Search results for: soluble tumor necrosis factor-like weak inducer of apoptosis

Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Alexander V. Laikov, Alexander V. Shestopalov

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Background. Neuropathy is a common complication of obesity. In this regard, the content of neurotrophins in such patients is of particular interest. Neurotrophins are the proteins that regulate neuron survival and neuroplasticity and include brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). However, the risk of complications depends on the metabolic type of obesity. Metabolically unhealthy obesity (MUHO) is associated with a high risk of complications, while this is not the case with metabolically healthy obesity (MHO). Therefore, the aim of our work was to study the effect of the obesity metabolic type on serum neurotrophins levels. Patients, materials, methods. The study included 134 healthy donors and 104 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=40) and MUHO (n=55). In the blood serum, the concentration of BDNF and NGF was determined. In addition, the content of adipokines (leptin, asprosin, resistin, adiponectin), myokines (irisin, myostatin, osteocrin), indicators of carbohydrate, and lipid metabolism were measured. Correlation analysis revealed the relationship between the studied parameters. Results. We found that serum BDNF concentration was not different between obese patients and healthy donors, regardless of obesity metabolic type. At the same time, in obese patients, there was a decrease in serum NGF level versus control. A similar trend was characteristic of both MHO and MUHO. However, MUHO patients had a higher NGF level than MHO patients. The literature indicates that obesity is associated with an increase in the plasma concentration of NGF. It can be assumed that in obesity, there is a violation of NGF storage in platelets, which accelerates neurotrophin degradation. We found that BDNF concentration correlated with irisin levels in MUHO patients. Healthy donors had a weak association between NGF and VEGF levels. No such association was found in obese patients, but there was an association between NGF and leptin concentrations. In MHO, the concentration of NHF correlated with the content of leptin, irisin, osteocrin, insulin, and the HOMA-IR index. But in MUHO patients, we found only the relationship between NGF and adipokines (leptin, asprosin). It can be assumed that in patients with MHO, the replenishment of serum NGF occurs under the influence of muscle and adipose tissue. In the MUHO patients only the effect of adipose tissue on NGF was observed. Conclusion. Obesity, regardless of metabolic type, is associated with a decrease in serum NGF concentration. We showed that muscle and adipose tissues make a significant contribution to the serum NGF pool in the MHO patients. In MUHO there is no effect of muscle on the NGF level, but the effect of adipose tissue remains.

Keywords: neurotrophins, nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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Authors: Paramita Banerjee, K. R. S. Chandrakumar, G. P. Das

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Bulk MgH2 has drawn much attention for the purpose of hydrogen storage because of its high hydrogen storage capacity (~7.7 wt %) as well as low cost and abundant availability. However, its practical usage has been hindered because of its high hydrogen desorption enthalpy (~0.8 eV/H2 molecule), which results in an undesirable desorption temperature of 3000C at 1 bar H2 pressure. To surmount the limitations of bulk MgH2 for the purpose of hydrogen storage, a detailed first-principles density functional theory (DFT) based study on the structure and stability of neutral (Mgm) and positively charged (Mgm+) Mg nanoclusters of different sizes (m = 2, 4, 8 and 12), as well as their interaction with molecular hydrogen (H2), is reported here. It has been found that due to the absence of d-electrons within the Mg atoms, hydrogen remained in molecular form even after its interaction with neutral and charged Mg nanoclusters. Interestingly, the H2 molecules do not enter into the interstitial positions of the nanoclusters. Rather, they remain on the surface by ornamenting these nanoclusters and forming new structures with a gravimetric density higher than 15 wt %. Our observation is that the inclusion of Grimme’s DFT-D3 dispersion correction in this weakly interacting system has a significant effect on binding of the H2 molecules with these nanoclusters. The dispersion corrected interaction energy (IE) values (0.1-0.14 eV/H2 molecule) fall in the right energy window, that is ideal for hydrogen storage. These IE values are further verified by using high-level coupled-cluster calculations with non-iterative triples corrections i.e. CCSD(T), (which has been considered to be a highly accurate quantum chemical method) and thereby confirming the accuracy of our ‘dispersion correction’ incorporated DFT calculations. The significance of the polarization and dispersion energy in binding of the H2 molecules are confirmed by performing energy decomposition analysis (EDA). A total of 16, 24, 32 and 36 H2 molecules can be attached to the neutral and charged nanoclusters of size m = 2, 4, 8 and 12 respectively. Ab-initio molecular dynamics (AIMD) simulation shows that the outermost H2 molecules are desorbed at a rather low temperature viz. 150 K (-1230C) which is expected. However, complete dehydrogenation of these nanoclusters occur at around 1000C. Most importantly, the host nanoclusters remain stable up to ~500 K (2270C). All these results on the adsorption and desorption of molecular hydrogen with neutral and charged Mg nanocluster systems indicate towards the possibility of reducing the dehydrogenation temperature of bulk MgH2 by designing new Mg-based nano materials which will be able to adsorb molecular hydrogen via this weak Mg-H2 interaction, rather than the strong Mg-H bonding. Notwithstanding the fact that in practical applications, these interactions will be further complicated by the effect of substrates as well as interactions with other clusters, the present study has implications on our fundamental understanding to this problem.

Keywords: density functional theory, DFT, hydrogen storage, molecular dynamics, molecular hydrogen adsorption, nanoclusters, physisorption

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Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

Procedia PDF Downloads 79

Authors: Ankita Singh

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Sex trafficking and child pornography are those kinds of borderless crimes which can not be effectively prevented only through the laws and efforts of one country because it requires a proper and smooth collaboration among countries. Eradication of international human trafficking syndicates, criminalisation of international cyber offenders, and effective ban on child pornography is not possible without applying effective universal laws; hence, continuous collaboration of all countries is much needed to adopt and routinely update these universal laws. Congregation of countries on an international platform is very necessary from time to time, where they can simultaneously adopt international agendas and create powerful universal laws to prevent sex trafficking and child pornography in this modern digital era. In the past, some international steps have been taken through The Convention on the Rights of the Child (CRC) and through The Optional Protocol to the Convention on the Rights of the Child on the Sale of Children, Child Prostitution, and Child Pornography, but in reality, these measures are quite weak and are not capable in effectively protecting children from sexual abuse in this modern & highly advanced digital era. The uncontrolled growth of artificial intelligence (AI) and its misuse, lack of proper legal jurisdiction over foreign child abusers and difficulties in their extradition, improper control over international trade of digital child pornographic content, etc., are some prominent issues which can only be controlled through some new, effective and powerful universal laws. Due to a lack of effective international standards and a lack of improper collaboration among countries, Indian laws are also not capable of taking effective actions against child abusers. This research will be conducted through both doctrinal as well as empirical methods. Various literary sources will be examined, and a questionnaire survey will be conducted to analyse the effectiveness of international standards and Indian laws against child pornography. Participants in this survey will be Indian University students. In this work, the existing international norms made for protecting children from sexual abuse will be critically analysed. It will explore why effective and strong collaboration between countries is required in modern times. It will be analysed whether existing international steps are enough to protect children from getting trafficked or being subjected to pornography, and if these steps are not found to be sufficient enough, then suggestions will be given on how international standards and protections can be made more effective and powerful in this digital era. The approach of India towards the existing international standards, the Indian laws to protect children from being subjected to pornography, and the contributions & capabilities of India in strengthening the international standards will also be analysed.

