Search results for: exponential expression profile

Authors: Qi Liu, Jiqin Yao, Xiaohu Zhou, Bo Zheng

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The first artificial cell was produced by Thomas Chang in the 1950s when he was trying to make a mimic of red blood cells. Since then, many different types of artificial cells have been constructed from one of the two approaches: a so-called bottom-up approach, which aims to create a cell from scratch, and a top-down approach, in which genes are sequentially knocked out from organisms until only the minimal genome required for sustaining life remains. In this project, bottom-up approach was used to build a new cell-free expression system which mimics artificial cell that capable of protein expression and communicate with each other. The artificial cells constructed from the bottom-up approach are usually lipid vesicles, polymersomes, hydrogels or aqueous droplets containing the nucleic acids and transcription-translation machinery. However, lipid vesicles based artificial cells capable of communication present several issues in the cell communication research: (1) The lipid vesicles normally lose the important functions such as protein expression within a few hours. (2) The lipid membrane allows the permeation of only small molecules and limits the types of molecules that can be sensed and released to the surrounding environment for chemical communication; (3) The lipid vesicles are prone to rupture due to the imbalance of the osmotic pressure. To address these issues, the hydrogel-based artificial cells were constructed in this work. To construct the artificial cell, polyacrylamide hydrogel was functionalized with Acrylate PEG Succinimidyl Carboxymethyl Ester (ACLT-PEG2000-SCM) moiety on the polymer backbone. The proteinaceous factors can then be immobilized on the polymer backbone by the reaction between primary amines of proteins and N-hydroxysuccinimide esters (NHS esters) of ACLT-PEG2000-SCM, the plasmid template and ribosome were encapsulated inside the hydrogel particles. Because the artificial cell could continuously express protein with the supply of nutrients and energy, the artificial cell-artificial cell communication and artificial cell-natural cell communication could be achieved by combining the artificial cell vector with designed plasmids. The plasmids were designed referring to the quorum sensing (QS) system of bacteria, which largely relied on cognate acyl-homoserine lactone (AHL) / transcription pairs. In one communication pair, “sender” is the artificial cell or natural cell that can produce AHL signal molecule by synthesizing the corresponding signal synthase that catalyzed the conversion of S-adenosyl-L-methionine (SAM) into AHL, while the “receiver” is the artificial cell or natural cell that can sense the quorum sensing signaling molecule form “sender” and in turn express the gene of interest. In the experiment, GFP was first immobilized inside the hydrogel particle to prove that the functionalized hydrogel particles could be used for protein binding. After that, the successful communication between artificial cell-artificial cell and artificial cell-natural cell was demonstrated, the successful signal between artificial cell-artificial cell or artificial cell-natural cell could be observed by recording the fluorescence signal increase. The hydrogel-based artificial cell designed in this work can help to study the complex communication system in bacteria, it can also be further developed for therapeutic applications.

Keywords: artificial cell, cell-free system, gene circuit, synthetic biology

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Authors: Francisco Domingos Francisco

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Tropical forests are key providers of many Ecosystem Services (ES), contributing to human wellbeing on a global and local scale. Communities around and within Moribane Forest Reserve (MFR), Manica Province - Mozambique, benefit from ES through the exploitation of non-wood and wood forest products. The objective was to assess the provisioning capacity of the MFR in woody forest products in species and profiles of interest to local communities in the main sources of extraction. Social data relating to the basic needs of local communities for these products were captured through an exploratory study before this one. From that study, it became known about the most collected wood species, the sources of collection, and their availability in the profiles of greatest interest to them. A field survey through 39 rectangular 50mx20m plots was conducted with 13 plots established in each of the three land-use types (LUT), namely Restricted Forest, Unrestricted Forest, and Disturbed areas. The results show that 89 species were identified, of which 28 (31.4%) are assumed to be the most used by the communities. The number of species of local interest does not vary across the LUT (p>0.05). The most used species (MUS) is distributed in 82% in Restricted Forest, 75% in Unrestricted, and also 75% in Disturbed. Most individuals of both general and MUS found in Unrestricted Forest, and Degraded areas have lower end profiles (5-7 cm), representing 0.77 and 0.26%, respectively. The profile of individuals of species of local interest varies by LUT (p<0.05), and their greatest proportion (0.51%) outside the lower end is found in Restricted Forest. There were no similarities between the LUT for the species in general (JCI <0.5) but between the MUS (JCI >0.5). Conclusion, the areas authorized for the exploitation of wood forest products in the MFR tend to reduce their ability to provide local communities with forest products in species and profiles of their interest. This reduction item is a serious threat to the biodiversity of the Restricted Forest. The study can help the academic community in future studies by replicating the methodology used for monitoring purposes or conducting studies in other similar areas, and the results may support decision-makers in designing better strategies for sustainability.

