Search results for: cell assembly

Authors: Anuj Kumar, Kummara M. Rao, Sung S. Han

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Bone tissue engineering has emerged as a potentially alternative method for localized bone defects or diseases, congenital deformation, and surgical reconstruction. The designing and the fabrication of the ideal scaffold is a great challenge, in restoring of the damaged bone tissues via cell attachment, proliferation, and differentiation under three-dimensional (3D) biological micro-/nano-environment. In this case, hydrogel system composed of high hydrophilic 3D polymeric-network that is able to mimic some of the functional physical and chemical properties of the extracellular matrix (ECM) and possibly may provide a suitable 3D micro-/nano-environment (i.e., resemblance of native bone tissues). Thus, this proposed hydrogel system is highly permeable and facilitates the transport of the nutrients and metabolites. However, the use of hydrogels in bone tissue engineering is limited because of their low mechanical properties (toughness and stiffness) that continue to posing challenges in designing and fabrication of tough and stiff hydrogels along with improved bioactive properties. For this purpose, in our lab, polyacrylamide-based hybrid hydrogels were synthesized by involving sodium alginate, cellulose nanocrystals and silica-based glass using one-step free-radical polymerization. The results showed good in vitro apatite-forming ability (biomineralization) and improved mechanical properties (under compression in the form of strength and stiffness in both wet and dry conditions), and in vitro osteoblastic (MC3T3-E1 cells) cytocompatibility. For in vitro cytocompatibility assessment, both qualitative (attachment and spreading of cells using FESEM) and quantitative (cell viability and proliferation using MTT assay) analyses were performed. The obtained hybrid hydrogels may potentially be used in bone tissue engineering applications after establishment of in vivo characterization.

Keywords: bone tissue engineering, cellulose nanocrystals, hydrogels, polyacrylamide, sodium alginate

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Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.

Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine

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Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

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A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

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Authors: Soumyadeep Bhaduri, Rahul Ghosh, Rahul Shukla, Manaswini Behera

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The textile industry consumes a substantial amount of water throughout the processing and production of textile fabrics. The water eventually turns into wastewater, where it acts as an immense damaging nuisance due to its dye content. Wastewater streams contain a percentage ranging from 2.0% to 50.0% of the total weight of dye used, depending on the dye class. The management of dye effluent in textile industries presents a formidable challenge to global sustainability. The current focus is on implementing wastewater treatment technology that enable the recycling of wastewater, reduce energy usage and offset carbon emissions. Microbial fuel cell (MFC) is a device that utilizes microorganisms as a bio-catalyst to effectively treat wastewater while also producing electricity. The MFC harnesses the chemical energy present in wastewater by oxidizing organic compounds in the anodic chamber and reducing an electron acceptor in the cathodic chamber, thereby generating electricity. This research investigates the potential of MFCs to tackle this challenge of azo dye removal with simultaneously generating electricity. Although MFCs are well-established for wastewater treatment, their application in dye decolorization with concurrent electricity generation remains relatively unexplored. This study aims to address this gap by assessing the effectiveness of MFCs as a sustainable solution for treating wastewater containing azo dyes. By harnessing microorganisms as biocatalysts, MFCs offer a promising avenue for environmentally friendly dye effluent management. The performance of MFCs in treating azo dyes and generating electricity was evaluated by optimizing the Chemical Oxygen Demand (COD) and Hydraulic Retention Time (HRT) of influent. COD and HRT values ranged from 1600 mg/L to 2400 mg/L and 5 to 9 days, respectively. Results showed that the maximum open circuit voltage (OCV) reached 648 mV at a COD of 2400 mg/L and HRT of 5 days. Additionally, maximum COD removal of 98% and maximum color removal of 98.91% were achieved at a COD of 1600 mg/L and HRT of 9 days. Furthermore, the study observed a maximum power density of 19.95 W/m3 at a COD of 2400 mg/L and HRT of 5 days. Electrochemical analysis, including linear sweep voltammetry (LSV), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were done to find out the response current and internal resistance of the system. To optimize pH and dye concentration, pH values were varied from 4 to 10, and dye concentrations ranged from 25 mg/L to 175 mg/L. The highest voltage output of 704 mV was recorded at pH 7, while a dye concentration of 100 mg/L yielded the maximum output of 672 mV. This study demonstrates that MFCs offer an efficient and sustainable solution for treating azo dyes in textile industry wastewater, while concurrently generating electricity. These findings suggest the potential of MFCs to contribute to environmental remediation and sustainable development efforts on a global scale.

Keywords: textile wastewater treatment, microbial fuel cell, renewable energy, sustainable wastewater treatment

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Authors: Raman Kumar, Jasgurpreet Singh Chohan, Chander Shekhar Verma

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Today, the manufacturing industries respond rapidly to new demands and compete in this continuously changing environment, thus seeking out new methods allowing them to remain competitive and flexible simultaneously. The aim of the manufacturing organizations is to reduce manufacturing costs and wastes through system simplification, organizational potential, and proper infrastructural planning by using modern techniques like lean manufacturing. In India, large number of medium and large scale manufacturing industries has successfully implemented lean manufacturing techniques. Keeping in view the above-mentioned facts, different tools will be involved in the successful implementation of the lean approach. The present work is focused on the auto part manufacturing industry to improve the performance of the recliner assembly line. There is a number of lean manufacturing tools available, but the experience and complete knowledge of manufacturing processes are required to select an appropriate tool for a specific process. Fishbone diagrams (scrap, inventory, and waiting) have been drawn to identify the root cause of different. Effect of cycle time reduction on scrap and inventory is analyzed thoroughly in the case company. Results have shown that there is a decrease in inventory cost by 7 percent after the successful implementation of the lean tool.

