Search results for: exponential expression profile

Authors: Fabiola M. Villalobos-Castaldi, Nicolás C. Kemper, Esther Rojas-Krugger, Laura G. Ramírez-Sánchez

Abstract:

This paper presents the classification results about exploring the combination of a motion based approach with a local appearance method to describe the facial motion caused by the muscle contractions and expansions that are presented in facial expressions. The proposed feature extraction method take advantage of the knowledge related to which parts of the face reflects the highest deformations, so we selected 4 specific facial regions at which the appearance descriptor were applied. The most common used approaches for feature extraction are the holistic and the local strategies. In this work we present the results of using a local appearance approach estimating the correlation coefficient to the 4 corresponding landmark-localized facial templates of the expression face related to the neutral face. The results let us to probe how the proposed motion estimation scheme based on the local appearance correlation computation can simply and intuitively measure the motion parameters for some of the most relevant facial regions and how these parameters can be used to recognize facial expressions automatically.

Keywords: facial expression recognition system, feature extraction, local-appearance method, motion-based approach

Procedia PDF Downloads 409

Authors: A. Pesin, D. Pustovoytov, A. Kolesnik, M. Sverdlik

Abstract:

Rolling disturbances often arise which might lead to defects such as nonflatness, warpage, corrugation, etc. Numerous methods of compensation for such disturbances are well known. However, most of them preserve the initial form of transverse flow of the strip, such as convex, concave or asymmetric (for example, sphenoid). Sometimes, the form inherited (especially asymmetric) is undesirable. Technical solutions have been developed which include providing conditions for transverse metal flow in deformation zone. It should be noted that greater reduction is followed by transverse flow increase, while less reduction causes a corresponding decrease in metal flow for differently deformed metal lengths to remain approximately the same and in order to avoid the defects mentioned above. One of the solutions suggests sequential strip deforming from rectangular cross-section profile with periodical rectangular grooves back into rectangular profile again. The work was carried out in DEFORM 3D program complex. Experimental rolling was performed on laboratory mill 150. Comparison of experimental and theoretical results demonstrated good correlation.

Keywords: FEM, cross-section deformation, mechanical engineering, applied mechanics

Procedia PDF Downloads 345

Authors: Maryam Monazzah, Ronak Samadpour, Mehdi Nasr-esfahani, Fatemeh Qalavand, Marziye Motamedi

Abstract:

Bipolaris sorokiniana, and Heterodera filipjevi, are important wheat diseases that lead to yield losses worldwide. Identifying novel resistant sources helps us combat these devastating diseases. In this study, we studied the role of Cre3 gene and antioxidant enzymes in the immune responses of wheat genotypes to H. filipjevi and B. sorokiniana. Therefore, real-time PCR analysis using Cre3 gene marker, a resistant gene to cereal cyst nematodes, was conducted on leaves and roots, along with changes ‎in the activity of antioxidant enzymes, peroxidase, and catalase. Enzyme activity assay was performed on roots attacked by nematode and in leaves infected with Bipolaris. Wheat accessions including “Bam” (resistant), “Parsi” (moderately-resistant), “Azar2”, “Ohadi”, “Homa” (highly-susceptible) were previously screened against both stresses under greenhouse and field conditions. Results showed that Cre3 expression against cyst nematodes was significantly higher in resistant cultivars compared to susceptible cultivars. Cre3 was used in marker-assisted selection programs to identify genotypes carrying resistant genes to cyst nematodes. Interestingly, Cre3 was also up-regulated in both tissues of resistant cultivars to B. sorokiniana. Therefore, Cre3 in wheat similarly modulates immunity against B. sorokiniana and might be one of the central components of the induced immune system in wheat. The activity of antioxidant enzymes also indicated the highest increase in resistant genotypes upon both stresses that subsequently neutralize oxidative stress in tissues and decrease damage. Further studies on these resistance components may help us gain insight into the molecular basis of resistance and shed new light on the interaction and overlap between different forms of stress.

Keywords: Bipolaris sorokiniana, Heterodera filipjevi, resistant gene expression, wheat

Procedia PDF Downloads 85

Authors: Jahanshah Ashkani, Kevin J. Naidoo

Abstract:

Glycosylation is the major posttranslational modification (PTM) process in cellular development. In tumour development, it is marked by structural alteration of carbohydrates (glycans) that is the result of aberrant glycosylation. Altered glycan structures affect cell surface ligand-receptor interactions that interfere with the regulation of cell adhesion, migration, and proliferation. The resulting changes in glycan biosynthesis pathways originate from altered expression of glycosyltransferases and glycosidases. While the alteration in glycosylation patterns is a recognized “hallmark of cancer”, the influential overview of the biology of cancer proposes eight hallmarks with no explicit suggestion to connectivity with glycosylation. Recently, we have discovered a connection between the glycosyltransferase gene expression and cancer type and subtype. Here we present an association between aberrant glycosylation and the biological hallmarks of breast cancer by exploring the common regulatory mechanisms at the genomic scale. The result of this study bridges the glycobiological and biological pathways that are accepted hallmarks of cancer by connecting their common regulatory pathways. This is an impetus for further investigation as target therapies of breast cancer are very likely to be uncovered from this.

