Search results for: therapeutic response

Authors: M. Moradi Dalini, M. R. Talebi

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This research revolves around a technical method according to combines econometric and multiobjective programming to select and obtain optimal solutions to management problems. It is taken for a generation that; it is important to analyze which combination of values of the explanatory variables -in an econometric method- would point to the simultaneous achievement of the best values of the response variables. In this case, if a certain degree of conflict is viewed among the response variables, we suggest a multiobjective method in order to the results obtained from a regression analysis. In fact, with the use of a multiobjective method, we will have the best decision about the conflicting relationship between the response variables and the optimal solution. The combined multiobjective programming and econometrics benefit is an assessment of a balanced “optimal” situation among them because a find of information can hardly be extracted just by econometric techniques.

Keywords: econometrics, multiobjective optimization, management problem, optimization

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Authors: K. Farheen, A. Munir

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Seismic response of the multi-storey buildings is created by the interaction of both the structure and underlying soil medium. The seismic design philosophy is incorporated using response modification factor 'R'. Current code based values of 'R' factor does not reflect the SSI problem as it is based on fixed base condition. In this study, the modified values of 'R' factor for moment resisting frame (MRF) considering SSI are evaluated. The response of structure with and without SSI has been compared using equivalent linear static and nonlinear static pushover analyses for 10-storied moment resisting frame building. The building is located in seismic zone 2B situated on different soils with shear wave velocity (Vₛ) of 300m/sec (SD) and 1200m/s (SB). Code based 'R' factor value for building frame system has been taken as 5.5. Soil medium is modelled using identical but mutually independent horizontal and vertical springs. It was found that the modified 'R' factor values have been decreased by 47% and 43% for soil SD and SB respectively as compared to that of code based 'R' factor.

Keywords: buildings, SSI, shear wave velocity, R factor

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Authors: Mohammad H. Yarmohamadian, Reza Safdari, Nahid Tavakoli

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In recent years, many countries have suffered various natural disasters. Disaster response continues to face the challenges in health care sector in all countries. Information and communication management is a significant challenge in disaster scene. During the last decades, rapid advances in information technology have led to manage information effectively and improve communication in health care setting. Information technology is a vital solution for effective response to disasters and emergencies so that if an efficient ICT-based health information system is available, it will be highly valuable in such situation. Of that, mobile technology represents a nearly computing technology infrastructure that is accessible, convenient, inexpensive and easy to use. Most projects have not yet reached the deployment stage, but evaluation exercises show that mHealth should allow faster processing and transport of patients, improved accuracy of triage and better monitoring of unattended patients at a disaster scene. Since there is a high prevalence of cell phones among world population, it is expected the health care providers and managers to take measures for applying this technology for improvement patient safety and public health in disasters. At present there are challenges in the utilization of mhealth in disasters such as lack of structural and financial issues in our country. In this paper we will discuss about benefits and challenges of mhealth technology in disaster setting considering connectivity, usability, intelligibility, communication and teaching for implementing this technology for disaster response.

Keywords: information technology, mhealth, disaster, effective response

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Authors: Josua K. Junias, Fillemon N. Nangolo, Petrina T. Johaness

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The deterioration of pavement can lead to the formation of potholes, which cause the wheels of a vehicle to experience unusual and uneven movement. In addition, improper loading practices of heavy vehicles can result in dynamic loading of the pavement due to the vehicle's response to the irregular movement caused by the potholes. Previous studies have only focused on the effects of either the road's uneven surface or the asymmetrical loading of the vehicle, but not both. This study aimed to model the pavement's dynamic response to heavy vehicles under different loading configurations and wheel movements. A sample of 225 cases with symmetrical and asymmetrical loading and kinematic movements was used, and 27 validated 3D pavement-vehicle interactive models were developed using SIMWISE 4D. The study found that the type of kinematic movement experienced by the heavy vehicle affects the pavement's dynamic loading, with eccentrically loaded, asymmetrically kinematic heavy vehicles having a statistically significant impact. The study also suggests that the mass of the vehicle's suspension system plays a role in the pavement's dynamic loading.

