Search results for: small target detection

Authors: Mohammed Ibrahim Girei

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Adamawa state is one the major producers of both crop and animals in Nigeria. Agricultural production serves as the major means livelihood of the people in the state. However, the agricultural activities of the farmers in the state are at subsistence level. However integration of these small scale farmers in local, national and international market is paramount importance. The paper was designed to categorize farmers based on market participation among the cattle farmers in Adamawa state, Nigeria. The multistage sampling procedure was employed. To achieve this procedure, structured questionnaires were used to collect data from 400 respondents. The data were analyzed using the descriptive statistics. The result revealed that the majority of market participants were net sellers (78.51 %) (Sales greater than purchase), net buyers were (purchase greater than sales) 12.95 % and only 9% were autarkic (sales equal purchase). The study recommends that Government should provide more effective security services in cattle farming communities, which is very important as the market participants in the study area were net sellers (producers), it will help in addressing the problem of cattle rustling and promote more investment in cattle industry. There is a need to establish a standard cattle market, veterinary services and grazing reserves in the area so that to facilitate the cattle production and marketing system in the area and to meet up with the challenging of livestock development as a result of rapid human population growth in developing countries like Nigeria.

Keywords: categories, cattle, farmers, market, participation

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Authors: Abdullah Mukhtar, Shehroz Mukhtar, Amina Mukhtar, Choudhry Shahid, Hafiz Raza Razzaq, Saif Ur Rahman

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The aim of this study is to find out the negative and positive impacts of social media platforms on the attitude of learning and educational environment of student’s community. Social Media platforms have become a source of collaboration with one another throughout the globe making it a small world. This study performs focalized investigation of the adverse and constructive factors that have a strong impact not only on the psychological adjustments but also on the academic performance of peers. This study is a quantitative research adopting random sampling method in which the participants were the students of university. Researcher distributed 1000 questionnaires among the university students from different departments and asked them to fill the data on Lickert Scale. The participants are from the age group of 18-24 years. Study applies user and gratification theory in order to examine behavior of students practicing social media in their academic and personal life. Findings of the study reveal that the use of social media platforms in Pakistani context has less positive impact as compared to negative impacts on the behavior of students towards learning. The research suggests that usage of online social media platforms should be taught to students; awareness must the created among the users of social media by the means of seminars, workshops and by media itself to overcome the negative impacts of social media leading towards sustainable education in Pakistan.

Keywords: social media, positive impact, negative impact, learning behaviour

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Authors: Fatemeh Haghiralsadat, Mohadese Hashemi, Elham Akhoundi Kharanaghi, Mojgan Yazdani, Mahboobe Sharafodini, Omid Javani

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Niosomes are colloidal particles formed from the self-assembly of non-ionic surfactants in aqueous medium resulting in closed bilayer structures. As a consequence of this hydrophilic and hydrophobic structure, niosomes have the capacity to entrap compounds of different solubilities. Niosomes are promising vehicle for drug delivery which protect sensitive drugs and improve the therapeutic index of drugs by restricting their action to target cells. Essential oils are complex mixtures of volatile compounds such as terpenoids, phenol-derived aromatic components that have been used for many biological properties including bactericidal, fungicidal, insecticidal, antioxidant, anti-tyrosinase and other medicinal properties. Encapsulation of essential oils in niosomes can be an attractive method to overcome their limitation such as volatility, easily decomposition by heat, humidity, light, or oxygen. Cuminum cyminum L. (Cumin) is an aromatic plant included in the Apiaceae family and is used to flavor foods, added to fragrances, and for medical preparations which is indigenous to Egypt, the Mediterranean region, Iran and India. The major components of the Cumin oil were reported as cuminaldehyde, γ -terpinene, β-pinene, p-cymene, p-mentha-1, 3-dien-7-al, and p-mentha-1, 4-dien-7-al which provide the antimicrobial and antioxidant activity. The aim of this work was to formulate Cumin essential oil-loaded niosomes to improve water solubility of natural product and evaluate its physico-chemical features and stability. Cumin oil was obtained through steam distillation using a clevenger-type apparatus and GC/MS was applied to identify the main components of the essential oil. Niosomes were prepared by using thin film hydration method and nanoparticles were characterized for particle size, dispersity index, zeta potential, encapsulation efficiency, in vitro release, and morphology.

Keywords: Cuminum cyminum L., Cumin, niosome, essential oil, encapsulation

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Authors: Chetna Tyagi. G. B. V. S. Lakshmi, Ambuj Tripathi, D. K. Avasthi