Keywords: child pornography, prevention of children from sexual offences act, the optional protocol to the convention on the rights of the child on the sale of children, child prostitution and child pornography, the convention on the rights of the child

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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Authors: M. A. H. Barry

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The concept of Good faith (husn al-niyyah) and fair-dealing (Nadl) are the fundamental guiding elements in all contracts and other agreements under Islamic law. The preaching of Al-Quran and Prophet Muhammad’s (Peace Be upon Him) firmly command people to act in good faith in all dealings. There are several Quran verses and the Prophet’s saying which stressed the significance of dealing honestly and fairly in all transactions. Under the English law, the good faith is not considered a fundamental requirement for the formation of a legal contract. However, the concept of Good Faith in private contracts is recognized by the civil law system and in Article 7(1) of the Convention on International Sale of Goods (CISG-Vienna Convention-1980). It took several centuries for the international trading community to recognize the significance of the concept of good faith for the international sale of goods transactions. Nevertheless, the recognition of good faith in Civil law is only confined for the commercial contracts. Subsequently to the CISG, this concept has made inroads into the private international law. There are submissions in favour of applying the good faith concept to public international law based on tacit recognition by the international conventions and International Tribunals. However, under public international law the concept of good faith is not recognized as a source of rights or obligations. This weakens the spirit of the good faith concept, particularly when determining the international disputes. This also creates a fundamental flaw because the absence of good faith application means the breaches tainted by bad faith are tolerated. The objective of this research is to evaluate, examine and analyze the application of the concept of good faith in the modern laws and identify its limitation, in comparison with Islamic concept of good faith. This paper also identifies the problems and issues connected with the non-application of this concept to public international law. This research consists of three key components (1) the preliminary inquiry (2) subject analysis and discovery of research results, and (3) examining the challenging problems, and concluding with proposals. The preliminary inquiry is based on both the primary and secondary sources. The same sources are used for the subject analysis. This research also has both inductive and deductive features. The Islamic concept of good faith covers all situations and circumstances where the bad faith causes unfairness to the affected parties, especially the weak parties. Under the Islamic law, the concept of good faith is a source of rights and obligations as Islam prohibits any person committing wrongful or delinquent acts in any dealing whether in a private or public life. This rule is applicable not only for individuals but also for institutions, states, and international organizations. This paper explains how the unfairness is caused by non-recognition of the good faith concept as a source of rights or obligations under public international law and provides legal and non-legal reasons to show why the Islamic formulation is important.

Keywords: good faith, the civil law system, the Islamic concept, public international law

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Authors: Monu Ojha, Rahul Rana, Satywati Sharma, Kavya Dashora

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The global production rate of plastics has increased enormously and global demand for polyethylene resins –High-density polyethylene (HDPE), Linear low-density polyethylene (LLDPE) and Low-density polyethylene (LDPE) is expected to rise drastically, with very high value. These get accumulated in the environment, posing a potential ecological threat as they are degrading at a very slow rate and remain in the environment indefinitely. The aim of the present study was to investigate the potential of commonly found soil microbes like Bacillus subtilus, Aspergillus niger, Pseudomonas fluroscence for their ability to biodegrade LDPE in the lab on solid and liquid media conditions as well as in presence of 1% salt in the soil. This study was conducted at Indian Institute of Technology, Delhi, India from July to September where average temperature and RH (Relative Humidity) were 33 degrees Celcius and 80% respectively. It revealed that the weight loss of LDPE strip obtained from market of approximately 4x6 cm dimensions is more in liquid broth media than in solid agar media. The percentage weight loss by P. fluroscence, A. niger and B. subtilus observed after 80 days of incubation was 15.52, 9.24 and 8.99% respectively in broth media and 6.93, 2.18 and 4.76 % in agar media. The LDPE strips from same source and on the same were subjected to soil in presence of above microbes with 1% salt (NaCl: obtained from commercial table salt) with temperature and RH 33 degree Celcius and 80%. It was found that the rate of degradation increased in the soil than under lab conditions. The rate of weight loss of LDPE strips under same conditions given in lab was found to be 32.98, 15.01 and17.09 % by P. fluroscence, A. niger and B. subtilus respectively. The breaking strength was found to be 9.65N, 29N and 23.85 N for P. fluroscence, A. niger and B. subtilus respectively. SEM analysis conducted on Zeiss EVO 50 confirmed that surface of LDPE becomes physically weak after biological treatment. There was the increase in the surface roughness indicating Surface erosion of LDPE film. FTIR (Fourier-transform infrared spectroscopy) analysis of the degraded LDPE films showed stretching of aldehyde group at 3334.92 and 3228.84 cm-1,, C–C=C symmetric of aromatic ring at 1639.49 cm-1.There was also C=O stretching of aldehyde group at 1735.93 cm-1. N=O peak bend was also observed which corresponds to 1365.60 cm-1, C–O stretching of ether group at 1217.08 and 1078.21 cm-1.

Keywords: microbial degradation, LDPE, Aspergillus niger, Bacillus subtilus, Peudomonas fluroscence, common salt

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Authors: Farah Amalina Mohamed Affandi, Redhwan Ahmad Al-Naggar, Seok Mui Wang, Thanikasalam Kathiresan

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Gestational choriocarcinoma is a condition in which there is an abnormal growth or a tumor inside the women’s uterus after conception. It is a type of gestational trophoblastic disease which is relatively rare and malignant. The current epidemiological data of this disease are inadequate. The purposes of this study are to examine the epidemiology of choriocarcinoma and their risk factors based on all available population-based and hospital-based data of the disease. In this study, we searched The MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases using the keywords ‘choriocarcinoma’, ‘gestational’, ‘gestational choriocarcinoma’ and ‘epidemiology’. We included only human studies published in English between 1995 and 2015 to ensure up to date evidence. Case studies, case reports, animal studies, letters to the editor, news, and review articles were excluded. Retrieved articles were screened in three phases. In the first phase, any articles that did not match the inclusion criteria based solely on titles were excluded. In the second phase, the abstracts of remaining articles were screened thoroughly; any articles that did not meet our inclusion criteria were excluded. In the final phase, full texts of the remaining articles were read and assessed to exclude articles that did not meet the inclusion criteria or any articles that fulfilled the exclusion criteria. Duplicates articles were also removed. Systematic reviews and meta-analysis were excluded. Extracted data were summarized in table and figures descriptively. The reference lists of included studies were thoroughly reviewed in search for other relevant studies. A total of ten studies met all the selection criteria. Nine were retrospective studies and one was cohort study. Total numbers of 4563 cases of choriocarcinoma were reviewed from several countries which are Korea, Japan, South Africa, USA, New Mexico, Finland, Turkey, China, Brazil and The Netherlands. Different studies included different range of age with their mean age of 28.5 to 30.0 years. All studies investigated on the disease’s incidence rate, only two studies examined on the risk factors or associations of the disease. Approximately 20% of the studies showed a reduction in the incidence of choriocarcinoma while the other 80% showed inconsistencies in rate. Associations of age, fertility age, occupations and socio-demographic with the status remains unclear. There is limited information on the epidemiological aspects of gestational choriocarcinoma. The observed results indicated there was a decrease in the incidence rate of gestational choriocarcinoma globally. These could be due to the reduction in the incidence of molar pregnancy and the efficacy of the treatment, mainly by chemotherapy.

