Search results for: solid Oxide Cells

Authors: Soultana Konstantinidou, Tiziana Schmidt, Elena Landi, Alessandro De Carli, Giovanni Maltinti, Darius Witt, Alicja Dziadosz, Agnieszka Lindstaedt, Michele Lai, Mauro Pistello, Valentina Cappello, Luciana Dente, Chiara Gabellini, Piotr Barski, Vittoria Raffa

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CRISPR/Cas9 technology has gained the interest of researchers in the field of biotechnology for genome editing. Since its discovery as a microbial adaptive immune defense, this system has been widely adopted and is acknowledged for having a variety of applications. However, critical barriers related to safety and delivery are persisting. Here, we propose a new concept of genome engineering, which is based on a nano-formulation of Cas9. The Cas9 enzyme was conjugated to a gold nanoparticle (AuNP-Cas9). The AuNP-Cas9 maintained its cleavage efficiency in vitro, to the same extent as the ribonucleoprotein, including non-conjugated Cas9 enzyme, and showed high gene editing efficiency in vivo in zebrafish embryos. Since CRISPR/Cas9 technology is extensively used in cancer research, melanoma was selected as a validation target. Cell studies were performed in A375 human melanoma cells. Particles per se had no impact on cell metabolism and proliferation. Intriguingly, the AuNP-Cas9 internalized spontaneously in cells and localized as a single particle in the cytoplasm and organelles. More importantly, the AuNP-Cas9 showed a high nuclear localization signal. The AuNP-Cas9, overcoming the delivery difficulties of Cas9, could be used in cellular biology and localization studies. Taking advantage of the plasmonic properties of gold nanoparticles, this technology could potentially be a bio-tool for combining gene editing and photothermal therapy in cancer cells. Further work will be focused on intracellular interactions of the nano-formulation and characterization of the optical properties.

Keywords: CRISPR/Cas9, gene editing, gold nanoparticles, nanotechnology

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Authors: Victor S. Klimin, Alexey A. Rezvan, Maxim S. Solodovnik, Oleg A. Ageev

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In this paper, the problems of existing methods of profiling and surface modification of nanoscale arsenide-gallium structures are analyzed. The use of a combination of methods of local anodic oxidation and plasma chemical etching to solve this problem is considered. The main features that make this technology one of the promising areas of modification and profiling of near-surface layers of solids are demonstrated. In this paper, we studied the effect of formation stress and etching time on the geometrical parameters of the etched layer and the roughness of the etched surface. Experimental dependences of the thickness of the etched layer on the time and stress of formation were obtained. The surface analysis was carried out using atomic force microscopy methods, the corresponding profilograms were constructed from the obtained images, and the roughness of the etched surface was studied accordingly. It was shown that at high formation voltage, the depth of the etched surface increased, this is due to an increase in the number of active particles (oxygen ions and hydroxyl groups) formed as a result of the decomposition of water molecules in an electric field, during the formation of oxide nanostructures on the surface of gallium arsenide. Oxide layers were used as negative masks for subsequent plasma chemical etching by the STE ICPe68 unit. BCl₃ was chosen as the chlorine-containing gas, which differs from analogs in some parameters for the effect of etching of nanostructures based on gallium arsenide in the low-temperature plasma. The gas mixture of reaction chamber consisted of a buffer gas NAr = 100 cm³/min and a chlorine-containing gas NBCl₃ = 15 cm³/min at a pressure P = 2 Pa. The influence of these methods modes, which are formation voltage and etching time, on the roughness and geometric parameters, and corresponding dependences are demonstrated. Probe nanotechnology was used for surface analysis.

Keywords: nanostructures, GaAs, plasma chemical etching, modification structures

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Authors: Yanqin Chen, Chao Jiang, Chongdu Cho

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This research presents the three-dimensional mechanical characteristics of a commercial gas diffusion layer by experiment and simulation results. Although the mechanical performance of gas diffusion layers has attracted much attention, its reliability and accuracy are still a major challenge. With the help of simulation analysis methods, it is beneficial to the gas diffusion layer’s extensive commercial development and the overall stress analysis of proton electrolyte membrane fuel cells during its pre-production design period. Therefore, in this paper, a three-dimensional constitutive model of a commercial gas diffusion layer, including its material stiffness matrix parameters, is developed and coded, in the user-defined material model of a commercial finite element method software for simulation. Then, the model is validated by comparing experimental results as well as simulation outcomes. As a result, both the experimental data and simulation results show a good agreement with each other, with high accuracy.

Keywords: gas diffusion layer, proton electrolyte membrane fuel cell, stiffness matrix, three-dimensional mechanical characteristics, user-defined material model

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Authors: Rutuja Upadhyay, Anurag Mehra

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Solid food foams/cellular foods are colloidal systems which impart structure, texture and mouthfeel to many food products such as bread, cakes, ice-cream, meringues, etc. Their heterogeneous morphology makes the quantification of structure/mechanical relationships complex. The porous structure of solid food foams is highly influenced by the processing conditions, ingredient composition, and their interactions. Sensory perceptions of food foams are dependent on bubble size, shape, orientation, quantity and distribution and determines the texture of foamed foods. The state and structure of the solid matrix control the deformation behavior of the food, such as elasticity/plasticity or fracture, which in turn has an effect on the force-deformation curves. The obvious step in obtaining the relationship between the mechanical properties and the porous structure is to quantify them simultaneously. Here, we attempt to research food foams such as bread dough, baked bread and steamed rice cakes to determine the link between ingredients and the corresponding effect of each of them on the rheology, microstructure, bubble size and texture of the final product. Dynamic rheometry (SAOS), confocal laser scanning microscopy, flatbed scanning, image analysis and texture profile analysis (TPA) has been used to characterize the foods studied. In all the above systems, there was a common observation that when the mean bubble diameter is smaller, the product becomes harder as evidenced by the increase in storage and loss modulus (G′, G″), whereas when the mean bubble diameter is large the product is softer with decrease in moduli values (G′, G″). Also, the bubble size distribution affects texture of foods. It was found that bread doughs with hydrocolloids (xanthan gum, alginate) aid a more uniform bubble size distribution. Bread baking experiments were done to study the rheological changes and mechanisms involved in the structural transition of dough to crumb. Steamed rice cakes with xanthan gum (XG) addition at 0.1% concentration resulted in lower hardness with a narrower pore size distribution and larger mean pore diameter. Thus, control of bubble size could be an important parameter defining final food texture.

