Search results for: periodic phononic crystal

Authors: Nikolai A. Khlebnikov, Vladimir N. Krasilnikov, Evgenii V. Polyakov, Anastasia A. Maltceva

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Carbon materials with advanced surfaces are widely used both in modern industry and in environmental protection. The physical-chemical nature of these materials is determined by the morphology of primary atomic and molecular carbon structures, which are the basis for synthesizing the following materials: zero-dimensional (fullerenes), one-dimensional (fiber, tubes), two-dimensional (graphene) carbon nanostructures, three-dimensional (multi-layer graphene, graphite, foams) with unique physical-chemical and functional properties. Experience shows that the microscopic morphological level is the basis for the creation of the next mesoscopic morphological level. The dependence of the morphology on the chemical way and process prehistory (crystallization, colloids formation, liquid crystal state and other) is the peculiarity of the last called level. These factors determine the consumer properties of carbon materials, such as specific surface area, porosity, chemical resistance in corrosive environments, catalytic and adsorption activities. Based on the developed ideology of thin precursor synthesis, the authors discuss one of the approaches of the porosity control of carbon-containing materials with a given aggregates morphology. The low-temperature thermolysis of precursors in a gas environment of a given composition is the basis of the above-mentioned idea. The processes of carbothermic precursor synthesis of two different compounds: tungsten carbide WC:nC and zinc oxide ZnO:nC containing an impurity phase in the form of free carbon were selected as subjects of the research. In the first case, the transition metal (tungsten) forming carbides was the object of the synthesis. In the second case, there was selected zinc that does not form carbides. The synthesis of both kinds of transition metals compounds was conducted by the method of precursor carbothermic synthesis from the organic solution. ZnO:nC composites were obtained by thermolysis of succinate Zn(OO(CH2)2OO), formate glycolate Zn(HCOO)(OCH2CH2O)1/2, glycerolate Zn(OCH2CHOCH2OH), and tartrate Zn(OOCCH(OH)CH(OH)COO). WC:nC composite was synthesized from ammonium paratungstate and glycerol. In all cases, carbon structures that are specific for diamond- like carbon forms appeared on the surface of WC and ZnO particles after the heat treatment. Tungsten carbide and zinc oxide were removed from the composites by selective chemical dissolution preserving the amorphous carbon phase. This work presents the results of investigating WC:nC and ZnO:nC composites and carbon nanopowders with tubular, tape, plate and onion morphologies of aggregates that are separated by chemical dissolution of WC and ZnO from the composites by the following methods: SEM, TEM, XPA, Raman spectroscopy, and BET. The connection between the carbon morphology under the conditions of synthesis and chemical nature of the precursor and the possibility of regulation of the morphology with the specific surface area up to 1700-2000 m2/g of carbon-structured materials are discussed.

Keywords: carbon morphology, composite materials, precursor synthesis, tungsten carbide, zinc oxide

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: J. Yang, M. Monnot, T. Eljaddi, L. Simonian, L. Ercolei, P. Moulin

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The application of membrane technology to wastewater treatment has expanded rapidly under increasing stringent legislation and environmental protection requirements. At the same time, the water resource is becoming precious, and water reuse has gained popularity. Particularly, ultrafiltration (UF) is a very promising technology for water reuse as it can retain organic matters, suspended solids, colloids, and microorganisms. Nevertheless, few studies dealing with operating optimization of UF as a tertiary treatment for water reuse on a semi-industrial scale appear in the literature. Therefore, this study aims to explore the permeate water quality and to optimize operating parameters (maximizing productivity and minimizing irreversible fouling) through the operation of a UF pilot plant under real conditions. The fully automatic semi-industrial UF pilot plant with periodic classic backwashes (CB) and air backwashes (AB) was set up to filtrate the secondary effluent of an urban wastewater treatment plant (WWTP) in France. In this plant, the secondary treatment consists of a conventional activated sludge process followed by a sedimentation tank. The UF process was thus defined as a tertiary treatment and was operated under constant flux. It is important to note that a combination of CB and chlorinated AB was used for better fouling management. The 200 kDa hollow fiber membrane was used in the UF module, with an initial permeability (for WWTP outlet water) of 600 L·m-2·h⁻¹·bar⁻¹ and a total filtration surface of 9 m². Fifteen filtration conditions with different fluxes, filtration times, and air backwash frequencies were operated for more than 40 hours of each to observe their hydraulic filtration performances. Through comparison, the best sustainable condition was flux at 60 L·h⁻¹·m⁻², filtration time at 60 min, and backwash frequency of 1 AB every 3 CBs. The optimized condition stands out from the others with > 92% water recovery rates, better irreversible fouling control, stable permeability variation, efficient backwash reversibility (80% for CB and 150% for AB), and no chemical washing occurrence in 40h’s filtration. For all tested conditions, the permeate water quality met the water reuse guidelines of the World Health Organization (WHO), French standards, and the regulation of the European Parliament adopted in May 2020, setting minimum requirements for water reuse in agriculture. In permeate: the total suspended solids, biochemical oxygen demand, and turbidity were decreased to < 2 mg·L-1, ≤ 10 mg·L⁻¹, < 0.5 NTU respectively; the Escherichia coli and Enterococci were > 5 log removal reduction, the other required microorganisms’ analysis were below the detection limits. Additionally, because of the COVID-19 pandemic, coronavirus SARS-CoV-2 was measured in raw wastewater of WWTP, UF feed, and UF permeate in November 2020. As a result, the raw wastewater was tested positive above the detection limit but below the quantification limit. Interestingly, the UF feed and UF permeate were tested negative to SARS-CoV-2 by these PCR assays. In summary, this work confirms the great interest in UF as intensified tertiary treatment for water reuse and gives operational indications for future industrial-scale production of reclaimed water.

Keywords: semi-industrial UF pilot plant, water reuse, fouling management, coronavirus

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Authors: Leigha C. Crout

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This paper will investigate the categorical disregard of the People’s Republic of China (PRC) in establishing and maintaining a baseline standard of civil guarantees for economic migrant women and their dependents. In light of the relative forward strides in terms of policy facilitating the ascension of female workers in China, this oft-invisible subgroup of women remains neglected from the modern-day “iron rice bowl” of the self-identified communist state. This study is being undertaken to rectify the absence of data on this subject and provide a baseline for future studies on the matter, as the human rights of migrants has become an established facet of transnational dialogue and debate. The basic methodology of this research will consist of the evaluation of China’s compliance with its own national guidelines, and the eight international human rights law treaties it has ratified. Data will be extracted and cross-checked from a number of relevant sources to monitor the extent of compliance, including but by no means limited to the United Nations Human Rights Council (UNHRC) Universal Periodic Review (UPR) reports and responses, submissions and responses of international human rights treaty bodies, local and international nongovernmental organizations (NGOs) and their annual reports, and articles and commentaries authored by specialists on the modern state and implementation of Chinese law. Together, these data will illuminate the vast network of compliance that has forced many migrant women to work within situations of extreme economic precarity. The structure will proceed as follows: first, an outline of the current status of migrant workers and the enforcement of stipulated protections will be provided; next, the analysis of the oft-debated regulations directing and the outline of mandatory services guaranteed to external and internal migrants; and finally, a conclusion incorporating various recommendations to improve transparency and gradually decrease the amount of migrant work turned forced labor that typifies the economic migrant experience, especially in the case of women. The internal and international migrant workers in China are bound by different and uncomplimentary systems. The first, which governs Chinese citizens moving to different regions or provinces to find more sustainable employment (internal migrants), is called the hukou (or huji) residency system. This law enforces strict regulation of the movement of peoples, while ensuring that residents of urban areas receive preferential benefits to those received by their so-called “agricultural” resident counterparts. Given the overwhelming presence of the Communist Party of China throughout the vast state, the management of internal migrants and the disregard for foreign domestic workers is, at minimum, a surprising oversight. This paper endeavors to provide a much-needed foundation for future commentary and discussion on the treatment of female migrant workers and their families in the People’s Republic of China.

