Search results for: injectable designs for new drugs

Authors: Wadha Alqahtani

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In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

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Authors: Krystof Kryniski, Asa Kassman Rudolphi, Su Zhao, Per Lindholm

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ABB offers range of turbochargers from 500 kW to 80+ MW diesel and gas engines. Those operate on ships, power stations, generator-sets, diesel locomotives and large, off-highway vehicles. The units need to sustain harsh operating conditions, exposure to high speeds, temperatures and varying loads. They are expected to work at over-critical speeds damping effectively any transients and encountered resonances. Components are often connected via friction joints. Designs of those interfaces need to account for surface roughness, texture, pre-stress, etc. to sustain against fretting fatigue. The experience from field contributed with valuable input on components performance in hash sea environment and their exposure to high temperature, speed and load conditions. Study of tribological interactions of oxide formations provided an insight into dynamic activities occurring between the surfaces. Oxidation was recognized as the dominant factor of a wear. Microscopic inspections of fatigue cracks on turbine indicated insufficient damping and unrestrained structural stress leading to catastrophic failure, if not prevented in time. The contact interface exhibits strongly non-linear mechanism and to describe it the piecewise approach was used. Set of samples representing the combinations of materials, texture, surface and heat treatment were tested on a friction rig under range of loads, frequencies and excitation amplitudes. Developed numerical technique extracted the friction coefficient, tangential contact stiffness and damping. Vast amount of experimental data was processed with the multi-harmonics balance (MHB) method to categorize the components subjected to the periodic excitations. At the pre-defined excitation level both force and displacement formed semi-elliptical hysteresis curves having the same area and secant as the actual ones. By cross-correlating the terms remaining in the phase and out of the phase, respectively it was possible to separate an elastic energy from dissipation and derive the stiffness and damping characteristics.

Keywords: contact interface, fatigue, rotor-dynamics, torsional resonances

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Authors: Jui-Teng Liao

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The selected-response (SR) format has been commonly adopted to assess academic reading in both formal and informal testing (i.e., standardized assessment and classroom assessment) because of its strengths in content validity, construct validity, as well as scoring objectivity and efficiency. When developing a second language (L2) reading test, researchers indicate that the longer the test (e.g., more test items) is, the higher reliability and validity the test is likely to produce. However, previous studies have not provided specific guidelines regarding the optimal length of a test or the most suitable number of test items or reading passages. Additionally, reading tests often include different question types (e.g., factual, vocabulary, inferential) that require varying degrees of reading comprehension and cognitive processes. Therefore, it is important to investigate the impact of question types on the number of items in relation to the score reliability of L2 reading tests. Given the popularity of the SR question format and its impact on assessment results on teaching and learning, it is necessary to investigate the degree to which such a question format can reliably measure learners’ L2 reading comprehension. The present study, therefore, adopted the generalizability (G) theory to investigate the score reliability of the SR format in L2 reading tests focusing on how many test items a reading test should include. Specifically, this study aimed to investigate the interaction between question types and the number of items, providing insights into the appropriate item count for different types of questions. G theory is a comprehensive statistical framework used for estimating the score reliability of tests and validating their results. Data were collected from 108 English as a second language student who completed an English reading test comprising factual, vocabulary, and inferential questions in the SR format. The computer program mGENOVA was utilized to analyze the data using multivariate designs (i.e., scenarios). Based on the results of G theory analyses, the findings indicated that the number of test items had a critical impact on the score reliability of an L2 reading test. Furthermore, the findings revealed that different types of reading questions required varying numbers of test items for reliable assessment of learners’ L2 reading proficiency. Further implications for teaching practice and classroom-based assessments are discussed.

Keywords: second language reading assessment, validity and reliability, Generalizability theory, Academic reading, Question format

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Authors: Po-Ching Wang

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Considering the notable effects of natural resource consumption and impacts on fragile ecosystems, reflection on contemporary sustainable design is critical. Nevertheless, the idea of ‘green’ has been misapplied and even abused, and, in fact, much damage to the environment has been done in its name. In 1996’s popular science fiction film Independence Day, an alien species, having exhausted the natural resources of one planet, moves on to another —a fairly obvious irony on contemporary human beings’ irresponsible use of the Earth’s natural resources in modern times. In fact, the human ambition to master nature and freely access the world’s resources has long been inherent in manifestos evinced by productions of the environmental design professions. Ron Herron’s Walking City, an experimental architectural piece of 1964, is one example that comes to mind here. For this design concept, the architect imagined a gigantic nomadic urban aggregate that by way of an insect-like robotic carrier would move all over the world, on land and sea, to wherever its inhabitants want. Given the contemporary crisis regarding natural resources, recently ideas pertinent to structuring a sustainable environment have been attracting much interest in architecture, a field that has been accused of significantly contributing to ecosystem degradation. Great art, such as Fallingwater building, has been regarded as nature-friendly, but its notion of ‘green’ might be inadequate in the face of the resource demands made by human populations today. This research suggests a more conservative and scrupulous attitude to attempting to modify nature for architectural settings. Designs that pursue spiritual or metaphysical interconnections through anthropocentric aesthetics are not sufficient to benefit ecosystem integrity; though high-tech energy-saving processes may contribute to a fine-scale sustainability, they may ultimately cause catastrophe in the global scale. Design with frugality is proposed in order to actively reduce environmental load. The aesthetic taste and ecological sensibility of design professions and the public alike may have to be reshaped in order to make the goals of environmental sustainability viable.

