Search results for: therapeutic response

Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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Authors: Hossein Motaghedi, Kaveh Arkani, Siavash Salamatpoor

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Usually the piles are important tools for safety and economical design of high and heavy structures. For this aim the response of single pile under dynamic load is so effective. Also, the agents which have influence on single pile response are properties of pile geometrical, soil and subjected loads. In this study the finite difference numerical method and by using FLAC 3D software is used for evaluation of single pile behavior under peak ground acceleration (PGA) of El Centro earthquake record in California (1940). The results of this models compared by experimental results of other researchers and it will be seen that the results of this models are approximately coincide by experimental data's. For example the maximum moment and displacement in top of the pile is corresponding to the other experimental results of pervious researchers. Furthermore, in this paper is tried to evaluate the effective properties between soil and pile. The results is shown that by increasing the pile diagonal, the pile top displacement will be decreased. As well as, by increasing the length of pile, the top displacement will be increased. Also, by increasing the stiffness ratio of pile to soil, the produced moment in pile body will be increased and the taller piles have more interaction by soils and have high inertia. So, these results can help directly to optimization design of pile dimensions.

Keywords: pile seismic response, interaction between soil and pile, numerical analysis, FLAC 3D

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Authors: Revalin Herdianto

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Recent climate changes increase uncertainties in vegetation conditions such as health and biomass globally and locally. The detection is, however, difficult due to the spatial and temporal scale of vegetation coverage. Due to unique vegetation response to its environmental conditions such as water availability, the interplay between vegetation dynamics and hydrologic conditions leave a signature in their feedback relationship. Vegetation indices (VI) depict vegetation biomass and photosynthetic capacity that indicate vegetation dynamics as a response to variables including hydrologic conditions and microclimate factors such as rainfall characteristics and land surface temperature (LST). It is hypothesized that the signature may be depicted by VI in its relationship with other variables. To study this signature, several catchments in Asia, Australia, and Indonesia were analysed to assess the variations in hydrologic characteristics with vegetation types. Methods used in this study includes geographic identification and pixel marking for studied catchments, analysing time series of VI and LST of the marked pixels, smoothing technique using Savitzky-Golay filter, which is effective for large area and extensive data. Time series of VI, LST, and rainfall from satellite and ground stations coupled with digital elevation models were analysed and presented. This study found that the hydrologic response of vegetation to rainfall variations may be shown in one hydrologic year, in which a drought event can be detected a year later as a suppressed growth. However, an annual rainfall of above average do not promote growth above average as shown by VI. This technique is found to be a robust and tractable approach for assessing catchment dynamics in changing climates.

Keywords: vegetation indices, land surface temperature, vegetation dynamics, catchment

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Authors: O. Tovide, N. Jahed, N. Mohammed, C. E. Sunday, H. R. Makelane, R. F. Ajayi, K. M. Molapo, A. Tsegaye, M. Masikini, S. Mailu, A. Baleg, T. Waryo, P. G. Baker, E. I. Iwuoha

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A graphenated–polyaniline (GR-PANI) nanocomposite sensor was constructed and used for the determination of anthracene. The direct electro-oxidation behavior of anthracene on the GR-PANI modified glassy carbon electrode (GCE) was used as the sensing principle. The results indicate thatthe response profile of the oxidation of anthracene on GR-PANI-modified GCE provides for the construction of sensor systems based onamperometric and potentiometric signal transductions. A dynamic linear range of 0.12- 100 µM anthracene and a detection limit of 0.044 µM anthracene were established for the sensor system.

