow sections of Fragaria’s viable leaves. The desired 3D structure was modeled, and 3D printing preparations took place. Cell-free and cell-laden hydrogels were printed at room temperature under sterile conditions. Post printing curing process was performed. The printed structure was further studied. Results: Positive results have been achieved using the altered 3D bioprinter where a 3D hydrogel construct of two layers made of the combination of sodium alginate to gelatin (15%: 0.5%) has been printed. DLP 3D printer was used to design the syringe component with a transparent PLA-Pro resin for the creation of a microfluidics system having two channels altered to the double extruder. The hydrogel extruder’s design was based on peristaltic pumps, which utilized a stepper motor. The design and fabrication were made using DIY-3D printed parts. Hard plastic PLA was the material utilized for printing. SEM was used to carry out the porous 3D construct imaging. Multiple physical and chemical tests were performed in order to ensure that the cell line was suitable for hosting. Fragaria plant was developed by suspending Fragaria’s cells from its leaves using the 3D bioprinter. Conclusion: 3D bioprinting is considered to be an emerging scientific field that can facilitate and improve many scientific tests and studies. Thus, having a 3D bioprinter in labs is considered to be an essential requirement. 3D bioprinters are very expensive; however, the fabrication of a 3D printer into a 3D bioprinter can lower the cost of the bioprinter. The 3D bioprinter implemented made use of peristaltic pumps instead of syringe-based pumps in order to extend the ability to print multiple types of materials and cells.

Keywords: scaffold, eco on chip, 3D bioprinter, DLP printer

Procedia PDF Downloads 99

Authors: Satoko Fujiwara, Kiyotaka Obunai, Kazuya Okubo

Abstract:

A skew is one of important problems for designing the conveyor and transmission with frictional flat belt, in which running belt is deviated in width direction due to the transverse force applied to the belt. The skew often not only degrades the stability of the path of belt but also causes some damages of the belt and auxiliary machines. However, the transverse behavior such as the skew has not been discussed quantitatively in detail for frictional belts. The objective of this study is to clarify the transverse behavior of frictional flat belt driven by tapered pulley. Commercially available rubber flat belt reinforced by polyamide film was prepared as the test belt where the thickness and length were 1.25 mm and 630 mm, respectively. Test belt was driven between two pulleys made of aluminum alloy, where diameter and inter-axial length were 50 mm and 150 mm, respectively. Some tapered pulleys were applied where tapered angles were 0 deg (for comparison), 2 deg, 4 deg, and 6 deg. In order to alternatively investigate the transverse behavior, the transverse force applied to the belt was measured when the skew was constrained at the string under driving state. The transverse force was measured by a load cell having free rollers contacting on the side surface of the belt when the displacement in the belt width direction was constrained. The conditions of observed bending stiffness in-plane of the belt were changed by preparing three types of belts (the width of the belt was 20, 30, and 40 mm) where their observed stiffnesses were changed. The contributions of the bending stiffness in-plane of belt and initial inter-axial force to the transverse were discussed in experiments. The inter-axial force was also changed by setting a distance (about 240 mm) between the two pulleys. Influence of observed bending stiffness in-plane of the belt and initial inter-axial force on the transverse force were investigated. The experimental results showed that the transverse force was increased with an increase of observed bending stiffness in-plane of the belt and initial inter-axial force. The transverse force acting on the belt running on the tapered pulley was classified into multiple components. Those were components of forces applied with the deflection of the inter-axial force according to the change of taper angle, the resultant force by the bending moment applied on the belt winding around the tapered pulley, and the reaction force applied due to the shearing deformation. The calculation result of the transverse force was almost agreed with experimental data when those components were formulated. It was also shown that the most contribution was specified to be the shearing deformation, regardless of the test conditions. This study found that transverse behavior of frictional flat belt driven by tapered pulley was explained by the summation of those components of forces.