Keywords: eccentricities, pavement dynamic loading, vertical displacement dynamic response, heavy vehicles

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

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Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: ¹⁷⁷Lu, adenocarcinoma breast cancer, DOTATOC, BALB/c mice

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Authors: I. F. Ejim, F. L. Kamen

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Aims: In this experiment, algae oil extraction with a combination of n-hexane and ethanol was investigated. The effects of extraction solvent concentration, extraction time and temperature on the yield and quality of oil were studied using Response Surface Methodology (RSM). Experimental Design: Optimization of algae oil extraction using Box-Behnken design was used to generate 17 experimental runs in a three-factor-three-level design where oil yield, specific gravity, acid value and saponification value were evaluated as the response. Result: In this result, a minimum oil yield of 17% and maximum of 44% was realized. The optimum values for yield, specific gravity, acid value and saponification value from the overlay plot were 40.79%, 0.8788, 0.5056 mg KOH/g and 180.78 mg KOH/g respectively with desirability of 0.801. The maximum point prediction was yield 40.79% at solvent concentration 66.68 n-hexane, temperature of 40.0°C and extraction time of 4 hrs. Analysis of Variance (ANOVA) results showed that the linear and quadratic coefficient were all significant at p<0.05. The experiment was validated and results obtained were with the predicted values. Conclusion: Algae oil extraction was successfully optimized using RSM and its quality indicated it is suitable for many industrial uses.

Keywords: algae oil, response surface methodology, optimization, Box-Bohnken, extraction

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Authors: Rama Debbarma

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The present study deals with the performance of Linear base isolation system to mitigate seismic response of structures characterized by random system parameters. This involves optimization of the tuning ratio and damping properties of the base isolation system considering uncertain system parameters. However, the efficiency of base isolator may reduce if it is not tuned to the vibrating mode it is designed to suppress due to unavoidable presence of system parameters uncertainty. With the aid of matrix perturbation theory and first order Taylor series expansion, the total probability concept is used to evaluate the unconditional response of the primary structures considering random system parameters. For this, the conditional second order information of the response quantities are obtained in random vibration framework using state space formulation. Subsequently, the maximum unconditional root mean square displacement of the primary structures is used as the objective function to obtain optimum damping parameters Numerical study is performed to elucidate the effect of parameters uncertainties on the optimization of parameters of linear base isolator and system performance.

Keywords: linear base isolator, earthquake, optimization, uncertain parameters

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Authors: Ambuj Kumar, Sunil Kumar Singh, Shrikant Singh, Zakir Husain, R. K. Jarial

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Sweep frequency response analysis has been turning out a powerful tool for investigation of mechanical as well as electrical integration of transformers. In this paper various aspect of practical application of SFRA has been studied. Open circuit and short circuit measurement were done on different phases of high voltage and low voltage winding. A case study was presented for the transformer of rating 31.5 MVA for various frequency ranges. A clear picture was presented for sub- frequency ranges for HV as well as LV winding. The main motive of work is to investigate high voltage short circuit response. The theoretical concept about SFRA responses is validated with expert system software results.

Keywords: transformer winding, SFRA, OCT & SCT, frequency deviation

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Authors: Dorota Witkowska, Paweł Gosek, Lukasz Swiecicki, Wojciech Jernajczyk, Bruce J. West, Miroslaw Latka

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In clinical practice, the selection of an antidepressant often degrades to lengthy trial-and-error. In this work we employ a normalized wavelet power of alpha waves as a biomarker of antidepressant treatment response. This novel EEG metric takes into account both non-stationarity and intersubject variability of alpha waves. We recorded resting, 19-channel EEG (closed eyes) in 22 inpatients suffering from unipolar (UD, n=10) or bipolar (BD, n=12) depression. The EEG measurement was done at the end of the short washout period which followed previously unsuccessful pharmacotherapy. The normalized alpha wavelet power of 11 responders was markedly different than that of 11 nonresponders at several, mostly temporoparietal sites. Using the prediction of treatment response based on the normalized alpha wavelet power, we achieved 81.8% sensitivity and 81.8% specificity for channel T4.

Keywords: alpha waves, antidepressant, treatment outcome, wavelet

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Authors: Mohd Salmi Md Noorani, Ghada Al-Mahbashi, Sakhinah Abu Bakar

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This paper investigates projective lag synchronization (PLS) behavior in drive response dynamical networks (DRDNs) model with identical nodes. A hybrid feedback control method is designed to achieve the PLS with mismatch and without mismatch terms. The stability of the error dynamics is proven theoretically using the Lyapunov stability theory. Finally, analytical results show that the states of the dynamical network with non-delayed coupling can be asymptotically synchronized onto a desired scaling factor under the designed controller. Moreover, the numerical simulations results demonstrate the validity of the proposed method.