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Graphene oxide provides a good host matrix for preparing nanocomposites due to the different functional groups attached to its edges and planes. Being biocompatible, it is used in therapeutic applications. As enzyme-based biosensor requires complicated enzyme purification procedure, high fabrication cost and special storage conditions, we need enzyme-less biosensors for use even in a harsh environment like high temperature, varying pH, etc. In this work, we have prepared both enzyme-based and enzyme-less graphene oxide-based biosensors for glucose detection using glucose-oxidase as enzyme and gold nanoparticles, respectively. These samples were characterized using X-ray diffraction, UV-visible spectroscopy, scanning electron microscopy, and transmission electron microscopy to confirm the successful synthesis of the working electrodes. Electrochemical measurements were performed for both the working electrodes using a 3-electrode electrochemical cell. Cyclic voltammetry curves showed the homogeneous transfer of electron on the electrodes in the scan range between -0.2V to 0.6V. The sensing measurements were performed using differential pulse voltammetry for the glucose concentration varying from 0.01 mM to 20 mM, and sensing was improved towards glucose in the presence of gold nanoparticles. Gold nanoparticles in graphene oxide nanocomposite played an important role in sensing glucose in the absence of enzyme, glucose oxidase, as evident from these measurements. The selectivity was tested by measuring the current response of the working electrode towards glucose in the presence of the other common interfering agents like cholesterol, ascorbic acid, citric acid, and urea. The enzyme-less working electrode also showed storage stability for up to 15 weeks, making it a suitable glucose biosensor.

Keywords: electrochemical, enzyme-less, glucose, gold nanoparticles, graphene oxide, nanocomposite

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Authors: Pulari C. Milu Maria Anto

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Background: Cognitive Rehabilitation/Retraining has been variously used in the research literature to represent non-pharmacological interventions that target the cognitive impairments with the goal of ameliorating cognitive function and functional behaviors to optimize the quality of life. Along with adult’s cognitive impairments, the need to address acquired cognitive impairments (due to any chronic illnesses like CHD - congenital heart diseases or ALL - Acute Lymphoblastic Leukemia) among child populations is inevitable. Also, it has to be emphasized as same we consider the cognitive impairments seen in the children having neurodevelopmental disorders. Methods: All published brain image studies (Hermann, B. et al,2002, Khalil, A. et al., 2004, Follin, C. et al, 2016, etc.) and studies emphasizing cognitive impairments in attention, memory, and/or executive function and behavioral aspects (Henkin, Y. et al,2007, Bellinger, D. C., & Newburger, J. W. (2010), Cheung, Y. T., et al,2016, that could be identified were reviewed. Based on a systematic review of the literature from (2000 -2021) different brain imaging studies, increased risk of neuropsychological and psychosocial impairments are briefly described. Clinical and research gap in the area is discussed. Results:30 papers, both Indian studies and foreign publications (Sage journals, Delhi psychiatry journal, Wiley Online Library, APA PsyNet, Springer, Elsevier, Developmental medicine, and child neurology), were identified. Conclusions: In India, a very limited number of brain imaging studies and neuropsychological studies have done by indicating the cognitive deficits of a child having or undergone chronic illness. None of the studies have emphasized the relevance nor the need of implementingCR among such children, even though its high time to address but still not established yet. The review of the current evidence is to bring out an insight among rehabilitation professionals in establishing a child specific CR and to publish new findings regarding the implementation of CR among such children. Also, this study will be an awareness on considering cognitive aspects of a child having acquired cognitive deficit (due to chronic illness), especially during their critical developmental period.

Keywords: cognitive rehabilitation, neuropsychological impairments, congenital heart diseases, acute lymphoblastic leukemia, epilepsy, and neuroplasticity

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Authors: Yuan Wan, Shumei Cui, Shaopeng Wu

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Toroidal windings were taken advantage of to reduce of axial length of the motor, so as to match the applications that have severe restrictions on the axial length. But slotting in the out edge of the stator will decrease the heat-dissipation capacity of the water cooling of the housing. Besides, the windings in the outer slots will increase the copper loss, which will further increase the difficult for heat dissipation of the motor. At present, carbon-fiber composite retaining sleeve are increasingly used to be mounted over the magnets to ensure the rotor strength at high speeds. Due to the poor thermal conductivity of carbon-fiber sleeve, the cooling of the rotor becomes very difficult, which may result in the irreversible demagnetization of magnets for the excessively high temperature. So it is necessary to analyze the temperature rise of such motor. This paper builds a computational fluid dynamic (CFD) model of a toroidal-winding high-speed permanent magnet synchronous motor (PMSM) with water cooling of housing and forced air cooling of rotor. Thermal analysis was carried out based on the model and the factors that affects the temperature rise were investigated. Then thermal optimization for the prototype was achieved. Finally, a small-size prototype was manufactured and the thermal analysis results were verified.

Keywords: thermal analysis, temperature rise, toroidal windings, high-speed PMSM, CFD

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Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Ayse Cagil Kandemir, Derya Erdem, Markus Niederberger, Ralph Spolenak

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Dip Pen nanolithography (DPN), which is a tip based method, serves a novel approach to produce nano and micro-scaled patterns due to its high resolution and pattern flexibility. It is introduced as a new constructive scanning probe lithography (SPL) technique. DPN delivers materials in the form of an ink by using the tip of a cantilever as pen and substrate as paper in order to form surface architectures. First studies rely on delivery of small organic molecules on gold substrate in ambient conditions. As time passes different inks such as; polymers, colloidal particles, oligonucleotides, metallic salts were examined on a variety of surfaces. Discovery of DPN also enabled patterning with multiple inks by using multiple cantilevers for the first time in SPL history. Specifically, polymer inks, which constitute a flexible matrix for various materials, can have a potential in MEMS, NEMS and drug delivery applications. In our study, it is aimed to construct polymer patterns using DPN by studying wetting behavior of polymer on semiconductor, metal and polymer surfaces. The optimum viscosity range of polymer and effect of environmental conditions such as humidity and temperature are examined. It is observed that there is an inverse relation with ink viscosity and depletion time. This study also yields the optimal writing conditions to produce consistent patterns with DPN. It is shown that written dot sizes increase with dwell time, indicating that the examined writing conditions yield repeatable patterns.