Keywords: epidemiology, gestational choriocarcinoma, incidence, prevalence, risk factor

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Authors: Natia Jalagonia, Tinatin Kuchukhidze

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Polymer electrolytes (PE) play an important part in electrochemical devices such as batteries and fuel cells. To achieve optimal performance, the PE must maintain a high ionic conductivity and mechanical stability at both high and low relative humidity. The polymer electrolyte also needs to have excellent chemical stability for long and robustness. According to the prevailing theory, ionic conduction in polymer electrolytes is facilitated by the large-scale segmental motion of the polymer backbone, and primarily occurs in the amorphous regions of the polymer electrolyte. Crystallinity restricts polymer backbone segmental motion and significantly reduces conductivity. Consequently, polymer electrolytes with high conductivity at room temperature have been sought through polymers which have highly flexible backbones and have largely amorphous morphology. The interest in polymer electrolytes was increased also by potential applications of solid polymer electrolytes in high energy density solid state batteries, gas sensors and electrochromic windows. Conductivity of 10-3 S/cm is commonly regarded as a necessary minimum value for practical applications in batteries. At present, polyethylene oxide (PEO)-based systems are most thoroughly investigated, reaching room temperature conductivities of 10-7 S/cm in some cross-linked salt in polymer systems based on amorphous PEO-polypropylene oxide copolymers.. It is widely accepted that amorphous polymers with low glass transition temperatures Tg and a high segmental mobility are important prerequisites for high ionic conductivities. Another necessary condition for high ionic conductivity is a high salt solubility in the polymer, which is most often achieved by donors such as ether oxygen or imide groups on the main chain or on the side groups of the PE. It is well established also that lithium ion coordination takes place predominantly in the amorphous domain, and that the segmental mobility of the polymer is an important factor in determining the ionic mobility. Great attention was pointed to PEO-based amorphous electrolyte obtained by synthesis of comb-like polymers, by attaching short ethylene oxide unit sequences to an existing amorphous polymer backbone. The aim of presented work is to obtain of solid polymer electrolyte membranes using PMHS as a matrix. For this purpose the hydrosilylation reactions of α,ω-bis(trimethylsiloxy)methyl¬hydrosiloxane with allyl triethylene-glycol mo¬nomethyl ether and vinyltriethoxysilane at 1:28:7 ratio of initial com¬pounds in the presence of Karstedt’s catalyst, platinum hydrochloric acid (0.1 M solution in THF) and platinum on the carbon catalyst in 50% solution of anhydrous toluene have been studied. The synthesized olygomers are vitreous liquid products, which are well soluble in organic solvents with specific viscosity ηsp ≈ 0.05 - 0.06. The synthesized olygomers were analysed with FTIR, 1H, 13C, 29Si NMR spectroscopy. Synthesized polysiloxanes were investigated with wide-angle X-ray, gel-permeation chromatography, and DSC analyses. Via sol-gel processes of doped with lithium trifluoromethylsulfonate (triflate) or lithium bis¬(trifluoromethylsulfonyl)¬imide polymer systems solid polymer electrolyte membranes have been obtained. The dependence of ionic conductivity as a function of temperature and salt concentration was investigated and the activation energies of conductivity for all obtained compounds are calculated

Keywords: synthesis, PMHS, membrane, electrolyte

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Authors: Amir Nazemi, Milad Ramezankhani, Marian Kӧrber, Abbas S. Milani

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The excellent strength to weight ratio of woven fabric composites, along with their high formability, is one of the primary design parameters defining their increased use in modern manufacturing processes, including those in aerospace and automotive. However, for emerging automated preform processes under the smart manufacturing paradigm, complex geometries of finished components continue to bring several challenges to the designers to cope with manufacturing defects on site. Wrinklinge. g. is a common defectoccurring during the forming process and handling of semi-finished textile composites. One of the main reasons for this defect is the weak bending stiffness of fibers in unconsolidated state, causing excessive relative motion between them. Further challenges are represented by the automated handling of large-area fiber blanks with specialized gripper systems. For fabric composites forming simulations, the finite element (FE)method is a longstanding tool usedfor prediction and mitigation of manufacturing defects. Such simulations are predominately meant, not only to predict the onset, growth, and shape of wrinkles but also to determine the best processing condition that can yield optimized positioning of the fibers upon forming (or robot handling in the automated processes case). However, the need for use of small-time steps via explicit FE codes, facing numerical instabilities, as well as large computational time, are among notable drawbacks of the current FEtools, hindering their extensive use as fast and yet efficient digital twins in industry. This paper presents a novel woven fabric simulation technique through the application of the material point method (MPM), which enables the use of much larger time steps, facing less numerical instabilities, hence the ability to run significantly faster and efficient simulationsfor fabric materials handling and forming processes. Therefore, this method has the ability to enhance the development of automated fiber handling and preform processes by calculating the physical interactions with the MPM fiber models and rigid tool components. This enables the designers to virtually develop, test, and optimize their processes based on either algorithmicor Machine Learning applications. As a preliminary case study, forming of a hemispherical plain weave is shown, and the results are compared to theFE simulations, as well as experiments.

Keywords: material point method, woven fabric composites, forming, material handling

Procedia PDF Downloads 162

Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis

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Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.

Keywords: artery, drug, nanoparticles, navigation

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Authors: Prashant Neupane, Asmi Pandey, Mumna Ehsan, Katie Davies, Richard Lowsby

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Introduction/Background & aims: Safe and effective prescribing in hospitals, directly and indirectly, impacts the health of the patients. Even though digital prescribing in the National Health Service (NHS), UK has been used in lots of tertiary centers along with district general hospitals, a significant number of NHS trusts are still using paper prescribing. We came across lots of irregularities in our daily clinical practice when we are doing paper prescribing. The main aim of the study was to assess how safely and effectively are we prescribing at our hospital where there is no access to digital prescribing. Method/Summary of work: We conducted a prospective audit in the critical care department at Mid Cheshire Hopsitals NHS Foundation Trust in which 20 prescription charts from different patients were randomly selected over a period of 1 month. We assessed 16 multiple categories from each prescription chart and compared them to the standard trust guidelines on prescription. Results/Discussion: We collected data from 20 different prescription charts. 16 categories were evaluated within each prescription chart. The results showed there was an urgent need for improvement in 8 different sections. In 85% of the prescription chart, all the prescribers who prescribed the medications were not identified. Name, GMC number and signature were absent in the required prescriber identification section of the prescription chart. In 70% of prescription charts, either indication or review date of the antimicrobials was absent. Units of medication were not documented correctly in 65% and the allergic status of the patient was absent in 30% of the charts. The start date of medications was missing and alternations of the medications were not done properly in 35%of charts. The patient's name was not recorded in all desired sections of the chart in 50% of cases and cancellations of the medication were not done properly in 45% of the prescription charts. Conclusion(s): From the audit and data analysis, we assessed the areas in which we needed improvement in prescription writing in the Critical care department. However, during the meetings and conversations with the experts from the pharmacy department, we realized this audit is just a representation of the specialized department of the hospital where access to prescribing is limited to a certain number of prescribers. But if we consider bigger departments of the hospital where patient turnover is much more, the results could be much worse. The findings were discussed in the Critical care MDT meeting where suggestions regarding digital/electronic prescribing were discussed. A poster and presentation regarding safe and effective prescribing were done, awareness poster was prepared and attached alongside every bedside in critical care where it is visible to prescribers. We consider this as a temporary measure to improve the quality of prescribing, however, we strongly believe digital prescribing will help to a greater extent to control weak areas which are seen in paper prescribing.

Keywords: safe prescribing, NHS, digital prescribing, prescription chart

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Authors: Ian Christopher Rocha

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This study aimed to determine the association of the quality of life (QOL) of the caregivers of children in need of special protection (CNSP) in child-caring institutions in Metro Manila with the levels of their role overload (RO) and role distress (RD). The CNSP in this study covered the orphaned, abandoned, abused, neglected, exploited, and mentally-challenged children. In this study, the domains of QOL included physical health (PH), psychological health, social health (SH), and living conditions (LC). It also intended to ascertain the association of their personal and work-related characteristics with their RO and RD levels. The respondents of this study were 130 CNSP caregivers in 17 residential child-rearing institutions in Metro Manila. A purposive non-probability sampling was used. Using a quantitative methodological approach, the survey method was utilized to gather data with the use of a self-administered structured questionnaire. Data were analyzed using both descriptive and inferential statistics. Results revealed that the level of RO, the level of RD, and the QOL of the CNSP caregivers were all moderate. Data also suggested that there were significant positive relationships between the RO level and the caregivers’ characteristics, such as age, the number of training, and years of service in the institution. At the same time, the findings revealed that there were significant positive relationships between the RD level and the caregivers’ characteristics, such as age and hours of care rendered to their care recipients. In addition, the findings suggested that all domains of their QOL obtained significant relationships with their RO level. For the correlations of their level of RO and their QOL domains, the PH and the LC obtained a moderate negative correlation with the RO level while the rest of the domains obtained weak negative correlations with RO level. For the correlations of their level of RD and the QOL domains, all domains, except SH, obtained strong negative correlations with the level of RD. The SH revealed to have a moderate negative correlation with RD level. In conclusion, caregivers who are older experience higher levels of RO and RD; caregivers who have more training and years of service experience the higher level of RO; and caregivers who have longer hours of rendered care experience the higher level of RD. In addition, the study affirmed that if the levels of RO and RD are high, the QOL is low, and vice versa. Therefore, the RO and RD levels are reliable predictors of the caregivers’ QOL. In relation, the caregiving situation in the Philippines revealed to be unique and distinct from other countries because the levels of RO and RD and the QOL of Filipino CNSP caregivers were all moderate in contrast with their foreign counterparts who experience high caregiving RO and RD leading to low QOL.

