Search results for: non-prismatic compound channels

Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: Chunyang Miao, Bingxin Li, Shanglong Ning, Christopher J. B. Ford

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While it is challenging to fabricate electronic devices close to atomic dimensions in conventional top-down lithography, molecular electronics is promising to help maintain the exponential increase in component densities via using molecular building blocks to fabricate electronic components from the bottom up. It offers smaller, faster, and more energy-efficient electronic and photonic systems. A self-assembled monolayer (SAM) of molecules is a layer of molecules that self-assembles on a substrate. They are mechanically flexible, optically transparent, low-cost, and easy to fabricate. A large-area multi-layer structure has been designed and investigated by the team, where a SAM of designed molecules is sandwiched between graphene and gold electrodes. Each molecule can act as a quantum dot, with all molecules conducting in parallel. When a source-drain bias is applied, significant current flows only if a molecular orbital (HOMO or LUMO) lies within the source-drain energy window. If electrons tunnel sequentially on and off the molecule, the charge on the molecule is well-defined and the finite charging energy causes Coulomb blockade of transport until the molecular orbital comes within the energy window. This produces ‘Coulomb diamonds’ in the conductance vs source-drain and gate voltages. For different tunnel barriers at either end of the molecule, it is harder for electrons to tunnel out of the dot than in (or vice versa), resulting in the accumulation of two or more charges and a ‘Coulomb staircase’ in the current vs voltage. This nanostructure exhibits highly reproducible Coulomb-staircase patterns, together with additional oscillations, which are believed to be attributed to molecular vibrations. Molecules are more isolated than semiconductor dots, and so have a discrete phonon spectrum. When tunnelling into or out of a molecule, one or more vibronic states can be excited in the molecule, providing additional transport channels and resulting in additional peaks in the conductance. For useful molecular electronic devices, achieving the optimum orbital alignment of molecules to the Fermi energy in the leads is essential. To explore it, a drop of ionic liquid is employed on top of the graphene to establish an electric field at the graphene, which screens poorly, gating the molecules underneath. Results for various molecules with different alignments of Fermi energy to HOMO have shown highly reproducible Coulomb-diamond patterns, which agree reasonably with DFT calculations. In summary, this large-area SAM molecular junction is a promising candidate for future electronic circuits. (1) The small size (1-10nm) of the molecules and good flexibility of the SAM lead to the scalable assembly of ultra-high densities of functional molecules, with advantages in cost, efficiency, and power dissipation. (2) The contacting technique using graphene enables mass fabrication. (3) Its well-observed Coulomb blockade behaviour, narrow molecular resonances, and well-resolved vibronic states offer good tuneability for various functionalities, such as switches, thermoelectric generators, and memristors, etc.

Keywords: molecular electronics, Coulomb blokade, electron-phonon coupling, self-assembled monolayer

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Authors: Vladimir Berezin, Aizhan Turmagambetova, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Irina Zaitceva, Nadezhda Sokolova

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Introduction: Influenza viruses could infect approximately 5% to 10% of the global human population annually, resulting in serious social and economic damage. Vaccination and etiotropic antiviral drugs are used for the prevention and treatment of influenza. Vaccination is important; however, antiviral drugs represent the second line of defense against new emerging influenza virus strains for which vaccines may be unsuccessful. However, the significant drawback of commercial synthetic anti-flu drugs is the appearance of drug-resistant influenza virus strains. Therefore, the search and development of new anti-flu drugs efficient against drug-resistant strains is an important medical problem for today. The aim of this work was a study of four phenolic acids of plant origin (Gallic, Syringic, Vanillic, and Protocatechuic acids) as a possible tool for treatment against influenza virus. Methods: Phenolic acids; gallic, syringic, vanillic, and protocatechuic have been prepared by extraction from plant tissues and purified using high-performance liquid chromatography fractionation. Avian influenza virus, strain A/Tern/South Africa/1/1961 (H5N3) and human epidemic influenza virus, strain A/Almaty/8/98 (H3N2) resistant to commercial anti-flu drugs (Rimantadine, Oseltamivir) were used for testing antiviral activity. Viruses were grown in the allantoic cavity of 10 days old chicken embryos. The chemotherapeutic index (CTI), determined as the ratio of an average toxic concentration of the tested compound (TC₅₀) to the average effective virus-inhibition concentration (EC₅₀), has been used as a criteria of specific antiviral action. Results: The results of study have shown that the structure of phenolic acids significantly affected their ability to suppress the reproduction of tested influenza virus strains. The highest antiviral activity among tested phenolic acids was detected for gallic acid, which contains three hydroxyl groups in the molecule at C3, C4, and C5 positions. Antiviral activity of gallic acid against A/H5N3 and A/H3N2 influenza virus strains was higher than antiviral activity of Oseltamivir and Rimantadine. gallic acid inhibited almost 100% of the infection activity of both tested viruses. Protocatechuic acid, which possesses 2 hydroxyl groups (C3 and C4) have shown weaker antiviral activity in comparison with gallic acid and inhibited less than 10% of virus infection activity. Syringic acid, which contains two hydroxyl groups (C3 and C5), was able to suppress up to 12% of infection activity. Substitution of two hydroxyl groups by methoxy groups resulted in the complete loss of antiviral activity. Vanillic acid, which is different from protocatechuic acid by replacing of C3 hydroxyl group to methoxy group, was able to suppress about 30% of infection activity of tested influenza viruses. Conclusion: For pronounced antiviral activity, the molecular of phenolic acid must have at least two hydroxyl groups. Replacement of hydroxyl groups to methoxy group leads to a reduction of antiviral properties. Gallic acid demonstrated high antiviral activity against influenza viruses, including Rimantadine and Oseltamivir resistant strains, and could be used as a potential candidate for the development of antiviral drug against influenza virus.

Keywords: antiviral activity, influenza virus, drug resistance, phenolic acids

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Authors: Blaga Alexandra Cristina, Kloetzer Lenuta, Bompa Amalia Stela, Galaction Anca Irina, Cascaval Dan

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Vitamin B9 is an important member of vitamins B group, being a growth factor, important for making genetic material as DNA and RNA, red blood cells, for building muscle tissues, especially during periods of infancy, adolescence and pregnancy. Its production by biosynthesis is based on the high metabolic potential of mutant Bacillus subtilis, due to a superior biodisponibility compared to that obtained by chemical pathways. Pertraction, defined as the extraction and transport through liquid membranes consists in the transfer of a solute between two aqueous phases of different pH-values, phases that are separated by a solvent layer of various sizes. The pertraction efficiency and selectivity could be significantly enhanced by adding a carrier in the liquid membrane, such as organophosphoric compounds, long chain amines or crown-ethers etc., the separation process being called facilitated pertraction. The aim of the work is to determine the impact of the presence of two extractants/carriers in the bulk liquid membrane, i.e. di(2-ethylhexyl) phosphoric acid (D2EHPA) and lauryltrialkylmetilamine (Amberlite LA2) on the transport kinetics of vitamin B9. The experiments have been carried out using two pertraction equipments for a free liquid membrane or bulk liquid membrane. One pertraction cell consists on a U-shaped glass pipe (used for the dichloromethane membrane) and the second one is an H-shaped glass pipe (used for h-heptane), having 45 mm inner diameter of the total volume of 450 mL, the volume of each compartment being of 150 mL. The aqueous solutions are independently mixed by means of double blade stirrers with 6 mm diameter and 3 mm height, having the rotation speed of 500 rpm. In order to reach high diffusional rates through the solvent layer, the organic phase has been mixed with a similar stirrer, at a similar rotation speed (500 rpm). The area of mass transfer surface, both for extraction and for reextraction, was of 1.59x10-³ m2. The study on facilitated pertraction with the mixture of two carriers, namely D2EHPA and Amberlite LA-2, dissolved in two solvents with different polarities: n-heptane and dichloromethane, indicated the possibility to obtain the synergic effect. The synergism has been analyzed by considering the vitamin initial and final mass flows, as well as the permeability factors through liquid membrane. The synergic effect has been observed at low D2EHPA concentrations and high Amberlite LA-2 concentrations, being more important for the low-polar solvent (n-heptane). The results suggest that the mechanism of synergic pertraction consists on the reaction between the organophosphoric carrier and vitamin B9 at the interface between the feed and membrane phases, while the aminic carrier enhances the hydrophobicity of this compound by solvation. However, the formation of this complex reduced the reextraction rate and, consequently, affects the synergism related to the final mass flows and permeability factor. For describing the influences of carriers concentrations on the synergistic coefficients, some equations have been proposed by taking into account the vitamin mass flows or permeability factors, with an average deviations between 4.85% and 10.73%.