Keywords: anthropocentric aesthetic, aquarium sustainability, biosphere 2, ecological aesthetic, ecological footprint, frugal design

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Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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Authors: Ben Main Piotr Ozieranski

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State government spending on pharmaceuticals stands at 1 trillion USD globally, promoting criticism of the pharmaceutical industry's monetization of drug efficacy, product cost overvaluation, and health injustice. This paper elucidates the mechanisms behind a state-institutional response to this problem through the sociological lens of the strategic relational approach to state power. To do so, 30 expert interviews, legal and policy documents are drawn on to explain how state elites in New Zealand have successfully contested a 30-year “pharmaceutical spending containment policy”. Proceeding from Jessop's notion of strategic “selectivity”, encompassing analyses of the enabling features of state actors' ability to harness state structures, a theoretical explanation is advanced. First, a strategic context is described that consists of dynamics around pharmaceutical dealmaking between the state bureaucracy, pharmaceutical pricing strategies (and their effects), and the industry. Centrally, the pricing strategy of "bundling" -deals for packages of drugs that combine older and newer patented products- reflect how state managers have instigated an “incentivization game” that is played by state and industry actors, including HTA professionals, over pharmaceutical products (both current and in development). Second, a protective context is described that is comprised of successive legislative-judicial responses to the strategic context and characterized by the regulation and the societalisation of commercial law. Third, within the policy, the achievement of increased pharmaceutical coverage (pharmaceutical “mix”) alongside contained spending is conceptualized as a state defence of a "social profit". As such, in contrast to scholarly expectations that political and economic cultures of neo-liberalism drive pharmaceutical policy-making processes, New Zealand's state elites' approach is shown to be antipathetic to neo-liberals within an overall capitalist economy. The paper contributes an analysis of state pricing strategies and how they are embedded in state regulatory structures. Additionally, through an analysis of the interconnections of state power and pharmaceutical value Abrahams's neo-liberal corporate bias model for pharmaceutical policy analysis is problematised.

Keywords: pharmaceutical governance, pharmaceutical bureaucracy, pricing strategies, state power, value theory

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Authors: Janet Modu, Jean-Francois Georgin, Laurent Briancon, Eric Antoinet

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The current practice during the repowering phase of wind turbines is deconstruction of existing foundations and construction of new foundations to accept larger wind loads or once the foundations have reached the end of their service lives. The ongoing research project FUI25 FEDRE (Fondations d’Eoliennes Durables et REpowering) therefore serves to propose scalable wind turbine foundation designs to allow reuse of the existing foundations. To undertake this research, numerical models and laboratory-scale models are currently being utilized and implemented in the GEOMAS laboratory at INSA Lyon following instrumentation of a reference wind turbine situated in the Northern part of France. Sensors placed within both the foundation and the underlying soil monitor the evolution of stresses from the foundation’s early age to stresses during service. The results from the instrumentation form the basis of validation for both the laboratory and numerical works conducted throughout the project duration. The study currently focuses on the effect of coupled mechanisms (Thermal-Hydro-Mechanical-Chemical) that induce stress during the early age of the reinforced concrete foundation, and scale factor considerations in the replication of the reference wind turbine foundation at laboratory-scale. Using THMC 3D models on COMSOL Multi-physics software, the numerical analysis performed on both the laboratory-scale and the full-scale foundations simulate the thermal deformation, hydration, shrinkage (desiccation and autogenous) and creep so as to predict the initial damage caused by internal processes during concrete setting and hardening. Results show a prominent effect of early age properties on the damage potential in full-scale wind turbine foundations. However, a prediction of the damage potential at laboratory scale shows significant differences in early age stresses in comparison to the full-scale model depending on the spatial position in the foundation. In addition to the well-known size effect phenomenon, these differences may contribute to inaccuracies encountered when predicting ultimate deformations of the on-site foundation using laboratory scale models.

Keywords: cement hydration, early age behavior, reinforced concrete, shrinkage, THMC 3D models, wind turbines

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Authors: Shivankar Agrawal, Sunil Kumar Deshmukh, Colin Barrow, Alok Adholeya

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A variety of genetic and environmental factors cause various cosmetics and dermatological problems. There are already claimed drugs available in market for treating these problems. However, the challenge remains in finding more potent, environmental friendly, causing minimal side effects and economical cosmeceuticals. This leads to an increased demand for natural cosmeceutical products in the last few decades. Plant derived ingredients are limited because plants either contain toxic metabolites, grow too slow or seasonal harvesting is a problem. To identify new bioactive cosmetics ingredients of marine microbial bioresource, we screened 35 marine fungi isolated from marine samples collected from Andaman Island and west coast of India. Fungal crude extracts were investigated for their antityrosinase, antioxidant and antibacterial activities for the purpose of identifying anti-aging, skin-whitening and anti-acne biomolecule with the potential in cosmetics. In the tyrosinase inhibition and 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays, two fungal extracts, including “P2”, Talaromyces stipitatus and “D4”, Aspergillus terreus showed high inhibitory activity at 1mg/mL for tyrosinase inhibition and 0.5mg/mL for DPPH scavenging. The in vitro antimicrobial activity was investigated by the agar well diffusion method. In the tyrosinase inhibition assay, 8 extracts showed significant antibacterial activity against bacteria causing skin and wound infection in humans. In the course of systematic screening program for bioactive marine fungi, strain “D5” was found to be most potent strain with MIC value of 1mg/mL, which was morphologically identified as Simplicillium lamellicola. The effects of the most active crude extracts against their susceptible test microorganisms were also investigated by SEM analysis. Further investigations will focus on purification and characterization major active components responsible for these activities.