Keywords: drive-response dynamical network, projective lag synchronization, hybrid feedback control, stability theory

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Authors: H. Masaeli, R. Ziaei, F. Khoshnoudian

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Shock response analysis of the soil–structure systems induced by near–fault pulses is investigated. Vibration transmissibility of the soil–structure systems is evaluated by Shock Response Spectra (SRS). Medium–to–high rise buildings with different aspect ratios located on different soil types as well as different foundations with respect to vertical load bearing safety factors are studied. Two types of mathematical near–fault pulses, i.e. forward directivity and fling step, with different pulse periods as well as pulse amplitudes are selected as incident ground shock. Linear versus nonlinear Soil–Structure Interaction (SSI) condition are considered alternatively and the corresponding results are compared. The results show that nonlinear SSI is likely to amplify the acceleration responses when subjected to long–period incident pulses with normalized period exceeding a threshold. It is also shown that this threshold correlates with soil type, so that increased shear–wave velocity of the underlying soil makes the threshold period decrease.

Keywords: nonlinear soil–structure interaction, shock response spectrum, near–fault ground shock, rocking isolation

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Authors: Edwina Owusu Panin, Kwame Baah Owusu Panin

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This abstract intends to demonstrate multiple strategies of autism management in Ghana by exploring the possibilities. The advantages of adopting creative art forms as a therapeutic method. Autism is a developmental disorder that includes social interaction, communication, and repetitive behaviours. In Ghana, as in many other countries, there is a rising demand for effective intervention and support for people with autism and their families. Creative arts such as music, dance, drama and visual arts have shown promise in promoting communication, social interaction and inclusion of people with autism. These art forms provide alternative channels for self-expression and can be powerful tools for autistic people to interact with the world, their friends and families around them. Creative art forms interventions have been found to improve social skills, improve emotion regulation, promote creativity and increase self-confidence in people with autism. This study examines existing programs and interventions in Ghana involving creative art forms for people with autism through a comparative analysis. It explores the different approaches, methods and results of these interventions. By comparing and evaluating these programs, the study aims to identify best practices, challenges and areas for development in managing autism through the creative arts in Ghana. Although many schools and rehabilitation centres employ various forms in therapeutic approaches for autism. There is no comparative analysis of which type of autism and which creative art forms is suitable. The results of this study will contribute to the development of evidence-based practices for the management of autism in Ghana. It provides valuable information about the effectiveness of creative arts interventions and helps inform policy makers, educators, therapists and other stakeholders involved in autism support. Ultimately, the goal is to improve the well-being and quality of life of people with autism in Ghana and their families by promoting inclusive and accessible interventions that harness the power of creative art forms.

Keywords: autism, therapeutic, creative art, art form

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Authors: W. Mohammedsaeed, A. J. Mcbain, S. M. Cruickshank, C. A. O’Neill