Keywords: female migrant worker’s rights, the People’s Republic of China, forced labor, Hukou residency system

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Authors: Ružica Tomičić, Zorica Tomičić, Peter Raspor

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An abundant growth of unwanted yeasts in food processing plants can lead to problems in quality and safety with significant financial losses. Candida and Pichia are the genera mainly involved in spoilage of products in the food and beverage industry. These contaminating microorganisms can form biofilms on food contact surfaces, being difficult to eradicate, increasing the probability of microbial survival and further dissemination during food processing. It is well known that biofilms are more resistant to antimicrobial agents compared to planktonic cells and this makes them difficult to eliminate. Among the strategies used to overcome resistance to antifungal drugs and preservatives, the use of natural substances such as plant extracts has shown particular promise, and many natural substances have been found to exhibit antifungal properties. This study aimed to investigated the impact of growth medium (Malt Extract broth (MEB) or Yeast Peptone Dextrose (YPD) broth) and temperatures (7°C, 37°C, 43°C for Candida strains and 7°C, 27°C, 32°C for Pichia strains) on the adhesion of Candida spp. and Pichia spp. to stainless steel (AISI 304) discs with different degrees of surface roughness (Ra = 25.20 – 961.9 nm), a material commonly used in the food industry. We also evaluated the antifungal and antiadhesion activity of plant extracts such as Humulus lupulus, Alpinia katsumadai and Evodia rutaecarpa against C. albicans, C glabrata and P. membranifaciens and investigated whether these plant extracts can interfere with biofilm formation. The adhesion was assessed by the crystal violet staining method, while the broth microdilution method CLSI M27-A3 was used to determine the minimum inhibitory concentration (MIC) of plant extracts. Our results indicated that the nutrient content of the medium significantly influenced the amount of adhered cells of the tested yeasts. The growth medium which resulted in a higher adhesion of C. albicans and C. glabrata was MEB, while for C. parapsilosis and C. krusei was YPD. In the case of P. pijperi and P. membranifaciens, YPD broth was more effective in promoting adhesion than MEB. Regarding the effect of temperature, C. albicans strain adhered to stainless steel surfaces in significantly higher level at a temperature of 43°C, while on the other hand C. glabrata, C. parapsilosis and C. krusei showed a different behavior with significantly higher adhesion at 37°C than at 7°C and 43°C. Further, the adherence ability of Pichia strains was highest at 27°C. Based on the MIC values, all plant extracts exerted significant antifungal effects with MIC values ranged from 100 to 400 μg/mL. It was observed that biofilm of C. glabrata were more resistance to plant extracts as compared to C. albicans. However, extracts of A. katsumadai and E. rutaecarpa promoted the growth and development of the preformed biofilm of P. membranifaciens. Thus, the knowledge of how these microorganisms adhere and which factors affect this phenomenon is of great importance in order to avoid their colonization on food contact surfaces.

Keywords: adhesion, Candida spp., Pichia spp., plant extracts

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Authors: Biswaranjan D. Mohapatra, Ipsha Hota, Swarna P. Mantry, Nibedita Behera, Kumar S. K. Varadwaj

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Designing highly active and low-cost oxygen evolution (2H₂O → 4H⁺ + 4e⁻ + O₂) electrocatalyst is one of the most active areas of advanced energy research. Some precious metal-based electrocatalysts, such as IrO₂ and RuO₂, have shown excellent performance for oxygen evolution reaction (OER); however, they suffer from high-cost and low abundance which limits their applications. Recently, layered double hydroxides (LDHs), composed of layers of divalent and trivalent transition metal cations coordinated to hydroxide anions, have gathered attention as an alternative OER catalyst. However, LDHs are insulators and coupled with carbon materials for the electrocatalytic applications. Graphene covalently doped with nitrogen has been demonstrated to be an excellent electrocatalyst for energy conversion technologies such as; oxygen reduction reaction (ORR), oxygen evolution reaction (OER) & hydrogen evolution reaction (HER). However, they operate at high overpotentials, significantly above the thermodynamic standard potentials. Recently, we reported remarkably enhanced catalytic activity of benzoate or 1-pyrenebutyrate functionalized N-doped graphene towards the ORR in alkaline medium. The molecular and heteroatom co-doping on graphene is expected to tune the electronic structure of graphene. Therefore, an innovative catalyst architecture, in which LDHs are anchored on aromatic acid functionalized ‘N’ doped graphene may presumably boost the OER activity to a new benchmark. Herein, we report fabrication of Co₂Fe-LDH on aromatic acid (AA) functionalized ‘N’ doped reduced graphene oxide (NG) and studied their OER activities in alkaline medium. In the first step, a novel polyol method is applied for synthesis of AA functionalized NG, which is well dispersed in aqueous medium. In the second step, Co₂Fe LDH were grown on AA functionalized NG by co-precipitation method. The hybrid samples are abbreviated as Co₂Fe LDH/AA-NG, where AA is either Benzoic acid or 1, 3-Benzene dicarboxylic acid (BDA) or 1, 3, 5 Benzene tricarboxylic acid (BTA). The crystal structure and morphology of the samples were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscope (TEM). These studies confirmed the growth of layered single phase LDH. The electrocatalytic OER activity of these hybrid materials was investigated by rotating disc electrode (RDE) technique on a glassy carbon electrode. The linear sweep voltammetry (LSV) on these catalyst samples were taken at 1600rpm. We observed significant OER performance enhancement in terms of onset potential and current density on Co₂Fe LDH/BTA-NG hybrid, indicating the synergic effect. This exploration of molecular functionalization effect in doped graphene and LDH system may provide an excellent platform for innovative design of OER catalysts.

Keywords: π-π functionalization, layered double hydroxide, oxygen evolution reaction, reduced graphene oxide

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Authors: Jan Masak, Eva Kvasnickova, Vladimir Scholtz, Olga Matatkova, Marketa Valkova, Alena Cejkova

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Microbial colonization of medical instruments, catheters, implants, etc. is a serious problem in the spread of nosocomial infections. Biofilms exhibit enormous resistance to environment. The resistance of biofilm populations to antibiotic or biocides often increases by two to three orders of magnitude in comparison with suspension populations. Subjects of interests are substances or physical processes that primarily cause the destruction of biofilm, while the released cells can be killed by existing antibiotics. In addition, agents that do not have a strong lethal effect do not cause such a significant selection pressure to further enhance resistance. Non-thermal plasma (NTP) is defined as neutral, ionized gas composed of particles (photons, electrons, positive and negative ions, free radicals and excited or non-excited molecules) which are in permanent interaction. In this work, the effect of NTP generated by the cometary corona with a metallic grid on the formation and stability of biofilm and metabolic activity of cells in biofilm was studied. NTP was applied on biofilm populations of Staphylococcus epidermidis DBM 3179, Pseudomonas aeruginosa DBM 3081, DBM 3777, ATCC 15442 and ATCC 10145, Escherichia coli DBM 3125 and Candida albicans DBM 2164 grown on solid media on Petri dishes and on the titanium alloy (Ti6Al4V) surface used for the production joint replacements. Erythromycin (for S. epidermidis), polymyxin B (for E. coli and P. aeruginosa), amphotericin B (for C. albicans) and ceftazidime (for P. aeruginosa) were used to study the combined effect of NTP and antibiotics. Biofilms were quantified by crystal violet assay. Metabolic activity of the cells in biofilm was measured using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) colorimetric test based on the reduction of MTT into formazan by the dehydrogenase system of living cells. Fluorescence microscopy was applied to visualize the biofilm on the surface of the titanium alloy; SYTO 13 was used as a fluorescence probe to stain cells in the biofilm. It has been shown that biofilm populations of all studied microorganisms are very sensitive to the type of used NTP. The inhibition zone of biofilm recorded after 60 minutes exposure to NTP exceeded 20 cm², except P. aeruginosa DBM 3777 and ATCC 10145, where it was about 9 cm². Also metabolic activity of cells in biofilm differed for individual microbial strains. High sensitivity to NTP was observed in S. epidermidis, in which the metabolic activity of biofilm decreased after 30 minutes of NTP exposure to 15% and after 60 minutes to 1%. Conversely, the metabolic activity of cells of C. albicans decreased to 53% after 30 minutes of NTP exposure. Nevertheless, this result can be considered very good. Suitable combinations of exposure time of NTP and the concentration of antibiotic achieved in most cases a remarkable synergic effect on the reduction of the metabolic activity of the cells of the biofilm. For example, in the case of P. aeruginosa DBM 3777, a combination of 30 minutes of NTP with 1 mg/l of ceftazidime resulted in a decrease metabolic activity below 4%.