Keywords: food foams, rheology, microstructure, texture

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Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Gizachew Belay Adugna

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Perovskite solar cells (PSCs) shows rapid development as an emerging photovoltaic material; however, the fast device degradation due to the organic nature, mainly hole transporting material (HTM) and lack of robust and reliable upscaling process for photovoltaic module hindered its commercialization. Herein, HTM molecules with/without fluorine-substituted cyclopenta[2,1-b;3,4-b’]dithiophene derivatives (HYC-oF, HYC-mF, and HYC-H) were developed for PSCs application. The fluorinated HTM molecules exhibited better hole mobility and overall charge extraction in the devices mainly due to strong molecular interaction and packing in the film. Thus, the highest power conversion efficiency (PCE) of 19.64% with improved long stability was achieved for PSCs based on HYC-oF HTM. Moreover, the fluorinated HYC-oF demonstrated excellent film processability in a larger-area substrate (10 cm×10 cm) prepared sequentially with the absorption perovskite underlayer via a scalable bar coating process in ambient air and owned a higher PCE of 18.49% compared to the conventional spiro-OMeTAD (17.51%). The result demonstrates a facile development of HTM towards stable and efficient PSCs for future industrial-scale PV modules.

Keywords: perovskite solar cells, upscaling film coating, power conversion efficiency, solution processing

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

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

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

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Authors: P. Michael Preetam Raj, Souri Banerjee, Souvik Kundu

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Oxide based memristors were fabricated in order to establish its potential applications in analog/digital electronics. BaTiO₃-BiFeO₃ (BT-BFO) was employed as an active material, whereas platinum (Pt) and Nb-doped SrTiO₃ (Nb:STO) were served as a top and bottom electrodes, respectively. Piezoelectric force microscopy (PFM) was utilized to present the ferroelectricity and repeatable polarization inversion in the BT-BFO, demonstrating its effectiveness for resistive switching. The fabricated memristors exhibited excellent electrical characteristics, such as hysteresis current-voltage (I-V), high on/off ratio, high retention time, cyclic endurance, and low operating voltages. The band-alignment between the active material BT-BFO and the substrate Nb:STO was experimentally investigated using X-Ray photoelectron spectroscopy, and it attributed to staggered heterojunction alignment. An energy band diagram was proposed in order to understand the electrical transport in BT-BFO/Nb:STO heterojunction. It was identified that the I-V curves of these memristors have several discontinuities. Curve fitting technique was utilized to analyse the I-V characteristic, and the obtained I-V equations were found to be parabolic. Utilizing this analysis, a non-linear BT-BFO memristors equivalent circuit model was developed. Interestingly, the obtained equivalent circuit of the BT-BFO memristors mimics the identical electrical performance, those obtained in the fabricated devices. Based on the developed equivalent circuit, a finite state machine (FSM) design was proposed. Efforts were devoted to fabricate the same FSM, and the results were well matched with those in the simulated FSM devices. Its multilevel noise filtering and immunity to external noise characteristics were also studied. Further, the feature of variable negative resistance was established by controlling the current through the memristor.

Keywords: band alignment, finite state machine, polarization inversion, resistive switching

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Authors: Sang-Myung Jung, Jeong Hyun Ju, Gwang Heum Yoon, Hwa Sung Shin

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Central nervous system (CNS) consists of neuronal cell and supporting cells. Astrocytes are the most common supporting cells and play roles in metabolism between neurons and blood vessel. For this function, engineered astrocytes have been studied as a therapeutic source for CNS injury. In neural tissue engineering, nanofiber has been suggested as an effective scaffold for providing structure and mechanical properties influencing physiology. Cellulose acetate (CA) has been investigated for material to fabricate scaffold because of its biocompatibility, biodegradability and fine thermal stability. In this research, CA nanofiber was modified via heat treatment and its effect on astrocyte activity was evaluated. Adhesion and viability of astrocyte were increased in proportion to stiffness. Additionally, expression of GFAP, a marker of astrocyte activation, was increased via stiffness of scaffold. This research suggests a simple modification method to change stiffness of CA nanofiber and shows cellular behavior affecting stiffness of three-dimensional scaffold independently. For the results, we highlight that the stiffness is a factor to regulate astrocyte activity.

Keywords: astrocyte, cellulose acetate, cell therapy, stiffness of scaffold

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Authors: Hamidreza Khodaei, Ali Daryabeigi Zand

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Ovulation is a physiologic process with an inflammatory response that depends on a coordinated activity of gonadotropins and steroid hormones, and inflammatory mediators such as cytokines, prostaglandins, leptin, nitric oxide (NO), etc. Conjugated linoleic acid (CLA) is composed of polyunsaturated fatty acids (PUFA) found in dairy products, beef, and lamb. There is strong evidence that dietary CLA affects mediators involved in ovulation. The objective of this study is to evaluate the impacts of various doses of dietary CLA on systemic and local hormones and parameters involved in ovulation. In this case-control research, 80 (50 ± 2-day old) female mice were randomly divided into 4 groups (C as control treatment and T1, T2 and T3 are considered as the treatment groups). There were four replicates in each group, and there were five mice in every replicate (20 mice, in total). The mice in the control group were fed with no CLA in their diet, but the ones in the treatment group received 0.1, 0.3 and 0.5g/kg of CLA (replacing corn oil in the diet), respectively for four months. After that, blood samples were obtained from the tails of animals that displayed estrus signs and estradiol (E2), progesterone (P4), LH, FSH, NO, leptin and TNFα were measured. In addition, the impacts of CLA on the ovarian production of prostaglandins (PGs) and NO were studied. The data were analyzed by SAS software. CLA considerably decreased serum levels of FSH (p < 0.05), LH, estradiol, NO, leptin and TNFα (p < 0.01). In addition, CLA decreased progesterone levels, but this effect was statistically not significant. The significantly adverse effects of CLA were observed in the ovarian production of PGE2 and PGF2α (p < 0.01). It seems that CLA may play an important role in reducing the ovulation rate in mice as CLA negatively affected female reproduction and it had adverse effects on systemic and local hormones involved in ovulation.