Keywords: dip pen nanolithography, polymer, surface patterning, surface science

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Authors: Thomais Tsoulia, Arvind Y. M. Sundaram, Stine Braaen, Øyvind Haugland, Espen Rimstad, Øystein Wessel, Maria K. Dahle

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Fish red blood cells (RBC) are nucleated, and in addition to their function in gas exchange, they have been characterized as mediators of immune responses. Salmonid RBC are the major target cells of Piscineorthoreovirus (PRV), a virus associated with heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. The activation of antiviral response genesin RBChas previously been described in ex vivo and in vivo PRV-infection models, but not explored in the initial virus encounter phase. In the present study, mRNA transcriptome responses were explored in erythrocytes from individual fish, kept ex vivo, and exposed to purified PRV for 24 hours. The responses were compared to responses in macrophage-like salmon head kidney (SHK-1) and endothelial-like Atlantic salmon kidney (ASK) cells, none of which support PRV replication. The comparative analysis showed that the antiviral response to PRV was strongest in the SHK-1 cells, with a set of 80 significantly induced genes (≥ 2-fold upregulation). In RBC, 46 genes were significantly upregulated, while ASK cells were not significantly responsive. In particular, the transcriptome analysis of RBC revealed that PRV significantly induced interferon regulatory factor 1 (IRF1) and interferon-induced protein with tetratricopeptide repeats 5-like (IFIT9). However, several interferon-regulated antiviral genes which have previously been reported upregulated in PRV infected RBC in vivo (myxovirus resistance (Mx), interferon-stimulated gene 15 (ISG15), toll-like receptor 3 (TLR3)), were not significantly induced after 24h of virus stimulation. In contrast to RBC, these antiviral response genes were significantly upregulated in SHK-1. These results confirm that RBC are involved in the innate immune response to viruses, but with a delayed antiviral response compared to SHK-1. A notable difference is that interferon regulatory factor 1 (IRF-1) is the most strongly induced gene in RBC, but not among the significantly induced genes in SHK-1. Putative differences in the binding, recognition, and response to PRV, and any link to effects on the ability of PRV to replicate remains to be explored.

Keywords: antiviral responses, atlantic salmon, piscine orthoreovirus-1, red blood cells, RNA-seq

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Authors: Muhammad Alif Bin Razali, Cheng-Gang Xie, Wai Lam Loh

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A venturi device is commonly used as an integral part of a multiphase flowmeter (MPFM) in real-time oil-gas production monitoring. For an accurate determination of individual phase fraction and flowrate, a gas-liquid flow ideally needs to be well mixed in the venturi measurement section. Partial flow mixing is achieved by installing a venturi vertically downstream of the blind-tee pipework that ‘homogenizes’ the incoming horizontal gas-liquid flow. In order to study in-depth the flow-mixing effect of the blind-tee, gas-liquid flows are captured at blind-tee and venturi sections by using a high-speed video camera and a purpose-built transparent test rig, over a wide range of superficial liquid velocities (0.3 to 2.4m/s) and gas volume fractions (10 to 95%). Electrical capacitance sensors are built to measure the instantaneous holdup (of oil-gas flows) at the venturi inlet and throat. Flow regimes and flow (a)symmetry are investigated based on analyzing the statistical features of capacitance sensors’ holdup time-series data and of the high-speed video time-stacked images. The perceived homogenization effect of the blind-tee on the incoming intermittent horizontal flow regimes is found to be relatively small across the tested flow conditions. A horizontal (blind-tee) to vertical (venturi) flow-pattern transition map is proposed based on gas and liquid mass fluxes (weighted by the Baker parameters).

Keywords: blind-tee, flow visualization, gas-liquid two-phase flow, MPFM

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Authors: Woosik Jang, Seung Heon Han, Seung Won Baek

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Natural gas (NG) is an energy resource in a few countries, and most NG producers do business in politically unstable countries. In addition, as 90% of the LNG market is controlled by a small number of international oil companies (IOCs) and national oil companies (NOCs), entry of latecomers into the market is extremely limited. To meet these challenges, project viability needs to be assessed based on limited information from a project screening perspective. However, the early stages of the project have the following difficulties: (1) What are the factors to consider? (2) How many professionals do you need to decide? (3) How to make the best decision with limited information? To address this problem, this study proposes a model for evaluating LNG project viability based on the Dempster-Shafer theory (DST). A total of 11 indicators for analyzing the gas field, reflecting the characteristics of the LNG industry, and 23 indicators for analyzing the market environment, were identified. The proposed model also evaluates the LNG project based on the survey and provides uncertainty of the results based on DST as well as quantified results. Thus, the proposed model is expected to be able to support the decision-making process of the gas field project using quantitative results as a systematic framework, and it was developed as a stand-alone system to improve its usefulness in practice. Consequently, the amount of information and the mathematical approach are expected to improve the quality and opportunity of decision making for LNG projects for enterprises.