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Many studies have demonstrated the importance of probiotics and their potential therapeutic effects within the gut. Recently, the possible therapeutic effects of probiotics in other tissues have also begun to be investigated. Comparatively few studies have evaluated the use of topical probiotics in relation to the skin. In this study, we have conducted preliminary investigations into whether a well-known probiotic, Lactobacillus rhamnosus GG (LGG), can increase the rate of re-epithelialization in a model wound. Full-thickness skin was obtained from individuals undergoing elective cosmetic surgery. This skin was wounded using excisional punch and cultured using a serum-free medium, either in the presence or absence of L. rhamnosus GG lysate. Histological staining of the sections was performed with Haematoxylin& Eosin E to quantify “epithelial tongue length”. This is the length of the new epithelial ‘tongue’ that grows and covers the exposed dermis at the inner wound edges. The length of the new epithelial ‘tongue’ was compared in untreated section and section treated with and L. rhamnosus GG made using108CFU/ml bacterial cells. L. rhamnosus GG lysate enhanced significantly the re-epithelialisation of treated wounds compared with that of untreated wounds (P=0.005, n=3). Tongue length, at day 1 was 7.55μm 0.15, at day 3 it was 18.5μm 0.25 and at day 7 was 22.9μm 0.35. These results can be compared with untreated cultures in which tongue length was 3.25μm 0.35, day 3 was 9.65μm 0.25 and day 7 was 13.5μm 0.15 post-wounding. In ex-vivo proliferation and migration cells were measured by determining the expression of nuclear proliferation marker Ki-67 and the expression of Phosphorylated cortactin respectively demonstrated that L. rhamnosus GG significantly increased NHEK proliferation and migration rates relative to controls. However, the dominant mechanism was migration because in ex-vivo skin treated with the L. rhamnosus GG up-regulated the gene expression of the chemokine receptor and ligands CXCR2 and CXCL2 comparing with controls (P=0.02, P=0.03 respectively, n=3). High levels of CXCL2/CXCL2 have already been implicated in multiple aspects of stimulation of wound healing through activation of keratinocyte migration. These data demonstrate that lysates from Lactobacillus rhamnosus GG increase re-epithelialization by stimulation of keratinocyte migration. The current study identifies the partial mechanism that contribute to stimulating the wound-healing process ex vivo in response to L. rhamnosus GG lysate is an increase in the production of CXCL2/ CXCR2 in ex vivo models. The use of probiotic lysates potentially offers new options to develop treatments that could improve wound healing.

Keywords: Lactobacillus rhamnosus GG, wounds, migration, lysate

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Authors: Pranee Liamputtong, Hala Kurban

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Based on the therapeutic landscape theory, this paper examines how young Middle-Eastern refugee individuals perceive their health and well-being and address the barriers they face in their new homeland and the means that helped them to form social connections in their new social environment. Qualitative methods (in-depth interviews and mapping activities) were conducted with ten young people from refugee backgrounds. Thematic analysis method was used to analyse the data. Findings suggested that the young refugees face various structural and cultural inequalities that significantly influenced their health and well-being. Mental health well-being was their greatest health concern. All reported the significant influence the English language had on their ability to adapt and form connections with their social environment. The presence of positive social support in their new social environment had a great impact on the health and well-being of the participants. The findings of this study have implications for social justice among refugees. They also contributed to the role of therapeutic landscapes and social support in helping young refugees to feel that they belonged to the society, and hence assisted them to adapt to their new living situation.

Keywords: young refugees, Middle-Eastern, social support, social justice

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Authors: Ahmed Guerine, Ali El Hafidi, Bruno Martin, Philippe Leclaire

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This paper investigates the nonlinear dynamic response of a mechanical torque limiter which is used to protect drive parts from overload (helical transmission gears). The system is driven by four excitations: two external excitations (aerodynamics torque and force) and two internal excitations (two mesh stiffness fluctuations). In this work, we develop a dynamic model with lumped components and 28 degrees of freedom. We use the Runge Kutta step-by-step time integration numerical algorithm to solve the equations of motion obtained by Lagrange formalism. The numerical results have allowed us to identify the sources of vibration in the wind turbine. Also, they are useful to help the designer to make the right design and correctly choose the times for maintenance.

Keywords: two-stage helical gear, lumped model, dynamic response, torque-limiter

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Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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Authors: Ayman Abd-Elhamed, Sayed Mahmoud

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The present research work investigates the seismic response of reinforced concrete (RC) frame building considering the effect of modeling masonry infill (MI) walls. The seismic behavior of a residential 6-storey RC frame building, considering and ignoring the effect of masonry, is numerically investigated using response spectrum (RS) analysis. The considered herein building is designed as a moment resisting frame (MRF) system following the Egyptian code (EC) requirements. Two developed models in terms of bare frame and infill walls frame are used in the study. Equivalent diagonal strut methodology is used to represent the behavior of infill walls, whilst the well-known software package ETABS is used for implementing all frame models and performing the analysis. The results of the numerical simulations such as base shear, displacements, and internal forces for the bare frame as well as the infill wall frame are presented in a comparative way. The results of the study indicate that the interaction between infill walls and frames significantly change the responses of buildings during earthquakes compared to the results of bare frame building model. Specifically, the seismic analysis of RC bare frame structure leads to underestimation of base shear and consequently damage or even collapse of buildings may occur under strong shaking. On the other hand, considering infill walls significantly decrease the peak floor displacements and drifts in both X and Y-directions.