Keywords: conjugated linoleic acid, nitric oxide, ovary, ovulation, prostaglandin, gonadotropin

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Authors: D. Bikiaris, M. Nerantzaki, I. Koliakou, A. Francone, N. Kehagias

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In the present study, the formation of structures in poly(lactic acid) (PLA) has been investigated with respect to producing areas of regular, superficial features with dimensions comparable to those of cells or biological macromolecules. Nanoimprint lithography, a method of pattern replication in polymers, has been used for the production of features ranging from tens of micrometers, covering areas up to 1 cm², down to hundreds of nanometers. Both micro- and nano-structures were faithfully replicated. Potentially, PLA has wide uses within biomedical fields, from implantable medical devices, including screws and pins, to membrane applications, such as wound covers, and even as an injectable polymer for, for example, lipoatrophy. The possibility of fabricating structured PLA surfaces, with structures of the dimensions associated with cells or biological macro- molecules, is of interest in fields such as cellular engineering. Imprint-based technologies have demonstrated the ability to selectively imprint polymer films over large areas resulting in 3D imprints over flat, curved or pre-patterned surfaces. Here, we compare nano-patterned with nano-patterned by nanoimprint lithography (NIL) PLA film. A silicon nanostructured stamp (provided by Nanotypos company) having positive and negative protrusions was used to pattern PLA films by means of thermal NIL. The polymer film was heated from 40°C to 60°C above its Tg and embossed with a pressure of 60 bars for 3 min. The stamp and substrate were demolded at room temperature. Scanning electron microscope (SEM) images showed good replication fidelity of the replicated Si stamp. Contact-angle measurements suggested that positive microstructuring of the polymer (where features protrude from the polymer surface) produced a more hydrophilic surface than negative micro-structuring. The ability to structure the surface of the poly(lactic acid), allied to the polymer’s post-processing transparency and proven biocompatibility. Films produced in this were also shown to enhance the aligned attachment behavior and proliferation of Wharton’s Jelly Mesenchymal Stem cells, leading to the observed growth contact guidance. The bacterial attachment patterns of some bacteria, highlighted that the nano-patterned PLA structure can reduce the propensity for the bacteria to attach to the surface, with a greater bactericidal being demonstrated activity against the Staphylococcus aureus cells. These biocompatible, micro- and nanopatterned PLA surfaces could be useful for polymer– cell interaction experiments at dimensions at, or below, that of individual cells. Indeed, post-fabrication modification of the microstructured PLA surface, with materials such as collagen (which can further reduce the hydrophobicity of the surface), will extend the range of applications, possibly through the use of PLA’s inherent biodegradability. Further study is being undertaken to examine whether these structures promote cell growth on the polymer surface.

Keywords: poly(lactic acid), nano-imprint lithography, anti-bacterial properties, PLA

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Authors: Lina, Arlends Chris, Bagus Mulyawan, Agus B. Dharmawan

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Blood cell analysis plays a significant role in the diagnosis of human health. As an alternative to the traditional technique conducted by laboratory technicians, this paper presents an automatic white blood cell (leukocyte) detection system using Image Stitching and Color Overlapping Windows. The advantage of this method is to present a detection technique of white blood cells that are robust to imperfect shapes of blood cells with various image qualities. The input for this application is images from a microscope-slide translation video. The preprocessing stage is performed by stitching the input images. First, the overlapping parts of the images are determined, then stitching and blending processes of two input images are performed. Next, the Color Overlapping Windows is performed for white blood cell detection which consists of color filtering, window candidate checking, window marking, finds window overlaps, and window cropping processes. Experimental results show that this method could achieve an average of 82.12% detection accuracy of the leukocyte images.

Keywords: color overlapping windows, image stitching, leukocyte detection, white blood cell detection

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Authors: Moumen Abdelhafidh, Stribu Bogdan, Laboureur Delphine, Gallant Johan, Hendrick Patrick

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This study is part of an ongoing effort to improve the understanding of phenomena occurring during the intermediate ballistic phase, such as muzzle flows. A thorough comprehension of muzzle flow fields is essential for optimizing muzzle device and projectile design. This flow characterization has heretofore been almost entirely limited to local and intrusive measurement techniques such as pressure measurements using pencil probes. Consequently, the body of quantitative experimental data is limited, so is the number of numerical codes validated in this field. The objective of the work presented here is to demonstrate the applicability of the Particle Image Velocimetry (PIV) technique in the challenging environment of the propellant flow of a .300 blackout weapon to provide accurate velocity measurements. The key points of a successful PIV measurement are the selection of the particle tracer, their seeding technique, and their tracking characteristics. We have experimentally investigated the aforementioned points by evaluating the resistance, gas dispersion, laser light reflection as well as the response to a step change across the Mach disk for five different solid tracers using two seeding methods. To this end, an experimental setup has been performed and consisted of a PIV system, the combustion chamber pressure measurement, classical high-speed schlieren visualization, and an aerosol spectrometer. The latter is used to determine the particle size distribution in the muzzle flow. The experimental results demonstrated the ability of PIV to accurately resolve the salient features of the propellant flow, such as the under the expanded jet and vortex rings, as well as the instantaneous velocity field with maximum centreline velocities of more than 1000 m/s. Besides, naturally present unburned particles in the gas and solid ZrO₂ particles with a nominal size of 100 nm, when coated on the propellant powder, are suitable as tracers. However, the TiO₂ particles intended to act as a tracer, surprisingly not only melted but also functioned as a combustion accelerator and decreased the number of particles in the propellant gas.

Keywords: intermediate ballistic, muzzle flow fields, particle image velocimetry, propellant gas, particle size distribution, under expanded jet, solid particle tracers

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Authors: Hao Yan, Xiaobing Zhang