Keywords: pertraction, synergism, vitamin B9, Amberlite LA-2, di(2-ethylhexyl) phosphoric acid

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Authors: Jonathan Kissi, Baozhen Dai, Wisdom W. K. Pomegbe, Abdul-Basit Kassim

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Protecting patient’s digital information is a growing concern for healthcare institutions as people nowadays perpetually live their lives through telemedicine services. These telemedicine services have been confronted with several determinants that hinder their successful implementations, especially in developing countries. Identifying such determinants that influence the acceptance of telemedicine services is also a problem for healthcare professionals. Despite the tremendous increase in telemedicine services, its adoption, and use has been quite slow in some healthcare settings. Generally, it is accepted in today’s globalizing world that the success of telemedicine services relies on users’ satisfaction. Satisfying health professionals and patients are one of the crucial objectives of telemedicine success. This study seeks to investigate the determinants that influence health professionals’ intention to utilize telemedicine services in clinical activities in a sub-Saharan African country in West Africa (Ghana). A hybridized model comprising of health adoption models, including technology acceptance theory, diffusion of innovation theory, and protection of motivation theory, were used to investigate these quandaries. The study was carried out in four government health institutions that apply and regulate telemedicine services in their clinical activities. A structured questionnaire was developed and used for data collection. Purposive and convenience sampling methods were used in the selection of healthcare professionals from different medical fields for the study. The collected data were analyzed based on structural equation modeling (SEM) approach. All selected constructs showed a significant relationship with health professional’s behavioral intention in the direction expected from prior literature including perceived usefulness, perceived ease of use, management strategies, financial sustainability, communication channels, patients security threat, patients privacy risk, self efficacy, actual service use, user satisfaction, and telemedicine services systems securities threat. Surprisingly, user characteristics and response efficacy of health professionals were not significant in the hybridized model. The findings and insights from this research show that health professionals are pragmatic when making choices for technology applications and also their willingness to use telemedicine services. They are, however, anxious about its threats and coping appraisals. The identified significant constructs in the study may help to increase efficiency, quality of services, quality patient care delivery, and satisfactory user satisfaction among healthcare professionals. The implantation and effective utilization of telemedicine services in the selected hospitals will aid as a strategy to eradicate hardships in healthcare services delivery. The service will help attain universal health access coverage to all populace. This study contributes to empirical knowledge by identifying the vital factors influencing health professionals’ behavioral intentions to adopt telemedicine services. The study will also help stakeholders of healthcare to formulate better policies towards telemedicine service usage.

Keywords: telemedicine service, perceived usefulness, perceived ease of use, management strategies, security threats

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Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

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Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

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Authors: Vaiddehi Bansal, Ridhi Sahai, Kareem Kysia

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Overseas labor migration is currently one of the most important contributors to the economy of Bangladesh and is a highly profitable form of labor for Gulf Cooperative Council (GCC) countries. In 2019, 700,159 migrant workers from Bangladeshtraveled abroad for employment. GCC countries are a major destination for Bangladeshi migrant workers, with Saudi Arabia being the most common destination for Bangladeshi migrant workers since 2016. Despite the high rate of migration between these countries every year, the OLR industry remains complex and often leaves migrants susceptible to human trafficking, forced labor, and modern slavery. While the prevalence of forced labor among Bangladeshi migrants in GCC countries is still unknown, the IOM estimates international migrant workers comprise one fourth of the victims of forced labor. Moreover, the onset of the global COVID-19 pandemic has exposed migrant workers to additional adverse situations, making them even more vulnerable to forced labor and health risks. This paper presents findings from a rapid assessment of the impacts of COVID-19 on OLR in Bangladesh, with an emphasis on the increased risk of forced labor among vulnerable migrant worker populations, particularly women.Rapid reviews are a useful approach to swiftly provide actionable evidence for informed decision-making during emergencies, such as the COVID-19 pandemic. The research team conducted semi-structured key information interviews (KIIs) with a range of stakeholders, including government officials, local NGOs, international organizations, migration researchers, and formal and informal recruiting agencies, to obtain insights on the multi-facted impacts of COVID-19 on the OLR sector. The research team also conducted a comprehensive review of available resources, including media articles, blogs, policy briefs, reports, white papers, and other online content, to triangulate findings from the KIIs. After screening for inclusion criteria, a total of 110 grey literature documents were included in the review. A total of 31 KIIs were conducted, data from which was transcribed and translated from Bangla to English, andanalyzed using a detailed codebook. Findings indicate that there was limited reintegration support for returnee migrants. Facing increasing amounts of debt, financial insecurity, and social discrimination, returnee migrants, were extremely vulnerable to forced labor and exploitation. Growing financial debt and limited job opportunities in their home country will likely push migrants to resort to unsafe migration channels. Evidence suggests that women, who are primarily domestic works in GCC countries, were exposed to increased risk of forced labor and workplace violence. Due to stay-at-home measures, women migrant workers were tasked with additional housekeeping working and subjected to longer work hours, wage withholding, and physical abuse. In Bangladesh, returnee women migrant workers also faced an increased risk of domestic violence.

Keywords: forced labor, migration, gender, human trafficking

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Authors: D. Malouch, M. Berchel, C. Dreanno, S. Stachowski-Haberkorn, P-A. Jaffres

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Biofouling is a complex natural phenomenon that involves biological, physical and chemical properties related to the environment, the submerged surface and the living organisms involved. Bio-colonization of artificial structures can cause various economic and environmental impacts. The increase in costs associated with the over-consumption of fuel from biocolonized vessels has been widely studied. Measurement drifts from submerged sensors, as well as obstructions in heat exchangers, and deterioration of offshore structures are major difficulties that industries are dealing with. Therefore, surfaces that inhibit biocolonization are required in different areas (water treatment, marine paints, etc.) and many efforts have been devoted to produce efficient and eco-compatible antifouling agents. The different steps of surface fouling are widely described in literature. Studying the biofilm and its stages provides a better understanding of how to elaborate more efficient antifouling strategies. Several approaches are currently applied, such as the use of biocide anti-fouling paint (mainly with copper derivatives) and super-hydrophobic coatings. While these two processes are proving to be the most effective, they are not entirely satisfactory, especially in a context of a changing legislation. Nowadays, the challenge is to prevent biofouling with non-biocide compounds, offering a cost effective solution, but with no toxic effects on marine organisms. Since the micro-fouling phase plays an important role in the regulation of the following steps of biofilm formation, it is desired to reduce or delate biofouling of a given surface by inhibiting the micro-fouling at its early stages. In our recent works, we reported that some amphiphilic compounds exhibited bacteriostatic or bactericidal properties at a concentration that did not affect mammalian eukaryotic cells. These remarkable properties invited us to assess this type of bio-inspired phospholipids to prevent the colonization of surfaces by marine bacteria. Of note, other studies reported that amphiphilic compounds interacted with bacteria leading to a reduction of their development. An amphiphilic compound is a molecule consisting of a hydrophobic domain and a polar head (ionic or non-ionic). These compounds appear to have interesting antifouling properties: some ionic compounds have shown antimicrobial activity, and zwitterions can reduce nonspecific adsorption of proteins. Herein, we investigate the potential of amphiphilic compounds as inhibitors of bacterial growth and marine biofilm formation. The aim of this study is to compare the efficacy of four synthetic phospholipids that features a cationic charge or a zwitterionic polar-head group to prevent microfouling with marine bacteria. Toxicity of these compounds was also studied in order to identify the most promising compounds that inhibit biofilm development and show low cytotoxicity on two links representative of coastal marine food webs: phytoplankton and oyster larvae.