Keywords: lean tool, fish-bone diagram, cycle time reduction, case study

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Authors: Yina A. Cifuentes Triana, Andrés M. Pinzón Velásco, Marío E. Velásquez Lozano

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In this work the sequencing and genome characterization of a natural isolate of Saccharomyces cerevisiae yeast (strain 202-3), identified with potential for the production of second generation ethanol from sugarcane bagasse hydrolysates is presented. This strain was selected because its capability to consume xylose during the fermentation of sugarcane bagasse hydrolysates, taking into account that many strains of S. cerevisiae are incapable of processing this sugar. This advantage and other prominent positive aspects during fermentation profiles evaluated in bagasse hydrolysates made the strain 202-3 a candidate strain to improve the production of second-generation ethanol, which was proposed as a first step to study the strain at the genomic level. The molecular characterization was carried out by genome sequencing with the Illumina HiSeq 2000 platform paired end; the assembly was performed with different programs, finally choosing the assembler ABYSS with kmer 89. Gene prediction was developed with the approach of hidden Markov models with Augustus. The genes identified were scored based on similarity with public databases of nucleotide and protein. Records were organized from ontological functions at different hierarchical levels, which identified central metabolic functions and roles of the S. cerevisiae strain 202-3, highlighting the presence of four possible new proteins, two of them probably associated with the positive consumption of xylose.

Keywords: cellulosic ethanol, Saccharomyces cerevisiae, genome sequencing, xylose consumption

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Authors: Abdolamir Allameh, Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi

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Non-Small Cell Lung Carcinoma (NSCLC) is associated with a number of gene mutations in epidermal growth factor receptor (EGFR). The prognostic significance of mutations in exons 19 and 21, together with serum levels of EGFR, amphiregulin (AR), and Transforming Growth Factor-alpha (TGF-α) are implicated in diagnosis and treatment. The aim of this study was to examine the relationship of EGFR mutations in selected exons with the expression of relevant ligands in sera samples of NSCLC patients. For this, a group of NSCLC patients (n=98) referred to the hospital for lung surgery with a mean age of 59±10.5 were enrolled (M/F: 75/23). Blood specimen was collected from each patient. Besides, formalin fixed paraffin embedded tissues were processed for DNA extraction. Gene mutations in exons 19 and 21 were detected by direct sequencing, following DNA amplification which was done by PCR (Polymerase Chain Reaction). Also, serum levels of EGFR, AR, and TGF-α were measured by ELISA. The results of our study show that EGFR mutations were present in 37% of Iranian NSCLC patients. The most frequently identified mutations were deletions in exon 19 (72.2%) and substitutions in exon 21 (27.8%). The most frequently identified alteration, which is considered as a rare mutation, was the E872K mutation in exon 21, which was found in 90% (9 out of 10) cases. EGFR mutation detected in exon 21 was significantly (P<0.05) correlated with the levels of its ligands, EGFR and TGF-α in serum samples. Furthermore, it was found that increased serum AR (>3pg/ml) and TGF-α (>10.5 pg/ml) were associated with shorter overall survival (P<0.05). The results clearly showed a close relationship between EGFR mutations and serum EGFR and serum TGF-α. Increased serum EGFR was associated with TGF-α and AR and linked to poor prognosis of NSCLC. These findings are implicated in clinical decision-making related to EGFR-Tyrosine kinase inhibitors (TKIs).

Keywords: lung cancer, Iranian patients, epidermal growth factor, mutation, prognosis

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Authors: Atef Y. Shenouda, Fei Xu

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Cu₃SbS₃ (CAS) was synthesized by direct solid-state reaction from elementary Cu, Sb, & S and hydrothermal reaction using thioacetamide (TAM). Crystal structure and morphology for the prepared phases of Cu₃SbS₃ were studied via X-ray diffraction (XRD) and field emission scanning electron microscope (FESEM). The band gap energies are 2 and 2.2 eV for the prepared samples. The two samples are as anode for Na ion storage. They show high initial capacity to 490 mAh/g. Na cell prepared from TAM sample shows 280 mAh/g after 25 cycles vs. 60 mAh/g for elemental sample.

Keywords: Cu3SbS3, sodium batteries, thioacetamide, sulphur sources

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Authors: W. T. Asheber, L. Chyi-Yeu

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An intelligent robot arm is expected to recognize the desired object, grasp it with appropriate force without dropping or damaging it, and also manipulate and deliver the object to the desired destination safely. This paper presents an intelligent multi-finger robot arm gripper design along with vision, proximity, and tactile sensor for efficient grasping and manipulation tasks. The generic design of the gripper makes it convenient for improved parts manipulation, multi-tasking and ease for components assembly. The proposed design emulates the human’s hand fingers structure using linkages and direct drive through power screw like transmission. The actuation and transmission mechanism is designed in such a way that it has non-back-drivable capability, which makes the fingers hold their position when even unpowered. The structural elements are optimized for a finest performance in motion and force transmissivity of the gripper fingers. The actuation mechanisms is designed specially to drive each finger and also rotate two of the fingers about the palm to form appropriate configuration to grasp various size and shape objects. The gripper has an automatic tool set fixture incorporated into its palm, which will reduce time wastage and do assembling in one go. It is equipped with camera-in-hand integrated into its palm; subsequently an image based visual-servoing control scheme is employed.