Keywords: anti-biofilm activity, antibiotic, non-thermal plasma, opportunistic pathogens

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Authors: Ennios Eros Giogos, Nefeli Katsarou, Giota Mantziorou, Elena Panou, Nikolaos Kourniatis, Socratis Giannoudis

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In the context of the postgraduate course Productive Design, Department of Interior Architecture of the University of West Attica in Athens, under the guidance of Professors Nikolaos Koyrniatis and Socratis Giannoudis, kinetic mechanisms with parametric models were examined for their further application in the design of objects. In the first phase, the students studied a motion mechanism that they chose from daily experience and then analyzed its geometric structure in relation to the geometric transformations that exist. In the second phase, the students tried to design it through a parametric model in Grasshopper3d for Rhino algorithmic processor and plan the design of its application in an everyday object. For the project presented, our team began by studying the movement of living beings, specifically the snake. By studying the snake and the role that the environment has in its movement, four basic typologies were recognized: serpentine, concertina, sidewinding and rectilinear locomotion, as well as its ability to perform spiral formations. Most typologies are characterized by ripples, a series of sinusoidal curves. For the application of the snake movement in a polymorphic space divider, the use of a coil-type joint was studied. In the Grasshopper program, the simulation of the desired motion for the polymorphic surface was tested by applying a coil on a sinusoidal curve and a spiral curve. It was important throughout the process that the points corresponding to the nodes of the real object remain constant in number, as well as the distances between them and the elasticity of the construction had to be achieved through a modular movement of the coil and not some elastic element (material) at the nodes. Using mesh (repeating coil), the whole construction is transformed into a supporting body and combines functionality with aesthetics. The set of elements functions as a vertical spatial network, where each element participates in its coherence and stability. Depending on the positions of the elements in terms of the level of support, different perspectives are created in terms of the visual perception of the adjacent space. For the implementation of the model on the scale (1:3), (0.50m.x2.00m.), the load-bearing structure that was studied has aluminum rods for the basic pillars Φ6mm and Φ 2.50 mm, for the secondary columns. Filling elements and nodes are of similar material and were made of MDF surfaces. During the design process, four trapezoidal patterns were picketed, which function as filling elements, while in order to support their assembly, a different engraving facet was done. The nodes have holes that can be pierced by the rods, while their connection point with the patterns has a half-carved recess. The patterns have a corresponding recess. The nodes are of two different types depending on the column that passes through them. The patterns and knots were designed to be cut and engraved using a Laser Cutter and attached to the knots using glue. The parameters participate in the design as mechanisms that generate complex forms and structures through the repetition of constantly changing versions of the parts that compose the object.

Keywords: polymorphic, locomotion, sinusoidal curves, parametric

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Authors: Zubair Ahmed, Andrea Barbieri

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The need to reduce energy consumption has prompted a considerable research effort for developing alternative energy-efficient lighting systems to replace conventional light sources (i.e., incandescent and fluorescent lamps). Organic light emitting device (OLED) technology offers the distinctive possibility to fabricate large area flat devices by vacuum or solution processing. Lanthanide β-diketonates complexes, due to unique photophysical properties of Ln(III) ions, have been explored as emitting layers in OLED displays and in solid-state lighting (SSL) in order to achieve high efficiency and color purity. For such applications, the excellent photoluminescence quantum yield (PLQY) and stability are the two key points that can be achieved simply by selecting the proper organic ligands around the Ln ion in a coordination sphere. Regarding the strategies to enhance the PLQY, the most common is the suppression of the radiationless deactivation pathways due to the presence of high-frequency oscillators (e.g., OH, –CH groups) around the Ln centre. Recently, a different approach to maximize the PLQY of Ln(β-DKs) has been proposed (named 'Escalate Coordination Anisotropy', ECA). It is based on the assumption that coordinating the Ln ion with different ligands will break the centrosymmetry of the molecule leading to less forbidden transitions (loosening the constraints of the Laporte rule). The OLEDs based on such complexes are available, but with low efficiency and stability. In order to get efficient devices, there is a need to develop some new Ln complexes with enhanced PLQYs and stabilities. For this purpose, the Ln complexes, both visible and (NIR) emitting, of variant coordination structures based on the various fluorinated/non-fluorinated β-diketones and O/N-donor neutral ligands were synthesized using a one step in situ method. In this method, the β-diketones, base, LnCl₃.nH₂O and neutral ligands were mixed in a 3:3:1:1 M ratio in ethanol that gave air and moisture stable complexes. Further, they were characterized by means of elemental analysis, NMR spectroscopy and single crystal X-ray diffraction. Thereafter, their photophysical properties were studied to select the best complexes for the fabrication of stable and efficient OLEDs. Finally, the OLEDs were fabricated and investigated using these complexes as emitting layers along with other organic layers like NPB,N,N′-Di(1-naphthyl)-N,N′-diphenyl-(1,1′-biphenyl)-4,4′-diamine (hole-transporting layer), BCP, 2,9-Dimethyl-4,7-diphenyl-1,10-phenanthroline (hole-blocker) and Alq3 (electron-transporting layer). The layers were sequentially deposited under high vacuum environment by thermal evaporation onto ITO glass substrates. Moreover, co-deposition techniques were used to improve charge transport in the devices and to avoid quenching phenomena. The devices show strong electroluminescence at 612, 998, 1064 and 1534 nm corresponding to ⁵D₀ →⁷F₂(Eu), ²F₅/₂ → ²F₇/₂ (Yb), ⁴F₃/₂→ ⁴I₉/₂ (Nd) and ⁴I1₃/₂→ ⁴I1₅/₂ (Er). All the devices fabricated show good efficiency as well as stability.

Keywords: electroluminescence, lanthanides, paramagnetic NMR, photoluminescence

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Authors: Mustapha A. Tijjani, Fanna I. Abdulrahman, Irfan Z. Khan, Umar K. Sandabe, Cong Li

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Air dried sample V. doniana after collection and identification was extracted with ethanol and further partition with chloroform, ethyl acetate and n-butanol. Ethanolic extract (11.9g) was fractionated on a silica gel accelerated column chromatography using solvents such as n-hexane, ethyl acetate and methanol. Each eluent fractions (150ml aliquots) were collected and monitored with thin layer chromatography. Fractions with similar Rf values from same solvents system were pooled together. Phytochemical test of all the fractions were performed using standard procedure. Complete elution yielded 48 fractions (150ml/fraction) which were pooled to 24 fractions base on the Rf values. It was further recombined and 12 fractions were obtained on the basis on Rf values and coded Vd1 to Vd12 fractions. Vd8 was further eluted with ethylacetate and methanol and gave fourteen sub fractions Vd8-a, -Vd8-m. Fraction Vd8-a (56mg) gave a white crystal compound coded V1. It was further checked on TLC and observed under ultraviolet lamp and was found to give a single spot. The Rf values were calculated to be 0.433. The melting point was determined using Gallenkamp capillary melting point apparatus and found to be 241-243°C uncorrected. Characterization of the isolated compound coded V1 was done using FT-infra-red spectroscopy, HNMR, 13CNMR(1and 2D) and HRESI-MS. The IR spectrum of compound V1 shows prominent peaks that corresponds to OHstr (3365cm-1) and C=0 (1652cm-1) etc. This spectrum suggests that among the functional moiety in compound V1 are the carbonyl and hydroxyl group. The 1H NMR (400 MHz) spectrum of compound V1 in DMSO-d6 displayed five singlet signals at δ 0.72 (3H, s, H-18), 0.79 (3H, s, H-19), 1.03 (3H, s, H-21), 1.04 (3H, s, H-26), 1.06 (3H, s, H-27) each integrating for three protons indicating the five methyl functional groups present in the compound. It further showed a broad singlet at δ 5.58 integrated for 1 H due to an olefinic H-atom adjacent to the carbonyl carbon atom. Three signals at δ 3.10 (d, J = 9.0 Hz, H-22), 3.59 (m, 1H, 2H-a) and 3.72 (m, 1H, 3H-e), each integrating for one proton is due to oxymethine protons indicating that three oxymethine H-atoms are present in the compound. These all signals are characteristic to the ecdysteroid skeletons. The 13C-NMR spectrum showed the presence of 27 carbon atoms, suggesting that may be steroid skeleton. The DEPT-135 experiment showed the presence of five CH3, eight CH2, and seven CH groups, and seven quaternary C-atoms. The molecular formula was established as C27H44O7 by high resolution electron spray ionization-mass spectroscopy (HRESI-MS) positive ion mode m/z 481.3179. The signals in mass spectrum are 463, 445, and 427 peaks corresponding to losses of one, two, three, or four water molecules characteristic for ecdysterone skeleton reported in the literature. Based on the spectral analysis (HNMR, 13CNMR, DEPT, HMQC, IR, HRESI-MS) the compound V1 is thus concluded to have ecdysteriod skeleton and conclusively conforms with 2β, 3β 14α, 20R, 22R, 25-hexahydroxy-5 β cholest-7-ene-6- one, or 2, 3, 14, 20, 22, 25 hexahydroxy cholest-7-ene-6-one commonly known as 20-hydroxyecdysone.