Keywords: ecosystem services, land-use types, local communities, species profile, wellbeing, wood forest product

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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Authors: Giulia Bonaldo, Alberto Vaccheri, Ottavio D'Annibali, Domenico Motola

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The Human Papilloma Virus (HPV) was shown to be the cause of different types of carcinomas, first of all of the cervical intraepithelial neoplasia. Since the early 80s to today, thanks first to the preventive screening campaigns (pap-test) and following to the introduction of HPV vaccines on the market; the number of new cases of cervical cancer has decreased significantly. The HPV vaccines currently approved are three: Cervarix® (HPV2 - virus type: 16 and 18), Gardasil® (HPV4 - 6, 11, 16, 18) and Gardasil 9® (HPV9 - 6, 11, 16, 18, 31, 33, 45, 52, 58), which all protect against the two high-risk HPVs (6, 11) that are mainly involved in cervical cancers. Despite the remarkable effectiveness of these vaccines has been demonstrated, in the recent years, there have been many complaints about their risk-benefit profile due to Adverse Events Following Immunization (AEFI). The purpose of this study is to provide a support about the ongoing discussion on the safety profile of HPV vaccines based on real life data deriving from spontaneous reports of suspected AEFIs collected in the Vaccine Adverse Events Reporting System (VAERS). VAERS is a freely-available national vaccine safety surveillance database of AEFI, co-administered by the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA). We collected all the reports between January 2007 to December 2017 related to the HPV vaccines with a brand name (HPV2, HPV4, HPV9) or without (HPVX). A disproportionality analysis using Reporting Odds Ratio (ROR) with 95% confidence interval and p value ≤ 0.05 was performed. Over the 10-year period, 54889 reports of AEFI related to HPV vaccines reported in VAERS, corresponding to 224863 vaccine-event pairs, were retrieved. The highest number of reports was related to Gardasil (n = 42244), followed by Gardasil 9 (7212) and Cervarix (3904). The brand name of the HPV vaccine was not reported in 1529 cases. The two events more frequently reported and statistically significant for each vaccine were: dizziness (n = 5053) ROR = 1.28 (CI95% 1.24 – 1.31) and syncope (4808) ROR = 1.21 (1.17 – 1.25) for Gardasil. For Gardasil 9, injection site pain (305) ROR = 1.40 (1.25 – 1.57) and injection site erythema (297) ROR = 1.88 (1.67 – 2.10) and for Cervarix, headache (672) ROR = 1.14 (1.06 – 1.23) and loss of consciousness (528) ROR = 1.71 (1.57 – 1.87). In total, we collected 406 reports of death and 2461 cases of permanent disability in the ten-year period. The events consisting of incorrect vaccine storage or incorrect administration were not considered. The AEFI analysis showed that the most frequently reported events are non-serious and listed in the corresponding SmPCs. In addition to these, potential safety signals arose regarding less frequent and severe AEFIs that would deserve further investigation. This already happened with the referral of the European Medicines Agency (EMA) for the adverse events POTS (Postural Orthostatic Tachycardia Syndrome) and CRPS (Complex Regional Pain Syndrome) associated with anti-papillomavirus vaccines.

Keywords: adverse drug reactions, pharmacovigilance, safety, vaccines

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Authors: Rada Somkhuean, Sa-aat Niwitpong, Suparat Niwitpong

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This paper presents the generalized p-values for testing the difference between two future population means when the variances are unknown, in both cases for when the variances are equal and unequal. We also derive a closed form expression of the upper bound of the proposed generalized p-value.

Keywords: generalized p-value, two future population means, upper bound, variances

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Authors: Jhonnatan Eduardo Zamudio Palacios, Oscar Leonardo Mosquera Dussan, Daniel Guzman Perez, Daniel Alfonso Botero Rosas, Oscar Fabian Rubiano Espinosa, Jose Antonio Garcia Torres, Ivan Dario Chavarro, Ivan Ramiro Rodriguez Camacho, Jaime Orlando Rodriguez

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The training of cilsitas with some type of disability finds in the technological development an indispensable ally, generating every day advances to contribute to the quality of life allowing to maximize the capacities of the athletes. The performance of a cyclist depends on physiological and biomechanical factors, such as aerodynamic profile, bicycle measurements, connecting rod length, pedaling systems, type of competition, among others. This study particularly focuses on the description of the dynamic model of a transtibial prosthesis for Paralympic cyclists. To make the model, two points are chosen: in the radius centers of rotation of the plate and pinion of the track bicycle. The parametric scheme of the track bike represents a model of 6 degrees of freedom due to the displacement in X - Y of each of the reference points of the angles of the curve profile β, cant of the velodrome α and the angle of rotation of the connecting rod φ. The force exerted on the crank of the bicycle varies according to the angles of the curve profile β, the velodrome cant of α and the angle of rotation of the crank φ. The behavior is analyzed through the Matlab R2015a software. The average strength that a cyclist exerts on the cranks of a bicycle is 1,607.1 N, the Paralympic cyclist must perform a force on each crank about 803.6 N. Once the maximum force associated with the movement has been determined, it is continued to the dynamic modeling of the transtibial prosthesis that represents a model of 6 degrees of freedom with displacement in X - Y in relation to the angles of rotation of the hip π, knee γ and ankle λ. Subsequently, an analysis of the kinematic behavior of the prosthesis was carried out by means of SolidWorks 2017 and Matlab R2015a, which was used to model and analyze the variation of the hip angles π, knee γ and ankle of the λ prosthesis. The reaction forces generated in the prosthesis were performed on the ankle of the prosthesis, performing the summation of forces on the X and Y axes. The same analysis was then applied to the tibia of the prosthesis and the socket. The reaction force of the parts of the prosthesis varies according to the hip angles π, knee γ and ankle of the prosthesis λ. Therefore, it can be deduced that the maximum forces experienced by the ankle of the prosthesis is 933.6 N on the X axis and 2.160.5 N on the Y axis. Finally, it is calculated that the maximum forces experienced by the tibia and the socket of the transtibial prosthesis in high performance competitions is 3.266 N on the X axis and 1.357 N on the Y axis. In conclusion, it can be said that the performance of the cyclist depends on several physiological factors, linked to biomechanics of training. The influence of biomechanical factors such as aerodynamics, bicycle measurements, connecting rod length, or non-circular pedaling systems on the cyclist performance.