Keywords: gripper, intelligent gripper, transmissivity, vision sensor

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Authors: Weihao Wang, Zhulin Zong

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Two-dimensional ordered statistical constant false alarm detection is a widely used method for detecting weak target signals in radar signal processing applications. The method is based on analyzing the statistical characteristics of the noise and clutter present in the radar signal and then using this information to set an appropriate detection threshold. In this approach, the reference cell of the unit to be detected is divided into several reference subunits. These subunits are used to estimate the noise level and adjust the detection threshold, with the aim of minimizing the false alarm rate. By using an ordered statistical approach, the method is able to effectively suppress the influence of clutter and noise, resulting in a low false alarm rate. The detection process involves a number of steps, including filtering the input radar signal to remove any noise or clutter, estimating the noise level based on the statistical characteristics of the reference subunits, and finally, setting the detection threshold based on the estimated noise level. One of the main advantages of two-dimensional ordered statistical constant false alarm detection is its ability to detect weak target signals in the presence of strong clutter and noise. This is achieved by carefully analyzing the statistical properties of the signal and using an ordered statistical approach to estimate the noise level and adjust the detection threshold. In conclusion, two-dimensional ordered statistical constant false alarm detection is a powerful technique for detecting weak target signals in radar signal processing applications. By dividing the reference cell into several subunits and using an ordered statistical approach to estimate the noise level and adjust the detection threshold, this method is able to effectively suppress the influence of clutter and noise and maintain a low false alarm rate.

Keywords: two-dimensional, ordered statistical, constant false alarm, detection, weak target signals

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Authors: Manisha Dubey, Gaurav Gupta, Anoop Arya

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The demand for power supply increases day by day in developing countries like India henceforth demand of reactive power support in the form of ancillary services provider also has been increased. The multi-line and multi-type Flexible alternating current transmission system (FACTS) controllers are playing a vital role to regulate power flow through the transmission line. Unified power flow controller and interline power flow controller can be utilized to control reactive power flow through the transmission line. In a restructured power system, the demand of such controller is being popular due to their inherent capability. The transmission pricing by using reactive power cost allocation through modified matrix methodology has been proposed. The FACTS technologies have quite costly assembly, so it is very useful to apportion the expenses throughout the restructured electricity industry. Therefore, in this work, after embedding the FACTS devices into load flow, the impact on the costs allocated to users in fraction to the transmission framework utilization has been analyzed. From the obtained results, it is clear that the total cost recovery is enhanced towards the Reactive Power flow through the different transmission line for 5 bus test system. The fair pricing policy towards reactive power can be achieved by the proposed method incorporating FACTS controller towards cost recovery of the transmission network.

Keywords: interline power flow controller, transmission pricing, unified power flow controller, cost allocation

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Authors: Taiheng Zhang, Hongbin Zhao

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Compressed air energy storage become increasingly vital for solving intermittency problem of some renewable energies. In this study, a new hybrid system on a combination of compressed air energy storage (CAES), solid oxide fuel cell (SOFC), gas turbine (GT), and organic Rankine cycle (ORC) is proposed. In the new system, excess electricity during off-peak time is utilized to compress air. Then, the compressed air is stored in compressed air storage tank. During peak time, the compressed air enters the cathode of SOFC directly instead of combustion chamber of traditional CAES. There is no air compressor consumption of SOFC-GT in peak demand, so SOFC- GT can generate power with high-efficiency. In addition, the waste heat of exhaust from GT is recovered by applying an ORC. Three different organic working fluid (R123, R601, R601a) of ORC are chosen to evaluate system performance. Based on Aspen plus and Engineering Equation Solver (EES) software, energy and exergoeconomic analysis are used to access the viability of the combined system. Besides, the effect of two parameters (fuel flow and ORC turbine inlet pressure) on energy efficiency is studied. The effect of low-price electricity at off-peak hours on thermodynamic criteria (total unit exergy cost of products and total cost rate) is also investigated. Furthermore, for three different organic working fluids, the results of round-trip efficiency, exergy efficiency, and exergoeconomic factors are calculated and compared. Based on thermodynamic performance and exergoeconomic performance of different organic working fluids, the best suitable working fluid will be chosen. In conclusion, this study can provide important guidance for system efficiency improvement and viability.

Keywords: CAES, SOFC, ORC, energy and exergoeconomic analysis, organic working fluids

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Authors: Zbigniew Czyz, Ksenia Siadkowska, Krzysztof Skiba, Karol Scislowski

