Search results for: exponential expression profile

Authors: David A. Padilla, Rodolfo Villamizar

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In recent years, closed loop control strategies have been developed in order to establish a healthy glucose profile in type 1 diabetic mellitus (T1DM) patients. However, the controller itself is unable to define a suitable reference trajectory for glucose. In this paper, a control strategy Is proposed where the shape of the reference trajectory is generated bases in the amount of carbohydrates present during the digestive process, due to the effect of carbohydrate intake. Since there no exists a sensor to measure the amount of carbohydrates consumed, an estimator is proposed. Thus this paper presents the entire process of designing a carbohydrate estimator, which allows estimate disturbance for a predictive controller (MPC) in a T1MD patient, the estimation will be used to establish a profile of reference and improve the response of the controller by providing the estimated information of ingested carbohydrates. The dynamics of the diabetic model used are due to the equations described by the UVA/Padova model of the T1DMS simulator, the system was developed and simulated in Simulink, taking into account the noise and limitations of the glucose control system actuators.

Keywords: estimation, glucose control, predictive controller, MPC, UVA/Padova

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Authors: Amit Singla, Amit Chauhan

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The non-circular journal bearings provide better thermal stability and lesser oil-film temperature rise as compared to circular journal bearings. Experimentation on simultaneous measurement of pressure and temperature of lubricated oil-film along the profile of the bearing will help the designer to design journal bearings. In this paper, pressure and temperature of oil-film along orthogonally displaced non-circular journal bearing have been measured on a designed journal bearing test rig. The orthogonal non-circular journal bearing has been fabricated by displacing two circular halves away from the centers in the orthogonal direction. The data acquisition for oil film pressure and temperature has been carried out at journal speed=3000 rpm and by increasing the static radial load from 500 N to 2000 N in steps of 500 N using three different grades of oil (ISOVG 32, 68, and 150) named as oil-1, oil-2, and oil-3 respectively. The results show that the oil-film pressure and temperature increases with increase in radial load and change of lubricating oil towards increasing viscosity. Further, two lobes in the pressure and temperature profiles have been obtained which accounts for better thermal stability as it reduces cavitation zone inside the bearing.

Keywords: cavitation, non-circular journal bearing, orthogonally displaced, thermal stability

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Authors: X. Cervantes-López, C. Arriaga-Canon, L. Contreras Espinosa

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The goal of this study is to validate the overexpression of the lncRNA GATA3-AS1 associated with resistance to neoadjuvant chemotherapy of female patients with locally advanced mammary adenocarcinoma of luminal B subtype This study involved a cohort of one hundred thirty-seven samples for which total RNA was isolated from formalin fixed paraffin embedded (FFPE) tissue. Samples were cut using a Microtome Hyrax M25 Zeiss and RNA was isolated using the RNeasy FFPE kit and a deparaffinization solution, the next step consisted in the analysis of RNA concentration and quality, then 18 µg of RNA was treated with DNase I, and cDNA was synthesized from 50 ng total RNA, finally real-time PCR was performed with SYBR Green/ROX qPCR Master Mix in order to determined relative gene expression using RPS28 as a housekeeping gene to normalize in a fold calculation ΔCt. As a result, we validated by real-time PCR that the overexpression of the lncRNA GATA3-AS1 is associated with resistance to neoadjuvant chemotherapy in locally advanced breast cancer patients of luminal B subtype.

Keywords: breast cancer, biomarkers, genomics, neoadjuvant chemotherapy, lncRNAS

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Authors: Abd El Hady N. Ebraheim

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This paper introduces a new generalization of the two parameter Weibull distribution. To this end, the quadratic rank transmutation map has been used. This new distribution is named exponentiated transmuted Weibull (ETW) distribution. The ETW distribution has the advantage of being capable of modeling various shapes of aging and failure criteria. Furthermore, eleven lifetime distributions such as the Weibull, exponentiated Weibull, Rayleigh and exponential distributions, among others follow as special cases. The properties of the new model are discussed and the maximum likelihood estimation is used to estimate the parameters. Explicit expressions are derived for the quantiles. The moments of the distribution are derived, and the order statistics are examined.