Keywords: amphiphilic phospholipids, biofilm, marine fouling, non-toxique assays

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Authors: Khin Thi Htun, James Jain, Tim Andrews

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This study examines the under-researched phenomenon of crowdfunding use and effectiveness in developing non-western markets. More precisely, using an institutional theoretical lens, the research explores the attitudes, motivations, and practice surrounding the initiation, development, and receipt of crowdfunding campaignsin a business context symptomatic of widely dissimilar regulatory, normative cognitive institutional ‘pillars’ to those studied – and utilized in practice - to date. As, in essence, a form of alternative finance, crowdfunding is used primarily to fund a wide range of projects through the securement of small amounts of money from a large pool of investors/participants. Being tied almost inextricably to e-commerce channels, the practice of crowdfunding typically sources its means and communicates the purpose of each venture mainly, though not exclusively, online. The wide range of projects supported to date span social entrepreneurship, community benefits initiatives, creative and artistic endeavors, assistance to disadvantaged social cohorts, and small business start-ups. Adopting a longitudinal, comparative approach, the study reported here embodies an investigation centered on six case start-up campaigns within the Thai societal context, covering a range of fundings calls and cause choices. Data was sourced from a variety of respondents using semi-structured interviews, observation (direct and participant), and company information. Results suggest that the motives and effectiveness of crowdfunding campaigns differ significantly in non-western consumer contexts from the norms that have evolved to date in mature Western contexts(particularly the US and UK). Specifically, whereas data on the different regulatory pressures showed relatively insignificant variation, the results regarding cognitive and, especially, normative dissimilarities between the Thai and US/UK institutional profiles surfaced potentially important differences with far-reaching implications. Particular issuesto emerge from our data concerned consumer motivation in terms of support and engagement with different types of campaigns. This was found to stem from social norms symptomatic of ‘collectivist’ and ‘relations based/particularist’ cultural assistance behavior, in turn, linked to deeply-held societal values regarding interpersonal network (‘in group’) reciprocity. This research serves to refine and extend the limited body of knowledge to date on crowdfunding by exploring the phenomenon in a non-western, non-developed country contextswhere social norms and values differ. This was achieved through uncovering and explicating the effects of cultural dissimilarity on motivation, decision-making, construed ethics, and general engagement with crowdfunding ideas. Implications for theory into e-marketing and cross-cultural marketing, as well as for practitioners seeking to develop effective crowdfunding campaigns in a Southeast Asian cultural environment, are discussed to conclude the paper.

Keywords: crowdfunding, national culture, e-marketing, cross-cultural business

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Authors: N. Naz, A. D. Domenico, M. N. Huda

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Soft Robotics is a rapidly growing multidisciplinary field where robots are fabricated using highly deformable materials motivated by bioinspired designs. The high dexterity and adaptability to the external environments during contact make soft robots ideal for applications such as gripping delicate objects, locomotion, and biomedical devices. The actuation system of soft robots mainly includes fluidic, tendon-driven, and smart material actuation. Among them, Soft Pneumatic Actuator, also known as SPA, remains the most popular choice due to its flexibility, safety, easy implementation, and cost-effectiveness. However, at present, most of the fabrication of SPA is still based on traditional molding and casting techniques where the mold is 3d printed into which silicone rubber is cast and consolidated. This conventional method is time-consuming and involves intensive manual labour with the limitation of repeatability and accuracy in design. Recent advancements in direct 3d printing of different soft materials can significantly reduce the repetitive manual task with an ability to fabricate complex geometries and multicomponent designs in a single manufacturing step. The aim of this research work is to design and analyse the Soft Pneumatic Actuator (SPA) utilizing both conventional casting and modern direct 3d printing technologies. The mold of the SPA for traditional casting is 3d printed using fused deposition modeling (FDM) with the polylactic acid (PLA) thermoplastic wire. Hyperelastic soft materials such as Ecoflex-0030/0050 are cast into the mold and consolidated using a lab oven. The bending behaviour is observed experimentally with different pressures of air compressor to ensure uniform bending without any failure. For direct 3D-printing of SPA fused deposition modeling (FDM) with thermoplastic polyurethane (TPU) and stereolithography (SLA) with an elastic resin are used. The actuator is modeled using the finite element method (FEM) to analyse the nonlinear bending behaviour, stress concentration and strain distribution of different hyperelastic materials after pressurization. FEM analysis is carried out using Ansys Workbench software with a Yeon-2nd order hyperelastic material model. FEM includes long-shape deformation, contact between surfaces, and gravity influences. For mesh generation, quadratic tetrahedron, hybrid, and constant pressure mesh are used. SPA is connected to a baseplate that is in connection with the air compressor. A fixed boundary is applied on the baseplate, and static pressure is applied orthogonally to all surfaces of the internal chambers and channels with a closed continuum model. The simulated results from FEM are compared with the experimental results. The experiments are performed in a laboratory set-up where the developed SPA is connected to a compressed air source with a pressure gauge. A comparison study based on performance analysis is done between FDM and SLA printed SPA with the molded counterparts. Furthermore, the molded and 3d printed SPA has been used to develop a three-finger soft pneumatic gripper and has been tested for handling delicate objects.

Keywords: finite element method, fused deposition modeling, hyperelastic, soft pneumatic actuator

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Authors: Vladimir Smirnov, Roman Tominov, Vadim Avilov, Oleg Ageev

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The creation of a new generation micro- and nanoelectronics elements opens up unlimited possibilities for electronic devices parameters improving, as well as developing neuromorphic computing systems. Interest in the latter is growing up every year, which is explained by the need to solve problems related to the unstructured classification of data, the construction of self-adaptive systems, and pattern recognition. However, for its technical implementation, it is necessary to fulfill a number of conditions for the basic parameters of electronic memory, such as the presence of non-volatility, the presence of multi-bitness, high integration density, and low power consumption. Several types of memory are presented in the electronics industry (MRAM, FeRAM, PRAM, ReRAM), among which non-volatile resistive memory (ReRAM) is especially distinguished due to the presence of multi-bit property, which is necessary for neuromorphic systems manufacturing. ReRAM is based on the effect of resistive switching – a change in the resistance of the oxide film between low-resistance state (LRS) and high-resistance state (HRS) under an applied electric field. One of the methods for the technical implementation of neuromorphic systems is cross-bar structures, which are ReRAM cells, interconnected by cross data buses. Such a structure imitates the architecture of the biological brain, which contains a low power computing elements - neurons, connected by special channels - synapses. The choice of the ReRAM oxide film material is an important task that determines the characteristics of the future neuromorphic system. An analysis of literature showed that many metal oxides (TiO2, ZnO, NiO, ZrO2, HfO2) have a resistive switching effect. It is worth noting that the manufacture of nanocomposites based on these materials allows highlighting the advantages and hiding the disadvantages of each material. Therefore, as a basis for the neuromorphic structures manufacturing, it was decided to use ZnₓTiᵧHfzOᵢ nanocomposite. It is also worth noting that the ZnₓTiᵧHfzOᵢ nanocomposite does not need an electroforming, which degrades the parameters of the formed ReRAM elements. Currently, this material is not well studied, therefore, the study of the effect of resistive switching in forming-free ZnₓTiᵧHfzOᵢ nanocomposite is an important task and the goal of this work. Forming-free nanocomposite ZnₓTiᵧHfzOᵢ thin film was grown by pulsed laser deposition (Pioneer 180, Neocera Co., USA) on the SiO2/TiN (40 nm) substrate. Electrical measurements were carried out using a semiconductor characterization system (Keithley 4200-SCS, USA) with W probes. During measurements, TiN film was grounded. The analysis of the obtained current-voltage characteristics showed a resistive switching from HRS to LRS resistance states at +1.87±0.12 V, and from LRS to HRS at -2.71±0.28 V. Endurance test shown that HRS was 283.21±32.12 kΩ, LRS was 1.32±0.21 kΩ during 100 measurements. It was shown that HRS/LRS ratio was about 214.55 at reading voltage of 0.6 V. The results can be useful for forming-free nanocomposite ZnₓTiᵧHfzOᵢ films in neuromorphic systems manufacturing. This work was supported by RFBR, according to the research project № 19-29-03041 mk. The results were obtained using the equipment of the Research and Education Center «Nanotechnologies» of Southern Federal University.