Keywords: project screen, energy enterprise, decision support system, Dempster-Shafer theory

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Authors: Mahyar Maali, Merve Sagiroglu

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Steel, which is one of the base materials we prefer in the building construction, is the material with the highest ratio to weight of carrying capacity. Due to the carrying capacity, lighter and better quality steel in smaller sections and sizes has recently been used as a frame system in cold-formed steel structures. While light steel elements used as secondary frame elements during the past, they have nowadays started to be preferred as the main frame in low/middle story buildings and detached houses with advantages such as quick and easy installation, time-saving, and small amount of scrap. It is also economically ideal because the weight of structure is lighter than other steel profiles. Structural performances and failure modes of cold-formed structures are different from conventional ones due to their thin-walled structures. One of the most important elements of light steel structures to ensure stability is the connection. The screwed connections, which have self-drilling properties with special drilling tools, are widely used in the installation of cold-formed profiles. The length of the screw is selected according to the total thickness of the elements after the screw thickness is determined according to the elements of connections. The thickness of the material depends on the length of the drilling portion at the end of the screw. The shear tests of plates connected with self-drilling screws are carried out depending on the screw length, and their failure modes were evaluated in this study.

Keywords: cold-formed steel, screwed connection, connection, screw length

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Authors: Ssembatya Joseph Mary

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Introduction: Omphalocele, an abdominal wall defect, occurs in 1 out of 4,000 to 6,000 live births. It is characterized by visceral herniation of small and large intestines, liver, and sometimes spleen and gonads are involved. The viscera is always covered by a three-layered sac. The defect in the mesoderm is mainly due to the failure of lateral abdominal wall folds to unite. About 350,000 ventral hernia repairs are done annually in the united states of America. Surgical repair with a mesh is the gold standard surgical method. With conservative management of Omphalocele, children are eventually closed between the age of 1 and 5 years. Herein, we present a late manifestation of ventral hernia following Omphalocele in a female Ugandan. Case presentation: A 56-year-old female with no known chronic illnesses and normal perinatal history presented with an umbilical swelling since birth with no associated symptoms. She is a married woman to one husband and has five children, and all of them are in good general condition with no such symptoms. She had normal vitals with an umbilical defect measuring about 20cm from the xiphoid process and 10 cm from the symphysis pubis. Surgery was done (component separation) on the second inpatient day, and it was uneventful. The patient was discharged on the 4th postoperative day in good general condition with a dry and clean surgical site. Conclusion: Despite adequate literature about Omphalocele and clear management guidelines, there have been reported cases of adult presentation of ventral hernias secondary to Omphalocele.

Keywords: omphalocele, ventral hernia, uganda, late presentation

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Authors: Biaou Jean-Baptiste Kouchoro, Anissa Meziane, Philippe Micheau, Mathieu Renier, Nicolas Quaegebeur

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Numerous experimental and numerical studies have shown the interest of the local defects resonance (LDR) for the Non-Destructive Testing of metallic and composite plates. Indeed, guided ultrasonic waves such as Lamb waves, which are increasingly used for the inspection of these flat structures, enable the generation of local resonance phenomena by their interaction with a damaged area, allowing the detection of defects. When subjected to a large amplitude motion, a nonlinear behavior can predominate in the damaged area. This work presents a 2D Finite Element Model of the local resonance of a 12 mm long and 5 mm deep Flat Bottom Hole (FBH) in a 6 mm thick aluminum plate under the excitation induced by an incident A0 Lamb mode. The analysis of the transient response of the FBH enables the precise determination of its resonance frequencies and the associate modal deformations. Then, a linear parametric study varying the geometrical properties of the FBH highlights the sensitivity of the resonance frequency with respect to the plate thickness. It is demonstrated that the resonance effect disappears when the ratio of thicknesses between the FBH and the plate is below 0.1. Finally, the nonlinear behavior of the FBH is considered and studied introducing geometrical (taken into account the nonlinear component of the strain tensor) nonlinearities that occur at large vibration amplitudes. Experimental analysis allows observation of the resonance effects and nonlinear response of the FBH. The differences between these experimental results and the numerical results will be commented on. The results of this study are promising and allow to consider more realistic defects such as delamination in composite materials.

Keywords: guided waves, non-destructive testing, dynamic field testing, non-linear ultrasound/vibration

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Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam

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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.

Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin

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Authors: Darshani Premaratne, Afshin Kandampath Puthiyadath

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The Government of Qatar is taking active steps in improving quality of health care industry in the state of Qatar. In this initiative development and market introduction of Clinical Information System and Electronic Health Record (EHR) system are proved to be a highly challenging process. Along with an organization specialized on EHR system development and with the blessing of Health Ministry of Qatar the process of introduction of EHR system in Qatar healthcare industry was undertaken. Initially a market survey was carried out to understand the requirements. Secondly, the available government regulations, needs and possible upcoming regulations were carefully studied before deployment of resources for software development. Sufficient flexibility was allowed to cater for both the changes in the market and the regulations. As the first initiative a system that enables integration of referral network where referral clinic and laboratory system for all single doctor (and small scale) clinics was developed. Setting of isolated single doctor clinics all over the state to bring in to an integrated referral network along with a referral hospital need a coherent steering force and a solid top down framework. This paper discusses about the lessons learned in developing, in obtaining approval of the health ministry and in introduction to the industry of the single doctor referral network along with an EHR system. It was concluded that development of this nature required continues balance between the market requirements and upcoming regulations. Further accelerating the development based on the emerging needs, implementation based on the end user needs while tallying with the regulations, diffusion, and uptake of demand-driven and evidence-based products, tools, strategies, and proper utilization of findings were equally found paramount in successful development of end product. Development of full scale Clinical Information System and EHR system are underway based on the lessons learned. The Government of Qatar is taking active steps in improving quality of health care industry in the state of Qatar. In this initiative development and market introduction of Clinical Information System and Electronic Health Record (EHR) system are proved to be a highly challenging process. Along with an organization specialized on EHR system development and with the blessing of Health Ministry of Qatar the process of introduction of EHR system in Qatar healthcare industry was undertaken. Initially a market survey was carried out to understand the requirements. Secondly the available government regulations, needs and possible upcoming regulations were carefully studied before deployment of resources for software development. Sufficient flexibility was allowed to cater for both the changes in the market and the regulations. As the first initiative a system that enables integration of referral network where referral clinic and laboratory system for all single doctor (and small scale) clinics was developed. Setting of isolated single doctor clinics all over the state to bring in to an integrated referral network along with a referral hospital need a coherent steering force and a solid top down framework. This paper discusses about the lessons learned in developing, in obtaining approval of the health ministry and in introduction to the industry of the single doctor referral network along with an EHR system. It was concluded that development of this nature required continues balance between the market requirements and upcoming regulations. Further accelerating the development based on the emerging needs, implementation based on the end user needs while tallying with the regulations, diffusion, and uptake of demand-driven and evidence-based products, tools, strategies, and proper utilization of findings were equally found paramount in successful development of end product. Development of full scale Clinical Information System and EHR system are underway based on the lessons learned.

Keywords: clinical information system, electronic health record, state regulations, integrated referral network of clinics

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Authors: Angelis P. Barlampas

Abstract:

PURPOSE: The purpose of this paper is to demonstrate the important role of taking an appropriate and detailed history, in order to reach the best possible diagnostic conclusion. MATERIAL: A patient presented to the emergency department due to the sudden onset of continuous abdominal pain, during the last hour and with the clinical symptoms of an acute abdomen. During the clinical examination, signs of peritoneal irritation and diffuse abdominal tenderness were found. The rest of the clinical and laboratory tests did not reveal anything important. From the reported medical history, nothing of note was found, except for the report of a large liver cyst, for which he was advised not to take any further action, except from regular ultrasound examination . METHOD: A computed tomography examination was performed after per os administration of gastrografin, which revealed a hyperdense ascitic effusion, similar in density to that of gastrografin within the intestinal tract. The presence of a large cyst of the left hepatic lobe was confirmed, contacting and pushing against the stomach. In the area of the contact between the liver cyst and the pylorus, there were extraluminal air bubbles and local opacity of the peritoneal fat, with a small hyperdense effusion. Result : The above, as well as the absence of a history of stomach ulcer or recent trauma, or other pathology, argue in favor of acute pyloric perforation, due to mural necrosis, in response to chronic external pressure from the pre-existing large liver cyst.

Keywords: perforation, stomach, large liver cyst, CT abdomen, acute abdominal pain, intraperitoneal leakage, constrast leakage

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Authors: Kristel Dame Bañez Sumagaysay, Marie Victoria Cruz-javier

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The current subject is a case of a 21 year-old woman at 29 1/7 weeks of gestation with Pre-B cell Acute Lymphoblastic Leukemia who was admitted to the coronary care unit (CCU) of the St. Luke’s Medical Center-Global City for Severe Acute Respiratory Distress Syndrome (ARDS) secondary to hospital-acquired pneumonia secondary to pneumocystis jiroveci; central line-associated bloodstream infection (E. aerogenes). She presented with chronic hypoxemia caused by Pulmonary edema, probably secondary to heart failure secondary to cardiomyopathy chemotherapy-induced. Due to worsening feto-maternal status, extracorporeal membrane oxygenation (ECMO) for respiratory support was instituted, and an elective cesarean section was done due to multiple maternal factors and deteriorating health status under total intravenous anesthesia assisted by veno-venous extracorporeal membrane oxygenation. She delivered a live preterm newborn male, APGAR Score: 1, 0, 0, birth weight 985 grams, birth length: 40.5cm, small for gestational age.