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The working mechanism of miniaturized solid rocket motors (SRMs) is not yet fully understood. It is imperative to explore its unique features. However, there are many disadvantages to using common multi-objective evolutionary algorithms (MOEAs) in predicting the parameters of the miniaturized SRM during its conceptual design phase. Initially, the design variables and objectives are constrained in a lumped parameter model (LPM) of this SRM, which leads to local optima in MOEAs. In addition, MOEAs require a large number of calculations due to their population strategy. Although the calculation time for simulating an LPM just once is usually less than that of a CFD simulation, the number of function evaluations (NFEs) is usually large in MOEAs, which makes the total time cost unacceptably long. Moreover, the accuracy of the LPM is relatively low compared to that of a CFD model due to its assumptions. CFD simulations or experiments are required for comparison and verification of the optimal results obtained by MOEAs with an LPM. The conceptual design phase based on MOEAs is a lengthy process, and its results are not precise enough due to the above shortcomings. An artificial neural network (ANN) based parameter prediction is proposed as a way to reduce time costs and improve prediction accuracy. In this method, an ANN is used to build a surrogate model that is trained with a 3D numerical simulation. In design, the original LPM is replaced by a surrogate model. Each case uses the same MOEAs, in which the calculation time of the two models is compared, and their optimization results are compared with 3D simulation results. Using the surrogate model for the parameter prediction process of the miniaturized SRMs results in a significant increase in computational efficiency and an improvement in prediction accuracy. Thus, the ANN-based surrogate model does provide faster and more accurate parameter prediction for an initial design scheme. Moreover, even when the MOEAs converge to local optima, the time cost of the ANN-based surrogate model is much lower than that of the simplified physical model LPM. This means that designers can save a lot of time during code debugging and parameter tuning in a complex design process. Designers can reduce repeated calculation costs and obtain accurate optimal solutions by combining an ANN-based surrogate model with MOEAs.

Keywords: artificial neural network, solid rocket motor, multi-objective evolutionary algorithm, surrogate model

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Authors: Aleksander Ejsmont, Stefan Wuttke, Joanna Goscianska

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Gaining control over particle shape, size and crystallinity is an ongoing challenge for many materials. Especially metalorganic frameworks (MOFs) are recently widely studied. Besides their remarkable porosity and interesting topologies, morphology has proven to be a significant feature. It can affect the further material application. Thus seeking new approaches that enable MOF morphology modulation is important. MOFs are reticular structures, where building blocks are made up of organic linkers and metallic nodes. The most common strategy of ensuring metal source is using salts, which usually exhibit high solubility and hinder morphology control. However, there has been a growing interest in using metal oxides as structure-directing agents towards MOFs due to their very low solubility and shape preservation. Metal oxides can be treated as a metal reservoir during MOF synthesis. Up to now, reports in which receiving MOFs from metal oxides mostly present ZnO conversion to ZIF-8. However, there are other oxides, for instance, Co₃O₄, which often is overlooked due to their structural stability and insolubility in aqueous solutions. Cobalt-based materials are famed for catalytic activity. Therefore the development of their efficient synthesis is worth attention. In the presented work, an optimized Co₃O₄transition to Co-MOFviaa solvothermal approach was proposed. The starting point of the research was the synthesis of Co₃O₄ flower petals and needles under hydrothermal conditions using different cobalt salts (e.g., cobalt(II) chloride and cobalt(II) nitrate), in the presence of urea, and hexadecyltrimethylammonium bromide (CTAB) surfactant as a capping agent. After receiving cobalt hydroxide, the calcination process was performed at various temperatures (300–500 °C). Then cobalt oxides as a source of cobalt cations were subjected to reaction with trimesic acid in solvothermal environment and temperature of 120 °C leading to Co-MOF fabrication. The solution maintained in the system was a mixture of water, dimethylformamide, and ethanol, with the addition of strong acids (HF and HNO₃). To establish how solvents affect metal oxide conversion, several different solvent ratios were also applied. The materials received were characterized with analytical techniques, including X-ray powder diffraction, energy dispersive spectroscopy,low-temperature nitrogen adsorption/desorption, scanning, and transmission electron microscopy. It was confirmed that the synthetic routes have led to the formation of Co₃O₄ and Co-based MOF varied in shape and size of particles. The diffractograms showed receiving crystalline phase for Co₃O₄, and also for Co-MOF. The Co₃O₄ obtained from nitrates and with using low-temperature calcination resulted in smaller particles. The study indicated that cobalt oxide particles of different size influence the efficiency of conversion and morphology of Co-MOF. The highest conversion was achieved using metal oxides with small crystallites.

Keywords: Co-MOF, solvothermal synthesis, morphology control, core-shell

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Authors: Saba Didarataee, Abbas Ali Khodadadi, Yadollah Mortazavi, Fatemeh Mousavi

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Photocatalytic water splitting is one of the most attractive alternative methods for hydrogen evolution. A variety of nanoparticle engineering techniques were introduced to improve the activity of semiconductor photocatalysts. Among these methods, heterojunction formation is an appealing method due to its ability to effectively preventing electron-hole recombination and improving photocatalytic activity. Reaching an optimal ratio of the two target semiconductors for the formation of heterojunctions is still an open question. Considering environmental issues as well as the cost and availability, ZnS and ZnO are frequently studied as potential choices. In this study, first, the ZnS nanoparticle was synthesized in a hydrothermal process; the formation of ZnS nanorods with a diameter of 14-30 nm was confirmed by field emission scanning electron microscope (FESEM). Then two different methods, partial oxidation and chemical precipitation were employed to construct ZnS/ZnO core-shell heterojunction. X-ray diffraction (XRD), BET, and diffuse reflectance spectroscopy (DRS) analysis were carried out to determine crystallite phase, surface area, and bandgap of photocatalysts. Furthermore, the temperature of oxidation was specified by a temperature programmed oxidation (TPO) and was fixed at 510℃, at which mild oxidation occurred. The bandgap was calculated by the Kubelka-Munk method and decreased by increasing oxide content from 3.53 (pure ZnS) to 3.18 (pure ZnO). The optimal samples were determined by testing the photocatalytic activity of hydrogen evolution in a quartz photoreactor with side irradiation of UVC lamps with a wavelength of 254 nm. In both procedures, it was observed that the photocatalytic activity of the ZnS/ZnO composite was sensibly higher than the pure ZnS and ZnO, which is attributed to forming a type-II heterostructure. The best ratio of oxide to sulfide was 0.24 and 0.37 in partial oxidation and chemical precipitation, respectively. The highest hydrogen evolution was 1081 µmol/gr.h, gained from partial oxidizing of ZnS nanoparticles at 510℃ for 30 minutes.

Keywords: heterostructure, hydrogen, partial oxidation, photocatalyst, water splitting, ZnS

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Khawar Naeem, Adel Elomri, Adel Zghibi

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Contamination leakage from municipal solid waste (MSW) landfills is a serious environmental challenge that poses a threat to interconnected ecosystems. It not only contaminates the soil of the saturated zone, but it also percolates down the earth and contaminates the groundwater (GW). In this concise literature review, an effort is made to understand the environmental hazards posed by this contamination to the soil and groundwater, the type of contamination, and possible solutions proposed in the literature. In the study’s second phase, the MSW management practices are explored as the landfill site dump rate and type of MSW into the landfill site directly depend on the MSW management strategies. Case studies from multiple developed and underdeveloped countries are presented, and the complex MSW management system is investigated from an operational perspective to minimize the contamination of GW. One of the significant tools used in the literature was found to be Systems Dynamic Modeling (SDM), which is a simulation-based approach to study the stakeholder’s approach. By employing the SDM approach, the risk of GW contamination can be reduced by devising effective MSW management policies, ultimately resulting in water resource sustainability and regional sustainable development.