Keywords: aberrant glycosylation, biological hallmarks, breast cancer, regulatory mechanism

Procedia PDF Downloads 245

Authors: Leelavinothan Pari , Ayyasamy Rathinam

Abstract:

Diabetes mellitus (DM) is a major and growing public health problem throughout the world. Pterocarpus marsupium (Roxb.) (Family: Fabaceae) is widely used as a traditional medicine to treat various diseases including diabetes. However, the molecular mechanism of Pterocarpus marsupium has not been investigated so far. Two fractions (2.5% and 5%) of extract from the medicinal plant, Pterocarpus marsupium (PME) were conducted in a dose dependent manner in streptozotocin (45 mg/kg b.w.) induced type 2 diabetic rats. Each fraction of PME was administered to diabetic rats intragastrically at a dose of 50, 100 and 200 mg/kg b.w for 45 days. The effective dose 200 mg/kg b.w of 5% fraction was more pronounced in reducing the levels of blood glucose (95.65 mg/dL) and glycosylated hemoglobin (HbA1c) (0.41 mg/g Hb), and increasing the plasma insulin (16.20 µU/mL) level. Moreover, PME (200 mg/kg b.w) significantly ameliorated lipid peroxidation products (thiobarbituric reactive substances, lipid hydroperoxides) enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E and reduced glutathione) levels. The altered activities of the key enzymes of lipid metabolism along with the lipid profile in diabetic rats were significantly reverted to near normal levels by the administration of PME 5% 200 mg/kg b.w fraction. PME (200 mg/kg b.w) has the ability to reduce the inflammatory cytokines, such as TNF-α, IL-6 mRNA, as well as protein expression and apoptotic marker, such as caspase-3 enzyme in diabetic hepatic tissue. The above biochemical findings were also supported by histological studies such as improvement in pancreas and liver. Pterocarpus marsupium could effectively reduce the hyperglycemia, oxidative-stress, inflammation and hyperlipedimea in diabetic rats; hence it could be a useful drug in the management of diabetes without any side effects.

Keywords: diabetes mellitus, streptozotocin, Pterocarpus marsupium, lipid peroxidation, Antioxidants, inflammatory cytokines

Procedia PDF Downloads 372

Authors: Nizar Chaira

Abstract:

Dates, main products of the oases, due to their therapeutic interests, are considered highly nutritious fruit. Several studies on the valuation biotechnology and technology of dates are made, and several products are already prepared. Isolation of the yeast Saccharomyces cerevisiae, naturally presents in a scrap of date, optimization of growth in the medium based on date syrup and production biomass can potentially expand the range of secondary products of dates. To this end, this paper tries to study the suitability for processing dates technology and biotechnology to use the date pulp as a carbon source for biological transformation. Two strains of Saccharomyces cerevisiae isolated from date syrup (S1, S2) and a commercial strain have used for this study. After optimization of culture conditions, production in a fermenter on two different media (date syrup and beet molasses) was performed. This is followed by studying the kinetics of growth, protein production and consumption of sugars in crops strain 1, 2 and the commercial strain and on both media. The results obtained showed that a concentration of 2% sugar, 2.5 g/l yeast extract, pH 4.5 and a temperature between 25 and 35°C are the optimal conditions for cultivation in a bioreactor. The exponential phase of the specific growth rate of a strain on both media showed that it is about 0.3625 h-1 for the production of a medium based on date syrup and 0.3521 h-1 on beet molasses with a generation time equal to 1.912 h and on the medium based on date syrup, yeast consumes preferentially the reducing sugars. For the production of protein, we showed that this latter presents an exponential phase when the medium starts to run out of reducing sugars. For strain 2, the specific growth rate is about 0.261h-1 for the production on a medium based on date syrup and 0207 h-1 on beet molasses and the base medium syrup date of the yeast consumes preferentially reducing sugars. For the invertase and other metabolits, these increases rapidly after exhaustion of reducing sugars. The comparison of productivity between the three strains on the medium based on date syrup showed that the maximum value is obtained with the second strain: p = 1072 g/l/h as it is about of 0923 g/l/h for strain 1 and 0644 g/l/h for the commercial strain. Thus, isolates of date syrup are more competitive than the commercial strain and can give the same performance in a shorter time with energy gain.

Keywords: date palm, fermentation, molasses, Saccharomyces, syrup

Procedia PDF Downloads 317

Authors: Muhammad Abu-Khaizaran, Ahmad Faza’, Tariq Othman, Yahia Yousef

Abstract:

This paper presents a study to provide sufficient and reliable information about constructing a Photovoltaic energy profile of the Birzeit University campus (BZU) based on the weather forecast. The developed Photovoltaic energy profile helps to predict the energy yield of the Photovoltaic systems based on the weather forecast and hence helps planning energy production and consumption. Two models will be developed in this paper; a Clear Sky Irradiance model and a Cloud-Cover Radiation model to predict the irradiance for a clear sky day and a cloudy day, respectively. The adopted procedure for developing such models takes into consideration two levels of abstraction. First, irradiance and weather data were acquired by a sensory (measurement) system installed on the rooftop of the Information Technology College building at Birzeit University campus. Second, power readings of a fully operational 51kW commercial Photovoltaic system installed in the University at the rooftop of the adjacent College of Pharmacy-Nursing and Health Professions building are used to validate the output of a simulation model and to help refine its structure. Based on a comparison between a mathematical model, which calculates Clear Sky Irradiance for the University location and two sets of accumulated measured data, it is found that the simulation system offers an accurate resemblance to the installed PV power station on clear sky days. However, these comparisons show a divergence between the expected energy yield and actual energy yield in extreme weather conditions, including clouding and soiling effects. Therefore, a more accurate prediction model for irradiance that takes into consideration weather factors, such as relative humidity and cloudiness, which affect irradiance, was developed; Cloud-Cover Radiation Model (CRM). The equivalent mathematical formulas implement corrections to provide more accurate inputs to the simulation system. The results of the CRM show a very good match with the actual measured irradiance during a cloudy day. The developed Photovoltaic profile helps in predicting the output energy yield of the Photovoltaic system installed at the University campus based on the predicted weather conditions. The simulation and practical results for both models are in a very good match.

