Search results for: genetic similarity

Authors: Sadaf Moeez, Madiha Khalid, Zoya Khalid, Sania Shaheen, Sumbul Khalid

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Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.

Keywords: Diabetes, T2DM, SLC47A1, Pakistan, polymorphism.

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Authors: Parisa Shirzadeh

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Drug delivery systems in which drugs are traditionally used, multi-stage and at specified intervals by patients, do not meet the needs of the world's up-to-date drug delivery. In today's world, we are dealing with a huge number of recombinant peptide and protean drugs and analogues of hormones in the body, most of which are made with genetic engineering techniques. Most of these drugs are used to treat critical diseases such as cancer. Due to the limitations of the traditional method, researchers sought to find ways to solve the problems of the traditional method to a large extent. Following these efforts, controlled drug release systems were introduced, which have many advantages. Using controlled release of the drug in the body, the concentration of the drug is kept at a certain level, and in a short time, it is done at a higher rate. Graphene is a natural material that is biodegradable, non-toxic, natural and wide surfaces of graphene plates makes it more effective to modify graphene than carbon nanotubes. Graphene oxide is often synthesized using concentrated oxidizers such as sulfuric acid, nitric acid, and potassium permanganate based on Hummer method. graphene oxide is very hydrophilic and easily dissolves in water and creates a stable solution. Graphene oxide (GO) has been modified by chitosan (CS) covalently, developed for control release of doxorubicin (DOX). In this study, GO is produced by the hummer method under acidic conditions. Then, it is chlorinated by oxalyl chloride to increase its reactivity against amine. After that, in the presence of CS, the amino reaction was performed to form amide transplantation, and the DOX was connected to the carrier surface by π-π interaction in buffer phosphate. GO, GO-CS, and GO-CS-DOX were characterized by FT-IR and TGA to recognize new functional groups which show the new bonding of CS to GO, RAMA and SEM to recognize size of layers that show changing in size and number of layers. The ability to load and release is determined by UV-Visible spectroscopy. The loading result showed a high capacity of DOX absorption (99%) and pH dependence identified as a result of DOX release from GO-CS nanosheet at pH 5.3 and 7.4, which show a fast release rate in acidic conditions.

Keywords: Graphene oxide, chitosan, nanosheet, controlled drug release, doxorubicin.

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Authors: Krzysztof J. Czarnocki, F. Silveira, E. Czarnocka, K. Szaniawska

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Research background: Problems related to the occupational health and decreasing level of safety occur commonly in the construction industry. Important factor in the occupational safety in construction industry is scaffold use. All scaffolds used in construction, renovation, and demolition shall be erected, dismantled and maintained in accordance with safety procedure. Increasing demand for new construction projects unfortunately still is linked to high level of occupational accidents. Therefore, it is crucial to implement concrete actions while dealing with scaffolds and risk assessment in construction industry, the way on doing assessment and liability of assessment is critical for both construction workers and regulatory framework. Unfortunately, professionals, who tend to rely heavily on their own experience and knowledge when taking decisions regarding risk assessment, may show lack of reliability in checking the results of decisions taken. Purpose of the article: The aim was to indicate crucial parameters that could be modeling with Risk Assessment Model (RAM) use for improving both building enterprise productivity and/or developing potential and safety climate. The developed RAM could be a benefit for predicting high-risk construction activities and thus preventing accidents occurred based on a set of historical accident data. Methodology/Methods: A RAM has been developed for assessing risk levels as various construction process stages with various work trades impacting different spheres of enterprise activity. This project includes research carried out by teams of researchers on over 60 construction sites in Poland and Portugal, under which over 450 individual research cycles were carried out. The conducted research trials included variable conditions of employee exposure to harmful physical and chemical factors, variable levels of stress of employees and differences in behaviors and habits of staff. Genetic modeling tool has been used for developing the RAM. Findings and value added: Common types of trades, accidents, and accident causes have been explored, in addition to suitable risk assessment methods and criteria. We have found that the initial worker stress level is more direct predictor for developing the unsafe chain leading to the accident rather than the workload, or concentration of harmful factors at the workplace or even training frequency and management involvement.

Keywords: Civil engineering, occupational health, productivity, safety climate.