Keywords: vitex, phytochemical, purification, isolation, chromatography, spectroscopy

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Authors: Fatih Kılıç, Burak Birol, Necmettin Maraşlı

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The directional solidification process is generally used for homogeneous compound production, single crystal growth, and refining (zone refining), etc. processes. The most important two parameters that control eutectic structures are temperature gradient and grain growth rate which are called as solidification parameters The solidification behavior and microstructure characteristics is an interesting topic due to their effects on the properties and performance of the alloys containing eutectic compositions. The solidification behavior of multicomponent and multiphase systems is an important parameter for determining various properties of these materials. The researches have been conducted mostly on the solidification of pure materials or alloys containing two phases. However, there are very few studies on the literature about multiphase reactions and microstructure formation of multicomponent alloys during solidification. Because of this situation, it is important to study the microstructure formation and the thermodynamical, thermophysical and microstructural properties of these alloys. The production process is difficult due to easy oxidation of magnesium and therefore, there is not a comprehensive study concerning alloys containing high Mg (> 30 wt.% Mg). With the increasing amount of Mg inside Al alloys, the specific weight decreases, and the strength shows a slight increase, while due to formation of β-Al8Mg5 phase, ductility lowers. For this reason, production, examination and development of high Mg containing alloys will initiate the production of new advanced engineering materials. The original value of this research can be described as obtaining high Mg containing (> 30% Mg) Al based multicomponent alloys by melting under vacuum; controlled directional solidification with various growth rates at a constant temperature gradient; and establishing relationship between solidification rate and microstructural, mechanical, electrical and thermal properties. Therefore, within the scope of this research, some > 30% Mg containing ternary or quaternary Al alloy compositions were determined, and it was planned to investigate the effects of directional solidification rate on the mechanical, electrical and thermal properties of these alloys. Within the scope of the research, the influence of the growth rate on microstructure parameters, microhardness, tensile strength, electrical conductivity and thermal conductivity of directionally solidified high Mg containing Al-32,2Mg-0,37Si; Al-30Mg-12Zn; Al-32Mg-1,7Ni; Al-32,2Mg-0,37Fe; Al-32Mg-1,7Ni-0,4Si; Al-33,3Mg-0,35Si-0,11Fe (wt.%) alloys with wide range of growth rate (50-2500 µm/s) and fixed temperature gradient, will be investigated. The work can be planned as; (a) directional solidification of Al-Mg based Al-Mg-Si, Al-Mg-Zn, Al-Mg-Ni, Al-Mg-Fe, Al-Mg-Ni-Si, Al-Mg-Si-Fe within wide range of growth rates (50-2500 µm/s) at a constant temperature gradient by Bridgman type solidification system, (b) analysis of microstructure parameters of directionally solidified alloys by using an optical light microscopy and Scanning Electron Microscopy (SEM), (c) measurement of microhardness and tensile strength of directionally solidified alloys, (d) measurement of electrical conductivity by four point probe technique at room temperature (e) measurement of thermal conductivity by linear heat flow method at room temperature.

Keywords: directional solidification, electrical conductivity, high Mg containing multicomponent Al alloys, microhardness, microstructure, tensile strength, thermal conductivity

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Authors: Luminiţa Duţică, Gheorghe Duţică

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One of the most powerful language innovation in the twentieth century music was the heterophony–hypostasis of the vertical syntax entered into the sphere of interest of many composers, such as George Enescu, Pierre Boulez, Mauricio Kagel, György Ligeti and others. The heterophonic syntax has a history of its growth, which means a succession of different concepts and writing techniques. The trajectory of settling this phenomenon does not necessarily take into account the chronology: there are highly complex primary stages and advanced stages of returning to the simple forms of writing. In folklore, the plurimelodic simultaneities are free or random and originate from the (unintentional) differences/‘deviations’ from the state of unison, through a variety of ornaments, melismas, imitations, elongations and abbreviations, all in a flexible rhythmic and non-periodic/immeasurable framework, proper to the parlando-rubato rhythmics. Within the general framework of the multivocal organization, the heterophonic syntax in elaborate (academic) version has imposed itself relatively late compared with polyphony and homophony. Of course, the explanation is simple, if we consider the causal relationship between the sound vocabulary elements – in this case, the modalism – and the typologies of vertical organization appropriate for it. Therefore, adding up the ‘classic’ pathway of the writing typologies (monody – polyphony – homophony), heterophony - applied equally to the structures of modal, serial or synthesis vocabulary – reclaims necessarily an own macrotemporal form, in the sense of the analogies enshrined by the evolution of the musical styles and languages: polyphony→fugue, homophony→sonata. Concerned about the prospect of edifying a new musical ontology, the composer Ştefan Niculescu experienced – along with the mathematical organization of heterophony according to his own original methods – the possibility of extrapolation of this phenomenon in macrostructural plan, reaching this way to the unique form of ‘synchrony’. Founded on coincidentia oppositorum principle (involving the ‘one-multiple’ binom), the sound architecture imagined by Ştefan Niculescu consists in one (temporal) model / algorithm of articulation of two sound states: 1. monovocality state (principle of identity) and 2. multivocality state (principle of difference). In this context, the heterophony becomes an (auto)generative mechanism, with macrotemporal amplitude, strategy that will be grown by the composer, practically throughout his creation (see the works: Ison I, Ison II, Unisonos I, Unisonos II, Duplum, Triplum, Psalmus, Héterophonies pour Montreux (Homages to Enescu and Bartók etc.). For the present demonstration, we selected one of the most edifying works of Ştefan Niculescu – Simphony II, Opus dacicum – where the form of (heterophony-)synchrony acquires monumental-symphonic features, representing an emblematic case for the complexity level achieved by this type of vertical syntax in the twentieth century music.

Keywords: heterophony, modalism, serialism, synchrony, syntax

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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Authors: Radik D. Aglyamov, Alexander K. Naumov, Alexey A. Shavelev, Oleg A. Morozov, Arsenij D. Shishkin, Yury P.Brodnikovsky, Alexander A.Karabutov, Alexander A. Oraevsky, Vadim V. Semashko

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The development of medical optoacoustic tomography with the using human blood as endogenic contrast agent is constrained by the lack of reliable, easy-to-use and inexpensive sources of high-power pulsed laser radiation in the spectral region of 750-900 nm [1-2]. Currently used titanium-sapphire, alexandrite lasers or optical parametric light oscillators do not provide the required and stable output characteristics, they are structurally complex, and their cost is up to half the price of diagnostic optoacoustic systems. Here we are developing the lasers based on Cr:LiCaAlF6 crystals which are free of abovementioned disadvantages and provides intensive ten’s ns-range tunable laser radiation at specific absorption bands of oxy- (~840 nm) and -deoxyhemoglobin (~757 nm) in the blood. Cr:LiCAF (с=3 at.%) crystals were grown in Kazan Federal University by the vertical directional crystallization (Bridgman technique) in graphite crucibles in a fluorinating atmosphere at argon overpressure (P=1500 hPa) [3]. The laser elements have cylinder shape with the diameter of 8 mm and 90 mm in length. The direction of the optical axis of the crystal was normal to the cylinder generatrix, which provides the π-polarized laser action correspondent to maximal stimulated emission cross-section. The flat working surfaces of the active elements were polished and parallel to each other with an error less than 10”. No any antireflection coating was applied. The Q-switched master oscillator-power amplifiers laser system (MOPA) with the dual-Xenon flashlamp pumping scheme in diffuse-reflectivity close-coupled head were realized. A specially designed laser cavity, consisting of dielectric highly reflective reflectors with a 2 m-curvature radius, a flat output mirror, a polarizer and Q-switch sell, makes it possible to operate sequentially in a circle (50 ns - laser one pulse after another) at wavelengths of 757 and 840 nm. The programmable pumping system from Tomowave Laser LLC (Russia) provided independent to each pulses (up to 250 J at 180 μs) pumping to equalize the laser radiation intensity at these wavelengths. The MOPA laser operates at 10 Hz pulse repetition rate with the output energy up to 210 mJ. Taking into account the limitations associated with physiological movements and other characteristics of patient tissues, the duration of laser pulses and their energy allows molecular and functional high-contrast imaging to depths of 5-6 cm with a spatial resolution of at least 1 mm. Highly likely the further comprehensive design of laser allows improving the output properties and realizing better spatial resolution of medical multispectral optoacoustic tomography systems.