Keywords: exponentiated, inversion method, maximum likelihood estimation, transmutation map

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Authors: Sandeep Sharma, Sarabjit Singh

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As per the user demand and growth trends of large free data the storage solutions are now becoming more challenge-able to protect, store and to retrieve data. The days are not so far when the storage companies and organizations are start saying 'no' to store our valuable data or they will start charging a huge amount for its storage and protection. On the other hand as per the environmental conditions it becomes challenge-able to maintain and establish new data warehouses and data centers to protect global warming threats. A challenge of small data is over now, the challenges are big that how to manage the exponential growth of data. In this paper we have analyzed the growth trend of big data and its future implications. We have also focused on the impact of the unstructured data on various concerns and we have also suggested some possible remedies to streamline big data.

Keywords: big data, unstructured data, volume, variety, velocity

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Authors: Tribhuvan N. Soorya

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Charging and discharging of a capacitor through a resistor can be shown as exponential curve. Theoretically, it takes infinite time to fully charge or discharge a capacitor. The flow of charge is due to electrons having finite and fixed value of charge. If we carefully examine the charging and discharging process after several time constants, the points on q vs t graph become discrete and curve become discontinuous. Moreover for all practical purposes capacitor with charge (q0-e) can be taken as fully charged, as it introduces an error less than one part per million. Similar is the case for discharge of a capacitor, where the capacitor with the last electron (charge e) can be taken as fully discharged. With this, we can estimate the finite value of time for fully charging and discharging a capacitor.

Keywords: charging, discharging, RC Circuit, capacitor

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Authors: Bosiacki Mateusz, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka

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Exposure to cold temperatures can be considered a stressor that can lead to adaptive responses. The present study hypothesized the possibility of a positive effect of cold water exercise on mitochondrial biogenesis and muscle energy metabolism in aging rats. The purpose of this study was to evaluate the effects of cold water exercise on energy status, purine compounds, and mitochondrial biogenesis in the muscles of aging rats as indicators of the effects of cold water exercise and their usefulness in monitoring adaptive changes. The study was conducted on 64 aging rats of both sexes, 15 months old at the time of the experiment. The rats (male and female separately) were randomly assigned to the following study groups: control, sedentary animals; 5°C groups animals - training swimming in cold water at 5°C; 36°C groups - animals training swimming in water at thermal comfort temperature. The study was conducted with the approval of the Local Ethical Committee for Animal Experiments. The animals in the experiment were subjected to swimming training for 9 weeks. During the first week of the study, the duration of the first swimming training was 2 minutes (on the first day), increasing daily by 0.5 minutes up to 4 minutes on the fifth day of the first week. From the second to the eighth week, the swimming training was 4 minutes per day, five days a week. At the end of the study, forty-eight hours after the last swim training, the animals were dissected. In the skeletal muscle tissue of the thighs of the rats, we determined the concentrations of ATP, ADP, AMP, Ado (HPLC), PGC-1a protein expression (Western blot), PGC1A, Mfn1, Mfn2, Opa1, and Drp1 gene expression (qRT PCR). The study showed that swimming in water at a thermally comfortable temperature improved the energy metabolism of the aging rat muscles by increasing the metabolic rate (increase in ATP, ADP, TAN, AEC) and enhancing mitochondrial fusion (increase in mRNA expression of regulatory proteins Mfn1 and Mfn2). Cold water swimming improved muscle energy metabolism in aging rats by increasing the rate of muscle energy metabolism (increase in ATP, ADP, TAN, AEC concentrations) and enhancing mitochondrial biogenesis and dynamics (increase in the mRNA expression of proteins of fusion-regulating factors – Mfn1, Mfn2, and Opa1, and the factor regulating mitochondrial fission – Drp1). The concentration of high-energy compounds and the expression of proteins regulating mitochondrial dynamics in the muscle may be a useful indicator in monitoring adaptive changes occurring in aging muscles under the influence of exercise in cold water. It represents a short-term adaptation to changing environmental conditions and has a beneficial effect on maintaining the bioenergetic capacity of muscles in the long term. Conclusion: exercise in cold water can exert positive effects on energy metabolism, biogenesis and dynamics of mitochondria in aging rat muscles. Enhancement of mitochondrial dynamics under cold water exercise conditions can improve mitochondrial function and optimize the bioenergetic capacity of mitochondria in aging rat muscles.