Keywords: antioxidant, antimicrobial activity, tyrosinase, cosmeceuticals, marine fungi

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Authors: Zakaria Baka, Halima Alem

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Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

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Authors: A. Aslihan Gokaltun, Martin L. Yarmush, Ayse Asatekin, O. Berk Usta

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Poly(dimethylsiloxane) (PDMS) is one of the most widely used materials in the fabrication of microfluidic devices. It is easily patterned and can replicate features down to nanometers. Its flexibility, gas permeability that allows oxygenation, and low cost also drive its wide adoption. However, a major drawback of PDMS is its hydrophobicity and fast hydrophobic recovery after surface hydrophilization. This results in significant non-specific adsorption of proteins as well as small hydrophobic molecules such as therapeutic drugs limiting the utility of PDMS in biomedical microfluidic circuitry. While silicon, glass, and thermoplastics have been used, they come with problems of their own such as rigidity, high cost, and special tooling needs, which limit their use to a smaller user base. Many strategies to alleviate these common problems with PDMS are lack of general practical applicability, or have limited shelf lives in terms of the modifications they achieve. This restricts large scale implementation and adoption by industrial and research communities. Accordingly, we aim to tailor biocompatible PDMS surfaces by developing a simple and one step bulk modification approach with novel smart materials to reduce non-specific molecular adsorption and to stabilize long-term cell analysis with PDMS substrates. Smart polymers that blended with PDMS during device manufacture, spontaneously segregate to surfaces when in contact with aqueous solutions and create a < 1 nm layer that reduces non-specific adsorption of organic and biomolecules. Our methods are fully compatible with existing PDMS device manufacture protocols without any additional processing steps. We have demonstrated that our modified PDMS microfluidic system is effective at blocking the adsorption of proteins while retaining the viability of primary rat hepatocytes and preserving the biocompatibility, oxygen permeability, and transparency of the material. We expect this work will enable the development of fouling-resistant biomedical materials from microfluidics to hospital surfaces and tubing.

Keywords: cell culture, microfluidics, non-specific protein adsorption, PDMS, smart polymers

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Authors: Simone F. Medeiros, Jessica M. Fonseca, Gizelda M. Alves, Danilo M. Santos, Sérgio P. Campana-Filho, Amilton M. Santos

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Stimuli responsive and biocompatible hydrogel nanoparticles have gained special attention as systems for potential applications in controlled release of drugs to improve their therapeutic efficacy while minimizing side effects. In this work, novel solid dispersions based on thermo- and pH-responsive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate) hydrogel nanoparticles embedded in chitosan matrices were prepared via spray drying for controlled release of ketoprofen. Firstly, the hydrogel nanoparticles containing ketoprofen were prepared via precipitation polymerization and their stimuli-responsive behavior, thermal properties, chemical composition, encapsulation efficiency and morphology were characterized. Then, hydrogel nanoparticles with different particles size were embedded into chitosan matrices via spray-drying. Scanning electron microscopy (SEM) analyses were performed to investigate the particles size, dispersity and morphology. Finally, ketoprofen release profiles were studied as a function of pH and temperature. Chitosan/poly(NVCL-co-IA-co-EGDMA)-ketoprofen microparticles presented spherical shape, rough surface and pronounced agglomeration, indicating that hydrogels nanoparticles loaded with ketoprofen modified the surface of chitosan matrix. The maximum encapsulation efficiency of ketoprofen into hydrogel nanoparticles was 57.8% and the electrostatic interactions between amino groups from chitosan and carboxylic groups from hydrogel nanoparticles were able to control ketoprofen release. The hydrogel nanoparticles themselves were capable to retard the release of ketoprofen-loaded until 48h of in vitro release tests, while their incorporation into chitosan matrix achieved a maximum percentage of drug release of 45%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 10:7, and 69%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 5:2.

Keywords: hydrogel nanoparticles, poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate), chitosan, ketoprofen, spray-drying

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Authors: H. Haseena Banu, D. Karthick, R. Stalin, E. Nandha Kumar, T. P. Sachidanandam, P. Shanthi

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Background of the study: Type 2 diabetes is emerging as the predominant metabolic disorder in the world among adults characterized mainly by the resistance of the insulin sensitive tissues towards insulin followed by the decrease in the insulin secretion. The treatment for this disease usually involves treatment with oral synthetic drugs which are known to cause several side effects. Therefore, identification of new biomarkers as therapeutic target is the need of the hour. miRNAs are small, non–protein-coding RNAs that negatively regulate gene expression by promoting degradation and/or inhibit the translation of target mRNAs and have emerged as biomarkers in predicting diabetes mellitus. Objective of the study: To elucidate the therapeutic role of gallic acid in modulating the alterations in glucose metabolism induced by miRNAs 194 and 135a in Type 2 diabetic rats. Materials and Methods: T2D was induced in rats by feeding them with a high fat diet for 2 weeks followed by intraperitoneal injection of 35 mg/kg/body weight (b.wt.) of streptozotocin. Microarrays were used to assess the expression of miRNAs in control, diabetic and gallic acid treated rats. Gene expression studies were carried out by RT PCR analysis. Results: Forty one miRNAs were differentially expressed in Type 2 diabetic rats. Among these, the expression of miRNA 194 was significantly decreased whereas miRNA 135a was significantly increased in Type 2 diabetic rats. The glucose metabolism was also altered significantly in skeletal muscle of Type 2 diabetic rats. Conclusion: T2D is associated with alterations in the expression of miRNAs in skeletal muscle. Both these miRNAs 194 and 135a play an important role in glucose metabolism in skeletal muscle of diabetic rats. Gallic acid effectively ameliorated the alterations in glucose metabolism. Hence, both these miRNAs can serve as biomarkers and therapeutic targets in diabetes mellitus. The study also establishes the role of gallic acid as therapeutic agent. Acknowledgment: The financial assistance provided in the form of ICMR women scientist by ICMR DHR INDIA is gratefully acknowledged here.