Keywords: biomechanics, dynamic model, paralympic cyclist, transtibial prosthesis

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Authors: Haruka Ito, Toru Maruyama, Michihiro Ito, Chuya Shinzato, Hiroyuki Fujimura, Yoshikatsu Nakano, Shoichiro Suda, Sachiyo Aburatani, Haruko Takeyama

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Clarifying symbiotic relationships is one of the most important theme for understanding the marine eco-system. Coral reef has been regarded as an important environmental resource. Coral holobiont composed by coral, symbiotic microalgae zooxanthellae, and bacteria have complexed relationship. Zooxanthellae mainly supply organic matter to the host corals through their photosynthetic activity. The symbiotic relationship is indispensable for corals but may easily collapses due to the rise of seawater temperature. However, the molecular mechanism how seawater temperature influences their relationships still remain unclear. In this study, the transcriptomic analysis has applied to elucidate the coral-zooxanthellae relationships under high seawater temperature stress. To observe reactions of corals and zooxanthellae against the rise of seawater temperature, meta-gene expression in coral have been analyzed. The branches from six different colonies of a stony coral, Acropora tenuis, were sampled at nine times by 2016 at two locations, Ishikawabaru and South of Sesoko Island, Okinawa, Japan. The mRNAs extracted from the branches including zooxanthellae were sequenced by illumina HiSeq. Gene Set Enrichment Analysis (GSEA) based on hyper geometric distribution was performed. The seawater temperature at 2016 summer was unusually high, which was caused by El Niño event, and the number of zooxanthellae in coral was decreased in August. GSEA derived the several specific genes expressed in A. tenuis under heat stress conditions. The upregulated genes under heat stress highly related with infection immunity. The downregulated genes significantly contained cell cycle related genes. Thu, it is considered that heat stress cause disorder in cell metabolism of A. tenuis, resulting in serious influence to coral holobiont.

Keywords: coral, symbiosis, thermal stress response, transcriptome analysis

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Authors: Tania Sharmin Khaleque, Mohammad Ferdows

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The flow and heat transfer characteristics of a convection with temperature-dependent viscosity and thermal diffusivity along a vertical plate with internal heat generation effect have been studied. The plate temperature is assumed to follow a power law of the distance from the leading edge. The resulting governing two-dimensional equations are transformed using suitable transformations and then solved numerically by using fifth order Runge-Kutta-Fehlberg scheme with a modified version of the Newton-Raphson shooting method. The effects of the various parameters such as variable viscosity parameter β_1, the thermal diffusivity parameter β_2, heat generation parameter c and the Prandtl number Pr on the velocity and temperature profiles, as well as the local skin- friction coefficient and the local Nusselt number are presented in tabular form. Our results suggested that the presence of internal heat generation leads to increase flow than that of without exponentially decaying heat generation term.

Keywords: free convection, heat generation, thermal diffusivity, variable viscosity

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Authors: Madhulika Pathak, Polani Seshagiri, Vani Venkatappa

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Blastocyst hatching is an indispensable process for successful implantation. One of the major reasons for implantation failure in IVF clinic is poor quality of embryo, which are not development/hatching-competent. Therefore, attempts are required to develop or enhance the culture system with a molecule recapitulating the autocrine/paracrine factors containing the environment of in-vivo endometrial milieu. We have tried to explore the functional molecules involved in the hamster hatching phenomenon. Blastocyst hatching is governed by several molecules that are entwined and regulate this process, among which cytokines are known to be expressed and are still least explored. Two of such cytokines we have used for our study are IL-1β and its natural antagonist IL-1ra to understand the functional dynamics of cytokines involved in the hatching process. Using hamster, an intriguing experimental model for hatching behavior, we have shown the mRNA (qPCR) and protein (ICC) expression of IL-1β, IL-1ra and IL-1 receptor type 1 throughout all the stages of morula, blastocyst and hatched blastocyst. Post-asserting the expression, the functional role is shown by supplementation studies, where IL-1β supplementation showed enhancement in hatching level (IL-1β treated: 84.1 ± 4.2% vs control: 63.7 ± 3.1 %, N=11), further confirmed by the diminishing effect of IL-1ra on hatching rate (IL-1ra treated: 27.5 ± 11.1% vs control: 67.9 ± 3.1%). The exogenous supplementation of IL-1ra decreased the survival rate of embryos and affected the viability in dose-dependent manner, establishing the importance of IL-1β in blastocyst cell survival. Previously, the cathepsin L and B were established as the proteases that were involved in the hamster hatching process. The inducing effect of IL-1β was correlated with enhanced mRNA level, as analyzed by qPCR, for both CAT L (by 1.9 ± 0.5 fold) and CAT B (by 3.5 ± 0.1) fold which was diminished in presence of IL-1ra (Cat L by 88 percent and Cat B by 94 percent. Moreover, using a specific fluorescent substrate-based assay kit, the enzymatic activity of these proteases was found to be increased in presence of IL-1β (Cat L by 2.1 ± 0.1 fold and CAT B by 2.3 ± 0.7 fold) and was curtailed in presence of IL-1ra. These observations provide functional insights with respect to the involvement of cytokines in the hatching process. This has implications in understanding the hatching biology and improving the embryo development quality in IVF clinics.