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Today’s progress in the rotorcraft is mostly associated with an optimization of aircraft performance achieved by active and passive modifications of main rotor assemblies and a tail propeller. The key task is to improve their performance, improve the hover quality factor for rotors but not change in specific fuel consumption. One of the tasks to improve the helicopter is an active optimization of the main rotor providing for flight stages, i.e., an ascend, flight, a descend. An active interference with the airflow around the rotor blade section can significantly change characteristics of the aerodynamic airfoil. The efficiency of actuator systems modifying aerodynamic coefficients in the current solutions is relatively high and significantly affects the increase in strength. The solution to actively change aerodynamic characteristics assumes a periodic change of geometric features of blades depending on flight stages. Changing geometric parameters of blade warping enables an optimization of main rotor performance depending on helicopter flight stages. Structurally, an adaptation of shape memory alloys does not significantly affect rotor blade fatigue strength, which contributes to reduce costs associated with an adaptation of the system to the existing blades, and gains from a better performance can easily amortize such a modification and improve profitability of such a structure. In order to obtain quantitative and qualitative data to solve this research problem, a number of numerical analyses have been necessary. The main problem is a selection of design parameters of the main rotor and a preliminary optimization of its performance to improve the hover quality factor for rotors. This design concept assumes a three-bladed main rotor with a chord of 0.07 m and radius R = 1 m. The value of rotor speed is a calculated parameter of an optimization function. To specify the initial distribution of geometric warping, a special software has been created that uses a numerical method of a blade element which respects dynamic design features such as fluctuations of a blade in its joints. A number of performance analyses as a function of rotor speed, forward speed, and altitude have been performed. The calculations were carried out for the full model assembly. This approach makes it possible to observe the behavior of components and their mutual interaction resulting from the forces. The key element of each rotor is the shaft, hub and pins holding the joints and blade yokes. These components are exposed to the highest loads. As a result of the analysis, the safety factor was determined at the level of k > 1.5, which gives grounds to obtain certification for the strength of the structure. The construction of the joint rotor has numerous moving elements in its structure. Despite the high safety factor, the places with the highest stresses, where the signs of wear and tear may appear, have been indicated. The numerical analysis carried out showed that the most loaded element is the pin connecting the modular bearing of the blade yoke with the element of the horizontal oscillation joint. The stresses in this element result in a safety factor of k=1.7. The other analysed rotor components have a safety factor of more than 2 and in the case of the shaft, this factor is more than 3. However, it must be remembered that the structure is as strong as the weakest cell is. Designed rotor for unmanned aerial vehicles adapted to work with blades with intelligent materials in its structure meets the requirements for certification testing. Acknowledgement: This work has been financed by the Polish National Centre for Research and Development under the LIDER program, Grant Agreement No. LIDER/45/0177/L-9/17/NCBR/2018.

Keywords: main rotor, rotorcraft aerodynamics, shape memory alloy, materials, unmanned helicopter

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Authors: Ahmad Ali Shahid, Mukhtar Ahmed

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The demand for long staple fiber having better strength and length is increasing with the introduction of modern spinning and weaving industry in Pakistan. Work on gene discovery from developing cotton fibers has helped to identify dozens of genes that take part in cotton fiber development and several genes have been characterized for their role in fiber development. Sucrose synthase (SuS) is a key enzyme in the metabolism of sucrose in a plant cell, in cotton fiber it catalyzes a reversible reaction, but preferentially converts sucrose and UDP into fructose and UDP-glucose. UDP-glucose (UDPG) is a nucleotide sugar act as a donor for glucose residue in many glycosylation reactions and is essential for the cytosolic formation of sucrose and involved in the synthesis of cell wall cellulose. The study was focused on successful Agrobacterium-mediated stable transformation of SuS gene in pCAMBIA 1301 into cotton under a CaMV35S promoter. Integration and expression of the gene were confirmed by PCR, GUS assay, and real-time PCR. Young leaves of SuS overexpressing lines showed increased total soluble sugars and plant biomass as compared to non-transgenic control plants. Cellulose contents from fiber were significantly increased. SEM analysis revealed that fibers from transgenic cotton were highly spiral and fiber twist number increased per unit length when compared with control. Morphological data from field plants showed that transgenic plants performed better in field conditions. Incorporation of genes related to cotton fiber length and quality can provide new avenues for fiber improvement. The utilization of this technology would provide an efficient import substitution and sustained production of long-staple fiber in Pakistan to fulfill the industrial requirements.

Keywords: agrobacterium-mediated transformation, cotton fiber, sucrose synthase gene, staple length

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Authors: Ching-Feng Chen, Ching-Chih Tsai

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With the size of the transistor gradually approaching the physical limit, it challenges the persistence of Moore’s Law due to the development of the high numerical aperture (high-NA) lithography equipment and other issues such as short channel effects. In the context of the ever-increasing technical requirements of portable devices and high-performance computing, relying on the law continuation to enhance the chip density will no longer support the prospects of the electronics industry. Weighing the chip’s power consumption-performance-area-cost-cycle time to market (PPACC) is an updated benchmark to drive the evolution of the advanced wafer nanometer (nm). The advent of two and half- and three-dimensional (2.5 and 3D)- Very-Large-Scale Integration (VLSI) packaging based on Through Silicon Via (TSV) technology has updated the traditional die assembly methods and provided the solution. This overview investigates the up-to-date and cutting-edge packaging technologies for 2.5D and 3D integrated circuits (ICs) based on the updated transistor structure and technology nodes. The author concludes that multi-chip solutions for 2.5D and 3D IC packagings are feasible to prolong Moore’s Law.