Keywords: electrochemical sensors, environmental pollutants, graphenated-polymers, polyaromatic hydrocarbon

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Authors: Wen Ma, Yong Peng, Zhixiang Li

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Security journey is a vital focus on the field of Rail Transportation. Accidents caused by the damage of the high-speed train windshield have occurred many times and have given rise to terrible consequences. Train windshield consists of tempered glass and polyvinyl butyral (PVB) film. In this work, the quasi-static tests and the split Hopkinson pressure bar (SHPB) tests were carried out first to obtain the mechanical properties and constitutive model for the tempered glass and PVB film. These tests results revealed that stress and Young’s modulus of tempered glass were wake-sensitive to strain rate, but stress and Young’s modulus of PVB film were strong-sensitive to strain rate. Then impact experiment of the windshield was carried out to investigate dynamic response and failure characteristics of train windshield. In addition, a finite element model based on the combined finite element method was proposed to investigate fracture and fragmentation responses of train windshield under different-velocity impact. The results can be used for further design and optimization of the windshield for high-speed train application.

Keywords: constitutive model, impact response, mechanism properties, PVB film, tempered glass

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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: Helnaz Soltani, J. N. Reddy

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Presence of fluid medium interacting with a structure can lead to failure of the structure. Since developing efficient computational model for fluid-structure interaction (FSI) problems has broader impact to realistic problems encountered in aerospace industry, ship industry, oil and gas industry, and so on, one can find an increasing need to find a method in order to investigate the effect of fluid domain on structural response. A coupled finite element formulation of problems involving FSI issue is an accurate method to predict the response of structures in contact with a fluid medium. This study proposes a finite element approach in order to study the transient response of the structures interacting with a fluid medium. Since beam and plate are considered to be the fundamental elements of almost any structure, the developed method is applied to beams and plates benchmark problems in order to demonstrate its efficiency. The formulation is a combination of the various structure theories and the solid-fluid interface boundary condition, which is used to represent the interaction between the solid and fluid regimes. Here, three different beam theories as well as three different plate theories are considered to model the solid medium, and the Navier-Stokes equation is used as the theoretical equation governed the fluid domain. For each theory, a coupled set of equations is derived where the element matrices of both regimes are calculated by Gaussian quadrature integration. The main feature of the proposed methodology is to model the fluid domain as an added mass; the external distributed force due to the presence of the fluid. We validate the accuracy of such formulation by means of some numerical examples. Since the formulation presented in this study covers several theories in literature, the applicability of our proposed approach is independent of any structure geometry. The effect of varying parameters such as structure thickness ratio, fluid density and immersion depth, are studied using numerical simulations. The results indicate that maximum vertical deflection of the structure is affected considerably in the presence of a fluid medium.

Keywords: beam and plate, finite element analysis, fluid-structure interaction, transient response

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Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

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Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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Authors: Mehdi Jalalpour, Mazdak Tootkaboni

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We present a computationally efficient method for reliability-based topology optimization under material properties uncertainty, which is assumed to be lognormally distributed and correlated within the domain. Computational efficiency is achieved through estimating the response statistics with stochastic perturbation of second order, using these statistics to fit an appropriate distribution that follows the empirical distribution of the response, and employing an efficient gradient-based optimizer. The proposed algorithm is utilized for design of new structures and the changes in the optimized topology is discussed for various levels of target reliability and correlation strength. Predictions were verified thorough comparison with results obtained using Monte Carlo simulation.

Keywords: material uncertainty, stochastic perturbation, structural reliability, topology optimization

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Authors: Naik Muhammad, Zahid Ullah, Dong-Ho Choi

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Submerged floating tunnel (SFT) is a new solution for the transportation infrastructure through sea straits, fjords, and inland waters, and can be a good alternative to long span suspension bridges. SFT is a massive cylindrical structure that floats at a certain depth below the water surface and subjected to extreme environmental conditions. The identification of dominant structural response of SFT becomes more important due to intended environmental conditions for the design of SFT. The time domain dynamic problem of SFT moored by vertical and inclined mooring cables/anchors is formulated. The dynamic time history analysis of SFT subjected to hydrodynamic and seismic excitations is performed. The SFT is modeled by finite element 3D beam, and the mooring cables are modeled by truss elements. Based on the dynamic time history analysis the displacements and internal forces of SFT were calculated. The response of SFT is presented for hydrodynamic and seismic excitations. The transverse internal forces of SFT were the maximum compared to vertical direction, for both hydrodynamic and seismic cases; this indicates that the cable system provides very small stiffness in transverse direction as compared to vertical direction of SFT.