Keywords: medical optoacoustic, endogenic contrast agent, multiwavelength tunable pulse lasers, MOPA laser system

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Authors: Laura Kocsor, Laszlo Peter, Laszlo Kovacs, Zsolt Kis

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The aim of our research is to prepare rare-earth-doped lithium niobate (LiNbO3) nanocrystals, having only a few dopant ions in the focal point of an exciting laser beam. These samples will be used to achieve individual addressing of the dopant ions by light beams in a confocal microscope setup. One method for the preparation of nanocrystalline materials is to reduce the particle size by mechanical grinding. High-energy ball-milling was used in several works to produce nano lithium niobate. Previously, it was reported that dry high-energy ball-milling of lithium niobate in a shaker mill results in the partial reduction of the material, which leads to a balanced formation of bipolarons and polarons yielding gray color together with oxygen release and Li2O segregation on the open surfaces. In the present work we focus on preparing LiNbO3 nanocrystals by high-energy ball-milling using a Fritsch Pulverisette 7 planetary mill. Every ball-milling process was carried out in zirconia vial with zirconia balls of different sizes (from 3 mm to 0.1 mm), wet grinding with water, and the grinding time being less than an hour. Gradually decreasing the ball size to 0.1 mm, an average particle size of about 10 nm could be obtained determined by dynamic light scattering and verified by scanning electron microscopy. High-energy ball-milling resulted in sample darkening evidenced by optical absorption spectroscopy measurements indicating that the material underwent partial reduction. The unwanted lithium oxide loss decreases the Li/Nb ratio in the crystal, strongly influencing the spectroscopic properties of lithium niobate. Zirconia contamination was found in ground samples proved by energy-dispersive X-ray spectroscopy measurements; however, it cannot be explained based on the hardness properties of the materials involved in the ball-milling process. It can be understood taking into account the presence of lithium hydroxide formed the segregated lithium oxide and water during the ball-milling process, through chemically induced abrasion. The quantity of the segregated Li2O was measured by coulometric titration. During the wet milling process in the planetary mill, it was found that the lithium oxide loss increases linearly in the early phase of the milling process, then a saturation of the Li2O loss can be seen. This change goes along with the disappearance of the relatively large particles until a relatively narrow size distribution is achieved in accord with the dynamic light scattering measurements. With the 3 mm ball size and 1100 rpm rotation rate, the mean particle size achieved is 100 nm, and the total Li2O loss is about 1.2 wt.% of the original LiNbO3. Further investigations have been done to minimize the Li2O segregation during the ball-milling process. Since the Li2O loss was observed to increase with the growing total surface of the particles, the influence of ball-milling parameters on its quantity has also been studied.

Keywords: high-energy ball-milling, lithium niobate, mechanochemical reaction, nanocrystals

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Authors: Mojtaba Eshraghi Arani

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Ship financing is the vital element in the development of shipping industry because while the ship constitutes the owners’ main asset, she is considered a reliable security in the financiers’ viewpoint as well. However, it is most probable that a financier who has accepted a ship as security will face many creditors who are privileged and rank before him for collecting, out of the ship, the money that they are owed. In fact, according to the current rule of maritime law, which was established by “Convention Internationale pour l’Unification de Certaines Règles Relatives aux Privilèges et Hypothèques Maritimes, Brussels, 10 April 1926”, the mortgages, hypotheques, and other charges on vessels rank after several secured claims referred to as “maritime liens”. Such maritime liens are an exhaustive list of claims including but not limited to “expenses incurred in the common interest of the creditors to preserve the vessel or to procure its sale and the distribution of the proceeds of sale”, “tonnage dues, light or harbour dues, and other public taxes and charges of the same character”, “claims arising out of the contract of engagement of the master, crew and other persons hired on board”, “remuneration for assistance and salvage”, “the contribution of the vessel in general average”, “indemnities for collision or other damage caused to works forming part of harbours, docks, etc,” “indemnities for personal injury to passengers or crew or for loss of or damage to cargo”, “claims resulting form contracts entered into or acts done by the master”. The same rule survived with only some minor change in the categories of maritime liens in the substitute conventions 1967 and 1993. The status que in maritime law have always been considered as a major obstacle to the development of shipping market and has inevitably led to increase in the interest rates and other related costs of ship financing. It seems that the national and international policy makers have yet to change their mind being worried about the deviation from the old marine traditions. However, it is crystal clear that the continuation of status que will harm, to a great extent, the shipowners and, consequently, the international merchants as a whole. It is argued in this article that the raison d'être for many categories of maritime liens cease to exist anymore, in view of which, the international community has to recognize only a minimum category of maritime liens which are created in the common interests of all creditors; to this effect, only two category of “compensation due for the salvage of ship” and “extraordinary expenses indispensable for the preservation of the ship” can be declared as taking priority over the mortgagee rights, in anology with the Geneva Convention on the International Recognition of Rights in Aircrafts (1948). A qualitative method with the concept of interpretation of data collection has been used in this manuscript. The source of the data is the analysis of international conventions and domestic laws.

Keywords: ship finance, mortgage, maritime liens, brussels convenion, geneva convention 1948

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Authors: Melanie Francois, Gilles Caboche, Frederic Demoisson, Francois Maeght, Maria Paola Carpanese, Lionel Combemale, Pascal Briois

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Finding new clean, and efficient way for energy production is one of the actual global challenges. Advances in fuel cell technology have shown that, for few years, Protonic Ceramic Fuel Cell (PCFC) has attracted much attention in the field of new hydrogen energy thanks to their lower working temperature, possible higher efficiency, and better durability than classical SOFC. On the contrary of SOFC, where O²⁻ oxygen ion is the charge carrier, PCFC works with H⁺ proton as a charge carrier. Consequently, the lower activation energy of proton diffusion compared to the one of oxygen ion explains those benefits and allows PCFC to work in the 400-600°C temperature range. Doped-BaCeO₃ is currently the most chosen material for this application because of its high protonic conductivity; for example, BaCe₀.₉Y₀.₁O₃ δ exhibits a total conductivity of 1.5×10⁻² S.cm⁻¹ at 600°C in wet H₂. However, BaCeO₃ based perovskite has low stability in H₂O and/or CO₂ containing atmosphere, which limits their practical application. On the contrary, BaZrO₃ based perovskite exhibits good chemical stability but lower total conductivity than BaCeO₃ due to its larger grain boundary resistance. By substituting zirconium with 20% of yttrium, it is possible to achieve a total conductivity of 2.5×10⁻² S.cm⁻¹ at 600°C in wet H₂. However, the high refractory property of BaZr₀.₈Y₀.₂O₃-δ (noted BZY20) causes problems to obtain a dense membrane with large grains. Thereby, using a synthesis process that gives fine particles could allow better sinterability and thus decrease the number of grain boundaries leading to a higher total conductivity. In this work, BaZr₀.₈Y₀.₂O₃-δ have been synthesized by classical batch hydrothermal device and by a continuous hydrothermal device developed at ICB laboratory. The two variants of this process are able to work in supercritical conditions, leading to the formation of nanoparticles, which could be sintered at a lower temperature. The as-synthesized powder exhibits the right composition for the perovskite phase, impurities such as BaCO₃ and YO-OH were detected at very low concentration. Microstructural investigation and densification rate measurement showed that the addition of 1 wt% of ZnO as sintering aid and a sintering at 1550°C for 5 hours give high densified electrolyte material. Furthermore, it is necessary to heat the synthesized powder prior to the sintering to prevent the formation of secondary phases. It is assumed that this thermal treatment homogenizes the crystal structure of the powder and reduces the number of defects into the bulk grains. Electrochemical impedance spectroscopy investigations in various atmospheres and a large range of temperature (200-700°C) were then performed on sintered samples, and the protonic conductivity of BZY20 has been highlighted. Further experiments on half-cell, NiO-BZY20 as anode and BZY20 as electrolyte, are in progress.

Keywords: hydrothermal synthesis, impedance measurement, Y-doped BaZrO₃, proton conductor

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Authors: M. P. S. Tomar, Neelam Bansal