Keywords: nanotechnology, nanocomposites, neuromorphic systems, RRAM, pulsed laser deposition, resistive switching effect

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Authors: Jorge Cortés, Alejandra Martínez, Carlos Pérez, Anaid Simón

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The presence of government, news media, and general citizenry in social media allows considering interactions between them as a form of political communication (i.e. the public exchange of contradictory discourses about politics). Twitter’s asymmetrical following model (users can follow, mention or reply to other users that do not follow them) could foster alternative democratic practices and have an impact on Mexican political culture, which has been marked by a lack of direct communication channels between these actors. The research aim is to assess Twitter’s role in political communication practices through the analysis of interaction dynamics between government, news media, and citizens by extracting and visualizing data from Twitter’s API to observe general behavior patterns. The hypothesis is that regardless the fact that Twitter’s features enable direct and horizontal interactions between actors, users repeat traditional dynamics of interaction, without taking full advantage of the possibilities of this medium. Through an interdisciplinary team including Communication Strategies, Information Design, and Interaction Systems, the activity on Twitter generated by the controversy over the presence of Uber in Mexico City was analysed; an issue of public interest, involving aspects such as public opinion, economic interests and a legal dimension. This research includes techniques from social network analysis (SNA), a methodological approach focused on the comprehension of the relationships between actors through the visual representation and measurement of network characteristics. The analysis of the Uber event comprised data extraction, data categorization, corpus construction, corpus visualization and analysis. On the recovery stage TAGS, a Google Sheet template, was used to extract tweets that included the hashtags #UberSeQueda and #UberSeVa, posts containing the string Uber and tweets directed to @uber_mx. Using scripts written in Python, the data was filtered, discarding tweets with no interaction (replies, retweets or mentions) and locations outside of México. Considerations regarding bots and the omission of anecdotal posts were also taken into account. The utility of graphs to observe interactions of political communication in general was confirmed by the analysis of visualizations generated with programs such as Gephi and NodeXL. However, some aspects require improvements to obtain more useful visual representations for this type of research. For example, link¬crossings complicates following the direction of an interaction forcing users to manipulate the graph to see it clearly. It was concluded that some practices prevalent in political communication in Mexico are replicated in Twitter. Media actors tend to group together instead of interact with others. The political system tends to tweet as an advertising strategy rather than to generate dialogue. However, some actors were identified as bridges establishing communication between the three spheres, generating a more democratic exercise and taking advantage of Twitter’s possibilities. Although interactions in Twitter could become an alternative to political communication, this potential depends on the intentions of the participants and to what extent they are aiming for collaborative and direct communications. Further research is needed to get a deeper understanding on the political behavior of Twitter users and the possibilities of SNA for its analysis.

Keywords: interaction, political communication, social network analysis, Twitter

Procedia PDF Downloads 194

Authors: G. Magalhães-Mota, C. Magro, S. Sério, E. Mateus, P. A. Ribeiro, A. B. Ribeiro, M. Raposo

Abstract:

Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol], belonging to the class of Pharmaceuticals and Personal Care Products (PPCPs), is a broad-spectrum antimicrobial agent and bactericide. Because of its antimicrobial efficacy, it is widely used in personal health and skin care products, such as soaps, detergents, hand cleansers, cosmetics, toothpastes, etc. However, it has been considered to disrupt the endocrine system, for instance, thyroid hormone homeostasis and possibly the reproductive system. Considering the widespread use of triclosan, it is expected that environmental and food safety problems regarding triclosan will increase dramatically. Triclosan has been found in river water samples in both North America and Europe and is likely widely distributed wherever triclosan-containing products are used. Although significant amounts are removed in sewage plants, considerable quantities remain in the sewage effluent, initiating widespread environmental contamination. Triclosan undergoes bioconversion to methyl-triclosan, which has been demonstrated to bio accumulate in fish. In addition, triclosan has been found in human urine samples from persons with no known industrial exposure and in significant amounts in samples of mother's milk, demonstrating its presence in humans. The action of sunlight in river water is known to turn triclosan into dioxin derivatives and raises the possibility of pharmacological dangers not envisioned when the compound was originally utilized. The aim of this work is to detect low concentrations of triclosan in an aqueous complex matrix through the use of a sensor array system, following the electronic tongue concept based on impedance spectroscopy. To achieve this goal, we selected the appropriate molecules to the sensor so that there is a high affinity for triclosan and whose sensitivity ensures the detection of concentrations of at least nano-molar. Thin films of organic molecules and oxides have been produced by the layer-by-layer (LbL) technique and sputtered onto glass solid supports already covered by gold interdigitated electrodes. By submerging the films in complex aqueous solutions with different concentrations of triclosan, resistance and capacitance values were obtained at different frequencies. The preliminary results showed that an array of interdigitated electrodes sensor coated or uncoated with different LbL and films, can be used to detect TCS traces in aqueous solutions in a wide range concentration, from 10⁻¹² to 10⁻⁶ M. The PCA method was applied to the measured data, in order to differentiate the solutions with different concentrations of TCS. Moreover, was also possible to trace a curve, the plot of the logarithm of resistance versus the logarithm of concentration, which allowed us to fit the plotted data points with a decreasing straight line with a slope of 0.022 ± 0.006 which corresponds to the best sensitivity of our sensor. To find the sensor resolution near of the smallest concentration (Cs) used, 1pM, the minimum measured value which can be measured with resolution is 0.006, so the ∆logC =0.006/0.022=0.273, and, therefore, C-Cs~0.9 pM. This leads to a sensor resolution of 0.9 pM for the smallest concentration used, 1pM. This attained detection limit is lower than the values obtained in the literature.

Keywords: triclosan, layer-by-layer, impedance spectroscopy, electronic tongue

Procedia PDF Downloads 224

Authors: Tomas Linas Šepetys

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In online content-sharing service platforms, the ability of creators to restrict illicit use of audiovisual creative works has effectively been abolished, largely due to specific infrastructure where a huge volume of copyrighted audiovisual content can be made available to the public. The European Union legislator has attempted to strengthen the positions of creators in the realm of online content-sharing services. Article 17 of the new Digital Single Market Directive considers online content-sharing service providers to carry out acts of communication to the public of any creative content uploaded to their platforms by users and posits requirements to obtain licensing agreements. While such regulation intends to assert authors‘ ability to effectively control the dissemination of their creative works, it also creates threats of parody content overblocking through automated content monitoring. Such potentially paradoxical outcome of the efforts of the EU legislator to deliver economic safeguards for the creators in the online content-sharing service platforms leads to presume lack of informity on legislator‘s part regarding creative works‘ economic exploitation opportunities provided to creators in the online content-sharing infrastructure. Analysis conducted in this scientific research discloses that the aforementioned irregularities of parody and other creative content dissemination are caused by EU legislators‘ lack of assessment of value extraction conditions for parody creators in the online content-sharing service platforms. Historical and modeling research method application reveals the existence of two creative content dissemination models and their unique mechanisms of commercial value creation. Obligations to obtain licenses and liability over creative content uploaded to their platforms by users set in Article 17 of the Digital Single Market Directive represent technological replication of the proprietary dissemination model where the creator is able to restrict access to creative content apart from licensed retail channels. The online content-sharing service platforms represent an open dissemination model where the economic potential of creative content is based on the infrastructure of unrestricted access by users and partnership with advertising services offered by the platform. Balanced modeling of proprietary dissemination models in such infrastructure requires not only automated content monitoring measures but also additional regulatory monitoring solutions to separate parody and other types of creative content. An example of the Digital Single Market Directive proves that regulation can dictate not only the technological establishment of a proprietary dissemination model but also a partial reduction of the open dissemination model and cause a disbalance between the economic interests of creators relying on such models. The results of this scientific research conclude an informative role of the creative works dissemination model in the EU copyright law modernization process. A thorough understanding of the commercial prospects of the open dissemination model intrinsic to the online content-sharing service platform structure requires and encourages EU legislators to regulate safeguards for parody content dissemination. Implementing such safeguards would result in a common application of proprietary and open dissemination models in the online content-sharing service platforms and balanced protection of creators‘ economic interests explicitly based on those creative content dissemination models.