Keywords: Blastocyst, Cytokines, Hatching, Interleukin

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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Authors: Salvatore Brischetto, Domenico Cesare

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Major improvements in future aircraft and spacecraft could be those dependent on an increasing use of conventional and unconventional multilayered structures embedding composite materials, functionally graded materials, piezoelectric or piezomagnetic materials, and soft foam or honeycomb cores. Layers made of such materials can be combined in different ways to obtain structures that are able to fulfill several structural requirements. The next generation of aircraft and spacecraft will be manufactured as multilayered structures under the action of a combination of two or more physical fields. In multifield problems for multilayered structures, several physical fields (thermal, hygroscopic, electric and magnetic ones) interact each other with different levels of influence and importance. An exact 3D shell model is here proposed for these types of analyses. This model is based on a coupled system including 3D equilibrium equations, 3D Fourier heat conduction equation, 3D Fick diffusion equation and electric and magnetic divergence equations. The set of partial differential equations of second order in z is written using a mixed curvilinear orthogonal reference system valid for spherical and cylindrical shell panels, cylinders and plates. The order of partial differential equations is reduced to the first one thanks to the redoubling of the number of variables. The solution in the thickness z direction is obtained by means of the exponential matrix method and the correct imposition of interlaminar continuity conditions in terms of displacements, transverse stresses, electric and magnetic potentials, temperature, moisture content and transverse normal multifield fluxes. The investigated structures have simply supported sides in order to obtain a closed form solution in the in-plane directions. Moreover, a layerwise approach is proposed which allows a 3D correct description of multilayered anisotropic structures subjected to field loads. Several results will be proposed in tabular and graphical formto evaluate displacements, stresses and strains when mechanical loads, temperature gradients, moisture content gradients, electric potentials and magnetic potentials are applied at the external surfaces of the structures in steady-state conditions. In the case of inclusions of piezoelectric and piezomagnetic layers in the multilayered structures, so called smart structures are obtained. In this case, a free vibration analysis in open and closed circuit configurations and a static analysis for sensor and actuator applications will be proposed. The proposed results will be useful to better understand the physical and structural behaviour of multilayered advanced composite structures in the case of multifield interactions. Moreover, these analytical results could be used as reference solutions for those scientists interested in the development of 3D and 2D numerical shell/plate models based, for example, on the finite element approach or on the differential quadrature methodology. The correct impositions of boundary geometrical and load conditions, interlaminar continuity conditions and the zigzag behaviour description due to transverse anisotropy will be also discussed and verified.

Keywords: composite structures, 3D shell model, stress analysis, multifield loads, exponential matrix method, layer wise approach

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Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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Authors: Mounia El Hafyani, Khalid El Himdi

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Precipitation is one of the key variables in water resource planning. The importance of modeling wet and dry durations is a crucial pointer in engineering hydrology. The objective of this study is to model and analyze the distribution of wet and dry durations. For this purpose, the daily rainfall data from 1967 to 2017 of the Moroccan city of Kenitra’s station are used. Three models are implemented for the distribution of wet and dry durations, namely the first-order Markov chain, the second-order Markov chain, and the truncated negative binomial law. The adherence of the data to the proposed models is evaluated using Chi-square and Kolmogorov-Smirnov tests. The Akaike information criterion is applied to assess the most effective model distribution. We go further and study the law of the number of wet and dry days among k consecutive days. The calculation of this law is done through an algorithm that we have implemented based on conditional laws. We complete our work by comparing the observed moments of the numbers of wet/dry days among k consecutive days to the calculated moment of the three estimated models. The study shows the effectiveness of our approach in modeling wet and dry durations of daily precipitation.

Keywords: Markov chain, rainfall, truncated negative binomial law, wet and dry durations

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Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam

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This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway

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Authors: Hadas Hirsch

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Clothing is aimed at concealing and revealing the body, protecting it, and manifesting religious, political, and social declarations. The material and symbolic meanings of clothing and its raw materials are evaluated through the context of their social, cultural, and religious systems. The raw materials for clothing that were frequent and familiar in the 7th century Arab Peninsula were wool, leather, cotton, and some kinds of silk. The spread of the Muslim empire and the intersections with other religions and cultures enable the trickling of new raw materials that were unknown to Muslims or unaccepted. The sources for this research are hadith collections that discuss in details various kinds of textiles and their origin, together with a legal explanation that permits or prohibits its use. The paper will describe and analyze this discussion by contextualizing it in social, religious, and cultural reality that creates a structure of socio-religious dependency. The aim is not to identify, catalogue, and technically analyze fabrics but to reveal their role in Muslims’ life as a means of creating dependency for the community and setting borders inside and outside. The analysis is built upon a scale that starts with the most recommended raw materials, then comes the permitted ones and, in the end, the prohibited raw materials. This mapping will provide an insight into the ways textiles, as a cultural medium, help to shape and redefine identities and, at the same time, enable a sphere for creative expression within socio-cultural and religious limits and context. To sum up, hadith literature has the main role is characterizing Muslim clothing, from garments to textiles and colors, including multiple variations and contradicting aspects. The Muslim style of clothing and, in particular, textiles is a manifestation of the socio-religious structure of dependency that creates differentiated Muslim identity together with subdivision of gendered groups. Some other aspects are the tension between authenticity and imitation and the jurists’ pragmatic and practice attitude that enables an individual sphere of expression within the limits of jurisprudence.