Keywords: cold water immersion, adaptive responses, muscle energy metabolism, aging

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Authors: Denise Schrama, Claudia Raposo, Pedro Rodrigues

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Background: Food allergies are conducted by a hypersensitive response of the immune system. These allergies are a global concern for the public health. Consumption of fish is increasing worldwide as it is a healthy meat with high nutritional value. Unfortunately, fish can cause adverse immune-mediate reactions, affecting part of the population with higher incidence in children. β-parvalbumin, a small, highly conserved stable, calcium or magnesium binding muscle protein is the main fish allergen. In fish-allergic patients, cross-reactivity between different fish species exist due to recognition of highly identical protein regions. Enolases, aldolases, or fish gelatin are other identified fish allergens in some fish species. With no available cure for fish allergies, clinical management is only based on an avoidance diet aiming at the total exclusion of offending food. Methods: Mediterranean fish (S. aurata and D. labrax) were fed specifically designed diets, enriched in components that target the expression or inactivation of parvalbumin (creatine and EDTA, respectively). After 90 days fish were sampled and biological tissues were excised. Proteomics was used to access fish allergens characterization and expression in muscle while IgE assays to confirm the lower allergenic potential are conducted in patients with history of fish allergies. Fish welfare and quality of flesh were established with biochemical, texture and sensorial analysis. Results: Fish welfare shows no major impact between diets. In case of creatine supplementation in D. labrax proteomic analysis show a slight decrease in parvalbumin expression. No accumulation of this compound was found in muscle. For EDTA supplementation in S. aurata IgE assay show a slight decrease in allergenicity when using sera of fish allergic patients. Conclusion: Supplementation with these two compounds seems to change slightly the allergenicity of the two mean Mediterranean species.

Keywords: fish allergies, fish nutrition, proteomics, aquaculture

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Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng

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Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ

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Authors: Katie Strong, Brian P. O'Connor, Jacqueline M. Kanippayoor

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To date, self-report measures of psychopathy have largely been conceptualized with a male-focused understanding of the disorder, with the presumption that psychopathy expression is uniform across genders. However, generalizing this understanding to the female population may be misleading. The objective of this research was to explore gender differences in the expression of psychopathy and to assess current self-report psychopathy measures for gender bias. It was hypothesized that some items in commonly used measures of psychopathy may show gender bias and that existing measures may not contain enough items that are relevant to the manifestation of psychopathy in women. An exploratory investigation was conducted on statistical bias in common measures of psychopathy, and novel, relevant, but previously neglected items and measures were included in a new data collection. The participant pool included a sample of 403 university students and 354 participants recruited using Amazon Mechanical Turk. Item Response Theory methods - including Differential Item Functioning - were used to assess for the item- and test- level bias across several common self-report measures of psychopathy. Analyses indicated occasional and modest levels of item-level bias, and that some additional female-relevant items merit consideration for inclusion in measures of psychopathy. These findings suggest that current self-report measures of psychopathy may be demonstrating gender-bias and warrant further examination.

Keywords: gender, measurement bias, personality, psychopathy

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Authors: Peña A. Roland R., Lozano P. Jean P.

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The waterflooding process is an enhanced oil recovery (EOR) method that appears tremendously successful. This paper shows the importance of the role of the numerical modelling of waterflooding and how to provide a better description of the fluid flow during this process. The mathematical model is based on the mass conservation equations for the oil and water phases. Rock compressibility and capillary pressure equations are coupled to the mathematical model. For discretizing and linearizing the partial differential equations, we used the Finite Volume technique and the Newton-Raphson method, respectively. The results of three scenarios for waterflooding in porous media are shown. The first scenario was estimating the water saturation in the media without rock compressibility and without capillary pressure. The second scenario was estimating the front of the water considering the rock compressibility and capillary pressure. The third case is to compare different fronts of water saturation for three fluids viscosity ratios without and with rock compressibility and without and with capillary pressure. Results of the simulation indicate that the rock compressibility and the capillary pressure produce changes in the pressure profile and saturation profile during the displacement of the oil for the water.