Keywords: copyright law, creative works dissemination model, digital single market directive, online content-sharing services

Procedia PDF Downloads 47

Authors: Kuan Lun Pan, Moo Been Chang

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Volatile organic compounds (VOCs) are one of major air contaminants, and they can react with nitrogen oxides (NOx) in atmosphere to form ozone (O3) and peroxyacetyl nitrate (PAN) with solar irradiation, leading to environmental hazards. In addition, some VOCs are toxic at low concentration levels and cause adverse effects on human health. How to effectively reduce VOCs emission has become an important issue. Thermal catalysis is regarded as an effective way for VOCs removal because it provides oxidation route to successfully convert VOCs into carbon dioxide (CO2) and water (H2O(g)). Single perovskite-type catalysts are promising for VOC removal, and they are of good potential to replace noble metals due to good activity and high thermal stability. Single perovskites can be generally described as ABO3 or A2BO4, where A-site is often a rare earth element or an alkaline. Typically, the B-site is transition metal cation (Fe, Cu, Ni, Co, or Mn). Catalytic properties of perovskites mainly rely on nature, oxidation states and arrangement of B-site cation. Interestingly, single perovskites could be further synthesized to form double perovskite-type catalysts which can simply be represented by A2B’B”O6. Likewise, A-site stands for an alkaline metal or rare earth element, and the B′ and B′′ are transition metals. Double perovskites possess unique surface properties. In structure, three-dimensional of B-site with ordered arrangement of B’O6 and B”O6 is presented alternately, and they corner-share octahedral along three directions of the crystal lattice, while cations of A-site position between the void of octahedral. It has attracted considerable attention due to specific arrangement of alternating B-site structure. Therefore, double perovskites may have more variations than single perovskites, and this greater variation may promote catalytic performance. It is expected that activity of double perovskites is higher than that of single perovskites toward VOC removal. In this study, double perovskite-type catalyst (La2CoMnO6) is prepared and evaluated for VOC removal. Also, single perovskites including LaCoO3 and LaMnO3 are tested for the comparison purpose. Toluene (C7H8) is one of the important VOCs which are commonly applied in chemical processes. In addition to its wide application, C7H8 has high toxicity at a low concentration. Therefore, C7H8 is selected as the target compound in this study. Experimental results indicate that double perovskite (La2CoMnO6) has better activity if compared with single perovskites. Especially, C7H8 can be completely oxidized to CO2 at 300oC as La2CoMnO6 is applied. Characterization of catalysts indicates that double perovskite has unique surface properties and is of higher amounts of lattice oxygen, leading to higher activity. For durability test, La2CoMnO6 maintains high C7H8 removal efficiency of 100% at 300oC and 30,000 h-1, and it also shows good resistance to CO2 (5%) and H2O(g) (5%) of gas streams tested. For various VOCs including isopropyl alcohol (C3H8O), ethanal (C2H4O), and ethylene (C2H4) tested, as high as 100% efficiency could be achieved with double perovskite-type catalyst operated at 300℃, indicating that double perovskites are promising catalysts for VOCs removal, and possible mechanisms will be elucidated in this paper.

Keywords: volatile organic compounds, Toluene (C7H8), double perovskite-type catalyst, catalysis

Procedia PDF Downloads 135

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

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

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

Procedia PDF Downloads 53

Authors: Elena Ionescu, Elena Iacob, Marie-Louise Ionescu, Carmen Elena Tebrencu, Oana Teodora Ciuperca

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Echinacea species (Asteraceae) has received a global attention because it is widely used for treatment of cold, flu and upper respiratory tract infections. Echinacea species contain a great variety of chemical components that contribute to their activity. The most important components responsible for the biological activity are those with high molecular-weight such as polysaccharides, polyacetylenes, highly unsaturated alkamides and caffeic acid derivatives. The principal factors that may influence the chemical composition of Echinacea include the species and the part of plant used (aerial parts or roots ). In recent years the market for Echinacea has grown rapidly and also the cases of adultery/replacement especially for Echinacea root. The identification of presence or absence of same biomarkers provide information for safe use of Echinacea species in food supplements industry. The aim of the study was the preliminary evaluation and fingerprinting by UV-VISIBLE spectroscopy of biomarkers in terms of content in phenolic derivatives of some Echinacea species (E. purpurea, E. angustifolia and E. pallida) for identification and authentication of the species. The steps of the study were: (1) samples (extracts) preparation from Echinacea species (non-hydrolyzed and hydrolyzed ethanol extracts); (2) samples preparation of reference substances (polyphenol acids: caftaric acid, caffeic acid, chlorogenic acid, ferulic acid; flavonoids: rutoside, hyperoside, isoquercitrin and their aglycones: quercitri, quercetol, luteolin, kaempferol and apigenin); (3) identification of specific absorption at wavelengths between 700-200 nm; (4) identify the phenolic compounds from Echinacea species based on spectral characteristics and the specific absorption; each class of compounds corresponds to a maximum absorption in the UV spectrum. The phytochemical compounds were identified at specific wavelengths between 700-200 nm. The absorption intensities were measured. The obtained results proved that ethanolic extract showed absorption peaks attributed to: phenolic compounds (free phenolic acids and phenolic acids derivatives) registrated between 220-280 nm, unsymmetrical chemical structure compounds (caffeic acid, chlorogenic acid, ferulic acid) with maximum absorption peak and absorption "shoulder" that may be due to substitution of hydroxyl or methoxy group, flavonoid compounds (in free form or glycosides) between 330-360 nm, due to the double bond in position 2,3 and carbonyl group in position 4 flavonols. UV spectra showed two major peaks of absorption (quercetin glycoside, rutin, etc.). The results obtained by UV-VIS spectroscopy has revealed the presence of phenolic derivatives such as cicoric acid (240 nm), caftaric acid (329 nm), caffeic acid (240 nm), rutoside (205 nm), quercetin (255 nm), luteolin (235 nm) in all three species of Echinacea. The echinacoside is absent. This profile mentioned above and the absence of phenolic compound echinacoside leads to the conclusion that species harvested as Echinacea angustifolia and Echinacea pallida are Echinacea purpurea also; It can be said that preliminary fingerprinting of Echinacea species through correspondence with the phenolic derivatives profile can be achieved by UV-VIS spectroscopic investigation, which is an adequate technique for preliminary identification and authentication of Echinacea in medicinal herbs.

Keywords: Echinacea species, Fingerprinting, Phenolic compounds, UV-VIS spectroscopy