Keywords: clear-sky irradiance model, cloud-cover radiation model, photovoltaic, weather forecast

Procedia PDF Downloads 126

Authors: Ram Sharan Mehta, Sanjeev Sharma

Abstract:

Introduction: Haemodialysis (HD) is a mechanical process of removing waste products from the blood and replacing essential substances in patients with renal failure. First artificial kidney developed in Netherlands in 1943 AD First successful treatment of CRF reported in 1960AD, life-saving treatment begins for CRF in 1972 AD. In 1973 AD Medicare took over financial responsibility for many clients and after that method become popular. BP Koirala institute of health science is the only center outside the Kathmandu, where HD service is available. In BPKIHS PD started in Jan.1998, HD started in August 2002 till September 2003 about 278 patients received HD. Day by day the number of HD patients is increasing in BPKIHS as with institutional growth. No such type of study was conducted in past hence there is lack of valid & reliable baseline data. Hence, the investigators were interested to conduct the study on " Profile of the Renal Failure patients under Haemodialysis at B.P. Koirala Institute of Health Sciences Nepal". Objectives: The objectives of the study were: to find out the Socio-demographic characteristics of the patients, to explore the knowledge of the patients regarding disease process and Haemodialysis and to identify the problems encountered by the patients. Methods: It is a hospital-based exploratory study. The population of the study was the clients under HD and the sampling method was purposive. Fifty-four patients undergone HD during the period of 17 July 2012 to 16 July 2013 of complete one year were included in the study. Structured interview schedule was used for collect data after obtaining validity and reliability. Results: Total 54 subjects had undergone for HD, having age range of 5-75 years and majority of them were male (74%) and Hindu (93 %). Thirty-one percent illiterate, 28% had agriculture their occupation, 80% of them were from very poor community, and about 30% subjects were unaware about the disease they suffering. Majority of subjects reported that they had no complications during dialysis (61%), where as 20% reported nausea and vomiting, 9% Hypotension, 4% headache and 2%chest pain during dialysis. Conclusions: CRF leading to HD is a long battle for patients, required to make major and continuous adjustment, both physiologically and psychologically. The study suggests that non-compliance with HD regimen were common. The socio-demographic and knowledge profile will help in the management and early prevention of disease and evaluate aspects that will influence care and patients can select mode of treatment themselves properly.

Keywords: profile, haemodialysis, Nepal, patients, treatment

Procedia PDF Downloads 373

Authors: Luis Enrique Bautista-Hinojosa, Luis A. Herrera, Cristian Arriaga-Canon

Abstract:

Text should be written in the third person. Please avoid using "I" “my” or the pronoun "one". It is best to say "It is believed..." rather than "I believe..." or "One believes...".

Keywords: transcriptomics, co-expression, cancer, biomarkers

Procedia PDF Downloads 69

Authors: Chia-Wen Yeh, Ting-Sheng Lin, Chih-Han Chang

Abstract:

Pressure garment has been used to prevent and treat the hypertrophic scars following serious burns since 1970s. The use of pressure garment is believed to hasten the maturation process and decrease the highness of scars. Pressure garment is custom made by reducing circumferential measurement of the patient by 10%~20%, called Reduction Factor. However the exact reducing value used depends on the subjective judgment of the therapist and the feeling of patients throughout the try and error process. The Laplace Law can be applied to calculate the pressure from the dimension of the pressure garment by the circumferential measurements of the patients and the tension profile of the fabrics. The tension profile currently obtained neglects the stress relaxation and hysteresis effect within most elastic fabrics. The purpose of this study was to investigate the influence of the tension attenuation, from stress relaxation and hysteresis effect of the fabrics. Samples of pressure garment were obtained from Sunshine Foundation Organization, a nonprofit organization for burn patients in Taiwan. The wall tension profile of pressure garments were measured on a material testing system. Specimens were extended to 10% of the original length, held for 1 hour for the influence of the stress relaxation effect to take place. Then, specimens were extended to 15% of the original length for 10 seconds, then reduced to 10% to simulate donning movement for the influence of the hysteresis effect to take place. The load history was recorded. The stress relaxation effect is obvious from the load curves. The wall tension is decreased by 8.5%~10% after 60mins of holding. The hysteresis effect is obvious from the load curves. The wall tension is increased slightly, then decreased by 1.5%~2.5% and lower than stress relaxation results after 60mins of holding. The wall tension attenuation of the fabric exists due to stress relaxation and hysteresis effect. The influence of hysteresis is more than stress relaxation. These effect should be considered in order to design and evaluate the pressure of pressure garment more accurately.

Keywords: hypertrophic scars, hysteresis, pressure garment, stress relaxation

Procedia PDF Downloads 508

Authors: Reham H. Soliman, Noha Noufal, Howayda AbdelAal

Abstract:

Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase (MAGUK) family and has been proposed as a mediator of cell-cell adhesion and proliferation, which can contribute to tumorogenesis. CASK has been linked as a good prognostic factor with some tumor subtypes, while considered as a poor prognostic marker in others. To our knowledge, no sufficient evidence of CASK role in colorectal cancer is available. The aim of this study is to evaluate the expression of Calcium/calmodulin-dependent serine protein kinase (CASK) in non-mucinous colorectal adenocarcinoma and adenomatous polyps as precursor lesions and assess its prognostic significance. The study included 42 cases of conventional colorectal adenocarcinoma and 15 biopsies of adenomatous polyps with variable degrees of dysplasia. They were reviewed for clinicopathological prognostic factors and stained by CASK; mouse, monoclonal antibody using heat-induced antigen retrieval immunohistochemical techniques. The results showed that CASK protein was significantly overexpressed (p <0.05) in CRC compared with adenoma samples. The CASK protein was overexpressed in the majority of CRC samples with 85.7% of cases showing moderate to strong expression, while 46.7% of adenomas were positive. CASK overexpression was significantly correlated with both TNM stage and grade of differentiation (p <0.05). There was a significantly higher expression in tumor samples with early stages (I/II) rather than advanced stage (III/IV) and with low grade (59.5%) rather than high grade (40.5%). Another interesting finding was found among the adenomas group, where the stronger intensity of staining was observed in samples with high grade dysplasia (33.3%) than those of lower grades (13.3%). In conclusion, this study shows that there is significant overexpression of CASK protein in CRC as well as in adenomas with high grade dysplasia. This indicates that CASK is involved in the process of carcinogenesis and functions as a potential trigger of the adenoma-carcinoma cascade. CASK was significantly overexpressed in early stage and low-grade tumors rather than tumors with advanced stage and higher histological grades. This suggests that CASK protein is a good prognostic factor. We suggest that CASK affects CRC in two different ways derived from its physiology. CASK as part of MAGUK family can stimulate proliferation and through its cell membrane localization and as a mediator of cell-cell adhesion might contribute in tumor confinement and localization.