Keywords: Hadith, jurisprudence, medieval Islam, material culture

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Authors: Moetazza M. Alshafei, Ahmed M. Mabrouk, Emtenan M. Hanafi, Manal M. Ramadan, Reda M. S. Korany, Seham S. Kassem, Dina Mostafa Mohammed

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Metabolic syndrome (MeS) is a major health problem with a high incidence of obese individuals worldwide. Increased related morbidity of diabetes, hypertension and fatty liver disease, and complicated cardiovascular disease are inevitable. Boswellia serrata gum (Bos) is a promising traditional medicinal plant; it has several pharmacological properties, including anti-inflammatory, antioxidant, and antilipase activities. Probiotics (Bac) supplements have good benefits on health and MeS, whether it is supplemented in combination with prebiotics or alone. Microencapsulation helps to mask unpalatable taste and odor and deliver active ingredients to targeted organs. Methodology MeS rat model was produced by feeding rats with a high fat, high CHO diet (HFD). Bos was extracted, and both Bos and the probiotic were microencapsulated with a spray drier. Female rats were divided into 5 groups (N8). HFD control, control normal receiving basic diet, HFD treated, from the start of the experiment, either with encapsulated Bos, Bac and Bos or Bac only, all treatments were received for eight weeks (after approval from NRC animal ethical committee). Serum was collected to analyze lipid profile, blood sugar, liver and kidney functions, antioxidants, leptin, and progesterone. Rat's organs and body fat were weighed and collected for histopathology. Statistical analysis was done by use of one way Anova test in the SPSS program. Results showed control of elevated body weight, lipid profile, and glucose levels as well as decrease of body fat index and improvement of histopathology of liver and heart, especially in combination. Conclusion: We concluded that both microencapsulated Bos and probiotics have a controlling effect on MeS parameters.

Keywords: metabolic syndrome, Boswellia serata, probiotic, micro-encapsulation, histopathology, liver steatosis

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Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

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Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

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Authors: Abirami Baleswaran, Christel Couderc, Loubnah Belahcen, Jean Dayde, Hélène Tormo, Gwénaëlle Jard

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Cheeses are often reported to be spoiled by Pseudomonas spp., responsible for defects in appearance, texture, taste, and smell, leading to their non-marketing and even their destruction. Despite preventive actions, problems linked to Pseudomonas spp. are difficult to control by the lack of knowledge and control of these contaminants during the cheese manufacturing. Lactic goat cheese producers are not spared by this problem and are looking for solutions to decrease the number of spoiled cheeses. To explore different hypotheses, experiments are needed. However, cheese-making experiments at the pilot scale are expensive and time consuming. Thus, there is a real need to develop a miniature cheeses model system under controlled conditions. In a previous study, several miniature cheese models corresponding to different type of commercial cheeses have been developed for different purposes. The models were, for example, used to study the influence of milk, starters cultures, pathogen inhibiting additives, enzymatic reactions, microflora, freezing process on cheese. Nevertheless, no miniature model was described on the lactic goat cheese. The aim of this work was to develop a miniature cheese model system under controlled laboratory conditions which resembles commercial lactic goat cheese to study Pseudomonas spp. spoilage during the manufacturing and ripening process. First, a protocol for the preparation of miniature cheeses (3.5 times smaller than a commercial one) was designed based on the cheese factorymanufacturing process. The process was adapted from “Rocamadour” technology and involves maturation of pasteurized milk, coagulation, removal of whey by centrifugation, moulding, and ripening in a little scale cellar. Microbiological (total bacterial count, yeast, molds) and physicochemical (pH, saltinmoisture, moisture in fat-free)analyses were performed on four key stages of the process (before salting, after salting, 1st day of ripening, and end of ripening). Factory and miniature cheeses volatilomewere also obtained after full scan Sift-MS cheese analysis. Then, Pseudomonas spp. strains isolated from contaminated cheeses were selected on their origin, their ability to produce pigments, and their enzymatic activities (proteolytic, lecithinasic, and lipolytic). Factory and miniature curds were inoculated by spotting selected strains on the cheese surface. The expression of cheese spoilage was evaluated by counting the level of Pseudomonas spp. during the ripening and by visual observation and under UVlamp. The physicochemical and microbiological compositions of miniature cheeses permitted to assess that miniature process resembles factory process. As expected, differences involatilomes were observed, probably due to the fact that miniature cheeses are made usingpasteurized milk to better control the microbiological conditions and also because the little format of cheese induced probably a difference during the ripening even if the humidity and temperature in the cellar were quite similar. The spoilage expression of Pseudomonas spp. was observed in miniature and factory cheeses. It confirms that the proposed model is suitable for the preparation of miniature cheese specimens in the spoilage study of Pseudomonas spp. in lactic cheeses. This kind of model could be deployed for other applications and other type of cheese.