Keywords: extracorporeal membrane oxygenation, pre-b cell acute lymphoblastic leukemia, severe acute respiratory distress syndrome, ethical dilemmas

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Authors: F. Ghazalnaz Sharifonnasabi, Iman Makhdoom

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Breast cancer is a serious health concern that affects many people around the world. According to a study published in the Breast journal, the global burden of breast cancer is expected to increase significantly over the next few decades. The number of deaths from breast cancer has been increasing over the years, but the age-standardized mortality rate has decreased in some countries. It’s important to be aware of the risk factors for breast cancer and to get regular check- ups to catch it early if it does occur. Machin learning techniques have been used to aid in the early detection and diagnosis of breast cancer. These techniques, that have been shown to be effective in predicting and diagnosing the disease, have become a research hotspot. In this study, we consider two deep learning approaches including: Multi-Layer Perceptron (MLP), and Convolutional Neural Network (CNN). We also considered the five-machine learning algorithm titled: Decision Tree (C4.5), Naïve Bayesian (NB), Support Vector Machine (SVM), K-Nearest Neighbors (KNN) Algorithm and XGBoost (eXtreme Gradient Boosting) on the Breast Cancer Wisconsin Diagnostic dataset. We have carried out the process of evaluating and comparing classifiers involving selecting appropriate metrics to evaluate classifier performance and selecting an appropriate tool to quantify this performance. The main purpose of the study is predicting and diagnosis breast cancer, applying the mentioned algorithms and also discovering of the most effective with respect to confusion matrix, accuracy and precision. It is realized that CNN outperformed all other classifiers and achieved the highest accuracy (0.982456). The work is implemented in the Anaconda environment based on Python programing language.

Keywords: breast cancer, multi-layer perceptron, Naïve Bayesian, SVM, decision tree, convolutional neural network, XGBoost, KNN

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Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju

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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.

Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis

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Authors: Andy Sand, Naama Massad – Ivanir, Nadav Nitzan, Elisa Valderrama, Alfred Wegenberger, Koranit Shlosman, Rotem Shemesh, Ester Segal

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Microbial spoilage of food products is of great concern in the food industry due to the direct impact on the shelf life of foods and the risk of foodborne illness. Therefore, food packaging may serve as a crucial contribution to keep the food fresh and suitable for consumption. Active packaging solutions that have the ability to inhibit the development of microorganism in food products attract a lot of interest, and many efforts have been made to engineer and assimilate such solutions on various food products. NanoPack is an EU-funded international project aiming to develop state-of-the-art antimicrobial packaging systems for perishable foods. The project is based on natural essential oils which possess significant antimicrobial activity against many bacteria, yeasts and molds. The essential oils are encapsulated in natural aluminosilicate clays, halloysite nanotubes (HNT's), that serves as a carrier for the volatile essential oils and enable their incorporation into polymer films. During the course of the project, several polyethylene films with diverse essential oils combinations were designed based on the characteristics of their target food products. The antimicrobial activity of the produced films was examined in vitro on a broad spectrum of microorganisms including gram-positive and gram-negative bacteria, aerobic and anaerobic bacteria, yeasts and molds. The films that showed promising in vitro results were successfully assimilated on in vivo active packaging of several food products such as cheese, bread, fruits and raw meat. The results of the in vivo analyses showed significant inhibition of the microbial spoilage, indicating the strong contribution of the NanoPack packaging solutions on the extension of shelf life and reduction of food waste caused by early spoilage throughout the supply chain.

Keywords: food safety, food packaging, essential oils, nanotechnology

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Authors: Mathieu Le Cam, Tejaswinee Darure, Mateusz Pawlucki

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Climate control of cabin aircraft is traditionally conditioned as a single unit by the environmental control system. Cabin temperature is controlled by the crew while passengers of the aircraft have control on the gaspers providing fresh air from the above head area. The small nozzles are difficult to reach and adjust to meet the passenger’s needs in terms of flow and direction. More dedicated control over the near environment of each passenger can be beneficial in many situations. The European project COCOON, funded under Clean Sky 2, aims at developing and demonstrating a microclimate conditioning module (MCM) integrated into a standard economy 3-seat row. The system developed will lead to improved passenger comfort with more control on their personal thermal area. This study focuses on the assessment of thermal comfort of passengers in the cabin aircraft through simulation on the TAITherm modelling platform. A first analysis investigates thermal comfort and sensation of passengers in varying cabin environmental conditions: from cold to very hot scenarios, with and without MCM installed in the seats. The modelling platform is also used to evaluate the impact of different physiologies of passengers on their thermal comfort as well as different seat locations. Under the current cabin conditions, a passenger of a 50th percentile body size is feeling uncomfortably cool due to the high velocity cabin air ventilation. The simulation shows that the in-seat MCM developed in COCOON project improves the thermal comfort of the passenger.