Keywords: gallic acid, high fat diet, type 2 diabetes mellitus, miRNAs

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Authors: Brahim Aissa

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Transparent conductive oxides (TCOs) used as front electrodes in solar cells must feature simultaneously high electrical conductivity, low contact resistance with the adjacent layers, and an appropriate refractive index for maximal light in-coupling into the device. However, these properties may conflict with each other, motivating thereby the search for TCOs with high performance. Additionally, due to the presence of temperature sensitive layers in many solar cell designs (for example, in thin-film silicon and silicon heterojunction (SHJ)), low-temperature deposition processes are more suitable. Several deposition techniques have been already explored to fabricate high-mobility TCOs at low temperatures, including sputter deposition, chemical vapor deposition, and atomic layer deposition. Among this variety of methods, to the best of our knowledge, magnetron sputtering deposition is the most established technique, despite the fact that it can lead to damage of underlying layers. The Sn doped In₂O₃ (ITO) is the most commonly used transparent electrode-contact in SHJ technology. In this work, we studied the properties of ITO thin films grown by RF sputtering. Using different oxygen fraction in the argon/oxygen plasma, we prepared ITO films deposited on glass substrates, on one hand, and on a-Si (p and n-types):H/intrinsic a-Si/glass substrates, on the other hand. Hall Effect measurements were systematically conducted together with total-transmittance (TT) and total-reflectance (TR) spectrometry. The electrical properties were drastically affected whereas the TT and TR were found to be slightly impacted by the oxygen variation. Furthermore, the time of flight-secondary ion mass spectrometry (TOF-SIMS) technique was used to determine the distribution of various species throughout the thickness of the ITO and at various interfaces. The depth profiling of indium, oxygen, tin, silicon, phosphorous, boron and hydrogen was investigated throughout the various thicknesses and interfaces, and obtained results are discussed accordingly. Finally, the extreme conditions were selected to fabricate rear emitter SHJ devices, and the photovoltaic performance was evaluated; the lower oxygen flow ratio was found to yield the best performance attributed to lower series resistance.

Keywords: solar cell, silicon heterojunction, oxygen content, optoelectronic properties

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Authors: F. Alaa Ali, S. A. Sherein Abdelgayed, S. Osama. EL-Tawil, M. Adel Bakeer

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Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD₅₀) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.

Keywords: albino rats, tartrazine, toxicity, pathology

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Authors: Urip Wahyuningsih, Indarti, Yuhri Inang Prihatina

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The current development of batik art has given rise to various batik industries. The emergence of the batik industry is in order to meet the needs of the increasing share of the batik fashion market. This gives rise to competitiveness between the batik industry to compete for a share of the existing batik clothing market. Conditions like this also occur in Klampar Pamekasan Maduira Village, as one of the Batik Tourism Villages in Indonesia, it must continue to improve by trying to maintain the characteristics of Klampar Pamekasan Madura batik fashion and must also always innovate so that it remains highly competitive so that it remains one of the places popular batik tourist destination. Ready-to-wear or ready-to-wear clothing is clothing that is mass produced and produced in various sizes and colors, which can be purchased directly and worn easily. Patterned batik cloth is basically batik cloth that has the pattern lines of the clothing parts arranged efficiently, so there is no need to bother designing the pattern layout of the clothing parts on the batik cloth to be cut. Quilting can be defined as the art of combining fabric materials of certain sizes and cuts to form unique motifs. Based on several things above, breakthrough production innovation is needed without abandoning the characteristic of Klampar Pamekasan Madura Batik as one of the Batik Tourism Villages in Indonesia. One innovation that can be done is creating ready-to-wear patterned batik clothing products using a quilting technique. The method used in this research is the Double Diamond Design Process method. This method is divided into 4 phases namely, discover (namely the stage of designing the theme of the ready-to-wear patterned batik fashion innovation concept using quilting techniques in the Batik Village, Klampar Village, Pamekasasan, Madura), define (determine the design summary and present challenges to the design), develop ( presents prototypes developed, tested, reviewed and refined) and deliver (selected designs are produced, pass final tests and are ready to be commercialized). The research produces patterned batik products that are ready to wear with quilting techniques that are validated by experts and accepted by the public.

Keywords: competitiveness, ready to wear, innovation, quilting, klampar batik vllage

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Ava Simone Arteaga

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This research explores the portrayal of drug use in U.K. digital news media, a topic of critical importance due to its influence on addiction treatment, recovery efforts, and public perceptions. Substance use disorder (SUD) as one of the most stigmatized health conditions globally, with media representations playing a crucial role in shaping societal attitudes. Despite the impact of media portrayals, there has been no comprehensive analysis of drug-related representations in U.K. digital news media for over thirteen years. This study aims to fill this gap by analyzing contemporary digital news depictions of drug use, focusing on how these portrayals influence public perception and contribute to stigma. This research will examine tabloid, national, and regional East Midlands press sites to understand current trends in drug-related reporting. The study will build on previous research, such as the 2010 UKDPC study, which revealed that drug users were often vilified, and that coverage was predominantly focused on criminal justice rather than recovery. Given the rise in drug-related deaths in the U.K. and the exacerbation of the drug crisis post-Brexit, this analysis is timely and crucial. The findings are expected to reveal how digital media continues to perpetuate stigma and misinformation about drug use. By comparing these findings with U.S. studies, the research will contribute to a better understanding of cross-cultural differences in drug-related media representations and inform policy discussions. The U.K. Government's ten-year plan to combat illegal drugs, which emphasizes reducing stigma, will benefit from this research by highlighting the need for improved media representations. Additionally, the study will engage with recent U.K. and international research on media stigma towards SUD to provide a broader context and comparative perspective. Ultimately, this study aims to drive changes in media reporting and contribute to the development of more effective public policies and interventions. By addressing current gaps in research and providing evidence-based recommendations, this work seeks to support the U.K. Government’s objectives and improve the media’s role in addressing drug-related issues.