Keywords: cheese, miniature, model, pseudomonas spp, spoilage

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Authors: Neritan Shkodrani

Abstract:

On November 26, 2019, an earthquake hit the central western part of Albania. It was assessed as Mw 6.4. Its epicenter was located offshore north western Durrës, about 7 km north of the city. In this paper, the consequences of settlements of very soft soils have been discussed for the case of a residential building, mentioned as “K Building”, which was suffering a significant tilting after the earthquake. “KBuilding” is an RC framed building having 12+1 (basement) storiesand a floor area of 21000 m2. The construction of the building was completed in 2012. “KBuilding”, located in Durres city, suffered severe non-structural damage during November 26, 2019, Durrës Earthquake sequences. During the in-site inspections immediately after the earthquake, the general condition of the buildings, the presence of observable settlements on the ground, and the crack situation in the structure were determined, and damage inspection were performed. It was significant to note that the “K Building” presented tilting that might be attributed, as it was believed at the beginning, partially to the failure of the columns of the ground floor and partially to liquefaction phenomena, but it did not collapse. At the first moment was not clear if the foundation had a bearing capacity failure or the foundation failed because of the soil liquefaction. Geotechnical soil investigations by using CPTU test were executed, and their data are usedto evaluatebearing capacity, consolidation settlement of the mat foundation, and soil liquefaction since they were believed to be the main reasons of this building tilting.Geotechnical soil investigation consist in 5 (five) Static Cone Penetration tests with pore pressure measurement (piezocone test). They reached a penetration depth of 20.0 m to 30.0 mand, clearly shown the presence of very soft and organic soils in the soil profile of the site. Geotechnical CPT based analysis of bearing capacity, consolidation, and secondary settlement are applied, and results are reported for each test. These results shown very small values of allowable bearing capacity and very high values of consolidation and secondary settlements. Liquefaction analysis based on the data of CPTU tests and the characteristics of ground shaking of the mentioned earthquake has shown the possibility of liquefaction for some layers of the considered soil profile, but the estimated vertical settlements are at a small range and clearly shown that the main reason of the building tilting was not related to the consequences of liquefaction, but was an existing settlement caused from the applied bearing pressure of this building. All the CPTU tests were carried out on August 2021, almost two years after the November 26, 2019, Durrës Earthquake and when the building itself was demolished. After removing the mat foundation on September 2021, it was possible to carry out CPTU tests even on the footprint of the existing building, which made possible to observe the effects of long time applied of foundation bearing pressure to the consolidation on the considered soil profile.

Keywords: bearing capacity, cone penetration test, consolidation settlement, secondary settlement, soil liquefaction, etc

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Authors: Nazaitul Idya Hamzah, Muhammad Syafiq Mazli, Maszatul Akmar Mustafa

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The peak demand forecast is crucial to identify the future generation plant up needed in the long-term capacity planning analysis for Peninsular Malaysia as well as for the transmission and distribution network planning activities. Currently, peak demand forecast (in Mega Watt) is derived from the generation forecast by using load factor assumption. However, a forecast using this method has underperformed due to the structural changes in the economy, emerging trends and weather uncertainty. The dynamic changes of these drivers will result in many possible outcomes of peak demand for Peninsular Malaysia. This paper will look into the independent model of peak demand forecasting. The model begins with the selection of driver variables to capture long-term growth. This selection and construction of variables, which include econometric, emerging trend and energy variables, will have an impact on the peak forecast. The actual framework begins with the development of system energy and load shape forecast by using the system’s hourly data. The shape forecast represents the system shape assuming all embedded technology and use patterns to continue in the future. This is necessary to identify the movements in the peak hour or changes in the system load factor. The next step would be developing the peak forecast, which involves an iterative process to explore model structures and variables. The final step is combining the system energy, shape, and peak forecasts into the hourly system forecast then modifying it with the forecast adjustments. Forecast adjustments are among other sales forecasts for electric vehicles, solar and other adjustments. The framework will result in an hourly forecast that captures growth, peak usage and new technologies. The advantage of this approach as compared to the current methodology is that the peaks capture new technology impacts that change the load shape.

Keywords: hourly load profile, load forecasting, long term peak demand forecasting, peak demand

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Authors: Jeferson Brito Fernades, Breno Padovezi Rocha, Roger Augusto Rodrigues, Heraldo Luiz Giacheti

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The geotechnical projects demand the appropriate knowledge of soil characteristics and parameters. The determination of geotechnical soil parameters can be done by means of laboratory or in situ tests. In countries with tropical weather, like Brazil, unsaturated soils are very usual. In these soils, the soil suction has been recognized as an important stress state variable, which commands the geo-mechanical behavior. Triaxial and direct shear tests on saturated soils samples allow determine only the minimal soil shear strength, in other words, no suction contribution. This paper briefly describes the triaxial test with controlled suction as well as discusses the influence of suction on the shear strength parameters of a lateritic tropical sandy soil from a Brazilian research site. In this site, a sample pit was excavated to retrieve disturbed and undisturbed soil blocks. The samples extracted from these blocks were tested in laboratory to represent the soil from 1.5, 3.0 and 5.0 m depth. The stress curves and shear strength envelopes determined by triaxial tests varying suction and confining pressure are presented and discussed. The water retention characteristics on this soil complement this analysis. In situ CPT tests were also carried out at this site in different seasons of the year. In this case, the soil suction profile was determined by means of the soil water retention. This extra information allowed assessing how soil suction also affected the CPT data and the shear strength parameters estimative via correlation. The major conclusions of this paper are: the undisturbed soil samples contracted before shearing and the soil shear strength increased hyperbolically with suction; and it was possible to assess how soil suction also influenced CPT test data based on the water content soil profile as well as the water retention curve. This study contributed with a better understanding of the shear strength parameters and the soil variability of a typical unsaturated tropical soil.