Keywords: quality of life, caregivers, children in need of special protection, physical health, psychological health, social health, living conditions, role overload, role distress

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Authors: Balogun R. Ayodeji, Adefisan E. Adesanya, Adeyewa Z. Debo, E. C. Okogbue

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The need to investigate diurnal weather circles in West Africa is coined in the fact that complex interactions often results from diurnal weather patterns. This study investigates diurnal circles of wind, rainfall and convective properties using six (6) hour interval data from the ERA-Interim and the Tropical Rainfall Measurement Mission (TRMM). The seven distinct zones, used in this work and classified as rainforest (west-coast, dry, Nigeria-Cameroon), Savannah (Nigeria, and Central Africa and South Sudan (CASS)), Sudano-Sahel, and Sahel, were clearly indicated by the rainfall pattern in each zones. Results showed that the land‐ocean warming contrast was more strongly sensitive to seasonal cycle and has been very weak during March-May (MAM) but clearly spelt out during June-September (JJAS). Dipoles of wind convergence/divergence and wet/dry precipitation, between CASS and Nigeria Savannah zones, were identified in morning and evening hours of MAM, whereas distinct night and day anomaly, in the same location of CASS, were found to be consistent during the JJAS season. Diurnal variation of convective properties showed that stratiform precipitation, due to the extremely low occurrence of flashcount climatology, was dominant during morning hours for both MAM and JJAS than other periods of the day. On the other hand, diurnal variation of the system sizes showed that small system sizes were most dominant during the day time periods for both MAM and JJAS, whereas larger system sizes were frequent during the evening, night, and morning hours. The locations of flashcount and system sizes agreed with earlier results that morning and day-time hours were dominated by stratiform precipitation and small system sizes respectively. Most results clearly showed that the eastern locations of Sudano and Sahel were consistently dry because rainfall and precipitation features were predominantly few. System sizes greater than or equal to 800 km² were found in the western axis of the Sudano and Sahel zones, whereas the eastern axis, particularly in the Sahel zone, had minimal occurrences of small/large system sizes. From the results of locations of extreme systems, flashcount greater than 275 in one single system was never observed during the morning (6Z) diurnal, whereas, the evening (18Z) diurnal had the most frequent cases (at least 8) of flashcount exceeding 275 in one single system. Results presented had shown the importance of diurnal variation in understanding precipitation, flashcount, system sizes patterns at diurnal scales, and understanding land-ocean contrast, precipitation, and wind field anomaly at diurnal scales.

Keywords: convective properties, diurnal circle, flashcount, system sizes

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Authors: Heba Salama, Barry Gibson, Jennifer Burr

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Introduction: It is often argued that better oral health leads to better wellbeing, and the goal of dental care is to improve wellbeing. Notwithstanding, to our best knowledge, there is a lack of evidence to support the relationship between oral health and wellbeing. Aim: The scoping review aims to examine current definitions of health and wellbeing as well as map the evidence to examine the relationship between oral health and wellbeing. Methods: The scoping review followed the Preferred Reporting Items for Systematic Reviews Extension for Scoping Review (PRISMA-ScR). A two-phase search strategy was followed because of the unmanageable number of hits returned. The first phase was to identify how well-being was conceptualised in oral health literacy, and the second phase was to search for extracted keywords. The extracted keywords were searched in four databases: PubMed, CINAHL, PsycINFO, and Web of Science. To limit the number of studies to a manageable amount, the search was limited to the open-access studies that have been published in the last five years (from 2018 to 2022). Results: Only eight studies (0.1%) of the 5455 results met the review inclusion criteria. Most of the included studies defined wellbeing based on the hedonic theory. And the Satisfaction with Life Scale is the most used. Although the research results are inconsistent, it has generally been shown that there is a weak or no association between oral health and wellbeing. Interpretation: The review revealed a very important point about how oral health literature uses loose definitions that have significant implications for empirical research. That results in misleading evidence-based conclusions. According to the review results, improving oral health is not a key factor in improving wellbeing. It appears that investing in oral health care to improve wellbeing is not a top priority to tell policymakers about. This does not imply that there should be no investment in oral health care to improve oral health. That could have an indirect link to wellbeing by eliminating the potential oral health-related barriers to quality of life that could represent the foundation of wellbeing. Limitation: Only the most recent five years (2018–2022), peer-reviewed English-language literature, and four electronic databases were included in the search. These restrictions were put in place to keep the volume of literature at a manageable level. This suggests that some significant studies might have been omitted. Furthermore, the study used a definition of wellbeing that is currently being evolved and might not everyone agrees with it. Conclusion: Whilst it is a ubiquitous argument that oral health is related to wellbeing, and this seems logical, there is little empirical evidence to support this claim. This question, therefore, requires much more detailed consideration. Funding: This project was funded by the Ministry of Higher Education and Scientific Research in Libya and Tripoli University.

Keywords: oral health, wellbeing, satisfaction, emotion, quality of life, oral health related quality of life

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Authors: P. T. Collett, M. Kershaw

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Introduction: The discussion regarding which method of anesthesia provides better results for lower limb arthroplasty is a continuing debate. Multiple meta-analysis has been performed with no clear consensus. The current recommendation is to use neuraxial anesthesia for lower limb arthroplasty; however, the evidence to support this decision is weak. The Enhanced Recovery After Surgery (ERAS) society has recommended, either technique can be used as part of a multimodal anesthetic regimen. A local study was performed to see if the current anesthetic practice correlates with the current recommendations and to evaluate the efficacy of the different techniques utilized. Method: 90 patients who underwent total hip or total knee replacements at Nevill Hall Hospital between February 2019 to July 2019 were reviewed. Data collected included the anesthetic technique, day one opiate use, pain score, and length of stay. The data was collected from anesthetic charts, and the pain team follows up forms. Analysis: The average of patients undergoing lower limb arthroplasty was 70. Of those 83% (n=75) received a spinal anaesthetic and 17% (n=15) received a general anaesthetic. For patients undergoing knee replacement under general anesthetic the average day, one pain score was 2.29 and 1.94 if a spinal anesthetic was performed. For hip replacements, the scores were 1.87 and 1.8, respectively. There was no statistical significance between these scores. Day 1 opiate usage was significantly higher in knee replacement patients who were given a general anesthetic (45.7mg IV morphine equivalent) vs. those who were operated on under spinal anesthetic (19.7mg). This difference was not noticeable in hip replacement patients. There was no significant difference in length of stay between the two anesthetic techniques. Discussion: There was no significant difference in the day one pain score between the patients who received a general or spinal anesthetic for either knee or hip replacements. The higher pain scores in the knee replacement group overall are consistent with this being a more painful procedure. This is a small patient population, which means any difference between the two groups is unlikely to be representative of a larger population. The pain scale has 4 points, which means it is difficult to identify a significant difference between pain scores. Conclusion: There is currently little standardization between the different anesthetic approaches utilized in Nevill Hall Hospital. This is likely due to the lack of adherence to a standardized anesthetic regimen. In accordance with ERAS recommends a standard anesthetic protocol is a core component. The results of this study and the guidance from the ERAS society will support the implementation of a new health board wide ERAS protocol.