Keywords: cabin aircraft, in-seat HVAC, microclimate conditioning module, thermal comfort

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Authors: Xian Chen

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In recent years, the tendency that the decline of material and social vitality of old city in China becomes more and more serious. Nowadays, transformation and renewal of the old city have become a hot topic in urban research. The traditional mode of large-scale promotion has been criticized. Thus, exploration of new ways to update the city turns to be a necessity on the way of sustainable urban development. Pocket Park is a small city open space, its location choose is based on abandoned or idle lands on urban structure, is scattered or hidden in corner of the urban. It has a great significance on improving the old city environment. Based on the theory of ‘pocket park’, this paper summarizes the successful experience of domestic and foreign practice, and discusses the update strategies which are suitable for China's national conditions according to the characteristics and predicament of the old city in China. The main methods and results are as follows: 1)Based on the conception of ‘pocket park’, though describing the research status in domestic and foreign, summarizing the experience which is worth learning and existing problems. 2) From the analysis of ‘pocket park’ function, general design principles and types of the deep-seated difficulties in renewal the old city and the possibility of the application of ‘pocket park’,the varied implementation of ‘pocket park’ form are established, and application value in the old city renewal are summed up. 3) It can’t be denied that pocket park plays an irreplaceable role in solving the recession and renewing the vitality of the old city. Anymore, It is recommended to develop corresponding supportive development policies.

Keywords: sustainable development, strategy, old city renewal, pocket park

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Authors: Delia Gabriela Moisa, Demos Parapanos, Tim Heap

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The tourism sector is mainly comprised of small and medium-sized tourism enterprises (SMEs), representing approximately 80% of global businesses in this field. These entities require focused attention and support to address challenges, ensuring their competitiveness and relevance in a dynamic industry characterized by continuously changing customer preferences. To address these challenges, it becomes imperative to consider not only socio-demographic factors but also delve into the intricate interplay of psychological elements influencing consumer behavior. This study investigates the impact of personality traits and travel motivations on visitor activities in Cumbria, United Kingdom, an iconic region marked by UNESCO World Heritage Sites, including The Lake District National Park and Hadrian's Wall. With a £4.1 billion tourism industry primarily driven by SMEs, Cumbria serves as an ideal setting for examining the relationship between tourist psychology and activities. Employing the Big Five personality model and the Travel Career Pattern motivation theory, this study aims to explain the relationship between psychological factors and tourist activities. The study further explores SME perspectives on personality-based market segmentation, providing strategic insights into addressing evolving tourist preferences.This pioneering mixed-methods study integrates quantitative data from 330 visitor surveys, subsequently complemented by qualitative insights from tourism SME representatives. The findings unveil that socio-demographic factors do not exhibit statistically significant variations in the activities pursued by visitors in Cumbria. However, significant correlations emerge between personality traits and motivations with preferred visitor activities. Open-minded tourists gravitate towards events and cultural activities, while Conscientious individuals favor cultural pursuits. Extraverted tourists lean towards adventurous, recreational, and wellness activities, while Agreeable personalities opt for lake cruises. Interestingly, a contrasting trend emerges as Extraversion increases, leading to a decrease in interest in cultural activities. Similarly, heightened Agreeableness corresponds to a decrease in interest in adventurous activities. Furthermore, travel motivations, including nostalgia and building relationships, drive event participation, while self-improvement and novelty-seeking lead to adventurous activities. Additionally, qualitative insights from tourism SME representatives underscore the value of targeted messaging aligned with visitor personalities for enhancing loyalty and experiences. This study contributes significantly to scholarship through its novel framework, integrating tourist psychology with activities and industry perspectives. The proposed conceptual model holds substantial practical implications for SMEs to formulate personalized offerings, optimize marketing, and strategically allocate resources tailored to tourist personalities. While the focus is on Cumbria, the methodology's universal applicability offers valuable insights for destinations globally seeking a competitive advantage. Future research addressing scale reliability and geographic specificity limitations can further advance knowledge on this critical relationship between visitor psychology, individual preferences, and industry imperatives. Moreover, by extending the investigation to other districts, future studies could draw comparisons and contrasts in the results, providing a more nuanced understanding of the factors influencing visitor psychology and preferences.

Keywords: personality trait, SME, tourist behaviour, tourist motivation, visitor activity

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Authors: Yi-Lin Chen, Sheng-Jou Hung, Tsunglin Liu

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Adaptive immune system recognizes a wide range of antigens via expressing a large number of structurally distinct T cell and B cell receptor genes. The distinct receptor genes arise from complex rearrangements called V(D)J recombination, and constitute the immune repertoire. A common method of profiling immune repertoire is via amplifying recombined receptor genes using multiple primers and high-throughput sequencing. This multiplex-PCR approach is efficient; however, the resulting repertoire can be distorted because of primer bias. To eliminate primer bias, 5’ RACE is an alternative amplification approach. However, the application of RACE approach is limited by its low efficiency (i.e., the majority of data are non-regular receptor sequences, e.g., containing intronic segments) and lack of the convenient tool for analysis. We propose a computational tool that can correctly identify non-regular receptor sequences in RACE data via aligning receptor sequences against the whole gene instead of only the exon regions as done in all other tools. Using our tool, the remaining regular data allow for an accurate profiling of immune repertoire. In addition, a RACE approach is improved to yield a higher fraction of regular T-cell receptor sequences. Finally, we quantify the degree of primer bias of a multiplex-PCR approach via comparing it to the RACE approach. The results reveal significant differences in frequency of VJ combination by the two approaches. Together, we provide a new experimental and computation pipeline for an unbiased profiling of immune repertoire. As immune repertoire profiling has many applications, e.g., tracing bacterial and viral infection, detection of T cell lymphoma and minimal residual disease, monitoring cancer immunotherapy, etc., our work should benefit scientists who are interested in the applications.