Keywords: addiction, UK news media, media representations, depiction of drug use

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Authors: Stephan Schiffer, Andreas Kain, Philipp Wilde, Maximilian Helbing, Bernard Bäker

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Automobile manufacturers progressively focus on a downsizing strategy to meet the EU's CO2 requirements concerning type-approval consumption cycles. The reduction in naturally aspirated engine power is compensated by increased levels of turbocharging. By downsizing conventional engines, CO2 emissions are reduced. However, it also implicates major challenges regarding longitudinal dynamic characteristics. An example of this circumstance is the delayed turbocharger-induced torque reaction which leads to a partially poor response behavior of the vehicle during acceleration operations. That is why it is important to focus conventional drive train design on real customer driving again. The currently considered dynamic maneuvers like the acceleration time 0-100 km/h discussed by journals and car manufacturers describe longitudinal dynamics experienced by a driver inadequately. For that reason we present the realization and evaluation of a comprehensive proband study. Subjects are provided with different vehicle concepts (electrified vehicles, vehicles with naturally aspired engines and vehicles with different concepts of turbochargers etc.) in order to find out which dynamic criteria are decisive for a subjectively strong acceleration and response behavior of a vehicle. Subsequently, realistic acceleration criteria are derived. By weighing the criteria an evaluation metric is developed to objectify customer-oriented transient dynamics. Fully-electrified vehicles are the benchmark in terms of customer-oriented longitudinal dynamics. The electric machine provides the desired torque almost without delay. This advantage compared to combustion engines is especially noticeable at low engine speeds. In conclusion, we will show the degree to which extent customer-relevant longitudinal dynamics of conventional vehicles can be approximated to electrified vehicle concepts. Therefore, various technical measures (turbocharger concepts, 48V electrical chargers etc.) and drive train designs (e.g. varying the final drive) are presented and evaluated in order to strengthen the vehicle’s customer-relevant transient dynamics. As a rating size the newly developed evaluation metric will be used.

Keywords: 48V, customer-oriented driving dynamics, electric charger, electrified vehicles, vehicle concepts

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Authors: Wei Wang, Yannick Liu, Lu Zhen, H. Wang

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Maritime transport plays an important role in global economic development but also inevitably faces increasing pressures from all sides, such as ship operating cost reduction and environmental protection. An ideal innovation to address these pressures is electric ships. The electric ship is in the early stage. Considering the special characteristics of electric ships, i.e., travel range limit, to guarantee the efficient operation of electric ships, the service network needs to be re-designed carefully. This research designs a cost-efficient and environmentally friendly service network for electric ships, including the location of charging stations, charging plan, route planning, ship scheduling, and ship deployment. The problem is formulated as a mixed-integer linear programming model with the objective of minimizing total cost comprised of charging cost, the construction cost of charging stations, and fixed cost of ships. A case study using data of the shipping network along the Yangtze River is conducted to evaluate the performance of the model. Two operating scenarios are used: an electric ship scenario where all the transportation tasks are fulfilled by electric ships and a conventional ship scenario where all the transportation tasks are fulfilled by fuel oil ships. Results unveil that the total cost of using electric ships is only 42.8% of using conventional ships. Using electric ships can reduce 80% SOx, 93.47% NOx, 89.47% PM, and 42.62% CO2, but will consume 2.78% more time to fulfill all the transportation tasks. Extensive sensitivity analyses are also conducted for key operating factors, including battery capacity, charging speed, volume capacity, and a service time limit of transportation task. Implications from the results are as follows: 1) it is necessary to equip the ship with a large capacity battery when the number of charging stations is low; 2) battery capacity will influence the number of ships deployed on each route; 3) increasing battery capacity will make the electric ship more cost-effective; 4) charging speed does not affect charging amount and location of charging station, but will influence the schedule of ships on each route; 5) there exists an optimal volume capacity, at which all costs and total delivery time are lowest; 6) service time limit will influence ship schedule and ship cost.

Keywords: cost reduction, electric ship, environmental protection, sustainable shipping

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Authors: Njabulo Ncube, Elena Kulinskaya, Nicholas Steel, Dmitry Pshezhetskiy

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Life expectancy in the United Kingdom (UK) has been near constant since 2010, particularly for the individuals of 65 years and older. This trend has been also noted in several other countries. This slowdown in the increase of life expectancy was concurrent with the increase in the number of deaths caused by non-communicable diseases. Of particular concern is the world-wide exponential increase in the number of diabetes related deaths. Previous studies have reported increased mortality hazards among diabetics compared to non-diabetics, and on the differing effects of antidiabetic drugs on mortality hazards. This study aimed to estimate the all-cause mortality hazards and related life expectancies among type 2 diabetes (T2DM) patients in the UK using the time-variant Gompertz-Cox model with frailty. The study also aimed to understand the major causes of the change in life expectancy growth in the last decade. A total of 221 182 (30.8% T2DM, 57.6% Males) individuals aged 50 years and above, born between 1930 and 1960, inclusive, and diagnosed between 2000 and 2016, were selected from The Health Improvement Network (THIN) database of the UK primary care data and followed up to 31 December 2016. About 13.4% of participants died during the follow-up period. The overall all-cause mortality hazard ratio of T2DM compared to non-diabetic controls was 1.467 (1.381-1.558) and 1.38 (1.307-1.457) when diagnosed between 50 to 59 years and 60 to 74 years, respectively. The estimated life expectancies among T2DM individuals without further comorbidities diagnosed at the age of 60 years were 2.43 (1930-1939 birth cohort), 2.53 (1940-1949 birth cohort) and 3.28 (1950-1960 birth cohort) years less than those of non-diabetic controls. However, the 1950-1960 birth cohort had a steeper hazard function compared to the 1940-1949 birth cohort for both T2DM and non-diabetic individuals. In conclusion, mortality hazards for people with T2DM continue to be higher than for non-diabetics. The steeper mortality hazard slope for the 1950-1960 birth cohort might indicate the sub-population contributing to a slowdown in the growth of the life expectancy.