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Histomorphological, histochemical and scanning electron microscopic observations were recorded in developing cornea of buffalo fetuses. The samples from fetal cornea were collected in appropriate fixative from slaughter house and Veterinary Clinics, GADVASU, Ludhiana. The microscopic slides were stained for detailed histomorphological and histochemical studies. The scanning electron microscopic studies were performed at Electron microscopy & Nanobiology Lab, PAU Ludhiana. In present study, it was observed that, in 36 days (d) fetus, the corneal epithelium was well marked single layered structure which was placed on stroma mesenchyme. Cornea appeared as the continuation of developing sclera. The thickness of cornea and its epithelium increased as well as the epithelium started becoming double layered in 47d fetus at corneo-scleral junction. The corneal thickness in this stage suddenly increased thus easily distinguished from developing sclera. The separation of corneal endothelium from stroma was evident as a single layered epithelium. The stroma possessed numerous fibroblasts in 49d stage eye. Descemet’s membrane was appeared at 52d stage. The limbus area was separated by a depression from the developing cornea in 61d stage. In 65d stage, the Bowman’s layer was more developed. Fibroblasts were arranged parallel to each other as well as parallel to the surface of developing cornea in superficial layers. These fibroblasts and fibers were arranged in wavy pattern in the center of stroma. Corneal epithelium started to be stratified as a double layered epithelium was present in this age of fetal eye. In group II (>120 Days), the corneal epithelium was stratified towards a well marked irido-corneal angle. The stromal fibroblasts followed a complete parallel arrangement in its entire thickness. In full term fetuses, a well developed cornea was observed. It was a fibrous layer which had five distinct layers. From outside to inwards were described as the outer most layer was the 7-8 layered corneal epithelial, subepithelial basement membrane (Bowman’s membrane), substantia propria or stroma, posterior limiting membrane (Descemet’s membrane) and the posterior epithelium (corneal endothelium). The corneal thickness and connective tissue elements were continued to be increased. It was 121.39 + 3.73µ at 36d stage which increased to 518.47 + 4.98 µ in group III fetuses. In fetal life, the basement membrane of corneal epithelium and endothelium depicted strong to intense periodic Acid Schiff’s (PAS) reaction. At the irido-corneal angle, the endothelium of blood vessels was also positive for PAS activity. However, cornea was found mild positive for alcian blue reaction. The developing cornea showed strong reaction for basic proteins in outer epithelium and the inner endothelium layers. Under low magnification scanning electron microscope, cornea showed two types of cells viz. light cells and dark cells. The light cells were smaller in size and had less number of microvilli in their surface than in the dark cells. Despite these surface differences between light and dark cells, the corneal surface showed the same general pattern of microvilli studding all exposed surfaces out to the cell margin. which were long (with variable height), slight tortuous slender and possessed a micro villus shaft with a very prominent knob.

Keywords: buffalo, cornea, eye, fetus, ontogeny, scanning electron microscopy

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: Linda Fellag, Arlene Caney

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E-learning has earned an essential place in academia because it promotes learner autonomy, student engagement, and technological aptitude, and allows for flexible learning. However, despite advantages, educators have been slower to embrace e-learning for ESL and other non-traditional students for fear that such students will not succeed without the direct faculty contact and academic support of face-to-face classrooms. This study aims to determine if a non-traditional student-friendly online course can produce student retention and performance rates that compare favorably with those of students in standard online sections of the same course aimed at traditional college-level students. One Music faculty member is currently collaborating with an English instructor to redesign an online college-level Music Appreciation course for non-traditional college students. At Community College of Philadelphia, Introduction to Music Appreciation was recently designated as one of the few college-level courses that advanced ESL, and developmental English students can take while completing their language studies. Beginning in Fall 2017, the course will be critical for international students who must maintain full-time student status under visa requirements. In its current online format, however, Music Appreciation is designed for traditional college students, and faculty who teach these sections have been reluctant to revise the course to address the needs of non-traditional students. Interestingly, presenters maintain that the online platform is the ideal place to develop language and college readiness skills in at-risk students while maintaining the course's curricular integrity. The two faculty presenters describe how curriculum rather than technology drives the redesign of the digitized music course, and self-study materials, guided assignments, and periodic assessments promote independent learning and comprehension of material. The 'scaffolded' modules allow ESL and developmental English students to build on prior knowledge, preview key vocabulary, discuss content, and complete graded tasks that demonstrate comprehension. Activities and assignments, in turn, enhance college success by allowing students to practice academic reading strategies, writing, speaking, and student-faculty and peer-peer communication and collaboration. The course components facilitate a comparison of student performance and retention in sections of the redesigned and existing online sections of Music Appreciation as well as in previous sections with at-risk students. Indirect, qualitative measures include student attitudinal surveys and evaluations. Direct, quantitative measures include withdrawal rates, tests of disciplinary knowledge, and final grades. The study will compare the outcomes of three cohorts in the two versions of the online course: ESL students, at-risk developmental students, and college-level students. These data will also be compared with retention and student outcomes data of the three cohorts in f2f Music Appreciation, which permitted non-traditional student enrollment from 1998-2005. During this eight-year period, the presenter addressed the problems of at-risk students by adding language and college success support, which resulted in strong retention and outcomes. The presenters contend that the redesigned course will produce favorable outcomes among all three cohorts because it contains components which proved successful with at-risk learners in f2f sections of the course. Results of their study will be published in 2019 after the redesigned online course has met for two semesters.

Keywords: college readiness, e-learning, music appreciation, online courses

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Authors: Adil Murtaza, Muhammad Tahir Khan, Awais Ghani, Chao Zhou, Sen Yang, Xiaoping Song

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The morphotropic phase boundary (MPB); a boundary between two different crystallographic symmetries in the composition–temperature phase diagram has been widely studied in ferroelectrics and recently has drawn interest in ferromagnets for obtaining enhanced large field-induced strain. At MPB, the system gets a compressed free energy state, which allows the polarization to freely rotate and hence results in a high magnetoelastic response (e.g., high magnetization, low coercivity, and large magnetostriction). Based on the same mechanism, we designed MPB in a ferromagnetic Tb₁₋ₓNdₓCo₂ system. The temperature-dependent magnetization curves showed spin reorientation (SR); which can be explained by a two-sublattice model. Contrary to previously reported MPB involved ferromagnetic systems, the MPB composition of Tb₀.₃₅Nd₀.₆₅Co₂ exhibits a low saturation magnetization (MS), indicating a compensation of the Tb and Nd magnetic moments at MPB. The coercive field (HC) under a low magnetic field and first anisotropy constant (K₁) shows a minimum value at MPB composition of x=0.65. A detailed spin configuration diagram is provided for the Tb₁₋ₓNdₓCo₂ around the composition for the anisotropy compensation; this can guide the development of novel magnetostrictive materials. The anisotropic magnetostriction (λS) first decreased until x=0.8 and then continuously increased in the negative direction with further increase of Nd concentration. In addition, the large ratio between magnetostriction and the absolute values of the first anisotropy constant (λS/K₁) appears at MPB, indicating that Tb₀.₃₅Nd₀.₆₅Co₂ has good magnetostrictive properties. Present work shows an anomalous type of MPB in ferromagnetic materials, revealing that MPB can also lead to a weakening of magnetoelastic behavior as shown in the ferromagnetic Tb₁₋ₓNdₓCo₂ system. Our work shows the universal presence of MPB in ferromagnetic materials and suggests the differences between different ferromagnetic MPB systems that are important for substantial improvement of magnetic and magnetostrictive properties. Based on the results of this study, similar MPB effects might be achieved in other ferroic systems that can be used for technological applications. The finding of magnetic MPB in the ferromagnetic system leads to some important significances. First, it provides a better understanding of the fundamental concept of spin reorientation transitions (SRT) like ferro-ferro transitions are not only reorientation of magnetization but also crystal symmetry change upon magnetic ordering. Second, the flattened free energy corresponding to a low energy barrier for magnetization rotation and enhanced magnetoelastic response near MPB. Third, to attain large magnetostriction with MPB approach two terminal compounds have different easy magnetization directions below Curie temperature Tc in order to accomplish the weakening of magnetization anisotropy at MPB (as in ferroelectrics), thus easing the magnetic domain switching and the lattice distortion difference between two terminal compounds should be large enough, e.g., lattice distortion of R symmetry ˃˃ lattice distortion of T symmetry). So that the MPB composition agrees to a nearly isotropic state along with large ‘net’ lattice distortion, which is revealed in a higher value of magnetostriction.

Keywords: magnetization, magnetostriction, morphotropic phase boundary (MPB), phase transition

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Authors: Gabriela Wyszogrodzka, Przemyslaw Dorozynski, Barbara Gil, Maciej Strzempek, Bartosz Marszalek, Piotr Kulinowski, Wladyslaw Piotr Weglarz, Elzbieta Menaszek

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MOFs (Metal-Organic Frameworks) belong to a new group of porous materials with a hybrid organic-inorganic construction. Their structure is a network consisting of metal cations or clusters (acting as metallic centers, nodes) and the organic linkers between nodes. The interest in MOFs is primarily associated with the use of their well-developed surface and large porous. Possibility to build MOFs of biocompatible components let to use them as potential drug carriers. Furthermore, forming MOFs structure from cations possessing paramagnetic properties (e.g. iron cations) allows to use them as MRI (Magnetic Resonance Imaging) contrast agents. The concept of formation of particles that combine the ability to transfer active substance with imaging properties has been called theranostic (from words combination therapy and diagnostics). By building MOF structure from iron cations it is possible to use them as theranostic agents and monitoring the distribution of the active substance after administration in real time. In the study iron-MOF: Fe-MIL-101-NH2 was chosen, consisting of iron cluster in nodes of the structure and amino-terephthalic acid as a linker. The aim of the study was to investigate the possibility of applying Fe-MIL-101-NH2 as inhalable theranostic particulate system for the first-line anti-tuberculosis antibiotic – isoniazid. The drug content incorporated into Fe-MIL-101-NH2 was evaluated by dissolution study using spectrophotometric method. Results showed isoniazid encapsulation efficiency – ca. 12.5% wt. Possibility of Fe-MIL-101-NH2 application as the MRI contrast agent was demonstrated by magnetic resonance tomography. FeMIL-101-NH2 effectively shortening T1 and T2 relaxation times (increasing R1 and R2 relaxation rates) linearly with the concentrations of suspended material. Images obtained using multi-echo magnetic resonance imaging sequence revealed possibility to use FeMIL-101-NH2 as positive and negative contrasts depending on applied repetition time. MOFs micronization via ultrasound was evaluated by XRD, nitrogen adsorption, FTIR, SEM imaging and did not influence their crystal shape and size. Ultrasonication let to break the aggregates and achieve very homogeneously looking SEM images. MOFs cytotoxicity was evaluated in in vitro test with a highly sensitive resazurin based reagent PrestoBlue™ on L929 fibroblast cell line. After 24h no inhibition of cell proliferation was observed. All results proved potential possibility of application of ironMOFs as an isoniazid carrier and as MRI contrast agent in inhalatory treatment of tuberculosis. Acknowledgments: Authors gratefully acknowledge the National Science Center Poland for providing financial support, grant no 2014/15/B/ST5/04498.