Keywords: moore’s law, high numerical aperture, power consumption-performance-area-cost-cycle time to market, 2.5 and 3D- very-large-scale integration, packaging, through silicon via

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Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

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Authors: Sanja O. Podunavac-Kuzmanović, Lidija R. Jevrić, Strahinja Z. Kovačević

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In last decade, metal-organic complexes have captured intensive attention because of their wide range of biological activities such as antibacterial, antifungal, anticancerous, antimicrobial and antiHIV. Therefore, it is of great importance for the development of coordination chemistry to explore the assembly of functional organic ligands with metal ion and to investigate the relationship between the structure and property. In view of our studies, we reasoned that benzimidazoles complexed to metal ions could act as a potent antibacterial agents. Thus, we have bioassayed the inhibitory potency of benzimidazoles and their metal salts (Co or Ni) against Gram negative bacteria Escherichia coli. In order to validate our in vitro study, we performed in silico studies using molecular docking software’s. The investigated compounds and their metal complexes (Co, Ni) showed good antibacterial activity against Escherichia coli. In silico docking studies of the synthesized compounds suggested that complexed benzimidazoles have a greater binding affinity and enhanced antibacterial activity in comparison with noncomplexed ligands. In view of their enhanced inhibitory properties we propose that the studied complexes can be used as potential pharmaceuticals. This study is financially supported by COST action CM1306 and the project No. 114-451-347/2015-02, financially supported by the Provincial Secretariat for Science and Technological Development of Vojvodina.

Keywords: benzimidazoles, complexes, antibacterial, Escherichia coli, metal

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Authors: Yi-Shiuan Chiu

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Deaf signers have been found to have better mental image performance than hearing nonsigners. The goal of this study was to investigate the ability to generate mental images, to maintain them, and to manipulate them in deaf signers of Taiwanese Sign Language (TSL). In the visual image task, participants first memorized digits formed in a cell of 4 × 5 grids. After presenting a cue of Chinese digit character shown on the top of a blank cell, participants had to form a corresponding digit. When showing a probe, which was a grid containing a red circle, participants had to decide as quickly as possible whether the probe would have been covered by the mental image of the digit. The ISI (interstimulus interval) between cue and probe was manipulated. In experiment 1, 24 deaf signers and 24 hearing nonsigners were asked to perform image generation tasks (ISI: 200, 400 ms) and image maintenance tasks (ISI: 800, 2000 ms). The results showed that deaf signers had had an enhanced ability to generate and maintain a mental image. To explore the process of mental image, in experiment 2, 30 deaf signers and 30 hearing nonsigners were asked to do visual searching when maintaining a mental image. Between a digit image cue and a red circle probe, participants were asked to search a visual search task to see if a target triangle apex was directed to the right or left. When there was only one triangle in the searching task, the results showed that both deaf signers and hearing non-signers had similar visual searching performance in which the searching targets in the mental image locations got facilitates. However, deaf signers could maintain better and faster mental image performance than nonsigners. In experiment 3, we increased the number of triangles to 4 to raise the difficulty of the visual search task. The results showed that deaf participants performed more accurately in visual search and image maintenance tasks. The results suggested that people may use eye movements as a mnemonic strategy to maintain the mental image. And deaf signers had enhanced abilities to resist the interference of eye movements in the situation of fewer distractors. In sum, these findings suggested that deaf signers had enhanced mental image processing.

Keywords: deaf signers, image maintain, mental image, visual search

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is a low-grade inflammatory state. Childhood obesity is a multisystem disease, which is associated with a number of complications as well as potentially negative consequences. Gender is an important universal risk factor for many diseases. Hematological indices differ significantly by gender. This should be considered during the evaluation of obese children. The aim of this study is to detect hematologic indices that differ by gender in morbid obese (MO) children. A total of 134 MO children took part in this study. The parents filled an informed consent form and the approval from the Ethics Committee of Namik Kemal University was obtained. Subjects were divided into two groups based on their genders (64 females aged 10.2±3.1 years and 70 males aged 9.8±2.2 years; p ≥ 0.05). Waist-to-hip as well as head-to-neck ratios and body mass index (BMI) values were calculated. The children, whose WHO BMI-for age and sex percentile values were > 99 percentile, were defined as MO. Hematological parameters [haemoglobin, hematocrit, erythrocyte count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell distribution width, leukocyte count, neutrophil %, lymphocyte %, monocyte %, eosinophil %, basophil %, platelet count, platelet distribution width, mean platelet volume] were determined by the automatic hematology analyzer. SPSS was used for statistical analyses. P ≤ 0.05 was the degree for statistical significance. The groups included children having mean±SD value of BMI as 26.9±3.4 kg/m² for males and 27.7±4.4 kg/m² for females (p ≥ 0.05). There was no significant difference between ages of females and males (p ≥ 0.05). Males had significantly increased waist-to-hip ratios (0.95±0.08 vs 0.91±0.08; p=0.005) and mean corpuscular hemoglobin concentration values (33.6±0.92 vs 33.1±0.83; p=0.001) compared to those of females. Significantly elevated neutrophil (4.69±1.59 vs 4.02±1.42; p=0.011) and neutrophil-to-lymphocyte ratios (1.70±0.71 vs 1.39±0.48; p=0.004) were detected in females. There was no statistically significant difference between groups in terms of C-reactive protein values (p ≥ 0.05). Adipose tissue plays important roles during the development of obesity and associated diseases such as metabolic syndrom and cardiovascular diseases (CVDs). These diseases may cause changes in complete blood cell count parameters. These alterations are even more important during childhood. Significant gender effects on the changes of neutrophils, one of the white blood cell subsets, were observed. The findings of the study demonstrate the importance of considering gender in clinical studies. The males and females may have distinct leukocyte-trafficking profiles in inflammation. Female children had more circulating neutrophils, which may be the indicator of an increased risk of CVDs, than male children within this age range during the late stage of obesity. In recent years, females represent about half of deaths from CVDs; therefore, our findings may be the indicator of the increasing tendency of this risk in females starting from childhood.