Keywords: skew, frictional flat belt, transverse force, tapered pulley

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Authors: Alireza Barari, Saeed Shirali, Ahmad Abdi

Abstract:

Introduction: Exercise has contradictory effects on the immune system. Glutamine supplementation may increase the resistance of the immune system in athletes. The Glutamine is one of the most recognized immune nutrients that as a fuel source, substrate in the synthesis of nucleotides and amino acids and is also known to be part of the antioxidant defense. Several studies have shown that improving glutamine levels in plasma and tissues can have beneficial effects on the function of immune cells such as lymphocytes and neutrophils. This study aimed to investigate the effects of resistance training and training combined with glutamine supplementation to improve the levels of cortisol and immunoglobulin in untrained young men. The research shows that physical training can increase the cytokines in the athlete’s body of course; glutamine can counteract the negative effects of resistance training on immune function and stability of the mast cell membrane. Materials and methods: This semi-experimental study was conducted on 30 male non-athletes. They were randomly divided into three groups: control (no exercise), resistance training, resistance training and glutamine supplementation, respectively. Resistance training for 4 weeks and glutamine supplementation in 0.3 gr/kg/day after practice was applied. The resistance-training program consisted of eight exercises (leg press, lat pull, chest press, squat, seatedrow, abdominal crunch, shoulder press, biceps curl and triceps press down) four times per week. Participants performed 3 sets of 10 repetitions at 60–75% 1-RM. Anthropometry indexes (weight, body mass index, and body fat percentage), oxygen uptake (VO2max) Maximal, cortisol levels of immunoglobulins (IgA, IgG, IgM) were evaluated Pre- and post-test. Results: Results showed four week resistance training with and without glutamine cause significant increase in body weight, BMI and significantly decreased (P < 0/001) in BF. Vo2max also increased in both groups of exercise (P < 0/05) and exercise with glutamine (P < 0/001), such as in both groups significant reduction in IgG (P < 0/05) was observed. But no significant difference observed in levels of cortisol, IgA, IgM in any of the groups. No significant change observed in either parameter in the control group. No significant difference observed between the groups. Discussion: The alterations in the hormonal and immunological parameters can be used in order to assess the effect overload on the body, whether acute or chronically. The plasmatic concentration of glutamine has been associated to the functionality of the immunological system in individuals sub-mitted to intense physical training. resistance training has destructive effects on the immune system and glutamine supplementation cannot neutralize the damaging effects of power exercise on the immune system.

Keywords: glutamine, resistance traning, immuglobulins, cortisol

Procedia PDF Downloads 463

Authors: Noureddine Henka, Sami Tazi, Mohamad Assaad

Abstract:

The electrical grid is a highly intricate system designed to transfer electricity from production areas to consumption areas. The Transmission System Operator (TSO) is responsible for ensuring the efficient distribution of electricity and maintaining the grid's safety and quality. However, due to the increasing integration of intermittent renewable energy sources, there is a growing level of uncertainty, which requires a faster responsive approach. A potential solution involves the use of electrical segmentation, which involves creating coherence zones where electrical disturbances mainly remain within the zone. Indeed, by means of coherent electrical zones, it becomes possible to focus solely on the sub-zone, reducing the range of possibilities and aiding in managing uncertainty. It allows faster execution of operational processes and easier learning for supervised machine learning algorithms. Electrical segmentation can be applied to various applications, such as electrical control, minimizing electrical loss, and ensuring voltage stability. Since the electrical grid can be modeled as a graph, where the vertices represent electrical buses and the edges represent electrical lines, identifying coherent electrical zones can be seen as a clustering task on graphs, generally called community detection. Nevertheless, a critical criterion for the zones is their ability to remain resilient to the electrical evolution of the grid over time. This evolution is due to the constant changes in electricity generation and consumption, which are reflected in graph structure variations as well as line flow changes. One approach to creating a resilient segmentation is to design robust zones under various circumstances. This issue can be represented through a multiplex graph, where each layer represents a specific situation that may arise on the grid. Consequently, resilient segmentation can be achieved by conducting community detection on this multiplex graph. The multiplex graph is composed of multiple graphs, and all the layers share the same set of vertices. Our proposal involves a model that utilizes a unified representation to compute a flattening of all layers. This unified situation can be penalized to obtain (K) connected components representing the robust electrical segmentation clusters. We compare our robust segmentation to the segmentation based on a single reference situation. The robust segmentation proves its relevance by producing clusters with high intra-electrical perturbation and low variance of electrical perturbation. We saw through the experiences when robust electrical segmentation has a benefit and in which context.

Keywords: community detection, electrical segmentation, multiplex graph, power grid

Procedia PDF Downloads 54