Keywords: capillary pressure, numerical simulation, rock compressibility, two-phase flow

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Authors: Phani Kiran, Prabodha Manas Yarlagadda

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This paper attempts to treat Shakespeare’s tragic hero, Hamlet as an existential hero who faces many dilemmas in the process of taking revenge for his father’s murder. Hamlet can be considered as a predecessor of existentialism, and Shakespeare, as a pioneer, focused on some serious existential issues in the play much before they were fully developed in 20th century. Hamlet's internal struggles reflect existential themes such as alienation, despair, and the quest for authenticity. Hamlet’s famous soliloquy, "To be, or not to be," is a quintessential expression of existential ponderings, contemplating the choice between life and death and the uncertainty of what lies beyond. Hamlet grapples with existential questions like the purpose and meaninglessness of life, the nature of morality, the inevitability of death, and the existence of an afterlife. He doubts the authenticity of appearance and the reliability of his own perceptions, highlighting the inherent ambiguity and uncertainty of existence. Overall, "Hamlet" aligns with existential philosophy by exploring the complexities of human existence, the search for meaning, and the individual's struggle to find their place in an inherently uncertain and perplexing world. The character of Hamlet and the play's exploration of existential themes continue to resonate with audiences and provoke contemplation on the nature of life and the human experience.

Keywords: to be or not to be, death, dilemmas, illusion and reality

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Authors: Fan Zhang

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In the process of urbanization in China, the new rural construction is in the ascendant, which is becoming more and more popular. Under the driving effect of rural urbanization, the house pattern and tectonic methods of traditional vernacular houses have shown great differences from the family structure and values of contemporary peasant families. Therefore, it is particularly important to find a prototype, form and strategy, to make a balance between the traditional memory and modern functional requirements. In order for research to combine the regional culture with modern life, under the situation of the current batch production of new rural residence, Badie village, in Linhai, Zhejiang province, is taken as the case. This paper aims to put forward a prototype which can not only meet the demand of modern life but also ensure the continuation of traditional culture and historical context for the new rural dwellings design. This research not only helps to extend the local context in the construction of the new site but also contributes to the fusion of old and new rural dwellings in the old site construction. Through the study and research of this case, the research methodology and results can be drawn as reference for the new rural construction in other areas.

Keywords: badie village, design strategy, new rural dwellings, regional context, regional expression

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Authors: Muhammad Sohail Sajid, Hafiz Muhammad Rizwan, Ashfaq Ahmad Chatta, Zafar Iqbal, Muhammad Saqib

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Changes in the climate are posing threats to the livestock community throughout the globe. Agro-grazing animals and natural vegetation as their forages are the most important components of animal production. Climate and local conditions not only determine the nature and kind of plants, their distribution, composition and nutritive value in different cropping belts and grazing sites but also influence number and kinds of grazing animals. Phytomineral supplementation can act as an indirect tool to boost-up immunological profile of animals leading to the development of resilience against parasitic infections. The present study correlates the trace element (Cu, Co, Mn, Zn) profile of grazing sheep, feedstuffs, respective soils and their GI helminths in a selected district of Sialkot, Punjab, Pakistan. Ten species of GI helminths were found during the survey. A significant (P < 0.05) variation in the concentrations (conc.) of Zn, Cu, Mn and Co was recorded in a total of 16 collected forages. During autumn, mean conc. of Cu, Zn and Co in sera were inversely proportional to the GI helminth burden; while, during spring, only Zn was inversely proportional to the GI helminth burden in grazing sheep. During autumn the highest conc. of Zn, Cu, Mn and Co were recorded in Echinochloa colona, Amaranthus viridis, Cannabis sativa, and Brachiaria ramose and during spring in Cichorium intybus, Cynodon dactylon, Parthenium hysterophorus and Coronopus didymus respectively. The trace element-rich forages, preferably Zn, found effective against helminth infection are advisable supplemental remedies to improve the trace element profile in grazing sheep. This mitigation strategy may ultimately improve the resilience against GI helminth infections especially in the resource poor countries like Pakistan.