Procedia PDF Downloads 227

Authors: Hossein Aghababaei, Sergio Vitale, Giampaolo Ferraioli

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In the context of Synthetic Aperture Radar (SAR) data, polarization is an important source of information for Earth's surface monitoring. SAR Systems are often considered to transmit only one polarization. This constraint leads to either single or dual polarimetric SAR imaging modalities. Single polarimetric systems operate with a fixed single polarization of both transmitted and received electromagnetic (EM) waves, resulting in a single acquisition channel. Dual polarimetric systems, on the other hand, transmit in one fixed polarization and receive in two orthogonal polarizations, resulting in two acquisition channels. Dual polarimetric systems are obviously more informative than single polarimetric systems and are increasingly being used for a variety of remote sensing applications. In dual polarimetric systems, the choice of polarizations for the transmitter and the receiver is open. The choice of circular transmit polarization and coherent dual linear receive polarizations forms a special dual polarimetric system called hybrid polarimetry, which brings the properties of rotational invariance to geometrical orientations of features in the scene and optimizes the design of the radar in terms of reliability, mass, and power constraints. The complete characterization of target scattering, however, requires fully polarimetric data, which can be acquired with systems that transmit two orthogonal polarizations. This adds further complexity to data acquisition and shortens the coverage area or swath of fully polarimetric images compared to the swath of dual or hybrid polarimetric images. The search for solutions to augment dual polarimetric data to full polarimetric data will therefore take advantage of full characterization and exploitation of the backscattered field over a wider coverage with less system complexity. Several methods for reconstructing fully polarimetric images using hybrid polarimetric data can be found in the literature. Although the improvements achieved by the newly investigated and experimented reconstruction techniques are undeniable, the existing methods are, however, mostly based upon model assumptions (especially the assumption of reflectance symmetry), which may limit their reliability and applicability to vegetation and forest scenarios. To overcome the problems of these techniques, this paper proposes a new framework for reconstructing fully polarimetric information from hybrid polarimetric data. The framework uses Deep Learning solutions to augment hybrid polarimetric data without relying on model assumptions. A convolutional neural network (CNN) with a specific architecture and loss function is defined for this augmentation problem by focusing on different scattering properties of the polarimetric data. In particular, the method controls the CNN training process with respect to several characteristic features of polarimetric images defined by the combination of different terms in the cost or loss function. The proposed method is experimentally validated with real data sets and compared with a well-known and standard approach from the literature. From the experiments, the reconstruction performance of the proposed framework is superior to conventional reconstruction methods. The pseudo fully polarimetric data reconstructed by the proposed method also agree well with the actual fully polarimetric images acquired by radar systems, confirming the reliability and efficiency of the proposed method.

Keywords: SAR image, polarimetric SAR image, convolutional neural network, deep learnig, deep neural network

Procedia PDF Downloads 44

Authors: Hossein Aghababaei, Sergio Vitale, Giampaolo ferraioli

Abstract:

In the context of Synthetic Aperture Radar (SAR) data, polarization is an important source of information for Earth's surface monitoring . SAR Systems are often considered to transmit only one polarization. This constraint leads to either single or dual polarimetric SAR imaging modalities. Single polarimetric systems operate with a fixed single polarization of both transmitted and received electromagnetic (EM) waves, resulting in a single acquisition channel. Dual polarimetric systems, on the other hand, transmit in one fixed polarization and receive in two orthogonal polarizations, resulting in two acquisition channels. Dual polarimetric systems are obviously more informative than single polarimetric systems and are increasingly being used for a variety of remote sensing applications. In dual polarimetric systems, the choice of polarizations for the transmitter and the receiver is open. The choice of circular transmit polarization and coherent dual linear receive polarizations forms a special dual polarimetric system called hybrid polarimetry, which brings the properties of rotational invariance to geometrical orientations of features in the scene and optimizes the design of the radar in terms of reliability, mass, and power constraints. The complete characterization of target scattering, however, requires fully polarimetric data, which can be acquired with systems that transmit two orthogonal polarizations. This adds further complexity to data acquisition and shortens the coverage area or swath of fully polarimetric images compared to the swath of dual or hybrid polarimetric images. The search for solutions to augment dual polarimetric data to full polarimetric data will therefore take advantage of full characterization and exploitation of the backscattered field over a wider coverage with less system complexity. Several methods for reconstructing fully polarimetric images using hybrid polarimetric data can be found in the literature. Although the improvements achieved by the newly investigated and experimented reconstruction techniques are undeniable, the existing methods are, however, mostly based upon model assumptions (especially the assumption of reflectance symmetry), which may limit their reliability and applicability to vegetation and forest scenarios. To overcome the problems of these techniques, this paper proposes a new framework for reconstructing fully polarimetric information from hybrid polarimetric data. The framework uses Deep Learning solutions to augment hybrid polarimetric data without relying on model assumptions. A convolutional neural network (CNN) with a specific architecture and loss function is defined for this augmentation problem by focusing on different scattering properties of the polarimetric data. In particular, the method controls the CNN training process with respect to several characteristic features of polarimetric images defined by the combination of different terms in the cost or loss function. The proposed method is experimentally validated with real data sets and compared with a well-known and standard approach from the literature. From the experiments, the reconstruction performance of the proposed framework is superior to conventional reconstruction methods. The pseudo fully polarimetric data reconstructed by the proposed method also agree well with the actual fully polarimetric images acquired by radar systems, confirming the reliability and efficiency of the proposed method.

Keywords: SAR image, deep learning, convolutional neural network, deep neural network, SAR polarimetry

Procedia PDF Downloads 50

Authors: Ishita Singh

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Social-dimension of Climate Change is no longer peripheral to Science, Technology and Innovation (STI). Indeed, STI is being mobilized to address small farmers’ vulnerability and adaptation to Climate Change. The experiences from the cold desert of Leh (Ladakh) in North-West Himalaya illustrate the potential of STI to address the challenges of Climate Change and the needs of small farmers through the use of Artificial Glacier Techniques. Small farmers have a unique technique of water harvesting to augment irrigation, called “Artificial Glaciers” - an intricate network of water channels and dams along the upper slope of a valley that are located closer to villages and at lower altitudes than natural glaciers. It starts to melt much earlier and supplements additional irrigation to small farmers’ improving their livelihoods. Therefore, the issue of vulnerability, adaptive capacity and adaptation strategy needs to be analyzed in a local context and the communities as well as regions where people live. Leh (Ladakh) in North-West Himalaya provides a Case Study for exploring the ways in which adaptation to Climate Change is taking place at a community scale using Artificial Glacier Technology. With the above backdrop, an attempt has been made to analyze the rural poor households' vulnerability and adaptation practices to Climate Change using this technology, thereby drawing lessons on vulnerability-livelihood interactions in the cold desert of Leh (Ladakh) in North-West Himalaya, India. The study is based on primary data and information collected from 675 households confined to 27 villages of Leh (Ladakh) in North-West Himalaya, India. It reveals that 61.18% of the population is driving livelihoods from agriculture and allied activities. With increased irrigation potential due to the use of Artificial Glaciers, food security has been assured to 77.56% of households and health vulnerability has been reduced in 31% of households. Seasonal migration as a livelihood diversification mechanism has declined in nearly two-thirds of households, thereby improving livelihood strategies. Use of tactical adaptations by small farmers in response to persistent droughts, such as selling livestock, expanding agriculture lands, and use of relief cash and foods, have declined to 20.44%, 24.74% and 63% of households. However, these measures are unsustainable on a long-term basis. The role of policymakers and societal stakeholders becomes important in this context. To address livelihood challenges, the role of technology is critical in a multidisciplinary approach involving multilateral collaboration among different stakeholders. The presence of social entrepreneurs and new actors on the adaptation scene is necessary to bring forth adaptation measures. Better linkage between Science and Technology policies, together with other policies, should be encouraged. Better health care, access to safe drinking water, better sanitary conditions, and improved standards of education and infrastructure are effective measures to enhance a community’s adaptive capacity. However, social transfers for supporting climate adaptive capacity require significant amounts of additional investment. Developing institutional mechanisms for specific adaptation interventions can be one of the most effective ways of implementing a plan to enhance adaptation and build resilience.

Keywords: climate change, adaptation, livelihood, stakeholders

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Authors: Stephen Tullis, M. David DiDonato, Hong Sung Park