Keywords: anaesthesia, orthopaedics, intensive care, patient centered decision making, treatment escalation

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Authors: Lamphong Volady

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The primary purpose of this study was to explore the traditional cuisine (local food) of Luangprabang Province in line with the Lao PDR’s One District One Product Policy. Another purpose of the study was to examine channels used to present local food, reasons to preserve and promote local food, as well as local food preservation and promotion strategies. It also aimed at testing correlation hypotheses whether there is a statistically significant relationship between enjoyment of having local food and willingness to promote local cuisines becoming international cuisines, attractiveness to consume local food, preservation and promotion of local food problems, and local people’s occupations. The Convergent Parallel Mixed Methods were employed in this study. The results of the study showed that several local cuisines were found to be local food of Luangprabang Province, namely Jeow Bon (Chilli dipping suace), Or Lam or aw lahm (stew buffalo skin, herbs, Mai sakaan), Kai Pan (River Weed Dry), Tam Mak Houng Luangprabang (Papaya Salad), Nang (Yam Buffalo Skin Dry), Sai Oor (Sausage), Laap Sin Koay Sai Mar-Keua Pao (Beef Salad with Roasted Eggplants), Orm Born (Taro leaves Stew), Oor Nor Mai (Bamboo Shoot Sausage), Jeow Nam Poo (Pickled Crab Chillies), Mok Dok Kae (steaming or roasting a Dok Kae Wrapp), Nor Sa Wan, Kao Noom Kee Noo, Kao Noom Ba Bin. It also depicted that YouTube, Facebook, and TikTok were multiple social channels or platforms which were found to be used to introduce traditional food as well as television, smartphone, word of mouth, Lao food fairs and other provincial events. The study also found that local food should be preserved and promoted since traditional food is not only ancestral, ancient, traditional, and local cuisines, but it is also wisdom, unique, and national cuisine. The study also found that people feel attracted to consuming local food because local food is delicious, unique, clean, nutritious, non-contaminated and natural. The study showed that lack of funds to produce local food, inadequate draw materials, lack material to store products, insufficient place to produce and lack of related organizations engagement were found to be problems for preserving and promoting traditional food. Finally, the result of the study revealed that there is a statistically significant weak relationship between enjoyment of having local food and willingness to promote local cuisines becoming international cuisines (R²= 4.5%), (p-value <0.001). There is a statistically significant moderate relationship between enjoyment of having local food and attractiveness to consume local food (R²= 7.8%), (p-value <0.001). However, there is a statistically insignificant relationship between enjoyment of having local food and preservation and promotion of local food problems (R²= 1.8%), (p-value = 0.086). It was found that there is a statistically insignificant relationship between enjoyment of having local food and local people’s occupations (R²= 0.0%), (p-value = 0.929).

Keywords: local food, preservation, promotion, traditional food, cuisines

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Authors: Ting Wu, Feiting Hu, Xinyue Zhang, Shuxin Tang, Xiaoyun Xu

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As a by-product of yuba, processing wastewater of Yuba (PWY) contains many bioactive components such as soybean isoflavones, soybean polysaccharides and soybean oligosaccharides, which is a good source of prebiotics and has a potential of high value utilization. The use of Lactobacillus plantarum to ferment PWY can be considered as a potential biogenic element, which can regulate the balance of intestinal microbiota. In this study, firstly, Lactobacillus plantarum was used to ferment PWY to improve its content of active components and antioxidant activity. Then, the health effect of fermented processing wastewater of yuba (FPWY) was measured in vitro. Finally, microencapsulation technology was used applied to improve the sustained release of FPWY and reduce the loss of active components in the digestion process, as well as to improving the activity of FPWY. The main results are as follows: (1) FPWY presented a good antioxidant capacity with DPPH free radical scavenging ability (0.83 ± 0.01 mmol Trolox/L), ABTS free radical scavenging ability (7.47 ± 0.35 mmol Trolox/L) and iron ion reducing ability (1.11 ± 0.07 mmol Trolox/L). Compared with non-fermented processing wastewater of yuba (NFPWY), there was no significant difference in the content of total soybean isoflavones, but the content of glucoside soybean isoflavones decreased, and aglyconic soybean isoflavones increased significantly. After fermentation, PWY can effectively reduce the soluble monosaccharides, disaccharides and oligosaccharides, such as glucose, fructose, galactose, trehalose, stachyose, maltose, raffinose and sucrose. (2) FPWY can significantly enhance the growth of beneficial bacteria such as Bifidobacterium, Ruminococcus and Akkermansia, significantly inhibit the growth of harmful bacteria E.coli, regulate the structure of intestinal microbiota, and significantly increase the content of short-chain fatty acids such as acetic acid, propionic acid, butyric acid, isovaleric acid. Higher amount of lactic acid in the gut can be further broken down into short chain fatty acids. (3) In order to improve the stability of soybean isoflavones in FPWY during digestion, sodium alginate and chitosan were used as wall materials for embedding. The FPWY freeze-dried powder was embedded by the method of acute-coagulation bath. The results show that when the core wall ratio is 3:1, the concentration of chitosan is 1.5%, the concentration of sodium alginate is 2.0%, and the concentration of calcium is 3%, the embossing rate is 53.20%. In the simulated in vitro digestion stage, the release rate of microcapsules reached 59.36% at the end of gastric digestion and 82.90% at the end of intestinal digestion. Therefore, the core materials with good sustained-release performance of microcapsules were almost all released. The structural analysis results of FPWY microcapsules show that the microcapsules have good mechanical properties. Its hardness, springness, cohesiveness, gumminess, chewiness and resilience were 117.75± 0.21 g, 0.76±0.02, 0.54±0.01, 63.28±0.71 g·sec, 48.03±1.37 g·sec, 0.31±0.01, respectively. Compared with the unembedded FPWY, the infrared spectrum results showed that the microcapsules had embedded effect on the FPWY freeze-dried powder.

Keywords: processing wastewater of yuba, lactobacillus plantarum, intestinal microbiota, microcapsule

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Authors: Nasser S. Shebka

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Fuzzy logic is used in complex adaptive systems where classical tools of representing knowledge are unproductive. Nevertheless, the incorporation of fuzzy logic, as it’s the case with all artificial intelligence tools, raised some inconsistencies and limitations in dealing with increased complexity systems and rules that apply to real-life situations and hinders the ability of the inference process of such systems, but it also faces some inconsistencies between inferences generated fuzzy rules of complex or imprecise knowledge-based systems. The use of fuzzy logic enhanced the capability of knowledge representation in such applications that requires fuzzy representation of truth values or similar multi-value constant parameters derived from multi-valued logic, which set the basis for the three t-norms and their based connectives which are actually continuous functions and any other continuous t-norm can be described as an ordinal sum of these three basic ones. However, some of the attempts to solve this dilemma were an alteration to fuzzy logic by means of non-monotonic logic, which is used to deal with the defeasible inference of expert systems reasoning, for example, to allow for inference retraction upon additional data. However, even the introduction of non-monotonic fuzzy reasoning faces a major issue of conflict resolution for which many principles were introduced, such as; the specificity principle and the weakest link principle. The aim of our work is to improve the logical representation and functional modelling of AI systems by presenting a method of resolving existing and potential rule conflicts by representing temporal modalities within defeasible inference rule-based systems. Our paper investigates the possibility of resolving fuzzy rules conflict in a non-monotonic fuzzy reasoning-based system by introducing temporal modalities and Kripke's general weak modal logic operators in order to expand its knowledge representation capabilities by means of flexibility in classifying newly generated rules, and hence, resolving potential conflicts between these fuzzy rules. We were able to address the aforementioned problem of our investigation by restructuring the inference process of the fuzzy rule-based system. This is achieved by using time-branching temporal logic in combination with restricted first-order logic quantifiers, as well as propositional logic to represent classical temporal modality operators. The resulting findings not only enhance the flexibility of complex rule-base systems inference process but contributes to the fundamental methods of building rule bases in such a manner that will allow for a wider range of applicable real-life situations derived from a quantitative and qualitative knowledge representational perspective.