Keywords: coprological examination, Trace elements, Sheep, Gastro-intestinal parasites, Prevalence, Sialkot, Pakistan

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Authors: Hani M. M. Alothaid, Louise Robson, Richmond Muimo

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This study will investigate cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) dependent calcineurin (Cn), known as protein phosphatase 2 B (PP2B) as well, regulation of chloride ion (Cl⁻) secretion and the release of pro-inflammatory molecules in immune cells such as cytokines. THP-1-derived monocytes, primary human monocytes and the bronchial epithelial cell line (16HBE14o-) were used in this study. The 16HBE14o- cells were chosen as positive control. Hence, to further confirm the expression of cystic fibrosis transmembrane conductance regulator (CFTR), calcium binding protein (S100A10), annexin A2 (AnxA2) and calcineurin A subunit (CnA) in all three cell types, cell lysate was probed against corresponding primary antibodies by immunoblotting. Western blot analyses show the expression of CFTR, AnxA2, CnA and S100A10 in THP-1-derived monocytes and primary human monocytes. In conclusion, CFTR, S100A10, CnA and AnxA2 are expressed in THP-1-derived monocytes and primary human monocytes and regulate Cl⁻ secretion. Also, they may play a role in the pro-inflammatory molecules release. The ongoing work will confirm interaction between these proteins in the cell lines.

Keywords: annexin A2, calcineurin, CFTR, chloride, monocytes, pro-inflammatory molecules, S100A10

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Authors: Zahir Bakiri, Saci Nacefa

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In this paper a comparison in made between two models, with and without dispersion term, and focused on the characterization of the movement of the sludge blanket in the secondary sedimentation tank using the solid flux theory and the velocity settling. This allowed us develop a one-dimensional models, with and without dispersion based on a thorough experimental study carried out in situ and the application of online data which are the mass load flow, transfer concentration, and influent characteristic. On the other hand, in the proposed model, the new settling velocity law (double-exponential function) used is based on the Vesilind function.

Keywords: wastewater, activated sludge, sedimentation, settling velocity, settling models

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Authors: Erfan Rahimi, Hadi Bahari Far, Mojgan Shikhpour

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Background: Urinary tract infection is one of the most common nosocomial infections, especially among women. E. coli is one of the main causes of urinary tract infections and one of the most common antibiotics to fight this bacterium is ampicillin. As conventional antibiotics led to bacterial antibiotic resistance, modification of the pure drugs can address this issue. The aim of this study was to prepare nanofluids containing carbon nanotubes conjugated with ampicillin to improve drug performance and reduce antibiotic resistance. Methods: Multi-walled carbon nanotubes (MWCNTs) were activated with thionyl chloride by reflux system and nanofluids containing antibiotics were prepared by ultrasonic method. The properties of the prepared nano-drug were investigated by general element analysis, infrared spectroscopy, Raman spectroscopy, scanning electron microscopy and transmission electron microscopy. After the treatment of the desired strain with nanofluid, microbial studies were performed to evaluate the antibacterial effects and molecular studies were carried out to measure the expression of the resistance gene AcrAB. Result: We have shown that the antimicrobial effect of ampicillin-functionalized MWCNTs at low concentrations performed better than that of the conventional drug in both resistant and ATCC strains. Also, a decrease in antibiotic resistance of bacteria treated with ampicillin-functionalized MWCNTs compared to the pure drug was observed. Also, ampicillin-functionalized MWCNTs downregulated the expression of AcrAB in treated bacteria. Conclusion: Because carbon nanotubes are capable of destroying the bacterial wall, which provides antibiotic resistance features in bacteria, their usage in the form of nanofluids can make lower dosages (about three times less) than that of the pure drug more effective. Additionally, the expression of the bacterial resistance gene AcrAB decreased, thereby reducing antibiotic resistance and improving drug performance against bacteria.

Keywords: urinary tract infection, antibiotic resistance, carbon nanotube, nanofluid

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Authors: Muhammad Maisam Abbas, Salman Tariq, Usama Riaz, Muhammad Tanveer, Humaira Abdul Ghafoor

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Autism Spectrum Disorder (ASD) refers to a developmental disorder that impairs an individual's communication and interaction ability. Individuals feel difficult to read facial expressions while communicating or interacting. Facial Expression Recognition (FER) is a unique method of classifying basic human expressions, i.e., happiness, fear, surprise, sadness, disgust, neutral, and anger through static and dynamic sources. This paper conducts a comprehensive comparison and proposed optimal method for a continued research project—a system that can assist people who have Autism Spectrum Disorder (ASD) in recognizing facial expressions. Comparison has been conducted on three supervised learning algorithms EigenFace, FisherFace, and LBPH. The JAFFE, CK+, and TFEID (I&II) datasets have been used to train and test the algorithms. The results were then evaluated based on variance, standard deviation, and accuracy. The experiments showed that FisherFace has the highest accuracy for all datasets and is considered the best algorithm to be implemented in our system.