Keywords: T2DM, Gompetz-Cox model with frailty, all-cause mortality, life expectancy

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Authors: M. Osibemhe, I. O. Onoagbe

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Diabetes mellitus is a common disease that has no known cure. The available orthodox drugs used for its management have one or more disadvantages. This study investigated the potency of aqueous and ethanol extracts of Strophanthus hispidus (SH) stem bark in the management of diabetes mellitus. Glucose concentration and lipid profile parameters of normal and streptozotocin-induced diabetic rats were monitored for 12weeks. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (55 mg/kg). Male rats (wistar strain) numbering 30 were randomly selected into six groups of five rats each. Groups 1 and 6 served as normal and diabetic control respectively and received distilled water for 12weeks. Groups 2 and 3 were normal rats treated orally with the aid of a gavage, 250 mg/kg of aqueous and ethanol extracts respectively for 12weeks. Groups 4 and 5 were diabetic rats and were treated with the respective dose of aqueous and ethanol extracts for the same period. A significant (P˂0.05) progressive decrease in blood glucose concentrations of both normal and diabetic rats treated with the extracts were observed from the 2nd to 12th weeks when compared with the respective controls. No significant (P˃0.05) effects were observed in the basal values of both normal and diabetic rats. Administration of both extracts of SH to diabetic rats significantly (P˂0.05) lowered the concentrations of Total cholesterol, TG, and LDL, whereas it increases the concentration of HDL when compared with diabetic control. The concentrations of total cholesterol and LDL in normal rats treated with SH were also reduced when compared with normal control whereas SH had no significant (P˃0.05) effect on HDL. However, TG level of normal control was significantly (P˂0.05) lower than normal rats treated with both extracts. A progressive increase in weight of normal and diabetic rats treated with the extracts was observed on the 2nd – 12th weeks of administration, whereas diabetic control showed a progressive decrease in weight. The findings from this study indicated that SH has hypoglycemic and anti-lipidemic properties as well as anti-diabetic potentials. It also showed that ethanol extract had greater glucose lowering effect. Hence, SH may be considered as a potent anti-diabetic plant and could be used as alternative drug for the management of diabetes mellitus.

Keywords: concentration, ethanol extract, hypoglycemic, total cholesterol

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Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Nanosized environmentally responsive materials are of special interest for various applications, including targeted drug to a considerable potential for treatment of many human diseases. The important technological advantages of nanoparticles (NPs) usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic (water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. As the next step of this research an evaluation of biocompatibility and bioavailability of the synthesized NPs has been performed, using two stable human cell culture lines – HeLa and A549. This part of study is still in progress now.

Keywords: amino acids, biodegradable polymers, nanoparticles (NPs), non-toxic building blocks

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Authors: Rong Li, Brian D. Wirth, Bing Liu

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Graphite is the matrix, and structural material in the high temperature gas-cooled reactor exhibits an irradiation response. It is of significant importance to analyze the defect production and evaluate the role of graphite under irradiation. A vast experimental literature exists for graphite on the dimensional change, mechanical properties, and thermal behavior. However, simulations have not been applied to the atomistic perspective. Remarkably few molecular dynamics simulations have been performed to study the irradiation response in graphite. In this paper, irradiation-induced damage cascades in graphite were investigated with molecular dynamics simulation. Statistical results of the graphite defects were obtained by sampling a wide energy range (1–30 KeV) and 10 different runs for every cascade simulation with different random number generator seeds to the velocity scaling thermostat function. The chemical bonding in carbon was described using the adaptive intermolecular reactive empirical bond-order potential (AIREBO) potential coupled with the standard Ziegler–Biersack–Littmack (ZBL) potential to describe close-range pair interactions. This study focused on analyzing the number of defects, the final cascade morphology and the distribution of defect clusters in space, the length-scale cascade properties such as the cascade length and the range of primary knock-on atom (PKA), and graphite mechanical properties’ variation. It can be concluded that the number of surviving Frenkel pairs increased remarkably with the increasing initial PKA energy but did not exhibit a thermal spike at slightly lower energies in this paper. The PKA range and cascade length approximately linearly with energy which indicated that increasing the PKA initial energy will come at expensive computation cost such as 30KeV in this study. The cascade morphology and the distribution of defect clusters in space mainly related to the PKA energy meanwhile the temperature effect was relatively negligible. The simulations are in agreement with known experimental results and the Kinchin-Pease model, which can help to understand the graphite damage cascades and lifetime span under irradiation and provide a direction to the designs of these kinds of structural materials in the future reactors.