Keywords: fuzzy rule-based systems, fuzzy tense inference, intelligent systems, temporal modalities

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Authors: Meral Huri, Sedef Şahin

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Post-traumatic stress disorder (PTSD) is characterized by psychiatric symptoms and triggered by a terrifying experience which may immediately effect cognitive, affective, behavioral and social skills of the individual. One of the most common noncutaneous cancer among men is prostate cancer. The incidence of psychological stress is quite common in men with prostate cancer. The aim of the study was to explore the PTSD frequency among prostate cancer and define the relationship between occupational participation, coping skills and level of perceived social support among patients with prostate cancer. Forty patients diagnosed with prostate cancer were included in the study. After dividing the patients into two groups ( study/ control) according to type of tumor, we recorded their characteristics and evaluations differences. We evaluated the demographic information form, Structured Clinical Interview for DSM-IV (SCID- I)- Clinical Version for PTSD, Multidimensional Scale of Perceived Social Support, Styles of Coping Inventory and Canadian Occupational Performance Measure (COPM) before and after 1 month from surgery. The mean age of the study group (n:18) was 65.85.6 years (range: 61-79 years). The mean age of the control group (n: 22) was a little bit higher than the study group with mean age 71.3±6.9 years (range: 60-85 years). There was no statistically significant difference between the groups for age and the other characteristics. According to the results of the study, statistically significant difference was found between the level of PTSD of study and the control group. 22% of study group showed PTSD while 13% of the control group showed PTSD (r: 0.02, p<0.001). The scores of study group and control group showed statistically significant difference in five sub-categories of Styles of Coping Inventory. Patients with prostate cancer showed decreased scores in optimistic, seeking social supports and self-confident approach, while increased scores in helpless and submissive sub-categories than the control group (p<0.001). The scores of Multidimensional Scale of Perceived Social Supports of study group and control group showed statistically significant difference. The total perceived social supports score of the study group was 71.34 ± 0.75 while it was 75.34 ± 0.64 for the control group. Total and the sub-category scores of study group were statistically significant lower than the control group. According to COPM, mean scores of occupational participation of study group for occupational performance were 4.32±2.24 and 7.01±1.52 for the control group, respectively). Mean Satisfaction scores were 3,22±2.31 and 7.45±1.74 for the study and control group, respectively. The patients with prostate cancer and benign prostate hyperplasia (BPH) did not show any statistically difference in activity performance (r:0.87) while patients with prostate cancer showed statistically lower scores than the patients with BPH in activity satisfaction (r:0.02, p<0.001).Psycho-social occupational therapy interventions might help to decrease the prevalence of PTSD by increasing associated factors such as the social support perception, using coping skills and activity participation of patients with prostate cancer.

Keywords: activity performance, occupational therapy, posttraumatic stress disorder, prostate cancer

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Authors: Christi Jackson, Chuka Onaga

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Introduction: We report a case of delayed diagnosis of extra-pulmonary INH-mono-resistant Tuberculosis (TB) in a South African patient with drug-resistant HIV. Case Presentation: A 36-year old male was initiated on 1st line (NNRTI-based) anti-retroviral therapy (ART) in September 2009 and switched to 2nd line (PI-based) ART in 2011, according to local guidelines. He was following up at the outpatient wellness unit of a public hospital, where he was diagnosed with Protease Inhibitor resistant HIV in March 2016. He had an HIV viral load (HIVVL) of 737000 copies/mL, CD4-count of 10 cells/µL and presented with complaints of productive cough, weight loss, chronic diarrhoea and a septic buttock wound. Several investigations were done on sputum, stool and pus samples but all were negative for TB. The patient was treated with antibiotics and the cough and the buttock wound improved. He was subsequently started on a 3rd-line ART regimen of Darunavir, Ritonavir, Etravirine, Raltegravir, Tenofovir and Emtricitabine in May 2016. He continued losing weight, became too weak to stand unsupported and started complaining of abdominal pain. Further investigations were done in September 2016, including a urine specimen for Line Probe Assay (LPA), which showed M. tuberculosis sensitive to Rifampicin but resistant to INH. A lymph node biopsy also showed histological confirmation of TB. Management and outcome: He was started on Rifabutin, Pyrazinamide and Ethambutol in September 2016, and Etravirine was discontinued. After 6 months on ART and 2 months on TB treatment, his HIVVL had dropped to 286 copies/mL, CD4 improved to 179 cells/µL and he showed clinical improvement. Pharmacy supply of his individualised drugs was unreliable and presented some challenges to continuity of treatment. He successfully completed his treatment in June 2017 while still maintaining virological suppression. Discussion: Several laboratory-related factors delayed the diagnosis of TB, including the unavailability of urine-lipoarabinomannan (LAM) and urine-GeneXpert (GXP) tests at this facility. Once the diagnosis was made, it presented a treatment dilemma due to the expected drug-drug interactions between his 3rd-line ART regimen and his INH-resistant TB regimen, and specialist input was required. Conclusion: TB is more difficult to diagnose in patients with severe immunosuppression, therefore additional tests like urine-LAM and urine-GXP can be helpful in expediting the diagnosis in these cases. Patients with non-standard drug regimens should always be discussed with a specialist in order to avoid potentially harmful drug-drug interactions.

Keywords: drug-resistance, HIV, line probe assay, tuberculosis

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Authors: N. K. Ambujam, V. Sudha

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Reservoirs are being contaminated all around the world with point source and Non-Point Source (NPS) pollution. The most common NPS pollutants are sediments and nutrients. Krishnagiri Reservoir (KR) has been chosen for the present case study, which is located in the tropical semi-arid climatic zone of Tamil Nadu, South India. It is the main source of surface water in Krishnagiri district to meet the freshwater demands. The reservoir has lost about 40% of its water holding capacity due to sedimentation over the period of 50 years. Hence, from the research and management perspective, there is a need for a sound knowledge on the spatial and seasonal variations of KR water quality. The present study encompasses the specific objectives as (i) to investigate the longitudinal heterogeneity and seasonal variations of physicochemical parameters, nutrients and biological characteristics of KR water and (ii) to examine the extent of degradation of water quality in KR. 15 sampling points were identified by uniform stratified method and a systematic monthly sampling strategy was selected due to high dynamic nature in its hydrological characteristics. The physicochemical parameters, major ions, nutrients and Chlorophyll a (Chl a) were analysed. Trophic status of KR was classified by using Carlson's Trophic State Index (TSI). All statistical analyses were performed by using Statistical Package for Social Sciences programme, version-16.0. Spatial maps were prepared for Chl a using Arc GIS. Observations in KR pointed out that electrical conductivity and major ions are highly variable factors as it receives inflow from the catchment with different land use activities. The study of major ions in KR exhibited different trends in their values and it could be concluded that as the monsoon progresses the major ions in the water decreases or water quality stabilizes. The inflow point of KR showed comparatively higher concentration of nutrients including nitrate, soluble reactive phosphorus (SRP), total phosphors (TP), total suspended phosphorus (TSP) and total dissolved phosphorus (TDP) during monsoon seasons. This evidently showed the input of significant amount of nutrients from the catchment side through agricultural runoff. High concentration of TDP and TSP at the lacustrine zone of the reservoir during summer season evidently revealed that there was a significant release of phosphorus from the bottom sediments. Carlson’s TSI of KR ranged between 81 and 92 during northeast monsoon and summer seasons. High and permanent Cyanobacterial bloom in KR could be mainly due to the internal loading of phosphorus from the bottom sediments. According to Carlson’s TSI classification Krishnagiri reservoir was ranked in the hyper-eutrophic category. This study provides necessary basic data on the spatio-temporal variations of water quality in KR and also proves the impact of point and NPS pollution from the catchment area. High TSI warrants a greater threat for the recovery of internal P loading and hyper-eutrophic condition of KR. Several expensive internal measures for the reduction of internal loading of P were introduced by many scientists. However, the outcome of the present research suggests for the innovative algae harvesting technique for the removal of sediment nutrients.