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Rowing boats (shells) are often steered by a small rudder operated by one of the backward-facing rowers; the attention required of that athlete then slightly decreases the power that that athlete can provide. Reducing the steering distraction would then increase the overall boat speed. Races are straight 2000 m courses with each boat in a 13.5 m wide lane marked by small (~15 cm) widely-spaced (~10 m) buoys, and the boat trajectory is affected by both cross-currents and winds. An optical buoy recognition and tracking system has been developed that provides the boat’s location and orientation with respect to the lane edges. This information is provided to the steering athlete as either: a simple overlay on a video display, or fed to a simplified autopilot system giving steering directions to the athlete or directly controlling the rudder. The system is then effectively a “lane-assist” device but with small, widely-spaced lane markers viewed from a very shallow angle due to constraints on camera height. The image is captured with a lightweight 1080p webcam, and most of the image analysis is done in OpenCV. The colour RGB-image is converted to a grayscale using the difference of the red and blue channels, which provides good contrast between the red/yellow buoys and the water, sky, land background and white reflections and noise. Buoy detection is done with thresholding within a tight mask applied to the image. Robust linear regression using Tukey’s biweight estimator of the previously detected buoy locations is used to develop the mask; this avoids the false detection of noise such as waves (reflections) and, in particular, buoys in other lanes. The robust regression also provides the current lane edges in the camera frame that are used to calculate the displacement of the boat from the lane centre (lane location), and its yaw angle. The interception of the detected lane edges provides a lane vanishing point, and yaw angle can be calculated simply based on the displacement of this vanishing point from the camera axis and the image plane distance. Lane location is simply based on the lateral displacement of the vanishing point from any horizontal cut through the lane edges. The boat lane position and yaw are currently fed what is essentially a stripped down marine auto-pilot system. Currently, only the lane location is used in a PID controller of a rudder actuator with integrator anti-windup to deal with saturation of the rudder angle. Low Kp and Kd values decrease unnecessarily fast return to lane centrelines and response to noise, and limiters can be used to avoid lane departure and disqualification. Yaw is not used as a control input, as cross-winds and currents can cause a straight course with considerable yaw or crab angle. Mapping of the controller with rudder angle “overall effectiveness” has not been finalized - very large rudder angles stall and have decreased turning moments, but at less extreme angles the increased rudder drag slows the boat and upsets boat balance. The full system has many features similar to automotive lane-assist systems, but with the added constraints of the lane markers, camera positioning, control response and noise increasing the challenge.

Keywords: auto-pilot, lane-assist, marine, optical, rowing

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Authors: Mohammadjavad Sotoudeheian

Abstract:

Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

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Authors: Eli Avraham

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The Arab Spring was widely covered in the global media and the number of Western tourists traveling to the area began to fall. The goal of this study was to analyze which media strategies marketers in Middle Eastern countries chose to employ in their attempts to repair the negative image of the area in the wake of the Arab Spring. Several studies were published concerning image-restoration strategies of destinations during crises around the globe; however, these strategies were not part of an overarching theory, conceptual framework or model from the fields of crisis communication and image repair. The conceptual framework used in the current study was the ‘multi-step model for altering place image’, which offers three types of strategies: source, message and audience. Three research questions were used: 1.What public relations crisis techniques and advertising campaign components were used? 2. What media policies and relationships with the international media were adopted by Arab officials? 3. Which marketing initiatives (such as cultural and sports events) were promoted? This study is based on qualitative content analysis of four types of data: 1) advertising components (slogans, visuals and text); (2) press interviews with Middle Eastern officials and marketers; (3) official media policy adopted by government decision-maker (e.g. boycotting or arresting newspeople); and (4) marketing initiatives (e.g. organizing heritage festivals and cultural events). The data was located in three channels from December 2010, when the events started, to September 31, 2013: (1) Internet and video-sharing websites: YouTube and Middle Eastern countries' national tourism board websites; (2) News reports from two international media outlets, The New York Times and Ha’aretz; these are considered quality newspapers that focus on foreign news and tend to criticize institutions; (3) Global tourism news websites: eTurbo news and ‘Cities and countries branding’. Using the ‘multi-step model for altering place image,’ the analysis reveals that Middle Eastern marketers and officials used three kinds of strategies to repair their countries' negative image: 1. Source (cooperation and media relations; complying, threatening and blocking the media; and finding alternatives to the traditional media) 2. Message (ignoring, limiting, narrowing or reducing the scale of the crisis; acknowledging the negative effect of an event’s coverage and assuring a better future; promotion of multiple facets, exhibitions and softening the ‘hard’ image; hosting spotlight sporting and cultural events; spinning liabilities into assets; geographic dissociation from the Middle East region; ridicule the existing stereotype) and 3. Audience (changing the target audience by addressing others; emphasizing similarities and relevance to specific target audience). It appears that dealing with their image problems will continue to be a challenge for officials and marketers of Middle Eastern countries until the region stabilizes and its regional conflicts are resolved.

Keywords: Arab spring, cultural events, image repair, Middle East, tourism marketing

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Authors: Serap Durkut, A. Eser Elcin, Y. Murat Elcin

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Stimuli-sensitive polymeric hydrogels have received extensive attention in the biomedical field due to their sensitivity to physical and chemical stimuli (temperature, pH, ionic strength, light, etc.). This study describes the rheological properties of a novel thermoresponsive poly(N-vinylcaprolactam)-g-collagen hydrogel. In the study, we first synthesized a facile and novel synthetic carboxyl group-terminated thermo-responsive poly(N-vinylcaprolactam)-COOH (PNVCL-COOH) via free radical polymerization. Further, this compound was effectively grafted with native collagen, by utilizing the covalent bond between the carboxylic acid groups at the end of the chains and amine groups of the collagen using cross-linking agent (EDC/NHS), forming PNVCL-g-Col. Newly-formed hybrid hydrogel displayed novel properties, such as increased mechanical strength and thermoresponsive characteristics. PNVCL-g-Col showed low critical solution temperature (LCST) at 38ºC, which is very close to the body temperature. Rheological studies determine structural–mechanical properties of the materials and serve as a valuable tool for characterizing. The rheological properties of hydrogels are described in terms of two dynamic mechanical properties: the elastic modulus G′ (also known as dynamic rigidity) representing the reversible stored energy of the system, and the viscous modulus G″, representing the irreversible energy loss. In order to characterize the PNVCL-g-Col, the rheological properties were measured in terms of the function of temperature and time during phase transition. Below the LCST, favorable interactions allowed the dissolution of the polymer in water via hydrogen bonding. At temperatures above the LCST, PNVCL molecules within PNVCL-g-Col aggregated due to dehydration, causing the hydrogel structure to become dense. When the temperature reached ~36ºC, both the G′ and G″ values crossed over. This indicates that PNVCL-g-Col underwent a sol-gel transition, forming an elastic network. Following temperature plateau at 38ºC, near human body temperature the sample displayed stable elastic network characteristics. The G′ and G″ values of the PNVCL-g-Col solutions sharply increased at 6-9 minute interval, due to rapid transformation into gel-like state and formation of elastic networks. Copolymerization with collagen leads to an increase in G′, as collagen structure contains a flexible polymer chain, which bestows its elastic properties. Elasticity of the proposed structure correlates with the number of intermolecular cross-links in the hydrogel network, increasing viscosity. However, at 8 minutes, G′ and G″ values sharply decreased for pure collagen solutions due to the decomposition of the elastic and viscose network. Complex viscosity is related to the mechanical performance and resistance opposing deformation of the hydrogel. Complex viscosity of PNVCL-g-Col hydrogel was drastically changed with temperature and the mechanical performance of PNVCL-g-Col hydrogel network increased, exhibiting lesser deformation. Rheological assessment of the novel thermo-responsive PNVCL-g-Col hydrogel, exhibited that the network has stronger mechanical properties due to both permanent stable covalent bonds and physical interactions, such as hydrogen- and hydrophobic bonds depending on temperature.

Keywords: poly(N-vinylcaprolactam)-g-collagen, thermoresponsive polymer, rheology, elastic modulus, stimuli-sensitive

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Authors: Turky Al-Qahtani, Roustem Miftahof

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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.