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Authors: Cherry Dhiman, Ayushi Paliwal, Mohd. Shahid Khan, M. N. Reddy, Vinay Gupta, Monika Tomar

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The laser based high resolution spectroscopic experimental techniques such as Laser Induced Breakdown Spectroscopy (LIBS), Rotating Disk Electrode Optical Emission spectroscopy (RDE-OES) and Surface Plasmon Resonance (SPR) have been used for the study of composition and degradation analysis of used engine oils. Engine oils are mainly composed of aliphatic and aromatics compounds and its soot contains hazardous components in the form of fine, coarse and ultrafine particles consisting of wear metal elements. Such coarse particulates matter (PM) and toxic elements are extremely dangerous for human health that can cause respiratory and genetic disorder in humans. The combustible soot from thermal power plants, industry, aircrafts, ships and vehicles can lead to the environmental and climate destabilization. It contributes towards global pollution for land, water, air and global warming for environment. The detection of such toxicants in the form of elemental analysis is a very serious issue for the waste material management of various organic, inorganic hydrocarbons and radioactive waste elements. In view of such important points, the current study on used engine oils was performed. The fundamental characterization of engine oils was conducted by measuring water content and kinematic viscosity test that proves the crude analysis of the degradation of used engine oils samples. The microscopic quantitative and qualitative analysis was presented by RDE-OES technique which confirms the presence of elemental impurities of Pb, Al, Cu, Si, Fe, Cr, Na and Ba lines for used waste engine oil samples in few ppm. The presence of such elemental impurities was confirmed by LIBS spectral analysis at various transition levels of atomic line. The recorded transition line of Pb confirms the maximum degradation which was found in used engine oil sample no. 3 and 4. Apart from the basic tests, the calculations for dielectric constants and refractive index of the engine oils were performed via SPR analysis.

Keywords: Laser induced breakdown spectroscopy, rotating disk electrode optical emission spectroscopy, surface plasmon resonance, ICCD spectrometer, Nd:YAG laser, engine oil.

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Authors: V. Keim, J. Spachtholz, J. Hammer

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The importance of fibre reinforced plastics continually increases due to the excellent mechanical properties, low material and manufacturing costs combined with significant weight reduction. Today, components are usually designed and calculated numerically by using finite element methods (FEM) to avoid expensive laboratory tests. These programs are based on material models including material specific deformation characteristics. In this research project, material models for short glass fibre reinforced plastics are presented to simulate the visco-elasto-plastic deformation behaviour. Prior to modelling specimens of the material EMS Grivory HTV-5H1, consisting of a Polyphthalamide matrix reinforced by 50wt.-% of short glass fibres, are characterized experimentally in terms of the highly time dependent deformation behaviour of the matrix material. To minimize the experimental effort, the cyclic deformation behaviour under tensile and compressive loading (R = −1) is characterized by isothermal complex low cycle fatigue (CLCF) tests. Combining cycles under two strain amplitudes and strain rates within three orders of magnitude and relaxation intervals into one experiment the visco-elastic deformation is characterized. To identify visco-plastic deformation monotonous tensile tests either displacement controlled or strain controlled (CERT) are compared. All relevant modelling parameters for this complex superposition of simultaneously varying mechanical loadings are quantified by these experiments. Subsequently, two different material models are compared with respect to their accuracy describing the visco-elasto-plastic deformation behaviour. First, based on Chaboche an extended 12 parameter model (EVP-KV2) is used to model cyclic visco-elasto-plasticity at two time scales. The parameters of the model including a total separation of elastic and plastic deformation are obtained by computational optimization using an evolutionary algorithm based on a fitness function called genetic algorithm. Second, the 12 parameter visco-elasto-plastic material model by Launay is used. In detail, the model contains a different type of a flow function based on the definition of the visco-plastic deformation as a part of the overall deformation. The accuracy of the models is verified by corresponding experimental LCF testing.

Keywords: Complex low cycle fatigue, material modelling, short glass fibre reinforced polyphthalamides, visco-elasto-plastic deformation.