Keywords: CASK, colorectal cancer, overexpression, prognosis

Procedia PDF Downloads 276

Authors: Attahiru Sifawa Ahmad

Abstract:

The media; electronic, print, and social, is playing very significant roles towards promoting political awareness and stability of any nation. However, for the media to play its role effectively, a clear and sound grasp of the language of communication is necessary. Otherwise, there is the tendency of the media spreading wrong and, or, misinterpreted information to the public, capable of generating rancour and political instability. One such clear misinterpretation or misrepresentation of information was the Hausa metaphorical expression, Kare Jinni Biri Jinni quoted from the statement made by Rtd. General Muhammadu Buhari, sometimes in April, 2013, while addressing his supporters from Niger State. In the political presentation of the term Kare - Jini Biri – Jini, quoted and translated by many print media in Nigeria, it was interpreted to mean; ‘The Dog and the Baboon will be soaked in blood’, denoting bloodshed and declaration of war. However, the term Kare - jini Biri - Jini, literally; the Dog with blood and the Baboon with blood, or, the Dog is bleeding the Baboon is bleeding, or, both the Dog and the Baboon sustained injuries. It is a metaphorical expression denoting a hot competition, and serious struggle, between two competing parties that are closer in strength and stamina. The expression got its origin among the hunting communities in traditional Hausa Societies. From experience, it was always not easy to wrestle and hunt Baboon by the Hunter’s Dog. In many instances, it ended a futile exercise, and even at instances whereby the latter hunted the former, it would be after a serious struggle with both two sustaining injuries. This paper seeks to highlight the poverty of vocabulary, and poor grasp of Nigerian languages among Journalists and young citizens in the country. The paper, therefore, advocated for the retention and effective teaching of the indigenous languages in primary and secondary school’s curriculums in Nigeria. The paper equally analysed the political origin of the print media in Nigeria, how since its first appearance, the print Media is being assigned very important political role by political elites in the country.

Keywords: Baboon, dog, media, politics

Procedia PDF Downloads 216

Authors: Abdelkader Hocine, Abdelhakim Maizia

Abstract:

The exponential growth of reinforced fibers composite materials use has prompted researchers to step up their work on the prediction of their reliability. Owing to differences between the properties of the materials used for the composite, the manufacturing processes, the load combinations and types of environment, the prediction of the reliability of composite materials has become a primary task. Through failure criteria, TSAI-WU and the maximum stress, the reliability of multilayer tubular structures under pressure is the subject of this paper, where the failure probability of is estimated by the method of Monte Carlo.

Keywords: composite, design, monte carlo, tubular structure, reliability

Procedia PDF Downloads 457

Authors: Robert Kimutai Tewo, Hilary Limo Rutto, Tumisang Seodigeng

Abstract:

The rheological and morphological properties of paraffin wax, linear low-density polyethylene (LLDPE), and poly (methyl methacrylate) (PMMA) microbeads formulations were prepared via an extrusion process. The blends were characterized by rheometry, scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The results indicated that the viscosity of the blends increased as compared to that of neat wax. SEM confirmed that LLDPE alters the wax crystal habit at higher concentrations. The rheological experimental data fitted with predicted data using the modified Krieger and Dougherty expression. The SEM micrograph of wax/LLDPE/PMMA revealed a near-perfect spherical nature for the filler particles in the wax/EVA polymer matrix. The FT-IR spectra show the deformation vibrations stretch of a long-chain aliphatic hydrocarbon (C-H) and also the presence of carbonyls absorption group denoted by -C=O- stretch.

Keywords: investment casting pattern, paraffin wax, LLDPE, PMMA, rheological properties, modified Krieger and Dougherty expression

Procedia PDF Downloads 163

Authors: Rashi Rajput, Manisha Singh

Abstract:

Escitalopram oxalate (ETP), an FDA approved antidepressant drug from the category of SSRI (selective serotonin reuptake inhibitor) and is used in treatment of general anxiety disorder (GAD), major depressive disorder (MDD).When taken orally, it is metabolized to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT) in the liver with the help of enzymes CYP2C19, CYP3A4 and CYP2D6. Hence, causing side effects such as dizziness, fast or irregular heartbeat, headache, nausea etc. Therefore, targeted and sustained drug delivery will be a helpful tool for increasing its efficacy and reducing side effects. The present study is designed for formulating mucoadhesive nanoparticle formulation for the same Escitalopram loaded polymeric nanoparticles were prepared by ionic gelation method and characterization of the optimised formulation was done by zeta average particle size (93.63nm), zeta potential (-1.89mV), TEM (range of 60nm to 115nm) analysis also confirms nanometric size range of the drug loaded nanoparticles along with polydispersibility index of 0.117. In this research, we have studied the in vitro drug release profile for ETP nanoparticles, through a semi permeable dialysis membrane. The three important characteristics affecting the drug release behaviour were – particle size, ionic strength and morphology of the optimised nanoparticles. The data showed that on increasing the particle size of the drug loaded nanoparticles, the initial burst was reduced which was comparatively higher in drug. Whereas, the formulation with 1mg/ml chitosan in 1.5mg/ml tripolyphosphate solution showed steady release over the entire period of drug release. Then this data was further validated through mathematical modelling to establish the mechanism of drug release kinetics, which showed a typical linear diffusion profile in optimised ETP loaded nanoparticles.