Keywords: submerged floating tunnel, hydrodynamic analysis, time history analysis, seismic response

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Authors: Teklay Gebrecherkos

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Background: Serological testing for SARS-CoV-2 plays an important role in epidemiological studies, in aiding the diagnosis of COVID-19 and assess vaccine responses. Little is known about the dynamics of SARS-CoV-2 serology in African settings. Here, we aimed to characterize the longitudinal antibody response profile to SARS-CoV-2 in Ethiopia. Methods: In this prospective study, a total of 102 PCR-confirmed COVID-19 patients were enrolled. We obtained 802 plasma samples collected serially. SARS-CoV-2 antibodies were determined using four lateral flow immune assays (LFIAs) and an electrochemiluminescent immunoassay. We determined longitudinal antibody response to SARS-CoV-2 as well as seroconversion dynamics. Results: Serological positivity rate ranged between 12%-91%, depending on timing after symptom onset. There was no difference in the positivity rate between severe and non-severe COVID-19 cases. The specificity ranged between 90%-97%. Agreement between different assays ranged between 84%-92%. The estimated positive predictive value (PPV) for IgM or IgG in a scenario with seroprevalence at 5% varies from 33% to 58%. Nonetheless, when the population seroprevalence increases to 25% and 50%, there is a corresponding increase in the estimated PPVs. The estimated negative-predictive value (NPV) in a low seroprevalence scenario (5%) is high (>99%). However, the estimated NPV in a high seroprevalence scenario (50%) for IgM or IgG is reduced significantly from 80% to 85%. Overall, 28/102 (27.5%) seroconverted by one or more assays tested within a median time of 11 (IQR: 9–15) days post symptom onset. The median seroconversion time among symptomatic cases tended to be shorter when compared to asymptomatic patients [9 (IQR: 6–11) vs. 15 (IQR: 13–21) days; p = 0.002]. Overall, seroconversion reached 100% 5.5 weeks after the onset of symptoms. Notably, of the remaining 74 COVID-19 patients included in the cohort, 64 (62.8%) were positive for antibodies at the time of enrollment, and 10 (9.8%) patients failed to mount a detectable antibody response by any of the assays tested during follow-up. Conclusions: Longitudinal assessment of antibody response in African COVID-19 patients revealed heterogeneous responses. This underscores the need for a comprehensive evaluation of serum assays before implementation. Factors associated with failure to seroconvert need further research.

Keywords: COVID-19, antibody, rapid diagnostic tests, ethiopia

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Authors: Sahar Jahani, Meryem Ayse Yucel, David Boas, Seyed Kamaledin Setarehdan

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Near-infrared spectroscopy allows monitoring of oxy- and deoxy-hemoglobin concentration changes associated with hemodynamic response function (HRF). HRF is usually affected by natural physiological hemodynamic (systemic interferences) which occur in all body tissues including brain tissue. This makes HRF extraction a very challenging task. In this study, we used Kalman filter based on a general linear model (GLM) of brain activity to define the proportion of systemic interference in the brain hemodynamic. The performance of the proposed algorithm is evaluated in terms of the peak to peak error (Ep), mean square error (MSE), and Pearson’s correlation coefficient (R2) criteria between the estimated and the simulated hemodynamic responses. This technique also has the ability of real time estimation of single trial functional activations as it was applied to classify finger tapping versus resting state. The average real-time classification accuracy of 74% over 11 subjects demonstrates the feasibility of developing an effective functional near infrared spectroscopy for brain computer interface purposes (fNIRS-BCI).