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Authors: A. M. Tarola, R. Preti, A. M. Girelli, P. Campana

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Safeguarding, studying and enhancing biodiversity play an important and indispensable role in re-launching agriculture. The ancient local varieties are therefore a precious resource for genetic and health improvement. In order to protect biodiversity through the recovery and valorization of autochthonous varieties, in this study we analyzed 12 samples of four ancient apple cultivars representative of Friuli Venezia Giulia, selected by local farmers who work on a project for the recovery of ancient apple cultivars. The aim of this study is to evaluate the polyphenolic profile and the antioxidant capacity that characterize the organoleptic and functional qualities of this fruit species, besides having beneficial properties for health. In particular, for each variety, the following compounds were analyzed, both in the skins and in the pulp: gallic acid, catechin, chlorogenic acid, epicatechin, caffeic acid, coumaric acid, ferulic acid, rutin, phlorizin, phloretin and quercetin to highlight any differences in the edible parts of the apple. The analysis of individual phenolic compounds was performed by High Performance Liquid Chromatography (HPLC) coupled with a diode array UV detector (DAD), the antioxidant capacity was estimated using an in vitro essay based on a Free Radical Scavenging Method and the total phenolic compounds was determined using the Folin-Ciocalteau method. From the results, it is evident that the catechins are the most present polyphenols, reaching a value of 140-200 μg/g in the pulp and of 400-500 μg/g in the skin, with the prevalence of epicatechin. Catechins and phlorizin, a dihydrohalcone typical of apples, are always contained in larger quantities in the peel. Total phenolic compounds content was positively correlated with antioxidant activity in apple pulp (r² = 0,850) and peel (r² = 0,820). Comparing the results, differences between the varieties analyzed and between the edible parts (pulp and peel) of the apple were highlighted. In particular, apple peel is richer in polyphenolic compounds than pulp and flavonols are exclusively present in the peel. In conclusion, polyphenols, being antioxidant substances, have confirmed the benefits of fruit in the diet, especially as a prevention and treatment for degenerative diseases. They demonstrated to be also a good marker for the characterization of different apple cultivars. The importance of protecting biodiversity in agriculture was also highlighted through the exploitation of native products and ancient varieties of apples now forgotten.

Keywords: Apple, biodiversity, polyphenols, antioxidant activity, HPLC-DAD, characterization.

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Authors: Sotirios Raptis

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Health and Social care (HSc) services planning and scheduling are facing unprecedented challenges, due to the pandemic pressure and also suffer from unplanned spending that is negatively impacted by the global financial crisis. Data-driven approaches can help to improve policies, plan and design services provision schedules using algorithms that assist healthcare managers to face unexpected demands using fewer resources. The paper discusses services packing using statistical significance tests and machine learning (ML) to evaluate demands similarity and coupling. This is achieved by predicting the range of the demand (class) using ML methods such as Classification and Regression Trees (CART), Random Forests (RF), and Logistic Regression (LGR). The significance tests Chi-Squared and Student’s test are used on data over a 39 years span for which data exist for services delivered in Scotland. The demands are associated using probabilities and are parts of statistical hypotheses. These hypotheses, as their NULL part, assume that the target demand is statistically dependent on other services’ demands. This linking is checked using the data. In addition, ML methods are used to linearly predict the above target demands from the statistically found associations and extend the linear dependence of the target’s demand to independent demands forming, thus, groups of services. Statistical tests confirmed ML coupling and made the prediction statistically meaningful and proved that a target service can be matched reliably to other services while ML showed that such marked relationships can also be linear ones. Zero padding was used for missing years records and illustrated better such relationships both for limited years and for the entire span offering long-term data visualizations while limited years periods explained how well patients numbers can be related in short periods of time or that they can change over time as opposed to behaviours across more years. The prediction performance of the associations were measured using metrics such as Receiver Operating Characteristic (ROC), Area Under Curve (AUC) and Accuracy (ACC) as well as the statistical tests Chi-Squared and Student. Co-plots and comparison tables for the RF, CART, and LGR methods as well as the p-value from tests and Information Exchange (IE/MIE) measures are provided showing the relative performance of ML methods and of the statistical tests as well as the behaviour using different learning ratios. The impact of k-neighbours classification (k-NN), Cross-Correlation (CC) and C-Means (CM) first groupings was also studied over limited years and for the entire span. It was found that CART was generally behind RF and LGR but in some interesting cases, LGR reached an AUC = 0 falling below CART, while the ACC was as high as 0.912 showing that ML methods can be confused by zero-padding or by data’s irregularities or by the outliers. On average, 3 linear predictors were sufficient, LGR was found competing well RF and CART followed with the same performance at higher learning ratios. Services were packed only when a significance level (p-value) of their association coefficient was more than 0.05. Social factors relationships were observed between home care services and treatment of old people, low birth weights, alcoholism, drug abuse, and emergency admissions. The work found  that different HSc services can be well packed as plans of limited duration, across various services sectors, learning configurations, as confirmed by using statistical hypotheses.

Keywords: Class, cohorts, data frames, grouping, prediction, probabilities, services.