Keywords: children, gender, morbid obesity, neutrophil-to-lymphocyte ratio

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Authors: Jie Lin, Yiwen Pan, Li Zhang, Zhangyong Xia

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Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and extracellular matrix in the arterial walls. This pathological process can lead to the formation of plaques that can obstruct blood flow and trigger various cardiovascular diseases such as heart attack and stroke. The underlying molecular mechanisms still remain unclear, although many studies revealed the dysfunction of endothelial cells, recruitment and activation of monocytes and macrophages, and the production of pro-inflammatory cytokines and chemokines in atherosclerosis. This study aimed to identify hub genes involved in the progression of atherosclerosis and to analyze their biological function in silico, thereby enhancing our understanding of the disease’s molecular mechanisms. Through the analysis of microarray data, we examined the gene expression in media and neo-intima from plaques, as well as distant macroscopically intact tissue, across a cohort of 32 hypertensive patients. Initially, 112 differentially expressed genes (DEGs) were identified. Subsequent immune infiltration analysis indicated a predominant presence of 27 immune cell types in the atherosclerosis group, particularly noting an increase in monocytes and macrophages. In the Weighted gene co-expression network analysis (WGCNA), 10 modules with a minimum of 30 genes were defined as key modules, with blue, dark, Oliver green and sky-blue modules being the most significant. These modules corresponded respectively to monocyte, activated B cell, and activated CD4 T cell gene patterns, revealing a strong morphological-genetic correlation. From these three gene patterns (modules morphology), a total of 2509 key genes (Gene Significance >0.2, module membership>0.8) were extracted. Six hub genes (CD36, DPP4, HMOX1, PLA2G7, PLN2, and ACADL) were then identified by intersecting 2509 key genes, 102 DEGs with lipid-related genes from the Genecard database. The bio-functional analysis of six hub genes was estimated by a robust classifier with an area under the curve (AUC) of 0.873 in the ROC plot, indicating excellent efficacy in differentiating between the disease and control group. Moreover, PCA visualization demonstrated clear separation between the groups based on these six hub genes, suggesting their potential utility as classification features in predictive models. Protein-protein interaction (PPI) analysis highlighted DPP4 as the most interconnected gene. Within the constructed key gene-drug network, 462 drugs were predicted, with ursodeoxycholic acid (UDCA) being identified as a potential therapeutic agent for modulating DPP4 expression. In summary, our study identified critical hub genes implicated in the progression of atherosclerosis through comprehensive bioinformatic analyses. These findings not only advance our understanding of the disease but also pave the way for applying similar analytical frameworks and predictive models to other diseases, thereby broadening the potential for clinical applications and therapeutic discoveries.

Keywords: atherosclerosis, hub genes, drug prediction, bioinformatics

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Authors: Fulufhelo Amanda Doboro, Kgomotso Sebeko, Stephen Njiro, Moritz Van Vuuren

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Ovine herpesvirus 2 (OvHV-2) genome obtained from the lymphopblastoid cell line of a BJ1035 cow was recently sequenced in the United States of America (USA). Information on the sequences of OvHV-2 genes obtained from South African strains from bovine or other African countries and molecular characterization of OvHV-2 is not documented. Present investigation provides information on the nucleotide and derived amino acid sequences and genetic diversity of Ov 7, Ov 8 ex2, ORF 27 and ORF 73 genes, of these genes from OvHV-2 strains circulating in South Africa. Gene-specific primers were designed and used for PCR of DNA extracted from 42 bovine blood samples that previously tested positive for OvHV-2. The expected PCR products of 495 bp, 253 bp, 890 bp and 1632 bp respectively for Ov 7, Ov 8 ex2, ORF 27 and ORF 73 genes were sequenced and multiple sequence analysis done on the selected regions of the sequenced PCR products. Two genotypes for ORF 27 and ORF 73 gene sequences, and three genotypes for Ov 7 and Ov 8 ex2 gene sequences were identified, and similar groupings for the derived amino acid sequences were obtained for each gene. Nucleotide and amino acid sequence variations that led to the identification of the different genotypes included SNPs, deletions and insertions. Sequence analysis of Ov 7 and ORF 27 genes revealed variations that distinguished between sequences from SA and reference OvHV-2 strains. The implication of geographic origin among SA sequences was difficult to evaluate because of random distribution of genotypes in the different provinces, for each gene. However, socio-economic factors such as migration of people with animals, or transportation of animals for agricultural or business use from one province to another are most likely to be responsible for this observation. The sequence variations observed in this study have no impact on the antibody binding activities of glycoproteins encoded by Ov 7, Ov 8 ex2 and ORF 27 genes, as determined by prediction of the presence of B cell epitopes using BepiPred 1.0. The findings of this study will be used for selection of gene candidates for the development of diagnostic assays and vaccine development as well.