Keywords: masonry infill, bare frame, response spectrum, seismic response

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Authors: Manfred F. Maute, Olga Naumenko, Raymond T. Kong

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Using data from a nationally representative financial panel of Canadian households, this study develops a psychographic segmentation of the customers of a value-expressive credit card service and tests for effects on relational response differences. The variety of segments elicited by agglomerative and k means clustering and the familiar profiles of individual clusters suggest that the face validity of the psychographic segmentation was quite high. Segmentation had a significant effect on customer satisfaction and relationship depth. However, when socio-demographic characteristics like household size and income were accounted for in the psychographic segmentation, the effect on relational response differences was magnified threefold. Implications for the segmentation of financial services markets are considered.

Keywords: customer satisfaction, financial services, psychographics, response differences, segmentation

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Authors: M. S. Al-Assiri, M. M. El-Desoky, A. A. Bahgat

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Nanocrystalline thin film of Na0.1V2O5.nH2O xerogel obtained by sol-gel synthesis was used as a gas sensor. Gas sensing properties of different gases such as hydrogen, petroleum and humidity were investigated. Applying XRD and TEM the size of the nanocrystals is found to be 7.5 nm. SEM shows a highly porous structure with submicron meter-sized voids present throughout the sample. FTIR measurement shows different chemical groups identifying the obtained series of gels. The sample was n-type semiconductor according to the thermoelectric power and electrical conductivity. It can be seen that the sensor response curves from 130°C to 150°C show a rapid increase in sensitivity for all types of gas injection, low response values for heating period and the rapid high response values for cooling period. This result may suggest that this material is able to act as gas sensor during the heating and cooling process.

Keywords: sol-gel, thermoelectric power, XRD, TEM, gas sensing

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Authors: Frida Carrillo Morales, Maria Maricela Carrasco Yépez, Saúl Rojas Hernández

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Naegleria fowleri is the causative agent of primary amebic meningoencephalitis, this disease is acute and fulminant that affects humans. It has been reported that despite the existence of therapeutic options against this disease, its mortality rate is 97%. Therefore, the need arises to have vaccines that confer protection against this disease and, in addition to developing adjuvants to enhance the immune response. In this regard, in our work group, we obtained a peptide designed from the membrane protein MP2CL5 of Naegleria fowleri called Smp145 that was shown to be immunogenic; however, it would be of great importance to enhance its immunological response, being able to co-administer it with a non-toxic adjuvant. Therefore, the objective of this work was to carry out the bioinformatic design of a peptide of the Naegleria fowleri membrane protein MP2CL5 conjugated with a non-toxic modified adjuvant from the native A1 structure of Cholera Toxin. For which different bioinformatics tools were used to obtain a model with a modification in amino acid 61 of the A1 subunit of the CT (CTA1), to which the Smp145 peptide was added and both molecules were joined with a 13-glycine linker. As for the results obtained, the modification in CTA1 bound to the peptide produces a reduction in the toxicity of the molecule in in silico experiments, likewise, the prediction in the binding of Smp145 to the receptor of B cells suggests that the molecule is directed in specifically to the BCR receptor, decreasing its native enzymatic activity. The stereochemical evaluation showed that the generated model has a high number of adequately predicted residues. In the ERRAT test, the confidence with which it is possible to reject regions that exceed the error values was evaluated, in the generated model, a high score was obtained, which determines that the model has a good structural resolution. Therefore, the design of the conjugated peptide in this work will allow us to proceed with its chemical synthesis and subsequently be able to use it in the mouse meningitis protection model caused by N. fowleri.

Keywords: immunology, vaccines, pathogens, infectious disease

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Robespierre Chavez, Eden Bojorquez, Alfredo Reyes-Salazar

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This study compares the seismic response of regular and vertically irregular steel frames determined by nonlinear time history analysis and by using several sets of earthquake records, which are divided in two categories: The first category having 20 stiff-soil ground motion records obtained from the NGA database, and the second category having 30 soft-soil ground motions recorded in the Lake Zone of Mexico City and exhibiting a dominant period (Ts) of two seconds. The steel frames in both format regular and irregular were designed according to the Mexico City Seismic Design Provisions (MCSDP). The effects of irregularity throught the height on the maximum interstory drifts are estimated.