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Authors: Srinivas Bathini, Duraichelvan Raju, Simona Badilescu, Muthukumaran Packirisamy

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A bio-sensing method, based on the plasmonic property of gold nano-islands, has been developed for detection of exosomes in a clinical setting. The position of the gold plasmon band in the UV-Visible spectrum depends on the size and shape of gold nanoparticles as well as on the surrounding environment. By adsorbing various chemical entities, or binding them, the gold plasmon band will shift toward longer wavelengths and the shift is proportional to the concentration. Exosomes transport cargoes of molecules and genetic materials to proximal and distal cells. Presently, the standard method for their isolation and quantification from body fluids is by ultracentrifugation, not a practical method to be implemented in a clinical setting. Thus, a versatile and cutting-edge platform is required to selectively detect and isolate exosomes for further analysis at clinical level. The new sensing protocol, instead of antibodies, makes use of a specially synthesized polypeptide (Vn96), to capture and quantify the exosomes from different media, by binding the heat shock proteins from exosomes. The protocol has been established and optimized by using a glass substrate, in order to facilitate the next stage, namely the transfer of the protocol to a microfluidic environment. After each step of the protocol, the UV-Vis spectrum was recorded and the position of gold Localized Surface Plasmon Resonance (LSPR) band was measured. The sensing process was modelled, taking into account the characteristics of the nano-island structure, prepared by thermal convection and annealing. The optimal molar ratios of the most important chemical entities, involved in the detection of exosomes were calculated as well. Indeed, it was found that the results of the sensing process depend on the two major steps: the molar ratios of streptavidin to biotin-PEG-Vn96 and, the final step, the capture of exosomes by the biotin-PEG-Vn96 complex. The microfluidic device designed for sensing of exosomes consists of a glass substrate, sealed by a PDMS layer that contains the channel and a collecting chamber. In the device, the solutions of linker, cross-linker, etc., are pumped over the gold nano-islands and an Ocean Optics spectrometer is used to measure the position of the Au plasmon band at each step of the sensing. The experiments have shown that the shift of the Au LSPR band is proportional to the concentration of exosomes and, thereby, exosomes can be accurately quantified. An important advantage of the method is the ability to discriminate between exosomes having different origins.

Keywords: Exosomes, gold nano-islands, microfluidics, plasmonic biosensing.

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Authors: Thella Babu Rao, A. Gopala Krishna

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This investigation presents the formulation of kerf (width of slit) and optimal control parameter settings of wire electrochemical discharge machining which results minimum possible kerf while machining Al7075/SiCp MMCs. WEDM is proved its efficiency and effectiveness to cut the hard ceramic reinforced MMCs within the permissible budget. Among the distinct performance measures of WEDM process, kerf is an important performance characteristic which determines the dimensional accuracy of the machined component while producing high precision components. The lack of available of the machinability information such advanced MMCs result the more experimentation in the manufacturing industries. Therefore, extensive experimental investigations are essential to provide the database of effect of various control parameters on the kerf while machining such advanced MMCs in WEDM. Literature reviled the significance some of the electrical parameters which are prominent on kerf for machining distinct conventional materials. However, the significance of reinforced particulate size and volume fraction on kerf is highlighted in this work while machining MMCs along with the machining parameters of pulse-on time, pulse-off time and wire tension. Usually, the dimensional tolerances of machined components are decided at the design stage and a machinist pay attention to produce the required dimensional tolerances by setting appropriate machining control variables. However, it is highly difficult to determine the optimal machining settings for such advanced materials on the shop floor. Therefore, in the view of precision of cut, kerf (cutting width) is considered as the measure of performance for the model. It was found from the literature that, the machining conditions of higher fractions of large size SiCp resulting less kerf where as high values of pulse-on time result in a high kerf. A response surface model is used to predict the relative significance of various control variables on kerf. Consequently, a powerful artificial intelligence called genetic algorithms (GA) is used to determine the best combination of the control variable settings. In the next step the conformation test was conducted for the optimal parameter settings and found good agreement between the GA kerf and measured kerf. Hence, it is clearly reveal that the effectiveness and accuracy of the developed model and program to analyze the kerf and to determine its optimal process parameters. The results obtained in this work states that, the resulted optimized parameters are capable of machining the Al7075/SiCp MMCs more efficiently and with better dimensional accuracy.

Keywords: Al7075SiCP MMC, kerf, WEDM, optimization.

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