Keywords: complex dynamics, functional unit, the gut, dysrythmia

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Authors: Avdhesh K. Sharma

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Key, in the development of energy-efficient micro-scale heat exchanger devices, is to select large heat transfer surface to volume ratio without much expanse on re-circulated pumps. The increased interest in short heat exchanger (SHE) is due to accessibility of advanced technologies for manufacturing of micro-tubes in range of 1 micron m - 1 mm. Such SHE using micro-tubes are highly effective for high flux heat transfer technologies. Nanofluids, are used to enhance the thermal conductivity of re-circulated coolant and thus enhances heat transfer rate further. Higher viscosity associated with nanofluid expands more pumping power. Thus, there is a trade-off between heat transfer rate and pressure drop with geometry of micro-tubes. Herein, a novel design of short counter flow heat exchanger (SCFHE) using non-circular micro-tubes flooded with CuO-water nanofluid is conceptualized by varying the ratio of surface area to cross-sectional area of micro-tubes. A framework for comparative analysis of SCFHE using micro-tubes non-circular shape flooded by CuO-water nanofluid is presented. In SCFHE concept, micro-tubes having various geometrical shapes (viz., triangular, rectangular and trapezoidal) has been arranged row-wise to facilitate two aspects: (1) allowing easy flow distribution for cold and hot stream, and (2) maximizing the thermal interactions with neighboring channels. Adequate distribution of rows for cold and hot flow streams enables above two aspects. For comparative analysis, a specific volume or cross-section area is assigned to each elemental cell (which includes flow area and area corresponds to half wall thickness). A specific volume or cross-section area is assumed to be constant for each elemental cell (which includes flow area and half wall thickness area) and variation in surface area is allowed by selecting different geometry of micro-tubes in SCFHE. Effective thermal conductivity model for CuO-water nanofluid has been adopted, while the viscosity values for water based nanofluids are obtained empirically. Correlations for Nusselt number (Nu) and Poiseuille number (Po) for micro-tubes have been derived or adopted. Entrance effect is accounted for. Thermal and hydrodynamic performances of SCFHE are defined in terms of effectiveness and pressure drop or pumping power, respectively. For defining the overall performance index of SCFHE, two links are employed. First one relates heat transfer between the fluid streams q and pumping power PP as (=qj/PPj); while another link relates effectiveness eff and pressure drop dP as (=effj/dPj). For analysis, the inlet temperatures of hot and cold streams are varied in usual range of 20dC-65dC. Fully turbulent regime is seldom encountered in micro-tubes and transition of flow regime occurs much early (i.e., ~Re=1000). Thus, Re is fixed at 900, however, the uncertainty in Re due to addition of nanoparticles in base fluid is quantified by averaging of Re. Moreover, for minimizing error, volumetric concentration is limited to range 0% to ≤4% only. Such framework may be helpful in utilizing maximum peripheral surface area of SCFHE without any serious severity on pumping power and towards developing advanced short heat exchangers.

Keywords: CuO-water nanofluid, non-circular micro-tubes, performance index, short counter flow heat exchanger

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Anitha Kandasamy, Thirumurugan Ramaiah

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Interestingly, organic materials exhibit large optical nonlinearity with quick responses and having the flexibility of molecular tailoring using computational modelling and favourable synthetic methodologies. Pyridine based organic compounds and carboxylic acid contained aromatic compounds play a crucial role in crystal engineering of NCS complexes that displays admirable optical nonlinearity with fast response and favourable physicochemical properties such as low dielectric constant, wide optical transparency and large laser damage threshold value requires for optoelectronics device applications. Based on these facts, it was projected to form an acentric molecule of π-conjugated system interaction with appropriately replaced electron donor and acceptor groups for achieving higher SHG activity in which quinoline-2-carboyxlic acid is chosen as an electron acceptor and capable of acting as an acid as well as a base molecule, while 2-amino-4-methylpyridine is used as an electron donor and previously employed in numerous proton transfer complexes for synthesis of NLO materials for optoelectronic applications. 2-amino-4-mehtylpyridinium quinoline-2-carboxylate molecular complex (2AQ) is having π-donor-acceptor groups in which 2-amino-4-methylpyridine donates one of its electron to quinoline -2-carboxylic acid thereby forming a protonated 2-amino-4-methyl pyridinium moiety and mono ionized quinoline-2-carboxylate moiety which are connected via N-H…O intermolecular interactions with non-centrosymmetric crystal packing arrangement at microscopic scale is accountable to the enhancement of macroscopic second order NLO activity. The 2AQ crystal was successfully grown by a slow evaporation solution growth technique and its structure was determined in orthorhombic crystal system with acentric, P212121, space group. Hirshfeld surface analysis reveals that O…H intermolecular interactions primarily contributed with 31.0 % to the structural stabilization of 2AQ. The molecular structure of title compound has been confirmed by 1H and 13C NMR spectral studies. The vibrational modes of functional groups present in 2AQ have been assigned by using FTIR and FT-Raman spectroscopy. The grown 2AQ crystal exhibits high optical transparency with lower cut-off wavelength (275 nm) within the region of 275-1500 nm. The laser study confirmed that 2AQ exhibits high SHG efficiency of 12.6 times greater than that of KDP. TGA-DTA analysis revealed that 2AQ crystal had a thermal stability of 223 °C. The low dielectric constant and low dielectric loss at higher frequencies confirmed good crystalline nature with fewer defects of grown 2AQ crystal. The grown crystal exhibits soft material and positive photoconduction behaviour. Mulliken atomic distribution and FMOs analysis suggested that the strong intermolecular hydrogen bonding which lead to the enhancement of NLO activity. These properties suggest that 2AQ crystal is a suitable material for optoelectronic and laser frequency conversion applications.

Keywords: crystal growth, NLO activity, proton transfer complex, quantum chemical investigation

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Authors: J. Ticona Chambi, E. A. De Almeida, C. A. Andrade Raymundo Gaiotto, A. M. Do Espírito Santo, L. Infantes, S. L. Cuffini

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The solubility of active pharmaceutical ingredients (APIs) is challenging for the pharmaceutical industry. The new multicomponent crystalline forms as cocrystal and solvates present an opportunity to improve the solubility of APIs. Commonly, the procedure to obtain multicomponent crystalline forms of a drug starts by screening the drug molecule with the different coformers/solvents. However, it is necessary to develop methods to obtain multicomponent forms in an efficient way and with the least possible environmental impact. The Hansen Solubility Parameters (HSPs) is considered a tool to obtain theoretical knowledge of the solubility of the target compound in the chosen solvent. H-Bond Propensity (HBP), Molecular Complementarity (MC), Coordination Values (CV) are tools used for statistical prediction of cocrystals developed by the Cambridge Crystallographic Data Center (CCDC). The HSPs and the CCDC tools are based on inter- and intra-molecular interactions. The curcumin (Cur), target molecule, is commonly used as an anti‐inflammatory. The demethoxycurcumin (Demcur) and bisdemethoxycurcumin (Bisdcur) are natural analogues of Cur from turmeric. Those target molecules have differences in their solubilities. In this way, the work aimed to analyze and compare different tools for multicomponent forms prediction (solvates) of Cur, Demcur and Biscur. The HSP values were calculated for Cur, Demcur, and Biscur using the chemical group contribution methods and the statistical optimization from experimental data. The HSPmol software was used. From the HSPs of the target molecules and fifty solvents (listed in the HSP books), the relative energy difference (RED) was determined. The probability of the target molecules would be interacting with the solvent molecule was determined using the CCDC tools. A dataset of fifty molecules of different organic solvents was ranked for each prediction method and by a consensus ranking of different combinations: HSP, CV, HBP and MC values. Based on the prediction, 15 solvents were selected as Dimethyl Sulfoxide (DMSO), Tetrahydrofuran (THF), Acetonitrile (ACN), 1,4-Dioxane (DOX) and others. In a starting analysis, the slow evaporation technique from 50°C at room temperature and 4°C was used to obtain solvates. The single crystals were collected by using a Bruker D8 Venture diffractometer, detector Photon100. The data processing and crystal structure determination were performed using APEX3 and Olex2-1.5 software. According to the results, the HSPs (theoretical and optimized) and the Hansen solubility sphere for Cur, Demcur and Biscur were obtained. With respect to prediction analyses, a way to evaluate the predicting method was through the ranking and the consensus ranking position of solvates already reported in the literature. It was observed that the combination of HSP-CV obtained the best results when compared to the other methods. Furthermore, as a result of solvent selected, six new solvates, Cur-DOX, Cur-DMSO, Bicur-DOX, Bircur-THF, Demcur-DOX, Demcur-ACN and a new Biscur hydrate, were obtained. Crystal structures were determined for Cur-DOX, Biscur-DOX, Demcur-DOX and Bicur-Water. Moreover, the unit-cell parameter information for Cur-DMSO, Biscur-THF and Demcur-ACN were obtained. The preliminary results showed that the prediction method is showing a promising strategy to evaluate the possibility of forming multicomponent. It is currently working on obtaining multicomponent single crystals.

Keywords: curcumin, HSPs, prediction, solvates, solubility

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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