Keywords: hemodynamic response function, functional near-infrared spectroscopy, adaptive filter, Kalman filter

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Authors: Amine M. Benmehaia, Amine Oulmane

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The supply response of agricultural commodities to changes in price incentives is an important issue for the success of any policy reform in the agricultural sector. This study aims to quantify the responsiveness of producers of some livestock commodities to price incentives in Algerian context. Time series analysis is used on annual data for a period of 52 years (1966-2018). Both co-integration and vector error correction model (VECM) are used through the Nerlove model of partial adjustment. The study attempts to determine the long-run and short-run relationships along with the magnitudes of disequilibria in the selected commodities. Results show that the short-run price elasticities are low in cow and sheep meat sectors (8.7 and 8% respectively), while their respective long-run elasticities are 16.5 and 10.5, whereas eggs and milk have very high short-run price elasticities (82 and 90% respectively) with long-run elasticities of 40 and 46 respectively. The error correction coefficient, reflecting the speed of adjustment towards the long-run equilibrium, is statistically significant and have the expected negative sign. Its estimates are 12.7 for cow meat, 33.5 for sheep meat, 46.7 for eggs and 8.4 for milk. It seems that cow meat and milk producers have a weak feedback of about 12.7% and 8.4% respectively of the previous year's disequilibrium from the long-run price elasticity, whereas sheep meat and eggs producers adjust to correct long run disequilibrium with a high speed of adjustment (33.5% and 46.7 % respectively). The implication of this is that much more in-depth research is needed to identify those factors that affect agricultural supply and to describe the effect of factors that shift supply in response to price incentives. This could provide valuable information for government in the use of appropriate policy measures.

Keywords: Algeria, cointegration, livestock, supply response, vector error correction model

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Authors: Alyaa Abdlwahab

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Cutaneous leishmaniasis represents a serious health problem in Syria; this problem has become noticeably aggravated after the civil war in the country. Leishmania tropica parasite is the main cause of cutaneous leishmaniasis in Syria. In order to control the disease, we need an effective vaccine against leishmania parasite. DNA vaccination remains one of the favorable approaches that have been used to face cutaneous leishmaniasis. Ribosomal protein S4 is responsible for important roles in Leishmania parasite life. DNA vaccine based on S4 gene has been used against infections by many species of Leishmania parasite but leishmania tropica parasite, so this gene represents a good candidate for DNA vaccine construction. After proving the existence of ribosomal protein S4 gene in a Syrian strain of Leishmania tropica (LCED Syrian 01), sequencing it and cloning it into pCI plasmid, BALB/C mice were inoculated with pCI-S4 DNA vaccine. The immune response was determined by monitoring the lesion progression in inoculated BALB/C mice for six weeks after challenging mice with Leishmania tropica (LCED Syrian 01) parasites. IL-12, IFN-γ, and IL-4 were quantified in draining lymph nodes (DLNa) of the immunized BALB/C mice by using the RT-qPCR technique. The parasite burden was calculated in the final week for the footpad lesion and the DLNs of the mice. This study proved the existence and the expression of the ribosomal protein S4 gene in Leishmania tropica (LCED Syrian 01) promastigotes. The sequence of ribosomal protein cDNA S4 gene was determined and published in Genbank; the gene size was 822 bp. Expression was also demonstrated at the level of cDNA. Also, this study revealed that pCI-S4 DNA vaccine induces TH1\TH2 response in immunized mice; this response prevents partially developing a dermal lesion of Leishmania.

Keywords: ribosomal protein S4, DNA vaccine, Leishmania tropica, BALB\c

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Authors: Priya Kedia, Kiranmoy Das

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There is a rich literature on variable selection in regression setting. However, most of these methods assume normality for the response variable under consideration for implementing the methodology and establishing the statistical properties of the estimates. In many real applications, the distribution for the response variable may be non-Gaussian, and one might be interested in finding the best subset of covariates at some predetermined quantile level. We develop dynamic Bayesian approach for variable selection in quantile regression framework. We use a zero-inflated mixture prior for the regression coefficients, and consider the asymmetric Laplace distribution for the response variable for modeling different quantiles of its distribution. An efficient Gibbs sampler is developed for our computation. Our proposed approach is assessed through extensive simulation studies, and real application of the proposed approach is also illustrated. We consider the data from health and retirement study conducted by the University of Michigan, and select the important predictors when the outcome of interest is out-of-pocket medical cost, which is considered as an important measure for financial risk. Our analysis finds important predictors at different quantiles of the outcome, and thus enhance our understanding on the effects of different predictors on the out-of-pocket medical cost.