Keywords: irregular steel frames, maximum interstory drifts, seismic response, seismic records

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Authors: M. Eskandarighadi, C. R. McGann

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It is observed from past experiences of earthquakes that local site conditions can significantly affect the strong ground motion characteristics experience at the site. One-dimensional seismic site response analysis is the most common approach for investigating site response. This approach assumes that soil is homogeneous and infinitely extended in the horizontal direction. Therefore, tying side boundaries together is one way to model this behavior, as the wave passage is assumed to be only vertical. However, 1D analysis cannot capture the 2D nature of wave propagation, soil heterogeneity, and 2D soil profile with features such as inclined layer boundaries. In contrast, 2D seismic site response modeling can consider all of the mentioned factors to better understand local site effects on strong ground motions. 2D wave propagation and considering that the soil profile on the two sides of the model may not be identical clarifies the importance of a boundary condition on each side that can minimize the unwanted reflections from the edges of the model and input appropriate loading conditions. Ideally, the model size should be sufficiently large to minimize the wave reflection, however, due to computational limitations, increasing the model size is impractical in some cases. Another approach is to employ free-field boundary conditions that take into account the free-field motion that would exist far from the model domain and apply this to the sides of the model. This research focuses on implementing free-field boundary conditions in OpenSees for 2D site response analysisComparisons are made between 1D models and 2D models with various boundary conditions, and details and limitations of the developed free-field boundary modeling approach are discussed.

Keywords: boundary condition, free-field, opensees, site response analysis, wave propagation

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Authors: Sai Hung Cheung, Zhe Shao

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It is of our great interest to quantify the risk to structural dynamic systems due to earthquake-induced tsunamis in view of recent earthquake-induced tsunamis in Padang, 2004 and Tohoku, 2011 which brought huge losses of lives and properties. Despite continuous advancement in computational simulation of the tsunami and wave-structure interaction modeling, it still remains computationally challenging to evaluate the reliability of a structural dynamic system when uncertainties related to the system and its modeling are taken into account. The failure of the structure in a tsunami-wave-structural system is defined as any response quantities of the system exceeding specified thresholds during the time when the structure is subjected to dynamic wave impact due to earthquake-induced tsunamis. In this paper, an approach based on a novel integration of a recently proposed moving least squares response surface approach for stochastic sampling and the Subset Simulation algorithm is proposed. The effectiveness of the proposed approach is discussed by comparing its results with those obtained from the Subset Simulation algorithm without using the response surface approach.

Keywords: response surface, stochastic simulation, structural reliability tsunami, risk

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Authors: Mohammad Mahdi Mohammadi Dehnavi, Alessandra De Angelis, Maria Rosaria Pecce

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This paper deals with the role of studs in the structural response of steel-concrete composite beams. A tri-linear slip-shear strength law is assumed according to literature and codes provisions for developing a finite element (FE) model of a case study of a composite deck. The variation of the strength and ductility of the connection is implemented in the numerical model carrying out nonlinear analyses. The results confirm the utility of the model to evaluate the importance of the studs capacity, ductility and strength on the global response (ductility and strength) of the structures but also to analyze the trend of slip and shear at interface along the beams.

Keywords: stud connectors, finite element method, slip, shear load, steel-concrete composite bridge

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Authors: Ammara Khan

Abstract:

Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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Authors: Mahdi Asghari Ozma

Abstract:

Background and Objective:Maclurapomifera (Rafin.) Schneider, known as osage orange, is a north american native plant which has multiple applications in herbal medicine. The extract of this plant has many therapeutic effects, including antimicrobial, anti-tumor, anti-inflammation, etc., that discussed in this study. Materials and Methods: For this study, the keywords "Maclurapomifera", "osage orange, ""herbal medicine ", and "plant extract" in the databases PubMed and Google Scholar between 2002 and 2021 were searched, and 20 articles were chosen, studied and analyzed. Results: Due to the increased resistance of microbes to antibiotics, the need for antimicrobial plants is increasing. Maclurapomifera is one of the plants with antimicrobial properties that can affect all microbes, especially Gram-negative bacteria, and fungi. This plant also has anti-tumor, anti-inflammatory, anti-oxidant, anti-aging, antiviral, anti-fungal, anti-ulcerogenic, anti-diabetic, and anti-nociceptive effects, which can be used as a substance with many amazing therapeutic applications. Conclusion: These results suggest that the extract of Maclurapomifera can be used in clinical medicine as a remedial agent, which can be substituted for chemical drugs or help them in the treatment of diseases.