Keywords: immune repertoire, T-cell receptor, 5' RACE, high-throughput sequencing, sequence alignment

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Authors: Zulkifli Mohamed Udin, Lee Khai-Loon, Mohamad Ghozali Hassan

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In today’s dynamic business environment, the competition is no longer between firms, but between supply chains to gain competitive advantages. The global manufacturing sector, especially the textile and apparel industry are essentially known for its supply chain dependency. The delicate nature of its business leads to emphasis on the smooth movement of upstream and downstream supply chain. The nature of this industry, however, result in huge dynamic flow of physical, information, and financial. The dynamic management of these flows requires adoption of supply chain technologies. Even though technology is widely implemented and studied in many industries by researchers, adoption of supply chain technologies in Malaysian textile and apparel industry is limited. There is relatively a handful academic study conducted on recent developments in Malaysian textile and apparel industry and supply chain technology adoption indicate a major gap in supply chain performance studies. Considering the importance given to Third Industrial Master Plan by the government Malaysia, it is necessary to understand the power of supply chain technology adoptions. This study aims to investigate supply chain technology adoption by textile and apparel companies in Malaysia. The result highlighted the benefits perceived by textile and apparel companies from supply chain technologies. The indifference of small and medium enterprises to operation management acts as a major inhibitor to the adoption of supply chain technologies, since they have resource limitations. This study could be used as a precursor for further detailed studies on this issue.

Keywords: supply chain technology adoption, supply chain performance, textile, apparel industry

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Authors: Javad Mohiti-Ardekani, Shabodin Asadii, Ali Moradi

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Introduction: Curcumin, the yellow pigment in turmeric, has been shown as an anti-diabetic agent for centuries but only in recent few years, its mechanism of action has been under investigation. Some studies showed that curcumin might exert its anti-diabetic effect via increasing glucose transporter isotype-4 (GLUT4) gene and glycoprotein contents in cells. To investigate this possibility, we investigate the effects of extract and commercial curcumin with and without insulin on GLUT4 translocation from intracellular compartments of nuclear or endoplasmic reticulum membranes (N/ER) into the cytoplasmic membrane (CM). Methods and Material: C2C12 myoblastic cell line were seeded in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After myotubes formation, 40 µmolar Extract and Commercial curcumin, with or without insulin as intervention, and as control 1 % DMSO were added for 3 h. Cells were washed and homogenized followed by ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection using semi-quantitative Western blotting. Data analysis was done by two independent samples t-test for comparison of mean ± SD of GLUT4 percent in categories. GLUT4 contents were higher in CM groups curcumin and curcumin with insulin in comparison to 1 % DMSO-treated myotubes control group. Results: As our results have shown extract and commercial curcumin induces GLUT4 translocation from intra-cell into cell surface. The results have also shown synergic effect of curcumin on translocation of GLUT4 from intra-cell into cell surface in the presence of 100 nm insulin. Discussion: We conclude that curcumin may be a choice of type-2 diabetes mellitus treatment because its extract and commercial enhances GLUT4 contents in CM where it facilitates glucose entrance into the cell. However, it is necessary to trace the signaling pathways which are activated by curcumin.

Keywords: Curcumin, insulin, Diabetes type-2, GLUT4

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Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: Ziwei Wang, Andrea Lucotti, Luigi Brambilla, Matteo Tommasini, Chiara Bertarelli

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Surface-enhanced Raman Spectroscopy (SERS) is a highly sensitive detection that provides abundant information on low concentration analytes from various researching areas. Based on localized surface plasmon resonance, metal nanostructures including gold, silver and copper have been investigated as SERS substrate during recent decades. There has been increasing more attention of exploring good performance, homogenous, repeatable SERS substrates. Here, we show that electrospinning, which is an inexpensive technique to fabricate large-scale, self-standing and repeatable membranes, can be effectively used for producing SERS substrates. Nanoparticles and nanorods are added to the feed electrospinning solution to collect functionalized polymer fibrous mats. We report stable electrospun membranes as SERS substrate using gold nanorods (AuNRs) and poly(vinyl alcohol). Particularly, a post-processing crosslinking step using glutaraldehyde under acetone environment was carried out to the electrospun membrane. It allows for using the membrane in any liquid environment, including water, which is of interest both for sensing of contaminant in wastewater, as well as for biosensing. This crosslinked AuNRs/PVA membrane has demonstrated excellent performance as SERS substrate for low concentration 10-6 M Rhodamine 6G (Rh6G) aqueous solution. This post-processing for fabricating SERS substrate is the first time reported and proved through Raman imaging of excellent stability and outstanding performance. Finally, SERS tests have been applied to several analytes, and the application of AuNRs/PVA membrane is broadened by removing the detected analyte by rinsing. Therefore, this crosslinked AuNRs/PVA membrane is re-usable.

Keywords: SERS spectroscopy, electrospinning, crosslinking, composite materials

Procedia PDF Downloads 139