Keywords: site characterization, triaxial test, CPT, suction, variability

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Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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Authors: Saeed Moarrefi, Shou-Han Zhou, Liyuan Fan

Abstract:

Coupling with solid oxide fuel cells, methane dry reforming is a promising pathway for energy production while mitigating carbon emissions. However, the influence of carbon dioxide and electrochemical reactions on the internal dry reforming reaction within the fuel cells remains debatable, requiring accurate kinetic models to describe the internal reforming behaviors. We employed the Power-Law and Langmuir Hinshelwood–Hougen Watson models in an electrolyte-supported solid oxide fuel cell with a NiO-GDC-YSZ anode. The current density used in this study ranges from 0 to 1000 A/m2 at 973 K to 1173 K to estimate various kinetic parameters. The influence of the electrochemical reactions on the adsorption terms, the equilibrium of the reactions, the activation energy, the pre-exponential factor of the rate constant, and the adsorption equilibrium constant were studied. This study provides essential parameters for future simulations and highlights the need for a more detailed examination of reforming kinetic models.

Keywords: dry reforming kinetics, Langmuir Hinshelwood–Hougen Watson, power-law, SOFC

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Authors: Rahaf Mandura

Abstract:

Background: Idiopathic intracranial hypertension (IIH) is a disorder with elevated intracranial pressure (ICP) more than 250 mm H₂O, without evidence of meningeal inflammation, space-occupying lesion, or venous thrombosis. The aim of this research is to study the clinical profile, evaluation, management, and visual outcome in a hospital-based population of IIH cases in Jeddah. Methodology: This is a retrospective observational study that included the medical records of all patients referred to neuro-ophthalmology service for evaluation of papilledema. The medical records have been reviewed from October 2018 to February 2020 at Jeddah Eye Hospital (JEH), Saudi Arabia. A total of fifty-one patients presented with papilledema in the studied period. Forty-seven patients met our inclusion criteria and were included in the study. Results: Most of the patients were females (43, 91.5%) with a mean age of presentation of 30.83±11.40 years. The most common presenting symptom was headache (40 patients, 85.1%), followed by transient visual obscuration (20 patients, 42.6%), and reduced visual acuity (15 patients, 31.9%). All 47 patients were started on medical treatment with oral acetazolamide with four patients (8.5%) shifted to topiramate because of the lack of response or intolerance to acetazolamide while four patients (8.5%) underwent lumbar-peritoneal shunt because of inadequate control of the disease despite the treatment with medical therapy. For both eyes, the change in visual acuity across all assessment points was statistically significant. Nevertheless, there were no significant changes in the visual field findings among all of the compared assessment points. Conclusion: The present study has shown that IIH-related papilledema is common in young female patients with headaches, transient visual obscurations and reduced visual acuity. Those are the commonest symptoms in our IIH population. Medical treatment of IIH is significantly efficacious and should be considered in order to enhance the prognosis of IIH-related complications. Therefore, the visual status should be frequently monitored for these patients.

Keywords: idiopathic intracranial hypertension, intracranial hypertension, papilledema, headache

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Authors: S. D. N. K. Bathige, G. I. Godahewa, Navaneethaiyer Umasuthan, Jehee Lee

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Kunitz-type serine protease inhibitors (KTIs) are identified in various organisms including animals, plants and microbes. These proteins shared single or multiple Kunitz inhibitory domains link together or associated with other types of domains. Characteristic Kunitz type domain composed of around 60 amino acid residues with six conserved cysteine residues to stabilize by three disulfide bridges. KTIs are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis and inflammation. In this study, two Kunitz-type domain containing protein was identified from rock bream database and designated as RbKunitz. The coding sequence of RbKunitz encoded for 507 amino acids with 56.2 kDa theoretical molecular mass and 5.7 isoelectric point (pI). There are several functional domains including MANEC superfamily domain, PKD superfamily domain, and LDLa domain were predicted in addition to the two characteristic Kunitz domain. Moreover, trypsin interaction sites were also identified in Kunitz domain. Homology analysis revealed that RbKunitz shared highest identity (77.6%) with Takifugu rubripes. Completely conserved 28 cysteine residues were recognized, when comparison of RbKunitz with other orthologs from different taxonomical groups. These structural evidences indicate the rigidity of RbKunitz folding structure to achieve the proper function. The phylogenetic tree was constructed using neighbor-joining method and exhibited that the KTIs from fish and non-fish has been evolved in separately. Rock bream was clustered with Takifugu rubripes. The SYBR Green qPCR was performed to quantify the RbKunitz transcripts in different tissues and challenged tissues. The mRNA transcripts of RbKunitz were detected in all tissues (muscle, spleen, head kidney, blood, heart, skin, liver, intestine, kidney and gills) analyzed and highest transcripts level was detected in gill tissues. Temporal transcription profile of RbKunitz in rock bream blood tissues was analyzed upon LPS (lipopolysaccharide), Poly I:C (Polyinosinic:polycytidylic acid) and Edwardsiella tarda challenge to understand the immune responses of this gene. Compare to the unchallenged control RbKunitz exhibited strong up-regulation at 24 h post injection (p.i.) after LPS and E. tarda injection. Comparatively robust expression of RbKunits was observed at 3 h p.i. upon Poly I:C challenge. Taken together all these data indicate that RbKunitz may involve into to immune responses upon pathogenic stress, in order to protect the rock bream.