Keywords: NPS pollution, nutrients, hyper-eutrophication, krishnagiri reservoir

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: Sofia Lazareva, Artem Smolentsev

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Fluorescent photochromic materials collect strong interest due to their possible application in organic photonics such as optical logic systems, optical memory, visualizing sensors, as well as characterization of polymers and biological systems. In photochromic fluorescence switching systems the emission of fluorophore is modulated between ‘on’ and ‘off’ via the photoisomerization of photochromic moieties resulting in effective resonance energy transfer (FRET). In current work, we have studied both photochromic and fluorescent properties of several diarylethenes. It was found that coloured forms of these compounds are not fluorescent because of the efficient intramolecular energy transfer. Spectral and photochromic parameters of investigated substances have been measured in five solvents having different polarity. Quantum yields of photochromic transformation A↔B ΦA→B and ΦB→A as well as B isomer extinction coefficients were determined by kinetic method. It was found that the photocyclization reaction quantum yield of all compounds decreases with the increase of solvent polarity. In addition, the solvent polarity is revealed to affect fluorescence significantly. Increasing of the solvent dielectric constant was found to result in a strong shift of emission band position from 450 nm (nhexane) to 550 nm (DMSO and ethanol) for all three compounds. Moreover, the emission intensive in polar solvents becomes weak and hardly detectable in n-hexane. The only one exception in the described dependence is abnormally low fluorescence quantum yield in ethanol presumably caused by the loss of electron-donating properties of nitrogen atom due to the protonation. An effect of the protonation was also confirmed by the addition of concentrated HCl in solution resulting in a complete disappearance of the fluorescent band. Excited state dynamics were investigated by ultrafast optical spectroscopy methods. Kinetic curves of excited states absorption and fluorescence decays were measured. Lifetimes of transient states were calculated from the data measured. The mechanism of ring opening reaction was found to be polarity dependent. Comparative analysis of kinetics measured in acetonitrile and hexane reveals differences in relaxation dynamics after the laser pulse. The most important fact is the presence of two decay processes in acetonitrile, whereas only one is present in hexane. This fact supports an assumption made on the basis of steady-state preliminary experiments that in polar solvents occur stabilization of TICT state. Thus, results achieved prove the hypothesis of two channel mechanism of energy relaxation of compounds studied.

Keywords: diarylethenes, fluorescence switching, FRET, photochromism, TICT state

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Authors: Jacob Schwartz, Maxim Durach, Aniruddha Mitra, Abbas Rashidi, Glen Sage, Atin Adhikari

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NIOSH (National Institute for Occupational Safety and Health) approved N95 respirators are commonly used by workers in construction sites where there is a large amount of dust being produced from sawing, grinding, blasting, welding, etc., both electrostatically charged and not. A significant portion of airborne particles in construction sites could be nanoparticles created beside coarse particles. The penetration of the particles through the masks may differ depending on the size and charge of the individual particle. In field experiments relevant to this current study, we found that nanoparticles of medium size ranges are penetrating more frequently than nanoparticles of smaller and larger sizes. For example, penetration percentages of nanoparticles of 11.5 – 27.4 nm into a sealed N95 respirator on a manikin head ranged from 0.59 to 6.59%, whereas nanoparticles of 36.5 – 86.6 nm ranged from 7.34 to 16.04%. The possible causes behind this increased penetration of mid-size nanoparticles through mask filters are not yet explored. The objective of this study is to identify causes behind this unusual behavior of mid-size nanoparticles. We have considered such physical factors as Boltzmann distribution of the particles in thermal equilibrium with the air, kinetic energy of the particles at impact on the mask, Stoke’s drag force, and electrostatic forces in the mask stopping the particles. When the particles collide with the mask, only the particles that have enough kinetic energy to overcome the energy loss due to the electrostatic forces and the Stokes’ drag in the mask can pass through the mask. To understand this process, the following assumptions were made: (1) the effect of Stoke’s drag depends on the particles’ velocity at entry into the mask; (2) the electrostatic force is proportional to the charge on the particles, which in turn is proportional to the surface area of the particles; (3) the general dependence on electrostatic charge and thickness means that for stronger electrostatic resistance in the masks and thicker the masks’ fiber layers the penetration of particles is reduced, which is a sensible conclusion. In sampling situations where one mask was soaked in alcohol eliminating electrostatic interaction the penetration was much larger in the mid-range than the same mask with electrostatic interaction. The smaller nanoparticles showed almost zero penetration most likely because of the small kinetic energy, while the larger sized nanoparticles showed almost negligible penetration most likely due to the interaction of the particle with its own drag force. If there is no electrostatic force the fraction for larger particles grows. But if the electrostatic force is added the fraction for larger particles goes down, so diminished penetration for larger particles should be due to increased electrostatic repulsion, may be due to increased surface area and therefore larger charge on average. We have also explored the effect of ambient temperature on nanoparticle penetrations and determined that the dependence of the penetration of particles on the temperature is weak in the range of temperatures in the measurements 37-42°C, since the factor changes in the range from 3.17 10-3K-1 to 3.22 10-3K-1.

Keywords: respiratory protection, industrial hygiene, aerosol, electrostatic force

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Authors: Rajni Singh, Rakesh Mishra, Mukunda Upadhyay

Abstract:

India is among the nations born out of partition that led to one of the greatest forced migrations that marked the past century. The Indian subcontinent got partitioned into two nation-states, namely India and Pakistan. This led to an unexampled mass displacement of people accounting for about 20 million in the subcontinent as a whole. This exemplifies the socio-political version of displacement, but there are other identified reasons leading to human displacement viz., natural calamities, development projects and people-trafficking and smuggling. Although forced migrations are rare in incidence, they are mostly region-specific and a very less percentage of population appears to be affected by it. However, when this percentage is transcripted in terms of volume, the real impact created by such migration can be realized. Forced migration is thus an issue related to the lives of many people and requires to be addressed with proper intervention. Forced or involuntary migration decimates peoples' assets while taking from them their most basic resources and makes them migrate without planning and intention. This in most cases proves to be a burden on the destination resources. Thus, the question related to their security concerns arise profoundly with regard to the protection and safeguards to these migrants who need help at the place of destination. This brings the human security dimension of forced migration into picture. The present study is an analysis of a sample of 1501 persons by NSSO in India (National Sample Survey Organisation), which identifies three reasons for forced migration- natural disaster, social/political problem and displacement by development projects. It was observed that, of the total forced migrants, about 4/5th comprised of the internally displaced persons. However, there was a huge inflow of such migrants to the country from across the borders also, the major contributing countries being Bangladesh, Pakistan, Sri Lanka, Gulf countries and Nepal. Among the three reasons for involuntary migration, social and political problem is the most prominent in displacing huge masses of population; it is also the reason where the share of international migrants to that of internally displaced is higher compared to the other two factors /reasons. Second to political and social problems, natural calamities displaced a high portion of the involuntary migrants. The present paper examines the factors which increase people's vulnerability to forced migration. On perusing the background characteristics of the migrants it was seen that those who were economically weak and socially fragile are more susceptible to migration. Therefore, getting an insight about this fragile group of society is required so that government policies can benefit these in the most efficient and targeted manner.