Keywords: ionic gelation, mucoadhesive nanoparticle, semi-permeable dialysis membrane, zeta potential

Procedia PDF Downloads 288

Authors: Samia Moulebhar, Chahrazed Bendenia, Souhila Bendenia, Hanaa Merad-dib, Sarra Merabet, Sid Ahmed Khantar, Baghdad Hadri

Abstract:

The photovoltaic solar field is today experiencing exponential advancement with the exploitation of new technological sectors of nanoparticles, namely the field of solar cells based on organic polymer materials. These cells are flexible, easy to process and low cost. This work includes a presentation of the conjugated polymer materials used in the design of photovoltaic technology devices while determining their properties and then the models used for the modeling of thin film photovoltaic cells heterojunction.

Keywords: photovoltaic, cells, nanoparticles, organic

Procedia PDF Downloads 75

Authors: Ayon Mukherjee

Abstract:

Covariate-adjusted response-adaptive (CARA) designs use the available responses to skew the treatment allocation in a clinical trial in towards treatment found at an interim stage to be best for a given patient's covariate profile. Extensive research has been done on various aspects of CARA designs with the patient responses assumed to follow a parametric model. However, ranges of application for such designs are limited in real-life clinical trials where the responses infrequently fit a certain parametric form. On the other hand, robust estimates for the covariate-adjusted treatment effects are obtained from the parametric assumption. To balance these two requirements, designs are developed which are free from distributional assumptions about the survival responses, relying only on the assumption of proportional hazards for the two treatment arms. The proposed designs are developed by deriving two types of optimum allocation designs, and also by using a distribution function to link the past allocation, covariate and response histories to the present allocation. The optimal designs are based on biased coin procedures, with a bias towards the better treatment arm. These are the doubly-adaptive biased coin design (DBCD) and the efficient randomized adaptive design (ERADE). The treatment allocation proportions for these designs converge to the expected target values, which are functions of the Cox regression coefficients that are estimated sequentially. These expected target values are derived based on constrained optimization problems and are updated as information accrues with sequential arrival of patients. The design based on the link function is derived using the distribution function of a probit model whose parameters are adjusted based on the covariate profile of the incoming patient. To apply such designs, the treatment allocation probabilities are sequentially modified based on the treatment allocation history, response history, previous patients’ covariates and also the covariates of the incoming patient. Given these information, an expression is obtained for the conditional probability of a patient allocation to a treatment arm. Based on simulation studies, it is found that the ERADE is preferable to the DBCD when the main aim is to minimize the variance of the observed allocation proportion and to maximize the power of the Wald test for a treatment difference. However, the former procedure being discrete tends to be slower in converging towards the expected target allocation proportion. The link function based design achieves the highest skewness of patient allocation to the best treatment arm and thus ethically is the best design. Other comparative merits of the proposed designs have been highlighted and their preferred areas of application are discussed. It is concluded that the proposed CARA designs can be considered as suitable alternatives to the traditional balanced randomization designs in survival trials in terms of the power of the Wald test, provided that response data are available during the recruitment phase of the trial to enable adaptations to the designs. Moreover, the proposed designs enable more patients to get treated with the better treatment during the trial thus making the designs more ethically attractive to the patients. An existing clinical trial has been redesigned using these methods.

Keywords: censored response, Cox regression, efficiency, ethics, optimal allocation, power, variability

Procedia PDF Downloads 159

Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

Abstract:

Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

Procedia PDF Downloads 134

Authors: Rahul Saini, Roshan Lal

Abstract:

The present paper deals with the free axisymmetric vibrations of bi-directional functionally graded circular plates using Mindlin’s plate theory and physical neutral surface. The temperature-dependent, as well as temperature-independent mechanical properties of the plate material, varies in radial and transverse directions. Also, temperature profile for one- and two-dimensional temperature variations has been obtained from the heat conduction equation. A simple computational formulation for the governing differential equation of motion for such a plate model has been derived using Hamilton's principle for the clamped and simply supported plates at the periphery. Employing the generalized differential quadrature method, the corresponding frequency equations have been obtained and solved numerically to retain their lowest three roots as the natural frequencies for the first three modes. The effect of various other parameters such as temperature profile, functionally graded indices, and boundary conditions on the vibration characteristics has been presented. In order to validate the accuracy and efficiency of the method, the results have been compared with those available in the literature.

Keywords: bi-directionally FG, GDQM, Mindlin’s circular plate, neutral axis, vibrations

Procedia PDF Downloads 125

Authors: Maysam Mard-Soltani, Mohamad Javad Rasaee, Saeed Khalili, Abdol Karim Sheikhi, Mehdi Hedayati

Abstract:

Production of specific antibody responses against hTSH is a cumbersome process due to the high identity between the hTSH and the other members of the glycoprotein hormone family (FSH, LH and HCG) and the high identity between the human hTSH and host animals for antibody production. Therefore, two polyclonal antibodies were purified against two recombinant proteins. Four possible ELISA tests were designed based on these antibodies. These ELISA tests were checked against hTSH and other glycoprotein hormones, and their sensitivity and specificity were assessed. Bioinformatics tools were used to analyze the immunological properties. After the immunogen region selection from hTSH protein, c terminal of B hTSH was selected and applied. Two recombinant genes, with these cut pieces (first: two repeats of C terminal of B hTSH, second: tetanous toxin+B hTSH C terminal), were designed and sub-cloned into the pET32a expression vector. Standard methods were used for protein expression, purification, and verification. Thereafter, immunizations of the white New Zealand rabbits were performed and the serums of them were used for antibody titration, purification and characterization. Then, four ELISA tests based on two antibodies were employed to assess the hTSH and other glycoprotein hormones. The results of these assessments were compared with standard amounts. The obtained results indicated that the desired antigens were successfully designed, sub-cloned, expressed, confirmed and used for in vivo immunization. The raised antibodies were capable of specific and sensitive hTSH detection, while the cross reactivity with the other members of the glycoprotein hormone family was minimum. Among the four designed tests, the test in which the antibody against first protein was used as capture antibody, and the antibody against second protein was used as detector antibody did not show any hook effect up to 50 miu/l. Both proteins have the ability to induce highly sensitive and specific antibody responses against the hTSH. One of the antibody combinations of these antibodies has the highest sensitivity and specificity in hTSH detection.