Keywords: amino acid, genetic diversity, genes, nucleotide

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Authors: Jose Melena, Rosa Santander, Tanya Gonzalez, Richard Duque, Juan Illanes

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Ecuador is one of the countries with the greatest aquatic biodiversity worldwide. In particular, there are at least a dozen native marine species with great aquaculture potential locally. This research concerns one of those species. It has proposed to implement experimental protocols in order to induce spawning and to generate the early larval development of the penshell Atrina maura under controlled conditions. Bioassays were carried out with one adult batch (n= 26) with an average valvar length of 307,6 ± 9,4 mm, which were collected in the Puerto El Morro Mangrove (2° 42' 33'' S, 80° 14' 28'' W), Guayas Province. During a short acclimation stage, five adults of penshell A. maura were sacrificed in order to determine their sexual maturity degree and to estimate their sex ratio. Dissection showed that three were ripe females (60%) and two were ripe males (40%). Later, three groups (n= 7 by each) were tested with two treatments in order to induce the broodstock spawning: thermal stress, osmotic shock, and one control. Spawning induction was achieved by the immersion in water to 0 g L⁻¹ per 1 h and immersion in sea water to 34 g L⁻¹ per 1 h. After the delivery of gametes, it was achieved 1,35 × 10⁶ viable zygotes. As results, fertilized eggs had 60 µm diameter; while first and second cell divisions were observed to 1 h post-fertilization, with individual average length of 65 ± 4 µm and polar body. Latter cell divisions, including gastrula stage, appeared at 9 h post-fertilization, with individual average length of 71 ± 4 µm; and trochophore stage at 16 h post-fertilization with individual average length of 75 ± 5 µm. In addition, veliger stage was registered at 20 h post-fertilization with individual average length of 81 ± 5 µm. Umboned larvae appeared at day 8 post-fertilization, with individual average length of 145 ± 6 µm. These pioneering results in Ecuador can strengthen the local conservation process of the overexploited A. maura and to encourage its production for commercial purposes.

Keywords: Atrina maura, Ecuador, larval development, spawning induction

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Authors: Luz del Carmen Rubí Félix Peña, Jose Adan Felix-Ortiz, Ely Sara Lopez-Alvarez, Wenceslao Valenzuela-Quiñonez

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On a global scale, Mexico is the sixth largest producer of farmed white shrimp (Penaeus vannamei). The activity suffered significant economic losses due to acute hepatopancreatic necrosis (AHPND) caused by a strain of Vibrio parahaemolyticus. For control, the first option is the application of antibiotics in food, causing changes in the environment and bacterial communities, which has produced greater virulence and resistance of pathogenic bacteria. An alternative treatment is silver nanoparticles (AgNPs) generated by green synthesis, which have shown an antibacterial capacity by destroying the cell membrane or denaturing the cell. However, the doses at which these are effective are still unknown. The aim is to calculate the minimum inhibitory concentration (MIC) using the Gompertz, Richard, and Logistic model of biosynthesized AgNPs against a strain of V. parahaemolyticus. Through the testing of different formulations of AgNPs synthesized from Euphorbia prostrate (Ep) extracts against V. parahaemolyticus causing AHPND in white shrimp. Aqueous and ethanol extracts were obtained, and the concentration of phenols and flavonoids was quantified. In the antibiograms, AgNPs were formulated in ethanol extracts of Ep (20 and 30%). The inhibition halo at well dilution test were 18±1.7 and 17.67±2.1 mm against V. parahaemolyticus. A broth microdilution was performed with the inhibitory agents (aqueous and ethanolic extracts and AgNPs) and 20 μL of the inoculum of V. parahaemolyticus. The MIC for AgNPs was 6.2-9.3 μg/mL and for ethanol extract of 49-73 mg/mL. The Akaike index (AIC) was used to choose the Gompertz model for ethanol extracts of Ep as the best data descriptor (AIC=204.8, 10%; 45.5, 20%, and 204.8, 30%). The Richards model was at AgNPs ethanol extract with AIC=-9.3 (10%), -17.5 (20 and 30%). The MIC calculated for EP extracts with the modified Gompertz model were 20 mg/mL (10% and 20% extract) and 40 mg/mL at 30%, while Richard was winner for AgNPs-synthesized it was 5 μg/mL (10% and 20%) and 8 μg/mL (30%). The solver tool Excel was used for the calculations of the models and inhibition curves against V.parahaemolyticus.

Keywords: green synthesis, euphorbia prostata, phenols, flavonoids, bactericide

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Authors: Vidia A. Nuraini, Eugene M. H. Yee, Mohan Bhadbhade, David StC. Black, Naresh Kumar

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Flavonoids are naturally occurring compounds that have been shown to exhibit a wide range of biological properties including anticancer and anti-inflammatory activities. However, flavonoids suffer from low bioavailability, which limits their overall utility for therapeutic applications. One of the methods to overcome this limitation is through structural modification of natural flavonoids. In this study, flavanone, isoflavanone, and isoflavene, were structurally modified through the introduction of additional fused-ring systems via ortho-quinone methide intermediates (o-QMs). These intermediates can readily undergo a [4+2] cycloaddition through an inverse-electron-demand Diels–Alder reaction with electron-rich dienophiles. A regioselective Mannich reaction using bis-(N,N-dimethylamino)methane was employed to generate the o-QM precursors of flavanone, isoflavanone, and isoflavene. The o-QM intermediates were subsequently generated in situ through thermal elimination of the dimethylamine functionality and reacted with a variety of dienophiles to produce novel flavonoids with fused-ring systems. A total of 21 novel flavonoid analogs were successfully synthesized. The X-ray crystal structure of cycloaddition adducts, particularly those derived from 3,4-dihydro-2H-pyran and p-methoxystyrene revealed a special case of enantiomeric disorder, where two enantiomers in equal amounts superpose with one another, with the exception for atoms that have opposite configuration. The anticancer properties of fused-ring systems derived from isoflavene were evaluated against the neuroblastoma SKN-BE(2)C, the triple negative breast cancer MDA-MB-231, and the glioblastoma U87 cancer cell lines. One of these cycloaddition adducts had displayed improved anti-proliferative activity against MDA-MB-231 and U87 cancer cell lines as compared to the parent compound. Further anticancer and anti-inflammatory activities of the flavanone and isoflavanone analogs are currently being investigated.