Keywords: Kunitz-type, rock bream, immune response, serine protease inhibitor

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Authors: Pelin Yilmaz, Gizemnur Yildiz Uysal, Elcin Demirhan, Belma Ozbek

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The edible fig plant, Ficus carica Linn, belongs to the Moraceae family, and the leaves are mainly considered agricultural waste after harvesting. It has been demonstrated in the literature that fig leaves contain appealing properties such as high vitamins, fiber, amino acids, organic acids, and phenolic or flavonoid content. The extraction of these valuable products has gained importance. Microwave-assisted extraction (MAE) is a method using microwave energy to heat the solvents, thereby transferring the bioactive compounds from the sample to the solvent. The main advantage of the MAE is the rapid extraction of bioactive compounds. In the present study, the MAE was applied to extract the bioactive compounds from Ficus carica L. leaves, and the effect of microwave power (180-900 W), extraction time (60-180 s), and solvent to sample amount (mL/g) (10-30) on the antioxidant property of the leaves. Then, the volatile organic component profile was determined at the specified extraction point. Additionally, antimicrobial studies were carried out to determine the minimum inhibitory concentration of the microwave-extracted leaves. As a result, according to the data obtained from the experimental studies, the highest antimicrobial properties were obtained under the process parameters such as 540 W, 180 s, and 20 mL/g concentration. The volatile organic compound profile showed that isobergapten, which belongs to the furanocoumarins family exhibiting anticancer, antioxidant, and antimicrobial activity besides promoting bone health, was the main compound. Acknowledgments: This work has been supported by Yildiz Technical University Scientific Research Projects Coordination Unit under project number FBA-2021-4409. The authors would like to acknowledge the financial support from Tubitak 1515 - Frontier R&D Laboratory Support Programme.

Keywords: Ficus carica Linn leaves, volatile organic component, GC-MS, microwave extraction, isobergapten, antimicrobial

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Authors: Nazish Iftikhar, Adil Jhangeer, Tayyaba Naz

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The universe is expanding at an accelerated rate. Symmetries are useful in understanding universe’s behavior. Emmy Noether reported the relation between symmetries and conservation laws. These symmetries are known as Noether symmetries which correspond to a conserved quantity. In differential equations, conservation laws play an important role. Noether symmetries are helpful in modified theories of gravity. Time independent plane symmetric spacetime was classified by Noether`s theorem. By using Noether`s theorem, set of linear partial differential equations was obtained having A(r), B(r) and F(r) as unknown radial functions. The Lagrangian corresponding to considered spacetime in the Noether equation was used to get Noether operators. Different possibilities of radial functions were considered. Firstly, all functions were same. All the functions were considered as non-zero constant, linear, reciprocal and exponential respectively. Secondly, two functions were proportional to each other keeping third function different. Second case has four subcases in which four different relationships between A(r), B(r) and F(r) were discussed. In all cases, we obtained nontrivial Noether operators including gauge term. Conserved quantities for each Noether operators were also presented.

Keywords: Noether gauge symmetries, radial function, Noether operator, conserved quantities

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Authors: Altaf H. Khan, Frank Stenger, Mohammed A. Hussein, Reaz A. Chaudhuri, Sameera Asif

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This paper discusses a novel approach to approximate quadrature integrals that arise in the estimation of likelihood parameters for the generalized linear mixed models (GLMM) as well as Bayesian methodology also requires computation of multidimensional integrals with respect to the posterior distributions in which computation are not only tedious and cumbersome rather in some situations impossible to find solutions because of singularities, irregular domains, etc. An attempt has been made in this work to apply Sinc function based quadrature rules to approximate intractable integrals, as there are several advantages of using Sinc based methods, for example: order of convergence is exponential, works very well in the neighborhood of singularities, in general quite stable and provide high accurate and double precisions estimates. The Sinc function based approach seems to be utilized first time in statistical domain to our knowledge, and it's viability and future scopes have been discussed to apply in the estimation of parameters for GLMM models as well as some other statistical areas.

Keywords: generalized linear mixed model, likelihood parameters, qudarature, Sinc function

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Authors: Asma Qudrat, Abid Ullah, Rafi Ullah, Ali Raza, Shah Zeb, Syed Ali Shan Ul-Haq, Shahkar Ahmed Shah, Attiya Hameed Khan, Saad Zaheer, Umama Qasim, Kiran Jamal, Zahoor khan

Abstract:

Objectives: Coronary artery disease (CAD) is the major public health issue associated with high mortality and morbidity rate worldwide. Young patients with ACS have unique characteristics with different demographic profiles and risk factors. The precise diagnosis and early risk stratification is important in guiding treatment and predicting the prognosis of young patients with ACS. To evaluate the associated demographics, risk factors, and outcomes profile of ACS in young age patients. Methods: The research follow a retrospective design, the single centre study of patients diagnosis with the first event of ACS in young age (>18 and <40) were included. Data collection included demographic profiles, risk factors, and in-hospital outcomes of young ACS patients. The patient’s data was retrieved through Electronic Medical Records (EMR) of Peshawar Institute of Cardiology (PIC), and all characteristic were assessed. Results: In this study, 77% were male, and 23% were female patients. The risk factors were assessed with CAD and shown significant results (P < 0.01). The most common presentation was STEMI, with (45%) most in ACS young patients. The angiographic pattern showed single vessel disease (SVD) in 49%, double vessel disease (DVD) in 17% and triple vessel disease (TVD) was found in 10%, and Left Artery Disease (LAD) (54%) was present to be the most common involved artery. Conclusion: It is concluded that the male sex was predominant in ACS young age patients. SVD was the common coronary angiographic finding. Risk factors showed significant results towards CAD and common presentations.

Keywords: coronary artery disease, Non-ST elevation myocardial infarction, ST elevation myocardial infarction, unstable angina, acute coronary syndrome

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Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

Procedia PDF Downloads 106