Keywords: groundwater contamination, environmental risk, municipal solid waste management, system dynamic modeling, water resource sustainability, sustainable development

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Authors: Soha A Soliman, Yasser A Ahmed, Mohamed A Khalaf

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Although the enormous literature describing the histology of the stomach of different avian species during the posthatching development, the available literature on the pre-hatching development of quail stomach development is scanty. Thus, the current study was undertaken to provide a careful description of the main histological events during the embryonic development of quail stomach. To achieve this aim, daily histological specimens from the stomach of quail of 4 days post-incubation till the day 17 (few hours before hatching) were examined with light microscopy. The current study showed that the primitive gut tube of the embryonic quail appeared at the 4th day post incubation, and both parts of stomach (proventriculus and gizzard) were similar in structure and composed of endodermal epithelium of pseudostratified type surrounded by undifferentiated mesenchymal tissue. The sequences of the developmental events in the gut tube were preceded in a cranio-caudal pattern. By the 5th day, the endodermal covering of the primitive proventriculus gave rise to sac-like invaginations. The primitive gizzard was distinguished into thick-walled bodies and thin-walled sacs. In the 6th day, the prospective proventricular glandular epithelium became canalized and the muscular layer was developed in the cranial part of the proventriculus, whereas the primitive muscular coat of the gizzard was represented by a layer of condensed mesenchyme. In the 7th day, the proventricular glandular epithelial invaginations increased in depth and number, while, the muscularis mucosa and the muscular layer began to be distinguished. In the 8th day, the myoblasts differentiated into spindle shaped smooth muscle fibers. In the 10th day, branching of the proventricular glands began. The branching continued later on. The surface and the glandular epithelium were transformed into simple columnar type in the 12th day. The epithelial covering of the gizzard gave rise to tubular invaginations lined by simple cuboidal epithelium and the surface epithelium became simple columnar. Canalization of the tubular glands was recognized in the 14th day. In the 15th day, the proventricular surface epithelium invaginated in an concentric manner around a central cavity to form immature secretory units. The central cavity was lined by eosinophilic cells which form the ductal epithelia. The peripheral lamellae were lined by basophilic cells; the undifferentiated oxyntico-peptic cells. Entero-endocrine cells stained positive for silver impregnation in the proventricular glands. The mucosal folding in the gizzard appeared in the 15th day to form the plicae and the sulci. The wall of the proventriculus and gizzard in the 17th day acquired the main histological features of post-hatching birds, but neither the surface nor the ductal epithelium were differentiated to mucous producing cells. The current results shoed be considered in the molecular developmental studies.

Keywords: quail, proventriculus, gizzard, pre-hatching, histology

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Authors: Jessica P. Fiorotti, Maria C. Freitas, Caio J. B. Coutinho-Rodrigues, Mariana G. Camargo, Emily S. Mesquita, Amanda R. C. Corval, Ricardo O. B. Bitencourt, Allan F. Marciano, Diva D. Spadacci-Morena, Patricia S. Golo, Isabele C. Angelo, Vania R. E. P. Bittencourt

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The bovine tick, Rhipicephalus microplus, is an arthropod of great importance in veterinary medicine leading to anemia, weight loss, animals' leather depreciation and also acting as a vector of many pathogens. In this way, the parasitism causes a loss of 3.24 billion dollars per year in Brazil. Knowingly, entomopathogenic fungi act as natural controller of some arthropods, acting mainly by active penetration through the cuticle. However, it can also act on the hemolymph and through the production of mycotoxins. Hemocytes are responsible for the cellular immune response and participate in the processes of phagocytosis, nodulation and encapsulation and may undergo changes when challenged by pathogens. The aim of the present study was to evaluate changes in R. microplus hemocytes after inoculation of Metarhizium robertsii using transmission electron microscopy. The isolate ARSEF 2575 and 200 engorged R. microplus females were used. The groups were divided into control, in which the females were inoculated with 5 μL of sterile distilled water solution and 0.1% Tween 80, and a group inoculated with 5 μL of fungal suspension at the concentration of 10⁷ conidia mL⁻¹. The experiment was performed in duplicate and each group contained 50 females. Twenty-four hours after fungal inoculation, hemolymph was collected through the cuticle dorsal surface perforation of the tick females. After collection, the hemolymph samples were centrifuged at 500 x g for 3 minutes at 4 °C, the plasma was discarded and the hemocyte pellet was resuspended in 50 μl PBS. The suspension material was fixed in 2% glutaraldehyde in Millonig buffer for three hours. After fixation, the material was centrifuged at 500 x g for 3 minutes, the supernatant was discarded and the cells were resuspended in a wash solution. Subsequently, the cells were post-fixed with 1% osmium tetroxide in phosphate buffer for one hour at room temperature and dehydrated in increasing concentrations of ethanol, and then embedded in Epon resin. The ultrathin sections were examined under the LEO EM 906E transmission electron microscopy at 80kV. The ultrastructural results revealed that.in control group, the cells were considered intact, in which the granulocytes were observed with granules of different electrodensities, intact mitochondria and cytoplasm without vacuolization. In addition, granulocytes showed plasma membrane projections similar to pseudopodia. Plasmatocytes presented as irregularly shaped cells, with the eccentric nucleus, agranular cytoplasm and some cells presented pseudopodia. Nevertheless, in the group exposed to the fungus, most of the cells presented in degeneration. The granulocytes found had fewer granules in the cytoplasm and more vacuoles. Plasmatocytes, after treatment, presented many vacuoles also in the cytoplasm and the lysosomes presented great amount of electrodense material in their interior. Thus, the results suggest that the fungus has a depressant action in the immune system of the tick, not only by the cell degranulation, but also suggesting that this leads to morphological changes in the hemocytes and may even trigger processes such as phagocytosis.