Keywords: Diels-Alder reaction, flavonoids, Mannich reaction, ortho-quinone methide.

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Authors: Antonio Aguilar Aguilar, Eliezer Braun Guitler

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Using a previously developed procedure and with the aid of algebraic software, a two-dimensional generalized Ising model with a 4×2 unitary cell (UC), we obtain a Kagome Lattice with twelve different spin-spin values of interaction, in order to determine the partition function per spin L(T). From the partition function we can study the magnetic behavior of the system. Because of the competition phenomenon between spins, a very complex behavior among them in a variety of magnetic states can be observed.

Keywords: correlations, Ising, Kagome, exact functions

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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: Tahani Mashikhi

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Countries worldwide rely on electric power as a critical economic growth and progress factor. Renewable energy sources, often referred to as alternative energy sources, such as wind, solar energy, geothermal energy, biomass, and hydropower, have garnered significant interest in response to the rising consumption of fossil fuels. Dye-sensitized solar cells (DSSCs) are a highly promising alternative for energy production as they possess numerous advantages compared to traditional silicon solar cells and thin-film solar cells. These include their low cost, high flexibility, straightforward preparation methodology, ease of production, low toxicity, different colors, semi-transparent quality, and high power conversion efficiency. A solar cell, also known as a photovoltaic cell, is a device that converts the energy of light from the sun into electrical energy through the photovoltaic effect. The Gratzel cell is the initial dye-sensitized solar cell made from colloidal titanium dioxide. The operational mechanism of DSSCs relies on various key elements, such as a layer composed of wide band gap semiconducting oxide materials (e.g. titanium dioxide [TiO₂]), as well as a photosensitizer or dye that absorbs sunlight to inject electrons into the conduction band, the electrolyte utilizes the triiodide/iodide redox pair (I− /I₃−) to regenerate dye molecules and a counter electrode made of carbon or platinum facilitates the movement of electrons across the circuit. Electrospray deposition permits the deposition of fragile, non-volatile molecules in a vacuum environment, including dye sensitizers, complex molecules, nanoparticles, and biomolecules. Surface science techniques, particularly X-ray photoelectron spectroscopy, are employed to examine dye-sensitized solar cells. This study investigates the possible application of electrospray deposition to build high-quality layers in situ in a vacuum. Two distinct categories of dyes can be employed as sensitizers in DSSCs: organometallic semiconductor sensitizers and purely organic dyes. Most organometallic dyes, including Ru533, RuC, and RuP, contain a ruthenium atom, which is a rare element. This ruthenium atom enhances the efficiency of dye-sensitized solar cells (DSSCs). These dyes are characterized by their high cost and typically appear as dark purple powders. On the other hand, organic dyes, such as SQ2, RK1, D5, SC4, and R6, exhibit reduced efficacy due to the lack of a ruthenium atom. These dyes appear in green, red, orange, and blue powder-colored. This study will specifically concentrate on metal-organic dyes. The adsorption of dye molecules onto the rutile TiO₂ (110) surface has been deposited in situ under ultra-high vacuum conditions by combining an electrospray deposition method with X-ray photoelectron spectroscopy. The X-ray photoelectron spectroscopy (XPS) technique examines chemical bonds and interactions between molecules and TiO₂ surfaces. The dyes were deposited at varying times, from 5 minutes to 40 minutes, to achieve distinct layers of coverage categorized as sub-monolayer, monolayer, few layers, or multilayer. Based on the O 1s photoelectron spectra data, it can be observed that the monolayer establishes a strong chemical bond with the Ti atoms of the oxide substrate by deprotonating the carboxylic acid groups through 2M-bidentate bridging anchors. The C 1s and N 1s photoelectron spectra indicate that the molecule remains intact at the surface. This can be due to the existence of all functional groups and a ruthenium atom, where the binding energy of Ru 3d is consistent with Ru2+.

Keywords: deposit, dye, electrospray, TiO₂, XPS

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Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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Authors: Ali N. Suri, Ahmad A. Al-Makhlufi

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In this paper the problem of buckling of plates on foundation of finite length and with different side support is studied. The Finite Strip Method is used as tool for the analysis. This method uses finite strip elastic, foundation, and geometric matrices to build the assembly matrices for the whole structure, then after introducing boundary conditions at supports, the resulting reduced matrices is transformed into a standard Eigenvalue-Eigenvector problem. The solution of this problem will enable the determination of the buckling load, the associated buckling modes and the buckling wave length. To carry out the buckling analysis starting from the elastic, foundation, and geometric stiffness matrices for each strip a computer program FORTRAN list is developed. Since stiffness matrices are function of wave length of buckling, the computer program used an iteration procedure to find the critical buckling stress for each value of foundation modulus and for each boundary condition. The results showed the use of elastic medium to support plates subject to axial load increase a great deal the buckling load, the results found are very close with those obtained by other analytical methods and experimental work. The results also showed that foundation compensates the effect of the weakness of some types of constraint of side support and maximum benefit found for plate with one side simply supported the other free.

Keywords: buckling, finite strip, different sides support, plates on foundation

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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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