Keywords: hTSH, bioinformatics, protein expression, cross reactivity

Procedia PDF Downloads 183

Authors: Xing Wang, Lin Feng, Lingling E., Hongchen Liu

Abstract:

In patients with type 2 diabetes mellitus (DM) there is poorer quality osseointegration than in non-diabetic (n-DM) patients, and the success of dental implants is less. Recent studies have demonstrated that insulin could stimulate bone cells to produce and accelerate implant osseointegration in DM patients.This raised the question whether insulin could provide local bone anabolic effects in non-diabetic patients. In this study,48 SD rats were divided into four groups randomly: DM group, DM+insulin group, n-DM group, n-DM + insulin group. All rats were implanted the titanium implant near the epiphyseal end of tibia, then the DM + insulin and n-DM + insulin group received twice-daily subcutaneous injections of insulin (10U/day).Two,four and eight weeks after implantation, rats were killed in batches. Histomorphometry and immunohistochemistry were used to evaluate bone formation and osseointegration. The amount of newly formed bone, Implant–bone contact and the expression of OCN,RUNX2 in the DM+insulin, n-DM and n-DM+insulin group were significantly more than in the DM group (p<0.05). Compared with the n-DM group,the Implant–bone contact and expression of OCN,RUNX2 were significantly increased in n-DM+insulin group (p< 0.05). Taken together,these observations provide evidence that insulin has the potential to increase bone formation and osseointegration around implant not only in diabetic subjects but also in non-diabetic subject.

Keywords: insulin, diabetes mellitus, osseointegration, dental implants

Procedia PDF Downloads 461

Authors: H. K. Ratre, M. Roy, S. Roy, M. S. Parmar, V. Bhagat

Abstract:

Mastitis is a common problem of dairy industries. Reduction in milk production and an irreparable damage to the udder associated with the disease are common causes of culling of dairy cows. Milk from infected animals is not suitable for drinking and for making different milk products. So, it has a major economic importance in dairy cattle. The aims of this study were to investigate the bacteriological panorama in milk from udder quarters with subclinical mastitis and to carried out for the molecular characterization of the major isolated organisms, from subclinical mastitis-affected cows in and around Durg and Rajnandgaon district of Chhattisgarh. Isolation and identification of bacteria from the milk samples of subclinical mastitis-affected cows were done by standard and routine culture procedures. A total of 78 isolates were obtained from cows and among the various bacteria isolated, Staphylococcus spp. occupied prime position with occurrence rate of 51.282%. However, other bacteria isolated includeStreptococcus spp. (20.512%), Micrococcus spp. (14.102%), E. coli (8.974%), Klebsiela spp. (2.564%), Salmonella spp. (1.282%) and Proteus spp. (1.282%). Staphylococcus spp. was isolated as the major causative agent of subclinical mastitis in the studied area. Molecular characterization of Staphylococus aureusisolates was done for genetic expression of the virulence genes like ‘nuc’ encoding thermonucleaseexoenzyme, coa and spa by PCR amplification of the respective genes in 25 Staphylococcus isolates. In the present study, 15 isolates (77.27%) out of 20 coagulase positive isolates were found to be genotypically positive for ‘nuc’ where as 20 isolates (52.63%) out of 38 CNS expressed the presence of the same virulence gene. In the present study, three Staphylococcus isolates were found to be genotypically positive for coa gene. The Amplification of the coa gene yielded two different products of 627, 710 bp. The amplification of the gene segment encoding the IgG binding region of protein A (spa) revealed a size of 220 and 253bp in twostaphylococcus isolates. The X-region binding of the spa gene produced an amplicon of 315 bp in one Staphylococcal isolates. Staphylococcus aureus was found to be major isolate (51.28%) responsible for causing subclinical mastitis in cows which also showed expression of virulence genesnuc, coa and spa.

Keywords: mastitis, bacteria, characterization, expression, gene

Procedia PDF Downloads 210

Authors: Vincent Murray

Abstract:

The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

Procedia PDF Downloads 112

Authors: Harshita Raj, Joydeep Ghosh, Rakesh L. Tanna, Prabal K. Chattopadhyay, K. A. Jadeja, Sharvil Patel, Kaushal M. Patel, Narendra C. Patel, S. B. Bhatt, V. K. Panchal, Chhaya Chavda, C. N. Gupta, D. Raju, S. K. Jha, J. Raval, S. Joisa, S. Purohit, C. V. S. Rao, P. K. Atrey, Umesh Nagora, R. Manchanda, M. B. Chowdhuri, Nilam Ramaiya, S. Banerjee, Y. C. Saxena

Abstract:

Efficient gas fueling is a critical aspect that needs to be mastered in order to maintain plasma density, to carry out fusion. This requires a fair understanding of fuel recycling in order to optimize the gas fueling. In Aditya tokamak, multiple gas puffs are used in a precise and controlled manner, for hydrogen fueling during the flat top of plasma discharge which has been instrumental in achieving discharges with enhanced density as well as energy confinement time. Following each gas puff, we observe peaks in temporal profile of Hα emission, Soft X-ray (SXR) and chord averaged electron density in a number of discharges, indicating efficient gas fueling. Interestingly, Hα temporal profile exhibited an additional peak following the peak corresponding to each gas puff. These additional peak Hα appeared in between the two gas puffs, indicating the presence of a secondary hydrogen source apart from the gas puffs. A thorough investigation revealed that these secondary Hα peaks coincide with Hard X- ray bursts which come from the interaction of runaway electrons with vessel limiters. This leads to consider that the runaway electrons (REs), which hit the wall, in turn, bring out the absorbed hydrogen and oxygen from the wall and makes the interaction of REs with limiter a secondary hydrogen source. These observations suggest that runaway electron induced recycling should also be included in recycling particle source in the particle balance calculations in tokamaks. Observation of two Hα peaks associated with one gas puff and their roles in enhancing and maintaining plasma density in Aditya tokamak will be discussed in this paper.

Keywords: fusion, gas fueling, recycling, Tokamak, Aditya

Procedia PDF Downloads 397

Authors: Frank Boris Feutmba Keutchou, Saurelle Fabienne Bieghan Same, Verelle Elsa Fogang Pokam, Charles Ursula Metapi Meikeu, Angel Marilyne Messop Nzomo, Ousman Tamgue

Abstract:

Infectious diseases are one of the most important causes of morbidity and mortality worldwide. These diseases are caused by micro-pathogenic organisms, such as bacteria, viruses, parasites, and fungi. Heritable changes in gene expression that do not involve changes to the underlying DNA sequence are referred to as epigenetics. Emerging evidence suggests that epigenetic mechanisms are important in the emergence and progression of infectious diseases. Pathogens can manipulate host epigenetic machinery to promote their own replication and evade immune responses. The Human Genome Project has provided new opportunities for developing better tools for the diagnosis and identification of target genes. Several epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA expression, have been shown to influence infectious disease outcomes. Understanding the epigenetic mechanisms underlying infectious diseases may result in the progression of new therapeutic approaches focusing on host-pathogen interactions. The goal of this study is to show how different infectious agents interact with host cells after infection.

Keywords: epigenetic, infectious disease, micro-pathogenic organism, phenotype

Procedia PDF Downloads 76

Authors: Ahmed Ghachem, Denis Prud’homme, Rémi-Rabasa-Lhoret, M. Brochu

Abstract:

Objective: To compare the effects of a CR on body composition, lipid profile and glucose homeostasis in obese postmenopausal women with and without MetS. Methods: Secondary analyses were performed on seventy-three inactive obese postmenopausal women (age: 57.7 ± 4.8 yrs; body mass index: 32.4 ± 4.6 kg/m2) who participated in the 6-month caloric restriction arm of a study of the Montreal-Ottawa New Emerging Team. The harmonized MetS definition was used to categorized participants with MetS [n = 20, 27.39%] and without MetS [n = 53, 72.61%]. Variables of interest were: body composition (DXA), body fat distribution (CT scan), glucose homeostasis at the fasting state and during a euglycemic/hyperinsulinemic clamp, fasting lipids and resting blood pressure. Results: By design, the MetS group had a worse cardiometabolic profile; while both groups were comparable for age. Fifty-five patients out of seventy-three displayed no change in MetS status after the intervention. Twelve participants out of twenty (or 60.0%) in the MetS group had no more MetS after weight loss (P= NS); while six participants out of fifty three (or 11.3%) in the other group developed the MetS after the intervention (P= NS). Overall, indices of body composition and body fat distribution improved significantly and similarly in both groups (P between 0.03 and 0.0001). Furthermore, with the exception of triglyceride levels and triglycerides/HDL-C ratio, which decrease significantly more in the MetS group (P ≤ 0.05), no difference was observed between groups for the other variables of the cardiometabolic profile. Conclusion: Despite no overall significant effects on MetS, heterogeneous results were obtained in response to weight loss in the present study; with some improving the MetS while other displaying deteriorations. Further studies are needed in order to identify factors and phenotypes associated with positive and negative cardiometabolic responses to CR intervention.

Keywords: menopause, obesity, physical inactivity, metabolic syndrome, caloric restriction, weight loss

Procedia PDF Downloads 338

Authors: Elena Maria Scalisi

Abstract:

The increasing production and the use of TiO₂ nanoparticles (NPs) have inevitably led to their release into the environment, thereby posing a threat to organisms and also for human. Human exposure to TiO₂-NPs may occur during both manufacturing and use. TiO₂-NPs are common in consumer products for dermal application, toothpaste, food colorants, and nutritional supplements, then oral exposure may occur during use of such products. Into the body, TiO₂-NPs thanks to their small size (<100 nm), can, through testicular blood barrier inducing effect on testis and then on male reproductive health. The nanoscale size of TiO₂ increase the surface-to-volume ratio making them more reactive in a cell, then TiO₂ NPs increase their ability to produce reactive oxygen species (ROS). In male germ cells, ROS may have important implications in maintaining the normal functions of mature spermatozoa at physiological levels, moreover, in spermatozoa they are important signaling molecules for their hyperactivation and acrosome reaction. Nevertheless, an excess of ROS by external inputs such as NPs can increased the oxidative stress (OS), which results in damage DNA and apoptosis. The aim of our study has been investigate the impact of TiO₂ NPs on human spermatozoa, evaluating DNA damage and the expression of proteins involved in cell stress. According WHO guidelines 2021, we have exposed human spermatozoa in vitro to TiO₂ NP at concentrations 50 ppm, 100 ppm, 250 ppm, and 500 ppm for 1 hour (at 37°C and CO₂ at 5%). DNA damage was evaluated by Sperm Chromatin Dispersion Test (SCD) and TUNEL assay; moreover, we have evaluated the expression of biomarkers of oxidative stress like Heat Shock Protein 70 (HSP70) and Metallothioneins (MTs). Also, sperm parameters as motility viability have been evaluated. Our results not report a significant reduction in motility of spermatozoa at the end of the exposure. On the contrary, the progressive motility was increased at the highest concentration (500 ppm) and was statistically significant compared to control (p <0.05). Also, viability was not changed by exposure to TiO₂-NPs (p <0.05). However, increased DNA damage was observed at all concentrations, and the TUNEL assay highlighted the presence of single strand breaks in the DNA. The spermatozoa responded to the presence of TiO₂-NPs with the expression of Hsp70, which have a protective function because they allow the maintenance of cellular homeostasis in stressful/ lethal conditions. A positivity for MTs was observed mainly for the concentration of 4 mg/L. Although the biological and physiological function of the metallothionein (MTs) in the male genital organs is unclear, our results highlighted that the MTs expressed by spermatozoa maintain their biological role of detoxification from metals. Our results can give additional information to the data in the literature on the toxicity of TiO₂-NPs and reproduction.