Keywords: variable selection, quantile regression, Gibbs sampler, asymmetric Laplace distribution

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Authors: Meryam Labyad, Karima Fakiri, Widad Lahmini, Ghizlane Draiss, Mohamed Bouskraoui, Nadia Ouzennou

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Background: Asthma is the most common chronic disease in children, affecting nearly 235 million people worldwide (OMS). In Morocco, asthma is much more common in children than in adults; the prevalence rate in children between 13 and 14 years of age is 20%.1 This pathology is marked by high morbidity, a significant impact on the quality of life and development of children 2 This requires a rigorous management strategy in order to achieve clinical control and reduce any risk to the patient 3 A search for aggravating factors is mandatory if a child has difficulty maintaining good asthma control. The objective of the present study is to describe asthma control during this confinement period in children aged 4 to 11 years followed by a pneumo-paediatric consultation. For children whose asthma is not controlled, a search for associations with promoting factors and adherence to treatment is also among the objectives of the study. Knowing the level of asthma control and influencing factors is a therapeutic priority in order to reduce hospitalizations and emergency care use. Objective: To assess asthma control and determine the factors influencing asthma levels in children with asthma during confinement following the COVID 19 pandemic. Method: Prospective cross-sectional study by questionnaire and structured interview among 66 asthmatic children followed in pediatric pneumology consultation at the CHU MED VI of Marrakech from 13/06/2020 to 13/07/2020, asthma control was assessed by the Childhood Asthma Control Test (C-ACT). Results: 66 children and their parents were included (mean age is 7.5 years), asthma was associated with allergic rhinitis (13.5% of cases), conjunctivitis (9% of cases), eczema (12% of cases), occurrence of infection (10.5% of cases). The period of confinement was marked by a decrease in the number of asthma attacks translated by a decrease in the number of emergency room visits (7.5%) of these asthmatic children, control was well controlled in 71% of the children, this control was significantly associated with good adherence to treatment (p<0.001), no infection (p<0.001) and no conjunctivitis (p=002) or rhinitis (p<0.001). This improvement in asthma control during confinement can be explained by the measures taken in the Kingdom to prevent the spread of COVID 19 (school closures, reduction in industrial activity, fewer means of transport, etc.), leading to a decrease in children's exposure to triggers, which justifies the decrease in the number of children having had an infection, allergic rhinitis or conjunctivitis during this period. In addition, the close monitoring of parents resulted in better therapeutic adherence (42.4% were fully observant). Confinement was positively perceived by 68% of the parents; this perception is significantly associated with the level of asthma control (p<0.001). Conclusion: Maintaining good control can be achieved through improved therapeutic adherence and avoidance of triggers, both of which were achieved during the containment period following the VIDOC pandemic 19.

Keywords: Asthma, control , COVID-19 , children

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Authors: Christo Nicholls

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The National Electricity Grid (NEG) in South Africa has been under strain for the last five years. This overburden of the NEG led Eskom (the State-Owned Entity responsible for the NEG) to implement a blunt methodology to assist them in reducing the maximum demand (MD) on the NEG, when required, called Loadshedding. The challenge of this methodology is that not only does it lead to immense technical issues with the distribution network equipment, e.g., transformers, due to the frequent abrupt off and on switching, it also has a broader negative fiscal impact on the distributors, as their key consumers (commercial & industrial) are now grid defecting due to the lack of Electricity Security Provision (ESP). This paper provides a pragmatic alternative methodology utilizing specific functionalities embedded within direct-connect single and three-phase Advanced Meter Infrastructure (AMI) Solutions deployed within the distribution network, in conjunction with a Multi-Agent Systems Based AI implementation focused on Automated Negotiation Peer-2-Peer trading. The results of this research clearly illustrate, not only does methodology provide a factual percentage contribution towards the NEG MD at the point of consideration, it also allows the distributor to leverage the real-time MD data from key consumers to activate complex, yet impact-measurable Demand Response (DR) programs.