Keywords: imaging agents, metal-organic frameworks, theranostics, tuberculosis

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Authors: Mona Mihailescu, Rebeca Tudor, Irina A. Paun, Cristian Kusko, Eugen I. Scarlat, Mihai Kusko

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Specific intensity distributions in the laser beams are required in many fields: optical communications, material processing, microscopy, optical tweezers. In optical communications, the information embedded in specific beams and the superposition of multiple beams can be used to increase the capacity of the communication channels, employing spatial modulation as an additional degree of freedom, besides already available polarization and wavelength multiplexing. In this regard, optical vortices present interest due to their potential to carry independent data which can be multiplexed at the transmitter and demultiplexed at the receiver. Also, in the literature were studied their combinations: 1) axial or perpendicular superposition of multiple optical vortices or 2) with other laser beam types: Bessel, Airy. Optical vortices, characterized by stationary ring-shape intensity and rotating phase, are achieved using computer generated holograms (CGH) obtained by simulating the interference between a tilted plane wave and a wave passing through a helical phase object. Here, we propose a method to combine information through the reunion of two CGHs. One is obtained using the helical phase distribution, characterized by its topological charge, m. The other is obtained using conical phase distribution, characterized by its radial factor, r0. Each CGH is obtained using plane wave with different tilts: km and kr for CGH generated from helical phase object and from conical phase object, respectively. These reunions of two CGHs are calculated to be phase optical elements, addressed on the liquid crystal display of a spatial light modulator, to optically process the incident beam for investigations of the diffracted intensity pattern in far field. For parallel reunion of two CGHs and high values of the ratio between km and kr, the bright ring from the first diffraction order, specific for optical vortices, is changed in an asymmetric intensity pattern: a number of circle arcs. Both diffraction orders (+1 and -1) are asymmetrical relative to each other. In different planes along the optical axis, it is observed that this asymmetric intensity pattern rotates around its centre: in the +1 diffraction order the rotation is anticlockwise and in the -1 diffraction order, the rotation is clockwise. The relation between m and r0 controls the diameter of the circle arcs and the ratio between km and kr controls the number of arcs. For perpendicular reunion of the two CGHs and low values of the ratio between km and kr, the optical vortices are multiplied and focalized in different planes, depending on the radial parameter. The first diffraction order contains information about both phase objects. It is incident on the phase masks placed at the receiver, computed using the opposite values for topological charge or for the radial parameter and displayed successively. In all, the proposed method is exploited in terms of constructive parameters, for the possibility offered by the combination of different types of beams which can be used in robust optical communications.

Keywords: asymmetrical diffraction orders, computer generated holograms, conical phase distribution, optical vortices, spatial light modulator

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Authors: Abdullah Nurus Salam Khan, Farhana Karim, Mohiuddin Ahsanul Kabir Chowdhury, S. Masum Billah, Nabila Zaka, Alexander Manu, Shams El Arifeen

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Globally, pre-eclampsia (PE) and ante-partum haemorrhage (APH) are two major causes of maternal mortality. Prompt identification and management of these conditions depend on competency of the birth attendants. Since these conditions are infrequent to be observed, clinical vignette based assessment could identify the extent of health worker’s competence in managing emergency obstetric care (EmOC). During June-August 2016, competence of 39 medical officers (MO) and 95 nurses working in obstetric ward of 15 government health facilities (3 district hospital, 12 sub-district hospital) was measured using clinical vignettes on PE and APH. The vignettes resulted in three outcome measures: total vignette scores, scores for diagnosis component, and scores for management component. T-test was conducted to compare mean vignette scores and linear regression was conducted to measure the strength and association of vignette scores with different cadres of health workers, facility’s readiness for EmOC and average annual utilization of normal deliveries after adjusting for type of health facility, health workers’ work experience, training status on managing maternal complication. For each of the seven component of EmOC items (administration of injectable antibiotics, oxytocic and anticonvulsant; manual removal of retained placenta, retained products of conception; blood transfusion and caesarean delivery), if any was practised in the facility within last 6 months, a point was added and cumulative EmOC readiness score (range: 0-7) was generated for each facility. The yearly utilization of delivery cases were identified by taking the average of all normal deliveries conducted during three years (2013-2015) preceding the survey. About 31% of MO and all nurses were female. Mean ( ± sd) age of the nurses were higher than the MO (40.0 ± 6.9 vs. 32.2 ± 6.1 years) and also longer mean( ± sd) working experience (8.9 ± 7.9 vs. 1.9 ± 3.9 years). About 80% health workers received any training on managing maternal complication, however, only 7% received any refresher’s training within last 12 months. The overall vignette score was 8.8 (range: 0-19), which was significantly higher among MO than nurses (10.7 vs. 8.1, p < 0.001) and the score was not associated with health facility types, training status and years of experience of the providers. Vignette score for management component (range: 0-9) increased with higher annual average number of deliveries in their respective working facility (adjusted β-coefficient 0.16, CI 0.03-0.28, p=0.01) and increased with each unit increase in EmOC readiness score (adjusted β-coefficient 0.44, CI 0.04-0.8, p=0.03). The diagnosis component of vignette score was not associated with any of the factors except it was higher among the MO than the nurses (adjusted β-coefficient 1.2, CI 0.13-2.18, p=0.03). Lack of competence in diagnosing and managing obstetric complication by the nurses than the MO is of concern especially when majority of normal deliveries are conducted by the nurses. Better EmOC preparedness of the facility and higher utilization of normal deliveries resulted in higher vignette score for the management component; implying the impact of experiential learning through higher case management. Focus should be given on improving the facility readiness for EmOC and providing the health workers periodic refresher’s training to make them more competent in managing obstetric cases.

Keywords: Bangladesh, emergency obstetric care, clinical vignette, competence of health workers

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Authors: Yohann R. J. Thomas, Sébastien Solan

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Conventional battery technology includes the assembly of electrode/separator/electrode by standard techniques such as stacking or winding, depending on the format size. In that type of batteries, coating or pasting techniques are only used for the electrode process. The processes are suited for large scale production of batteries and perfectly adapted to plenty of application requirements. Nevertheless, as the demand for both easier and cost-efficient production modes, flexible, custom-shaped and efficient small sized batteries is rising. Thin-film, printable batteries are one of the key areas for printed electronics. In the frame of European BASMATI project, we are investigating the feasibility of a new design of lithium-ion battery: interdigitated planar core design. Polymer substrate is used to produce bendable and flexible rechargeable accumulators. Direct fully printed batteries lead to interconnect the accumulator with other electronic functions for example organic solar cells (harvesting function), printed sensors (autonomous sensors) or RFID (communication function) on a common substrate to produce fully integrated, thin and flexible new devices. To fulfill those specifications, a high resolution printing process have been selected: Aerosol jet printing. In order to fit with this process parameters, we worked on nanomaterials formulation for current collectors and electrodes. In addition, an advanced printed polymer-electrolyte is developed to be implemented directly in the printing process in order to avoid the liquid electrolyte filling step and to improve safety and flexibility. Results: Three different current collectors has been studied and printed successfully. An ink of commercial copper nanoparticles has been formulated and printed, then a flash sintering was applied to the interdigitated design. A gold ink was also printed, the resulting material was partially self-sintered and did not require any high temperature post treatment. Finally, carbon nanotubes were also printed with a high resolution and well defined patterns. Different electrode materials were formulated and printed according to the interdigitated design. For cathodes, NMC and LFP were efficaciously printed. For anodes, LTO and graphite have shown to be good candidates for the fully printed battery. The electrochemical performances of those materials have been evaluated in a standard coin cell with lithium-metal counter electrode and the results are similar with those of a traditional ink formulation and process. A jellified plastic crystal solid state electrolyte has been developed and showed comparable performances to classical liquid carbonate electrolytes with two different materials. In our future developments, focus will be put on several tasks. In a first place, we will synthesize and formulate new specific nano-materials based on metal-oxyde. Then a fully printed device will be produced and its electrochemical performance will be evaluated.