Keywords: bovine tick, cellular defense, entomopathogenic fungi, immune response

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Authors: Fernanda Gonçalves, Karla Alcântara, Vanessa Moura, Patrícia Nolasco, Jorge Kalil, Maristela Hernandez

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Introduction: Atherosclerosis is a chronic disease where two striking features are observed: retention of lipids and inflammation. Understanding the interaction between immune cells and lipoproteins involved in atherogenesis are urgent challenges, since cardiovascular diseases are the leading cause of death worldwide. Macrophages are critical to the development of atherosclerotic plaques and in the perpetuation of inflammation in these lesions. These cells are also directly involved in unstable plaque rupture. Recently different populations of macrophages are being identified in atherosclerotic lesions. Although the presence of M2 macrophages (macrophages activated by the alternative pathway, eg. The IL-4) has been identified, the function of these cells in atherosclerosis is not yet defined. M2 macrophages have a high endocytic capacity, they promote remodeling of tissues and to have anti-inflammatory activity. However, in atherosclerosis, especially unstable plaques, severe inflammatory reaction, accumulation of cellular debris and intense degradation of the tissue is observed. Thus, it is possible that the M2 macrophages have altered function (phenotype) in atherosclerosis. Objective: Our aim is to evaluate if the presence of oxidized LDL alters the phenotype and function of M2 macrophages in vitro. Methods: For this, we will evaluate whether the addition of lipoprotein in M2 macrophages differentiated in vitro with IL -4 induces 1) a reduction in the secretion of anti-inflammatory cytokines (CBA and ELISA), 2) secretion of inflammatory cytokines (CBA and ELISA), 3) expression of cell activation markers (Flow cytometry), 4) alteration in gene expression of molecules adhesion and extracellular matrix (Real-Time PCR) and 5) Matrix degradation (confocal microscopy). Results: In oxLDL stimulated M2 macrophages cultures we did not find any differences in the expression of the cell surface markers tested, including: HLA-DR, CD80, CD86, CD206, CD163 and CD36. Also, cultures stimulated with oxLDL had similar phagocytic capacity when compared to unstimulated cells. However, in the supernatant of these cultures an increase in the secretion of the pro-inflammatory cytokine IL-8 was detected. No significant changes where observed in IL-6, IL-10, IL-12 and IL-1b levels. The culture supernatant also induced massive extracellular matrix (produced by mouse embryo fibroblast) filaments degradation. When evaluating the expression of 84 extracellular matrix and adhesion molecules genes, we observed that the stimulation of oxLDL in M2 macrophages decreased 47% of the genes and increased the expression of only 3% of the genes. In particular we noted that oxLDL inhibit the expression of 60% of the genes constituents of extracellular matrix and collagen expressed by these cells, including fibronectin1 and collagen VI. We also observed a decrease in the expression of matrix protease inhibitors, such as TIMP 2. On the opposite, the matricellular protein thrombospondin had a 12 fold increase in gene expression. In the presence of native LDL 90% of the genes had no altered expression. Conclusion: M2 macrophages stimulated with oxLDL secrete the pro-inflammatory cytokine IL-8, have an altered extracellular matrix constituents gene expression, and promote the degradation of extracellular matrix. M2 macrophages may contribute to the perpetuation of inflammation in atherosclerosis and to plaque rupture.

Keywords: atherosclerosis, LDL, macrophages, m2

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Authors: Mahnoor Khan, Bashir Ahmad, Khizar Hayat, Saad Ahmad Khan, Laiba Ahmad, Shumaila Bashir, Abid Ali Khan

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The objective of this study was to synthesize the smallest possible size of ZnO NPs using a modified wet chemical synthesis method and to prepare core shell using polyethylene glycol (PEG) as shell material. Advanced and sophisticated techniques were used to confirm the synthesis, size, and shape of these NPs. Rounded, clustered NPs of size 5.343 nm were formed. Both the plain and core shell NPs were tested against MDR bacteria (E. cloacae, E. amnigenus, Shigella, S. odorifacae, Citrobacter, and E. coli). Both of the NPs showed excellent antibacterial properties, whereas E. cloacae showed maximum zone of inhibition of 16 mm, 27 mm, and 32 mm for 500 μg/ml, 1000 μg/ml, and 1500 μg/ml, respectively for plain ZnO NPs and 18 mm, 28 mm and 35 mm for 500 μg/ml, 1000 μg/ml and 1500 μg/ml for core shell NPs. These NPs were also biocompatible on human red blood cells showing little hemolysis of only 4% for 70 μg/ml for plain NPs and 1.5% for 70 μg/ml for core shell NPs. Core shell NPs were highly biocompatible because of the PEG. Their therapeutic effect as photosensitizers in photodynamic therapy (PDT) for cancer treatment was also monitored. The cytotoxicity of ZnO and PEG-ZnO was evaluated using MTT assay. Our results demonstrated that these NPs could generate ROS inside tumor cells after irradiation which in turn initiates an apoptotic pathway leading to cell death hence proving to be an effective candidate for PDT.

Keywords: ZnO, hemolysis, cytotoxiciy assay, photodynamic therapy, antibacterial

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Authors: Angelis P. Barlampas

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Purpose or Learning Objective It is well known that previous examinations play a major role in futural diagnosis, thus avoiding unnecessary new exams that cost in time and money both for the patient and the health system. A case is presented in which past patient’s results, in combination with the least needed new tests, give an easy final diagnosis. Methods or Background A middle aged man visited the emergency department complaining of hard controlled, persisting fever for the last few days. Laboratory tests showed an elevated number of white blood cells with neutrophil shift and abnormal CRP. The patient was admitted to hospital a month ago for continuing lungs symptomatology after a recent covid-19 infection. Results or Findings Computed tomography scanning showed a solid mass with spiculating margins in right lower lobe. After intravenous iodine contrast administration, there was mildly peripheral enhancement and eccentric non enhancing area. A pneumonic cancer was suspected. Comparison with the patient’s latest computed tomography revealed no mass in the area of interest but only signs of recent post covid-19 lung parenchyma abnormalities. Any new mass that appears in a month’s time span can not be a cancer but a benign lesion. It was obvious that an abscess was the most suitable explanation. The patient was admitted to hospital, and antibiotic therapy was given, with very good results. After a few days, the patient was afebrile and in good condition. Conclusion In this case , a PET scan or a biopsy was avoided, thanks to the patient’s medical history and the availability of previous examinations. It is worthy encouraging the patients to keep their medical records and organizing more efficiently the health system with the current technology of archiving the medical examinations, too.