Keywords: AI, AMI, demand response, multi-agent

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Authors: Trevor Sabiston, Mohsen Mohammadi, Mohammed Cherkaoui, Kaan Inal

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A new micromechanics framework is developed for long fibre reinforced composites using a single fibre surrounded by a functionally graded interphase and matrix as a representative unit cell. The unit cell is formulated to represent any number of aligned fibres by a single fibre. Using this model the elastic response of long fibre composites is predicted in all directions. The model is calibrated to experimental results and shows very good agreement in the elastic regime. The differences between the proposed model and existing models are discussed.

Keywords: computational mechanics, functionally graded interphase, long fibre composites, micromechanics

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Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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Authors: Burak Bal

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Mechanical characterization tests might come with a remarkable cost of time and money for both companies and academics. The inquiry to transform laboratory experiments to the computational media is getting a trend; accordingly, the literature supplies many analytical ways to explain the mechanics of deformation. In our work, we focused on the crystal plasticity finite element modeling (CPFEM) analysis on various materials in various crystal structures to predict the stress-strain curve without tensile tests. For FEM analysis, which we used in this study was ABAQUS, a standard user-defined material subroutine (UMAT) was prepared. The geometry of a specimen was created via DREAM 3D software with the inputs of Euler angles taken by Electron Back-Scattered Diffraction (EBSD) technique as orientation, or misorientation angles. The synthetic crystal created with DREAM 3D is also meshed in a way the grains inside the crystal meshed separately, and the computer can realize interaction of inter, and intra grain structures. The mechanical deformation parameters obtained from the literature put into the Fortran based UMAT code to describe how material will response to the load applied from specific direction. The mechanical response of a synthetic crystal created with DREAM 3D agrees well with the material response in the literature.

Keywords: crystal plasticity finite element modeling, ABAQUS, Dream.3D, microstructure

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Authors: Mohd Raish Ansari, Tauheed Alam Khan

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This research paper is a comparative study of the belt truss in the Regular RC frame structure at the different positions of the floor. The method used in this research is the response spectrum method with the help of the ETABS Software, there are six models in this paper with belt truss. The Indian standard code used in this work are IS 456:2000, IS 800:2007, IS 875 part-1, IS 875 part-1, and IS 1893 Part-1:2016. The cross-section of the belt truss is the I-section, a grade of steel that is made up of Mild Steel. The basic model in this research paper is the same, only position of the belt truss is going to change, and the dimension of the belt truss is remain constant for all models. The plan area of all models is 24.5 meters x 28 meters, and the model has G+20, where the height of the ground floor is 3.5 meters, and all floor height is 3.0 meters remains constant. This comparative research work selected some important seismic parameters to check the stability of all models, the parameters are base shear, fundamental period, storey overturning moment, and maximum storey displacement.

Keywords: belt truss, RC frames structure, ETABS, response spectrum analysis, special moment resisting frame

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Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

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Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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Authors: Dong Tran, Thanh Dac Van, Ly Le

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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.

Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution

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Authors: Kakali Bhadra

Abstract:

Binding of small molecules to DNA and recently to RNA, continues to attract considerable attention for developing effective therapeutic agents for control of gene expression. This work focuses towards understanding interaction of harmalol, a dihydro beta-carboline alkaloid, with different nucleic acid motifs viz. double stranded CT DNA, single stranded A-form poly(A), double-stranded A-form of poly(C)·poly(G) and clover leaf tRNAphe by different spectroscopic, calorimetric and molecular modeling techniques. Results of this study converge to suggest that (i) binding constant varied in the order of CT DNA > poly(C)·poly(G) > tRNAphe > poly(A), (ii) non-cooperative binding of harmalol to poly(C)·poly(G) and poly(A) and cooperative binding with CT DNA and tRNAphe, (iii) significant structural changes of CT DNA, poly(C)·poly(G) and tRNAphe with concomitant induction of optical activity in the bound achiral alkaloid molecules, while with poly(A) no intrinsic CD perturbation was observed, (iv) the binding was predominantly exothermic, enthalpy driven, entropy favoured with CT DNA and poly(C)·poly(G) while it was entropy driven with tRNAphe and poly(A), (v) a hydrophobic contribution and comparatively large role of non-polyelectrolytic forces to Gibbs energy changes with CT DNA, poly(C)·poly(G) and tRNAphe, and (vi) intercalated state of harmalol with CT DNA and poly(C)·poly(G) structure as revealed from molecular docking and supported by the viscometric data. Furthermore, with competition dialysis assay it was shown that harmalol prefers hetero GC sequences. All these findings unequivocally pointed out that harmalol prefers binding with ds CT DNA followed by ds poly(C)·poly(G), clover leaf tRNAphe and least with ss poly(A). The results highlight the importance of structural elements in these natural beta-carboline alkaloids in stabilizing different DNA and RNA of various motifs for developing nucleic acid based better therapeutic agents.

Keywords: calorimetry, docking, DNA/RNA-alkaloid interaction, harmalol, spectroscopy

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Authors: Meng Koon Lee, Mohammad Hosseini Fouladi, Satesh Narayana Namasivayam

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Research is focused on the response of soundboards of Classical guitars at frequencies up to 5 kHz as the soundboard is a major contributor to acoustic radiation at high frequencies when compared to the bridge and sound hole. A thin rectangular plate of variable thickness that is simply-supported on all sides is used as an analytical model of the research. This model is used to study the response of the guitar soundboard as the latter can be considered as a modified form of a rectangular plate. Homotopy Perturbation Method (HPM) is selected as a mathematical method to obtain an analytical solution of the 4th-order parabolic partial differential equation of motion of the rectangular plate of constant thickness viewed as a linear problem. This procedure is generalized to the nonlinear problem of the rectangular plate with variable thickness and an analytical solution can also be obtained. Sound power is used as a parameter to investigate the acoustic radiation of soundboards made from spruce using various bracing patterns. The sound power of soundboards made from Malaysian softwood such as damar minyak, sempilor or podo are investigated to determine the viability of replacing spruce as future materials for soundboards of Classical guitars.

Keywords: rectangular plates, analytical solution, homotopy perturbation, natural frequencies

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Authors: Seyedeh Belin Tavakoly Sany, Rosli Hashim, Majid Rezayi, Aishah Salleh

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The primary objectives of this study were to investigate the distribution and composition of the macrobenthic community and their response to environmental parameters in the North Port, west coastal waters of Malaysia. A total of 25 species were identified, including 13 bivalvia, 4 gastropoda, and 3 crustacea. The other taxa were less diversified. There were no temporal changes in the macrobenthic community composition, but significant effects (p < 0.05) on the benthic community composition were found on a spatial scale. The correlation analyses and similarity tests were in good agreement, confirming the significant response of macrobenthic community composition to variations of environmental parameters.

Keywords: distribution, macrobenthic community, diversity, North Port, Malaysia

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Authors: Tauseef Ahmad, Muhammad Ishaq, Mathew Eapen, Ahyoung Park, Sam Karpiniec, Vanni Caruso, Rajaraman Eri