Keywords: high resolution digital printing, lithium-ion battery, nanomaterials, solid-state electrolytes

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Authors: K. C. Apil, Keshab Sharma, Bigul Pokharel

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Kathmandu Valley, capital city of Nepal houses numerous historical monuments as well as religious structures which are as old as from the 4th century A.D. The city alone is home to seven UNESCO’s world heritage sites including various public squares and religious sanctums which are often regarded as living heritages by various historians and archeological explorers. Recently on April 25, 2015, the capital city including other nearby locations was struck with Gorkha earthquake of moment magnitude (Mw) 7.8, followed by the strongest aftershock of moment magnitude (Mw) 7.3 on May 12. This study reports structural failures and collapse of heritage structures in Kathmandu Valley during the earthquake and presents preliminary findings as to the causes of failures and collapses. Field reconnaissance was carried immediately after the main shock and the aftershock, in major heritage sites: UNESCO world heritage sites, a number of temples and historic buildings in Kathmandu Durbar Square, Patan Durbar Square, and Bhaktapur Durbar Square. Despite such catastrophe, a significant number of heritage structures stood high, performing very well during the earthquake. Preliminary reports from archeological department suggest that 721 of such structures were severely affected, whereas numbers within the valley only were 444 including 76 structures which were completely collapsed. This study presents recorded accelerograms and geology of Kathmandu Valley. Structural typology and architecture of the heritage structures in Kathmandu Valley are briefly described. Case histories of damaged heritage structures, the patterns, and the failure mechanisms are also discussed in this paper. It was observed that performance of heritage structures was influenced by the multiple factors such as structural and architecture typology, configuration, and structural deficiency, local ground site effects and ground motion characteristics, age and maintenance level, material quality etc. Most of such heritage structures are of masonry type using bricks and earth-mortar as a bonding agent. The walls' resistance is mainly compressive, thus capable of withstanding vertical static gravitational load but not horizontal dynamic seismic load. There was no definitive pattern of damage to heritage structures as most of them behaved as a composite structure. Some structures were extensively damaged in some locations, while structures with similar configuration at nearby location had little or no damage. Out of major heritage structures, Dome, Pagoda (2, 3 or 5 tiered temples) and Shikhara structures were studied with similar variables. Studying varying degrees of damages in such structures, it was found that Shikhara structures were most vulnerable one where Dome structures were found to be the most stable one, followed by Pagoda structures. The seismic performance of the masonry-timber and stone masonry structures were slightly better than that of the masonry structures. Regular maintenance and periodic seismic retrofitting seems to have played pivotal role in strengthening seismic performance of the structure. The study also recommends some key functions to strengthen the seismic performance of such structures through study based on structural analysis, building material behavior and retrofitting details. The result also recognises the importance of documentation of traditional knowledge and its revised transformation in modern technology.

Keywords: Gorkha earthquake, field observation, heritage structure, seismic performance, masonry building

Procedia PDF Downloads 117

Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

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Authors: Guenther Schuh, Michael Riesener, Jan Kantelberg

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Due to the fugacity of markets and the reduction of product lifecycles, manufacturing companies from high-wage countries are nowadays faced with the challenge to place more innovative products within even shorter development time on the market. At the same time, volatile customer requirements have to be satisfied in order to successfully differentiate from market competitors. One potential approach to address the explained challenges is provided by agile values and principles. These agile values and principles already proofed their success within software development projects in the form of management frameworks like Scrum or concrete procedure models such as Extreme Programming or Crystal Clear. Those models lead to significant improvements regarding quality, costs and development time and are therefore used within most software development projects. Motivated by the success within the software industry, manufacturing companies have tried to transfer agile mechanisms of action to the development of hardware products ever since. Though first empirical studies show similar effects in the agile development of hardware products, no comprehensive procedure model for the design of development iterations has been developed for hardware development yet due to different constraints of the domains. For this reason, this paper focusses on the design of agile product development processes by transferring mechanisms of action used in agile software development towards product development. This is conducted by decomposing the individual systems 'product development' and 'agile software development' into relevant elements and symbiotically composing the elements of both systems in respect of the design of agile product development processes afterwards. In a first step, existing product development processes are described following existing approaches of the system theory. By analyzing existing case studies from industrial companies as well as academic approaches, characteristic objectives, activities and artefacts are identified within a target-, action- and object-system. In partial model two, mechanisms of action are derived from existing procedure models of agile software development. These mechanisms of action are classified in a superior strategy level, in a system level comprising characteristic, domain-independent activities and their cause-effect relationships as well as in an activity-based element level. Within partial model three, the influence of the identified agile mechanism of action towards the characteristic system elements of product development processes is analyzed. For this reason, target-, action- and object-system of the product development are compared with the strategy-, system- and element-level of agile mechanism of action by using the graph theory. Furthermore, the necessity of existence of activities within iteration can be determined by defining activity-specific degrees of freedom. Based on this analysis, agile product development processes are designed in form of different types of iterations within a last step. By defining iteration-differentiating characteristics and their interdependencies, a logic for the configuration of activities, their form of execution as well as relevant artefacts for the specific iteration is developed. Furthermore, characteristic types of iteration for the agile product development are identified.

Keywords: activity-based process model, agile mechanisms of action, agile product development, degrees of freedom

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

Procedia PDF Downloads 353

Authors: Nivedita T. Patil, M. T. Patil, M. S. Shashidhar, R. G. Gonnade

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Cyclitols are cycloalkane polyols which have raise attention since they have numerous biological and pharmaceutical properties. Among these, inositols are important cyclitols, which constitute a group of naturally occurring polyhydric alcohols. Myo, scyllo, allo, neo, D-chiro- are naturally occurring structural isomer of inositol while other four isomers (L-chiro, allo, epi-, and cis-inositol) are derived from myo-inositol by chemical synthesis. Myo-inositol, most abundant isomer, plays an important role in signal transduction process and for the treatment of type 2 diabetes, bacterial infections, stimulation of menstruation, ovulation in polycystic ovary syndrome, improvement of osteogenesis, and in treatment of neurological disorders. Considering the vast application of the derivatives, it becomes important to supply these compounds for further studies in quantitative amounts, but the synthesis of suitably protected chiral inositol derivatives is the key intermediates in most of the synthesis which is difficult. Chiral inositol derivatives could also be of interest to synthetic organic chemists as they could serve as potential starting materials for the synthesis of several natural products and their analogs. Thus, obtaining chiral myo-inositol derivatives in a more eco-friendly way is need for current inositol chemistry. Thus, the resolution of nonracemates by preferential crystallization of enantiomers has not been reported as a method for inositol derivatives. We are optimistic that this work might lead to the development of the two tosylate enantiomers as synthetic chiral pool molecules for organic synthesis. Resolution of racemic 4-O-benzyl 6-O-tosyl myo-inositol 1, 3, 5 orthoformate was successfully achieved on multigram scale by preferential crystallization, which is more scalable, eco-friendly method of separation than other reported methods. The separation of the conglomeric mixture of tosylate was achieved by suspending the mixture in ethyl acetate till the level of saturation is obtained. To this saturated clear solution was added seed crystal of the desired enantiomers. The filtration of the precipitated seed was carried out at its filtration window to get enantiomerically enriched tosylate, and the process was repeated alternatively. These enantiomerically enriched samples were recrystallized to get tosylate as pure enantiomers. The configuration of the resolved enantiomers was determined by converting it to previously reported dibenzyl ether myo-inositol, which is an important precursor for mono- and tetraphosphates. We have also developed a convenient and practical method for the preparation of enantiomeric 4-O and 6-O-allyl myo-inositol orthoesters by resolution of diastereomeric allyl dicamphante orthoesters on multigram scale. These allyl ethers can be converted to other chiral protected myo-inositol derivatives using routine synthetic transformations. The chiral allyl ethers can be obtained in gram quantities, and the methods are amenable to further scale-up due to the simple procedures involved. We believe that the work described enhances the pace of research to understand the intricacies of the myo-inositol cycle as the methods described provide efficient access to enantiomeric phosphoinositols, cyclitols, and their derivatives from the abundantly available myo-inositol as a starting material.

Keywords: cyclitols, diastereomers, enantiomers, myo-inositol, preferential crystallization, signal transduction

Procedia PDF Downloads 116