Keywords: covid-19, chest ct, cancer, abscess, fever

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Authors: Sahin Yakut, H. Kemal Ulutas, Deniz Deger

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Plasma Assisted Physical Vapor Deposition (PAPVD) method used to produce Poly(ethylene oxide) (pPEO) thin films. Depositions were progressed at various plasma discharge powers as 0, 2, 5 and 30 W for pPEO at 500nm film thicknesses. The capacitance and dielectric dissipation of the thin films were measured at 0,1-107 Hz frequency range and 173-353 K temperature range by an impedance analyzer. Then, alternative conductivity (σac) and activation energies were derived from capacitance and dielectric dissipation. σac of conventional PEO (PEO precursor) was measured to determine the effect of plasma discharge. Differences were observed between the alternative conductivity of PEO’s and pPEO’s depending on plasma discharge power. By this purpose, structural characterization techniques such as Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FT-IR) were applied on pPEO thin films. Structural analysis showed that density of crosslinking is plasma power dependent. The crosslinking density increases with increasing plasma discharge power and this increase is displayed as increasing dynamic glass transition temperatures at DSC results. Also, shifting of frequencies of some type of bond vibrations, belonging to bond vibrations produced after fragmentation because of plasma discharge, were observed at FTIR results. The dynamic glass transition temperatures obtained from alternative conductivity results for pPEO consistent with the results of DSC. Activation energies exhibit Arrhenius behavior. Activation energies decrease with increasing plasma discharge power. This behavior supports the suggestion expressing that long polymer chains and long oligomers are fragmented into smaller oligomers or radicals.

Keywords: activation energy, dielectric spectroscopy, organic thin films, plasma polymer

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Authors: Zahra Khodabandeh, Leila Rezaeian, Mohammad Amin Edalatmanesh, Asghar Mogheiseh, Nader Tanideh, Mehdi Dianatpour, Shahrokh Zare, Hossein Bordbar, Neda Baghban, Amin Tamadon

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Background: In-utero xenotransplantation of stem cells in abnormal fetuses effectively treats several genetic illnesses. Objective: The current research aimed to evaluate structural and morphological alterations in the liver of rabbit fetuses following xenotransplantation of human Wharton’s jelly-derived mesenchymal stromal cells (hWJ-MSCs) using a stereological technique. Methods: hWJ-MSCs were isolated from the human umbilical cord, and their authenticity was established by flow cytometry and differentiation. At gestational day 14, the rabbits were anesthetized, and hWJ-MSCs were injected into the uteri of 24 fetuses. Twenty-two fetuses were born successfully. Ten rabbit liver specimens were prepared from injected fetuses, including eight rabbits on day three following birth and two rabbits on the 21st post-natal day. The non-injected fetuses were considered positive controls. The livers of the control and hWJ-MSCs-treated rabbits were fixed, processed, stained, and examined through stereological approaches. Results: In the hWJ-MSCs-treated group, the mean liver weight and volume increased by 42% and 78% compared to the control group. The total volume of the hepatocytes increased by 63% and that of sinusoids by threefold in the treated rabbits. The total volume of the central veins increased by 70%. The total number corresponding to hepatocytes in the experimental group increased by 112% compared to the rabbits in the control. The total volume of the hepatocyte nuclei in the experimental group increased by 117% compared to the rabbits in the control. Conclusion: After xenotransplantation of human MSCs, host tissue microenvironments (here, the rabbit liver) were altered, and these included quantitative factors corresponding to the liver tissue and hepatocyte morphometric indices.

Keywords: xenotransplantation, mesenchymal stromal, stem cell, Wharton ‘s jelly, liver

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Authors: Tong Ming Liu

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Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application, which have been used in over 1000 clinical trials to treat over 30 diseases due to multilineage differentiation potential, secretome and immunosuppression. Gene therapies of MSCs hold great promise in the treatment of many diseases due to enhanced MSC-based clinical outcomes. To identify genes for gene therapy of MSCs, by comparing gene expression profile before and after MSC differentiation following by functional screening, we have identified ZNF145 that regulated MSC differentiation. Forced expression of ZNF145 resulted in enhanced in vitro chondrogenesis of MSCs as an upstream factor of SOX9 and improved osteochondral repair upon implant into osteochondral defects in rodents. By comparing gene expression profile during differentiation of iPSCs toward MSCs, we also identified gene HOX regulating MSC stemness, which was much downregulated in late-passaged MSCs. Knockdown of this gene greatly compromised MSC stemness including abolished proliferation, decreased CFU-F, promoted senescence and reduced expression of cell surface antigens linked to the MSC phenotype. In addition, multi-linage differentiation was also greatly impaired. Notably, HOX overexpression resulted in improved multi-lineage differentiation. In the mechanism, HOX expression significantly deceased in late passage of MSCs compared with early passage of MSCs, correlating with MSC important genes. ChIP-seq data shown that HOX binds to genes related to MSC self-renewal and differentiation. Most importantly, most HOX binding sites are lost in late passage of MSCs. HOX exerts its effects by directing binding Twist1, one important gene of MSCs. The identification of the genes regulating MSC differentiation and stemness will provide and promising strategies for gene therapy of MSCs in regenerative medicine.

Keywords: mesenchymal stem cell, novel transcription factor, stemness, gene therapy, cartilage repair, signaling pathway

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Authors: Mariam Dianat Sabet Gilani, Lars M. Blank, Birgitta E. Ebert