Keywords: graphite damage cascade, molecular dynamics, cascade morphology, cascade distribution

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Authors: Pavel Porubiak, Lukas Kudlacek

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Introduction Transplant tourism is a controversial method of obtaining an organ, and that goes all the more for a country such as China, where sources of evidence point out to the possibility of organs being harvested illegally. This research aimed at listing the individual countries these tourists come from, or which medical companies sell transplant related products in there, with China being used as an example. Materials and methods The methodology of scoping study was used for both parts of the research. The countries from which transplant tourists come to China were identified by a search through existing medical studies in the NCBI PubMed database, listed under the keyword ‘transplantation in China’. The search was not limited by any other criteria, but only the studies available for free – directly on PubMed or a linked source – were used. Other research studies on this topic were considered as well. The companies were identified through multiple methods. The first was an online search focused on medical companies and their products. The Bloomberg Service, used by stock brokers worldwide, was then used to identify the revenue of these companies in individual countries – if data were available – as well as their business presence in China. A search through the U.S. Securities and Exchange Commission was done in the same way. Also a search on the Chinese internet was done, and to obtain more results, a second online search was done as well. The results and discussion The extensive search has identified 14 countries with transplant tourists to China. The search for a similar studies or reports resulted in finding additional six countries. The companies identified by our research also amounted to 20. Eight of them are sourcing China with organ preservation products – of which one is just trying to enter the Chinese market, six with immunosuppressive drugs, four with transplant diagnostics, one with medical robots which Chinese doctors use for transplantation as well, and another one trying to enter the Chinese market with a consumable-type product also related to transplantation. The conclusion The question of the ethicality of transplant tourism may be very pressing, since as the research shows, just the sheer amount of participating countries, sourcing transplant tourists to another one, amounts to 20. The identified companies are facing risks due to the nature of transplantation business in China, as officially executed prisoners are used as sources, and widely cited pieces of evidence point out to illegal organ harvesting. Similar risks and ethical questions are also relevant to the countries sourcing the transplant tourists to China.

Keywords: China, illegal organ harvesting, transplant tourism, organ harvesting technology

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Authors: Mario P. Walker, Masaaki Okuma

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Ships are subjected to motions which can disrupt on-board operations and damage equipment. Roll motion, in particular, is of great interest due to low damping conditions which may lead to capsizing. Therefore finding ways to reduce this motion is important in ship designs. Several techniques have been investigated to reduce rolling. These include the commonly used anti-roll tanks, fin stabilizers and bilge keels. However, these systems are not without their challenges. For example, water-flow in anti-roll tanks creates complications, and for fin stabilizers and bilge keels, an extremely large size is required to produce any significant damping creating operational challenges. Additionally, among these measures presented above only anti-roll tanks are effective in zero forward motion of the vessels. This paper proposes and investigates a method to reduce rolling by inducing Coriolis effect using water-flow in the radial direction. Motion in the radial direction of a rolling structure will induce Coriolis force and, depending on the direction of flow will either amplify or attenuate the structure. The system is modelled with two degrees of freedom, having rotational motion for parametric rolling and radial motion of the water-flow. Equations of motion are derived and investigated. Numerical examples are analyzed in detail. To demonstrate applicability parameters from a Ro-Ro vessel are used as extensive research have been conducted on these over the years. The vessel is investigated under free and forced roll conditions. Several models are created using various masses, heights, and velocities of water-flow at a given time. The proposed system was found to produce substantial roll reduction which increases with increase in any of the parameters varied as stated above, with velocity having the most significant effect. The proposed system provides a simple approach to reduce ship rolling. Water-flow control is very simple as the water flows in only one direction with constant velocity. Only needing to control the time at which the system should be turned on or off. Furthermore, the proposed system is effective in both forward and zero forward motion of the ship, and provides no hydrodynamic drag. This is a starting point for designing an effective and practical system. For this to be a viable approach further investigations are needed to address challenges that present themselves.

Keywords: Coriolis effect, damping, rolling, water-flow

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Authors: Wing Chi Wong

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Globally, studying parents caring for children with attention deficit/ hyperactivity disorder (ADHD) is valuable in order to design measures in supporting those parents by health care providers and government. Such parents in Hong Kong seem to encounter detrimental stress and enormous difficulties which are exacerbated by the traditional Chinese culture, exclusion from social members and fiercely competitive educational system. However, seldom studies scrutinize this issue in Hong Kong. This article aims to review the literature regarding parents caring offsprings with ADHD in Hong Kong. Criteria were set for searching among published studies listed in various databases, including MEDLINE, CINCAHL, PsycINFO, ProQuest, Embase, Cochrane Library and Springer Link. Articles with words 'Attention Deficit Hyperactivity Disorder', 'parenting', 'parent', 'family', 'father', 'mother', 'care' in titles and abstracts were identified. Articles with all types of research designs and methods, regardless in English or Chinese, were included. They were limited to years between January 2008 and September 2018. Four relevant studies have resulted. Of them, two were exploratory studies, one was a qualitative study, and one was a survey. Samples were recruited from child psychiatric clinic, Child and Adolescent Mental Health Unit, or multiple family group therapy centres. Authors proclaimed that quality of life of those parents was usually low; particularly mothers perceived a higher stress than fathers; parenting barriers existed; conflicts were commonly raised in parent-child relationship resulting in probable maltreatment to children. Previous studies generally suggested the potential negative outcomes of parents caring children with ADHD. The types and effectiveness of interventions to those parents on relieving their tortures under Hong Kong context had not been explored and systematically evaluated. The scanty studies and existing understanding could not give a promising conclusion pertaining to the appropriate family intervention to parents living with children with ADHD. A stringent research design is necessary to establish evidence on the effectiveness of interventions for those families.