Keywords: involuntary migration, displacement, natural disaster, social and political problem

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Authors: Shimeles Terefe Mengistue, Ascensión Del Olmo, Paola Marziani, Mirjana Pović, María Angeles Martínez-Carballo, Jaime Perea, Isabel M. Árquez

Abstract:

Quasars have historically been classified into two distinct classes, radio-loud (RL) and radio-quiet (RQ), taking into account the presence and absence of relativistic radio jets, respectively. The absence of spectra with a high S/N ratio led to the impression that all quasars (QSOs) are spectroscopically similar. Although different attempts were made to unify these two classes, there is a long-standing open debate involving the possibility of a real physical dichotomy between RL and RQ quasars. In this work, we present new high S/N spectra of 11 extremely powerful jetted quasars with radio-to-optical flux density ratio > 1000 that concomitantly cover the low-ionization emission of Mgii𝜆2800 and Hbeta𝛽 as well as the Feii blends in the redshift range 0.35 < z < 1, observed at Calar Alto Observatory (Spain). This work aims to quantify broad emission line differences between RL and RQ quasars by using the four-dimensional eigenvector 1 (4DE1) parameter space and its main sequence (MS) and to check the effect of powerful radio ejection on the low ionization broad emission lines. Emission lines are analysed by making two complementary approaches, a multicomponent non-linear fitting to account for the individual components of the broad emission lines and by analysing the full profile of the lines through parameters such as total widths, centroid velocities at different fractional intensities, asymmetry, and kurtosis indices. It is found that broad emission lines show large reward asymmetry both in Hbeta𝛽 and Mgii2800A. The location of our RL sources in a UV plane looks similar to the optical one, with weak Feii UV emission and broad Mgii2800A. We supplement the 11 sources with large samples from previous work to gain some general inferences. The result shows, compared to RQ, our extreme RL quasars show larger median Hbeta full width at half maximum (FWHM), weaker Feii emission, larger 𝑀BH, lower 𝐿bol/𝐿Edd, and a restricted space occupation in the optical and UV MS planes. The differences are more elusive when the comparison is carried out by restricting the RQ population to the region of the MS occupied by RL quasars, albeit an unbiased comparison matching 𝑀BH and 𝐿bol/𝐿Edd suggests that the most powerful RL quasars show the highest redward asymmetries in Hbeta.

Keywords: galaxies, active, line, profiles, quasars, emission lines, supermassive black holes

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Authors: B. Grygalewicz, R. Woroniecka, J. Rygier, K. Borkowska, A. Labak, B. Nowakowska, B. Pienkowska-Grela

Abstract:

Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. Hemizygous and or homozygous loss at 13q14 occur in more than half of cases and constitute the most frequent chromosomal abnormality in CLL. It is believed that deletions 13q14 play a role in CLL pathogenesis. Two microRNA genes miR-15a and miR- 16-1 are targets of 13q14 deletions and plays a tumor suppressor role by targeting antiapoptotic BCL2 gene. Deletion size, as a single change detected in FISH analysis, has haprognostic significance. Patients with small deletions, without RB1 gene involvement, have the best prognosis and the longest overall survival time (OS 133 months). In patients with bigger deletion region, containing RB1 gene, prognosis drops to intermediate, like in patients with normal karyotype and without changes in FISH with overall survival 111 months. Aim: Precise delineation of 13q14 deletions regions in two groups of CLL patients, with mono- and biallelic deletions and qualifications of their prognostic significance. Methods: Detection of 13q14 deletions was performed by FISH analysis with CLL probe panel (D13S319, LAMP1, TP53, ATM, CEP-12). Accurate deletion size detection was performed by CGH Haematological Cancer and SNP array (8x60K). Results: Our investigated group of CLL patients with the 13q14 deletion, detected by FISH analysis, comprised two groups: 18 patients with monoallelic deletions and 18 patients with biallelic deletions. In FISH analysis, in the monoallelic group the range of cells with deletion, was 43% to 97%, while in biallelic group deletion was detected in 11% to 94% of cells. Microarray analysis revealed precise deletion regions. In the monoallelic group, the range of size was 348,12 Kb to 34,82 Mb, with median deletion size 7,93 Mb. In biallelic group discrepancy of total deletions, size was 135,27 Kb to 33,33 Mb, with median deletion size 2,52 Mb. The median size of smaller deletion regions on one copy chromosome 13 was 1,08 Mb while the average region of bigger deletion on the second chromosome 13 was 4,04 Mb. In the monoallelic group, in 8/18 deletion region covered RB1 gene. In the biallelic group, in 4/18 cases, revealed deletion on one copy of biallelic deletion and in 2/18 showed deletion of RB1 gene on both deleted 13q14 regions. All minimal deleted regions included miR-15a and miR-16-1 genes. Genetic results will be correlated with clinical data. Conclusions: Application of CGH microarrays technique in CLL allows accurately delineate the size of 13q14 deletion regions, what have a prognostic value. All deleted regions included miR15a and miR-16-1, what confirms the essential role of these genes in CLL pathogenesis. In our investigated groups of CLL patients with mono- and biallelic 13q14 deletions, patients with biallelic deletion presented smaller deletion sizes (2,52 Mb vs 7,93 Mb), what is connected with better prognosis.

Keywords: CLL, deletion 13q14, CGH microarrays, SNP array

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Authors: W. A. Nalaka Wijesooriya

Abstract:

The increasing paddy production, stabilization of domestic rice consumption and the increasing dynamism of rice processing and domestic markets call for a rethinking of the general direction of the rice milling industry in Sri Lanka. The main purpose of the study was to explore levels of concentration in rice milling industry in Polonnaruwa and Hambanthota which are the major hubs of the country for rice milling. Concentration indices reveal that the rice milling industry in Polonnaruwa operates weak oligopsony and is highly competitive in Hambanthota. According to the actual quantity of paddy milling per day, 47 % is less than 8Mt/Day, while 34 % is 8-20 Mt/day, and the rest (19%) is greater than 20 Mt/day. In Hambanthota, nearly 50% of the mills belong to the range of 8-20 Mt/day. Lack of experience of the milling industry, poor knowledge on milling technology, lack of capital and finding an output market are the major entry barriers to the industry. Major problems faced by all the rice millers are the lack of a uniform electricity supply and low quality paddy. Many of the millers emphasized that the rice ceiling price is a constraint to produce quality rice. More than 80% of the millers in Polonnaruwa which is the major parboiling rice producing area have mechanical dryers. Nearly 22% millers have modern machineries like color sorters, water jet polishers. Major paddy purchasing method of large scale millers in Polonnaruwa is through brokers. In Hambanthota major channel is miller purchasing from paddy farmers. Millers in both districts have major rice selling markets in Colombo and suburbs. Huge variation can be observed in the amount of pledge (for paddy storage) loans. There is a strong relationship among the storage ability, credit affordability and the scale of operation of rice millers. The inter annual price fluctuation ranged 30%-35%. Analysis of market margins by using series of secondary data shows that farmers’ share on rice consumer price is stable or slightly increases in both districts. In Hambanthota a greater share goes to the farmer. Only four mills which have obtained the Good Manufacturing Practices (GMP) certification from Sri Lanka Standards Institution can be found. All those millers are small quantity rice exporters. Priority should be given for the Small and medium scale millers in distribution of storage paddy of PMB during the off season. The industry needs a proper rice grading system, and it is recommended to introduce a ceiling price based on graded rice according to the standards. Both husk and rice bran were underutilized. Encouraging investment for establishing rice oil manufacturing plant in Polonnaruwa area is highly recommended. The current taxation procedure needs to be restructured in order to ensure the sustainability of the industry.

Keywords: conduct, performance, structure (SCP), rice millers

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Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

Abstract:

Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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