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Plant-derived lupane-type, pentacyclic triterpenoids are biologically active compounds that are highly interesting for applications in medical, pharmaceutical, and cosmetic industries. Due to the low abundance of these valuable compounds in their natural sources, and the environmentally harmful downstream process, alternative production methods, such as microbial cell factories, are investigated. Engineered Saccharomyces cerevisiae strains, harboring the heterologous genes for betulinic acid synthesis, can produce up to 2 g L-1 triterpenoids, showing high potential for large-scale production of triterpenoids. One limitation of the microbial synthesis is the intracellular product accumulation. It not only makes cell disruption a necessary step in the downstream processing but also limits productivity and product yield per cell. To overcome these restrictions, the aim of this study is to develop an in-situ extraction method, which extracts triterpenoids into a second organic phase. Such a continuous or sequential product removal from the biomass keeps the cells in an active state and enables extended production time or biomass recycling. After screening of twelve different solvents, selected based on product solubility, biocompatibility, as well as environmental and health impact, isopropyl myristate (IPM) was chosen as a suitable solvent for in-situ product removal from S. cerevisiae. Impedance-based single-cell analysis and off-gas measurement of carbon dioxide emission showed that cell viability and physiology were not affected by the presence of IPM. Initial experiments demonstrated that after the addition of 20 vol % IPM to cultures in the stationary phase, 40 % of the total produced triterpenoids were extracted from the cells into the organic phase. In future experiments, the application of IPM in a repeated batch process will be tested, where IPM is added at the end of each batch run to remove triterpenoids from the cells, allowing the same biocatalysts to be used in several sequential batch steps. Due to its high biocompatibility, the amount of IPM added to the culture can also be increased to more than 20 vol % to extract more than 40 % triterpenoids in the organic phase, allowing the cells to produce more triterpenoids. This highlights the potential for the development of a continuous large-scale process, which allows biocatalysts to produce intracellular products continuously without the necessity of cell disruption and without limitation of the cell capacity.

Keywords: betulinic acid, biocompatible solvent, in-situ extraction, isopropyl myristate, process development, secondary metabolites, triterpenoids, yeast

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Authors: Amira Ben Rabeh, Faouzi Benzarti, Hamid Amiri, Mouna Bouaziz

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Alzheimer is a disease that affects the brain. It causes degeneration of nerve cells (neurons) and in particular cells involved in memory and intellectual functions. Early diagnosis of Alzheimer Diseases (AD) raises ethical questions, since there is, at present, no cure to offer to patients and medicines from therapeutic trials appear to slow the progression of the disease as moderate, accompanying side effects sometimes severe. In this context, analysis of medical images became, for clinical applications, an essential tool because it provides effective assistance both at diagnosis therapeutic follow-up. Computer Assisted Diagnostic systems (CAD) is one of the possible solutions to efficiently manage these images. In our work; we proposed an application to detect Alzheimer’s diseases. For detecting the disease in early stage we used the three sections: frontal to extract the Hippocampus (H), Sagittal to analysis the Corpus Callosum (CC) and axial to work with the variation features of the Cortex(C). Our method of classification is based on Support Vector Machine (SVM). The proposed system yields a 90.66% accuracy in the early diagnosis of the AD.

Keywords: Alzheimer Diseases (AD), Computer Assisted Diagnostic(CAD), hippocampus, Corpus Callosum (CC), cortex, Support Vector Machine (SVM)

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Authors: Ahmadali Tahmasebimoradi, Chetra Mang, Xavier Lorang

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Thanks to the additive manufacturing process, lattice structures are replacing the traditional structures in aeronautical and automobile industries. In order to evaluate the mechanical response of the lattice structures, one has to resort to numerical techniques. Ansys is a globally well-known and trusted commercial software that allows us to model the lattice structures and analyze their mechanical responses using either solid or beam elements. In this software, a script may be used to systematically generate the lattice structures for any size. On the one hand, solid elements allow us to correctly model the contact between the substrates (the supports of the lattice structure) and the lattice structure, the local plasticity, and the junctions of the microbeams. However, their computational cost increases rapidly with the size of the lattice structure. On the other hand, although beam elements reduce the computational cost drastically, it doesn’t correctly model the contact between the lattice structures and the substrates nor the junctions of the microbeams. Also, the notion of local plasticity is not valid anymore. Moreover, the deformed shape of the lattice structure doesn’t correspond to the deformed shape of the lattice structure using 3D solid elements. In this work, motivated by the pros and cons of the 3D and beam models, a numerically hybrid model is presented for the lattice structures to reduce the computational cost of the simulations while avoiding the aforementioned drawbacks of the beam elements. This approach consists of the utilization of solid elements for the junctions and beam elements for the microbeams connecting the corresponding junctions to each other. When the global response of the structure is linear, the results from the hybrid models are in good agreement with the ones from the 3D models for body-centered cubic with z-struts (BCCZ) and body-centered cubic without z-struts (BCC) lattice structures. However, the hybrid models have difficulty to converge when the effect of large deformation and local plasticity are considerable in the BCCZ structures. Furthermore, the effect of the junction’s size of the hybrid models on the results is investigated. For BCCZ lattice structures, the results are not affected by the junction’s size. This is also valid for BCC lattice structures as long as the ratio of the junction’s size to the diameter of the microbeams is greater than 2. The hybrid model can take into account the geometric defects. As a demonstration, the point clouds of two lattice structures are parametrized in a platform called LATANA (LATtice ANAlysis) developed by IRT-SystemX. In this process, for each microbeam of the lattice structures, an ellipse is fitted to capture the effect of shape variation and roughness. Each ellipse is represented by three parameters; semi-major axis, semi-minor axis, and angle of rotation. Having the parameters of the ellipses, the lattice structures are constructed in Spaceclaim (ANSYS) using the geometrical hybrid approach. The results show a negligible discrepancy between the hybrid and 3D models, while the computational cost of the hybrid model is lower than the computational cost of the 3D model.

Keywords: additive manufacturing, Ansys, geometric defects, hybrid finite element model, lattice structure

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Authors: Isik Cetintav, Cenk Misirli, Yilmaz Can

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This work investigates upsetting of the tri-metallic cylindrical billets both experimentally and analytically with a reduction ratio 30%. Steel, brass, and copper are used for the outer and outmost rings and aluminum for the inner core. Two different models have been designed to show material flow and the cavity took place over the two interfaces during forming after this reduction ratio. Each model has an outmost ring material as steel. Model 1 has an outer ring between the outmost ring and the solid core material as copper and Model 2 has a material as brass. Solid core is aluminum for each model. Billets were upset in press machine by using parallel flat dies. Upsetting load was recorded and compared for models and single billets. To extend the tests and compare with experimental procedure to a wider range of inner core and outer ring geometries, finite element model was performed. ABAQUS software was used for the simulations. The aim is to show how contact between outmost ring, outer ring and the inner core are carried on throughout the upsetting process. Results have shown that, with changing in height, between outmost ring, outer ring and inner core, the Model 1 and Model 2 had very good interaction, and the contact surfaces of models had various interface behaviour. It is also observed that tri-metallic materials have lower weight but better mechanical properties than single materials. This can give an idea for using and producing these new materials for different purposes.

Keywords: tri-metallic, upsetting, copper, brass, steel, aluminum

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