Keywords: attention deficit/ hyperactivity disorder, Hong Kong, parents, interventions

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Authors: Mine Koyaz, M. Cem Altun

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Selection of the materials satisfying the expected performances is significantly important for any design. Today, with the constantly evolving and developing technologies, the material options are so wide that the necessity of the use of some support tools in the selection process is arising. Therefore, as a sub process of building element design, a systematic material selection tool is developed, that defines four main steps of the material selection; definition, research, comparison and decision. The main purpose of the tool is being an educational instrument that would show a methodic way of material selection in architectural detailing for the use of architecture students. The tool predefines the possible uses of various material databases and other sources of information on material properties. Hence, it is to be used as a guidance for designers, especially with a limited material knowledge and experience. The material selection tool not only embraces technical properties of materials related with building elements’ functional requirements, but also its sensual properties related with the identity of design and its environmental impacts with respect to the sustainability of the design. The method followed in the development of the tool has two main sections; first the examination and application of the existing methods and second the development of trial versions and their applications. Within the scope of the existing methods; design support tools, methodic approaches for the building element design and material selection process, material properties, material databases, methodic approaches for the decision making process are examined. The existing methods are applied by architecture students and newly graduate architects through different design problems. With respect to the results of these applications, strong and weak sides of the existing material selection tools are presented. A main flow chart of the material selection tool has been developed with the objective to apply the strong aspects of the existing methods and develop their weak sides. Through different stages, a different aspect of the material selection process is investigated and the tool took its final form. Systematic material selection tool, within the building element design process, guides the users with a minimum background information, to practically and accurately determine the ideal material that is to be chosen, satisfying the needs of their design. The tool has a flexible structure that answers different needs of different designs and designers. The trial version issued in this paper shows one of the paths that could be followed and illustrates its application over a design problem.

Keywords: architectural education, building element design, material selection tool, systematic approach

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Authors: Jerzy Slowik, Elzbieta Grochowska-Niedworok

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The analysis of the market needs and trends in both treatment and prophylaxis shows the growing need to implement comprehensive solutions that would enable safe contact of the beneficiaries with the therapeutic and diagnostic support group. Based on the evaluation of the medical and sports industry services market, projects co-financed by the EFRR in the form of comprehensive care systems using IT tools for patients under treatment in the field of obesity and metabolism using the system were implemented under the Regional Operational Program of the Silesian Voivodeship for 2014-2020. SFAO 1.0 (Support for the Fight Against Obesity) number of the WND-RPSL project. 01.02.00-24-06EA / 16) as well as for competitors in qualified sports SK system (qualified sports) project number WND-RPSL. 01.02.00-24-0630 / 17-002. The service provided in accordance with SFAO 1.0 has shown a wide range of therapy possibilities - from monitoring the body's reactions during sports activities of healthy people to remote care for sick patients. As a result of the introduction of an innovative service, it was possible to increase the effectiveness of the therapy, which was manifested in the reduction of the starting doses of drugs by 10%, improvement of the efficiency of the respiratory and blood circulation system, and a 10% increase in bone density. Innovation in the provision of medical services in the field of qualified sports SK was a response to the needs of the athletes and their parents, coaches, physiotherapists, dieticians, and doctors who take care of people actively practicing qualified sports. The creation of the platform made it possible to constantly monitor the trainers necessary for both the proper training process and the control over the health of patients. Monitoring the patient's health by a specialized team in the field of various specialties allows for the proper targeting of the treatment and training process due to the increase in the availability of medical counseling. Specialists taking care of the patient can provide additional advice and modify the medical treatment of the patient on an ongoing basis, which is why we are dealing with a holistic approach.

Keywords: innovation of medical services, sport, obesity, innovation

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Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

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Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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Authors: Grzegorz Swiderski, Agata Jablonska-Trypuc, Natalia Popow, Renata Swislocka, Wlodzimierz Lewandowski

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Doxorubicin belongs to the group of anthracycline antitumor antibiotics. Because of the wide spectrum of actions, it is one of the most widely used anthracycline antibiotics, including the treatment of breast, ovary, bladder, lung cancers as well as neuroblastoma, lymphoma, leukemia and myeloid leukemia. Antitumor activity of doxorubicin is based on the same mechanisms as for most anthracyclines. Like the metal ions affect the nucleic acids on many biological processes, so the environment of the metal chelates of antibiotics can have a significant effect on the pharmacological properties of drugs. Complexation of anthracyclines with metal ions may contribute to the production of less toxic compounds. In the framework of this study, the composition of complexes obtained in aqueous solutions of doxorubicin with metal ions (Cu2+ and Zn2+). Complexation was analyzed by spectrophotometric titration in aqueous solution at pH 7.0. The pH was adjusted with 0.02M Tris-HCl buffer. The composition of the complexes found was Cu: doxorubicin (1: 2) and a Zn: doxorubicin (1: 1). The effect of Dox, Dox-Cu and Dox-Zn was examined in MCF-7 breast cancer cell line, which were obtained from American Type Culture Collection (ATCC). The compounds were added to the cultured cells for a final concentration in the range of 0,01µM to 0,5µM. The number of MCF-7 cells with division into living and dead, was determined by direct counts of cells with the use of trypan blue dye using LUNA Logos Biosystems cell counter. ApoTox-Glo Triplex Assay (Promega, Madison, Wisconsin, USA) was used according to the manufacturer’s instructions to measure the MCF-7 cells’ viability, cytotoxicity and apoptosis. We observed a decrease in cells proliferation in a dose-dependent manner. An increase in cytotoxicity and decrease in viability in the ApoTox Triplex assay was also showed for all tested compounds. Apoptosis, showed as caspase 3/7 activation, was observed only in Dox treatment. In Dox-Zn and Dox-Cu caspase 3/7 activation was not observed. This work was financially supported by National Science Centre, Poland, under the research project number 2014/13/B/NZ7/02 352.

Keywords: anticancer properties, anthracycline antibiotic, doxorubicine, metal complexes

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