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Fucoidans are complex, fucose-rich sulfated polymers discovered in brown seaweeds. Fucoidans are popular around the world, particularly in the nutraceutical and pharmaceutical industries, due to their promising medicinal properties. Fucoidans have been shown to have a variety of biological activities, including anti-inflammatory effects. They are known to inhibit inflammatory processes through a variety of mechanisms, including enzyme inhibition and selectin blockade. Inflammation is a part of the complicated biological response of living systems to damaging stimuli, and it plays a role in the pathogenesis of a variety of disorders, including arthritis, inflammatory bowel disease, cancer, and allergies. In the current investigation, various fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for inhibition of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) in LPS induced human macrophage cell line (THP-1) and human peripheral blood mononuclear cells (PBMCs). Furthermore, we also sought to catalogue these extracts based on their anti-inflammatory effects in the current in-vitro cell model. Materials and Methods: To assess the cytotoxicity of fucoidan extracts, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5, -diphenyltetrazolium bromide) cell viability assay was performed. Furthermore, a dose-response for fucoidan extracts was performed in LPS induced THP-1 cells and PBMCs after pre-treatment for 24 hours, and levels of TNF-α, IL-1β, and IL-6 cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: The MTT cell viability assay demonstrated that fucoidan extracts exhibited no evidence of cytotoxicity in THP-1 cells or PBMCs after 48 hours of incubation. The results of the sandwich ELISA revealed that all fucoidan extracts suppressed cytokine production in LPS-stimulated PBMCs and human THP-1 cells in a dose-dependent manner. Notably, at lower concentrations, the lower molecular fucoidan (5-30 kDa) extract from Macrocystis pyrifera was a highly efficient inhibitor of pro-inflammatory cytokines. Fucoidan extracts from all species including Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica exhibited significant anti-inflammatory effects. These findings on several fucoidan extracts provide insight into strategies for improving their efficacy against inflammation-related diseases. Conclusion: In the current research, we have successfully catalogued several fucoidan extracts based on their efficiency in LPS-induced macrophages and PBMCs in downregulating the key pro-inflammatory cytokines (TNF-, IL-1 and IL-6), which are prospective targets in human inflammatory illnesses. Further research would provide more information on the mechanism of action, allowing it to be tested for therapeutic purposes as an anti-inflammatory medication.

Keywords: fucoidan, PBMCs, THP-1, TNF-α, IL-1β, IL-6, inflammation

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Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: S. Suman, G. N. Singh

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The present manuscript addresses the estimation procedure of population parameter using Poisson probability distribution when characteristic under study possesses a rare sensitive attribute. The generalized form of unrelated randomized response model is suggested in order to acquire the truthful responses from respondents. The resultant estimators have been proposed for two situations when the information on an unrelated rare non-sensitive characteristic is known as well as unknown. The properties of the proposed estimators are derived, and the measure of confidentiality of respondent is also suggested for respondents. Empirical studies are carried out in the support of discussed theory.

Keywords: Poisson distribution, randomized response model, rare sensitive attribute, non-sensitive attribute

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Authors: Abolghasem Yousefi-Babadi, Ali Bozorgi-Amiri, Aida Kazempour, Reza Tavakkoli-Moghaddam, Maryam Irani

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All over the world, natural disasters (e.g., earthquakes, floods, volcanoes and hurricanes) causes a lot of deaths. Earthquakes are introduced as catastrophic events, which is accident by unusual phenomena leading to much loss around the world. Such could be replaced by disasters or any other synonyms strongly demand great long-term help and relief, which can be hard to be managed. Supplies and facilities are very important challenges after any earthquake which should be prepared for the disaster regions to satisfy the people's demands who are suffering from earthquake. This paper proposed disaster response facility allocation problem for disaster relief operations as a mathematical programming model. Not only damaged people in the earthquake victims, need the consumable commodities (e.g., food and water), but also they need non-consumable commodities (e.g., clothes) to protect themselves. Therefore, it is concluded that paying attention to disaster points and people's demands are very necessary. To deal with this objective, both commodities including consumable and need non-consumable commodities are considered in the presented model. This paper presented the multi-objective multi-period mathematical programming model regarding the minimizing the average of the weighted response times and minimizing the total operational cost and penalty costs of unmet demand and unused commodities simultaneously. Furthermore, a Chebycheff multi-objective solution procedure as a powerful solution algorithm is applied to solve the proposed model. Finally, to illustrate the model applicability, a case study of the Tehran earthquake is studied, also to show model validation a sensitivity analysis is carried out.

Keywords: facility location, multi-objective model, disaster response, commodity

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