Keywords: maclura pomifera, osage orange, herbal medicine, plant extract

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Authors: Chih-Rong Shyr, Chi-Ping Huang

Abstract:

Intravesical BCG is the gold-standard therapy for high risk non-muscle invasive bladder cancer (NMIBC) after TURBT, but if not responsive to BCG, these BCG unresponsive patients face cystectomy that causes morbidity and comes with a morality risk. To provide the bladder sparing options for patients with BCG-unresponsive NMIBC, several new treatments have been developed to salvage the bladders and prevent progression to muscle invasive or metastatic, but however, most approved or developed treatments still fail in a significant proportion of patients without long term success. Thus more treatment options and the combination of different therapeutic modalities are urgently needed to change the outcomes. Xenogeneic rejection has been proposed to a mechanism of action to induce anti-tumor immunity for the treatment of cancers due to the similarities between rejection mechanism to xenoantigens (proteins, glycans and lipids) and anti-tumor immunities to tumor specific antigens (neoantigens, tumor associated carbohydrates and lipids). Xenogeneic urothelial cells (XUC) of porcine origin have been shown to induce anti-tumor immune responses to inhibit bladder tumor progression in mouse bladder cancer models. To further demonstrate the efficacy of the distinct intravesical XUC treatment in NMIBC, and the combined effects with chemotherapy and immune checkpoint inhibitors (ICIs) as a alternate therapeutic option, this study investigated the therapeutic effects and mechanisms of intravesical XUC immunotherapy in an orthotopic mouse immune competent model of NMIBC, generated from a mouse bladder cancer cell line. We found that the tumor progression was inhibited by intravescial XUC treatment and there was a synergy between intravesical XUC with intravesical chemotherapeutic agent, gemcitabine or systemic ICI, anti-PD1 antibody treatment. The cancer cell proliferation was decreased but the cell death was increased by the intravecisal XUC treatment. Most importantly, the mechanisms of action of intravesical XUC immunotherapy were found to be linked to enhanced infiltration of CD4+ and CD8+ T-cell as well as NK cells, but decreased presence of myeloid immunosuppressive cells in XUC treated tumors. The increased stimulation of immune cells of XUC treated mice to xenogeneic urothelial cells and mouse bladder cancer cells in immune cell proliferation and cytokine secretion were observed both as a monotherapy and in combination with intravesical gemcitabine or systemic anti PD-L1 treatment. In sum, we identified the effects of intravesical XUC treatment in monotherapy and combined therapy on tumor progression and its cellular and molecular events related to immune activation to understand the anti-tumoral mechanisms behind intravesical XUC immunotherapy for NMIBC. These results contribute to the understanding of the mechanisms behind successful xenogeneic cell immunotherapy against NMIBC and characterize a novel therapeutic approach with a new xenogeneic cell modality for BCG-unresponsive NMIBC.

Keywords: xenoantigen, neoantigen, rejection, immunity

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Authors: Galit Harel

Abstract:

Deborah was referred for psychoanalytic psychotherapy following a suicide attempt and depression. She began a fascinating journey spanning more than 10 years. During therapy, many questions arose concerning the suicidal episode, which she could not register consciously. The author tried to understand the reasons for her depression and the attempted suicide through the unconscious process in the therapeutic relationship and through the music and poetry that she brought to sessions. In this paper, the author describes the process of listening for the signifiers of semiotic and symbolic language, both metaphoric and metonymic, as revealed in poetry and music according to the theories of Kristeva and Lacan. The poetry enabled the patient to retrieve childhood memories, experience the movement from unconscious to conscious, and mourn through the experience of transference and countertransference in the therapeutic relationship. Also illustrated is the transition from singing the music to more symbolic language, turning the patient’s sensory experience into language, and connecting her personal experience with the culture of her past. The patient’s mourning and the lost love objects are discussed through the prism of classical and object relations theories.

Keywords: depression, lost love object, psychoanalytic psychotherapy, suicide attempt, symbolization of desire

Procedia PDF Downloads 92