Keywords: human spermatozoa, DNA damage, TiO₂-NPs, biomarkers

Procedia PDF Downloads 141

Authors: Ambrish Tiwari, Sudhasini Panda, Archana Singh, Kalpana Luthra, S. K. Sharma

Abstract:

Introduction: On the basis of available literature we know that various host factors play a role in outcome of Tuberculosis (TB) infection by modulating innate immunity. One such factor is Inducible Nitric Oxide Synthase enzyme (iNOS) which help in the production of Nitric Oxide (NO), an antimicrobial agent. Expression of iNOS is in control of various host factors in which Vitamin D along with its nuclear receptor Vitamin D receptor (VDR) is one of them. Vitamin D along with its receptor also produces cathelicidin (antimicrobicidal agent). With this background, we attempted to investigate the levels of Vitamin D and NO along with their associated molecules in tuberculosis patients and household contacts as compared to healthy controls and assess the implication of these findings in susceptibility to tuberculosis (TB). Study subjects and methods: 100 active TB patients, 75 household contacts, and 70 healthy controls were taken. VDR and iNOS mRNA levels were studied using real-time PCR. Serum VDR, cathelicidin, iNOS levels were measured using ELISA. Serum Vitamin D levels were measured in serum samples using chemiluminescence based immunoassay. NO was measured using colorimetry based kit. Results: VDR and iNOS mRNA levels were found to be lower in active TB group compared to household contacts and healthy controls (P=0.0001 and 0.005 respectively). The serum levels of Vitamin D were also found to be lower in active TB group as compared to healthy controls (P =0.001). Levels of cathelicidin and NO was higher in patient group as compared to other groups (p=0.01 and 0.5 respectively). However, the expression of VDR and iNOS and levels of vitamin D was significantly (P < 0.05) higher in household contacts compared to both active TB and healthy control groups. Inference: Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to patients suggest that vitamin D might have a protective role against TB which prevents activation of the disease. From our data, we can conclude that decreased vitamin D levels could be implicated in disease progression and we can use cathelicidin and NO as a biomarker for early diagnosis of pulmonary tuberculosis.

Keywords: vitamin D, VDR, iNOS, tuberculosis

Procedia PDF Downloads 300

Authors: Ceyda Okudu, Secil Eroglu, Khandakar A. S. M. Saadat, Sibel O. Balci

Abstract:

Ring Finger Protein 2 (RNF2) is a member of polycomb repressive complex 1 (PRC1), which is one of the epigenetic regulators in the genome. When RNF2 combines with other PRC1 members, it mediates the mono-ubiquitination of Histon2A (H2A). In breast cancer, RNF2 is commonly overexpressed, and also it promotes metastasis and invasion in other aggressive tumors like melanoma, prostate, and hepatocarcinoma. The role of RNF2 in the metastasis and invasion of breast cancer has not yet been elucidated. Our aim is to observe the role of RNF2 in metastasis and invasion in this study by miRNA mediated RNF2 gene silencing in breast cancer cell lines. We selected miRNAs, targeting to RNF2 by searching online databases. miR-17-5p, miR20a-5p, and miR-106b-5p were transfected to breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3, and ZR-75-1), and also we used normal breast epithelial cell line (hTERT-HME1) to compare RNF2 gene expression level. After 48-72 hours post-transfection, mRNAs were isolated from the cells, and gene expressions were measured by RT-qPCR after from cDNA syntheses. We observed that RNF2 was highly expressed in SK-BR-3 and MDA-MB-231 cell lines opposite to MCF-7 and ZR-75-1 cell lines. RNF2 was downregulated 5, 5 and 7 fold by miR17-5p, miR20a-5p and miR106b-5p respectively in MCF-7. However, in SK-BR-3 and ZR-75-1 cell lines, miRNAs did not affect significantly RNF2 gene expression level. miR20a-5p decreased RNF2 3 fold and miR17-5p and miR106b-5p did not affect MDA-MB-231. After gene expression analysis, we performed metastasis and invasion assay in MCF-7 cells. For metastasis, we used both wound healing assay and Transwell Cell Migration Assay, and we used Transwell Cell Invasion Assay for invasion. The data of this assay showed that miR17-5p and miR20a-5p decreased both invasion and metastasis level, but miR106b-5p has no effect. We would like to conclude that RNF2 can be targeted by miR17-5p, miR20a-5p and miR106b-5p in MCF-7 cells and also RNF2, which is one of the upregulated genes in aggressive tumor, can be decreased by using these miRNAs. In future, we would like to confirm these results at the protein level and also whether these miRNAs are direct target of RNF2 or not.

Keywords: breast cancer, epigenetic, microRNAs, RNF2

Procedia PDF Downloads 174

Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

Abstract:

Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

Procedia PDF Downloads 60