Keywords: autism spectrum disorder, ASD, EigenFace, facial expression recognition, FisherFace, local binary pattern histogram, LBPH

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Authors: Chaudhary Muhammad Aqdus Ilyas, Matthias Rehm, Kamal Nasrollahi, Thomas B. Moeslund

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This paper presents the investigation of data collection procedures, associated with robots when placed with traumatic brain injured (TBI) patients for rehabilitation purposes through facial expression and mood analysis. Rehabilitation after TBI is very crucial due to nature of injury and variation in recovery time. It is advantageous to analyze these emotional signals in a contactless manner, due to the non-supportive behavior of patients, limited muscle movements and increase in negative emotional expressions. This work aims at the development of framework where robots can recognize TBI emotions through facial expressions to perform rehabilitation tasks by physical, cognitive or interactive activities. The result of these studies shows that with customized data collection strategies, proposed framework identify facial and emotional expressions more accurately that can be utilized in enhancing recovery treatment and social interaction in robotic context.

Keywords: computer vision, convolution neural network- long short term memory network (CNN-LSTM), facial expression and mood recognition, multimodal (RGB-thermal) analysis, rehabilitation, robots, traumatic brain injured patients

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: Shraddha Rane, Richard Warren, Stephen Eyre

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L-23 is a pro-inflammatory molecule that signals T cells to release cytokines such as IL-17A and IL-22. Psoriasis is driven by a dysregulated immune response, within which IL-23 is now thought to play a key role. Genome-wide association studies (GWAS) have identified a number of genetic risk loci that support the involvement of IL-23 signalling in psoriasis; in particular a robust susceptibility locus at a gene encoding a subunit of the IL-23 receptor (IL23R) (Stuart et al., 2015; Tsoi et al., 2012). The lead psoriasis-associated SNP rs9988642 is located approximately 500 bp downstream of IL23R but is in tight linkage disequilibrium (LD) with a missense SNP rs11209026 (R381Q) within IL23R (r2 = 0.85). The minor (G) allele of rs11209026 is present in approximately 7% of the population and is protective for psoriasis and several other autoimmune diseases including IBD, ankylosing spondylitis, RA and asthma. The psoriasis-associated missense SNP R381Q causes an arginine to glutamine substitution in a region of the IL23R protein between the transmembrane domain and the putative JAK2 binding site in the cytoplasmic portion. This substitution is expected to affect the receptor’s surface localisation or signalling ability, rather than IL23R expression. Recent studies have also identified a psoriatic arthritis (PsA)-specific signal at IL23R; thought to be independent from the psoriasis association (Bowes et al., 2015; Budu-Aggrey et al., 2016). The lead PsA-associated SNP rs12044149 is intronic to IL23R and is in LD with likely causal SNPs intersecting promoter and enhancer marks in memory CD8+ T cells (Budu-Aggrey et al., 2016). It is therefore likely that the PsA-specific SNPs affect IL23R function via a different mechanism compared with the psoriasis-specific SNPs. It could be hypothesised that the risk allele for PsA located within the IL23R promoter causes an increase IL23R expression, relative to the protective allele. An increased expression of IL23R might then lead to an exaggerated immune response. The independent genetic signals identified for psoriasis and PsA in this locus indicate that different mechanisms underlie these two conditions; although likely both affecting the function of IL23R. It is very important to further characterise these mechanisms in order to better understand how the IL-23 receptor and its downstream signalling is affected in both diseases. This will help to determine how psoriasis and PsA patients might differentially respond to therapies, particularly IL-23 biologics. To investigate this further we have developed an in vitro model using CD4 T cells which express either wild type IL23R and IL12Rβ1 or mutant IL23R (R381Q) and IL12Rβ1. Model expressing different isotypes of IL23R is also underway to investigate the effects on IL23R expression. We propose to further investigate the variants for Ps and PsA and characterise key intracellular processes related to the variants.

Keywords: IL23R, psoriasis, psoriatic arthritis, SNP

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Authors: Garance Liaboeuf, Mohamed Bouteldja, Antoine Martinet, Nicolas Grignard, Damien Pilet, Ali Daouadji, Alain Le Bot

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A series of in-situ tests is set up to evaluate and quantify the long-term effects of scraping operations using steel plows on the skid resistance of pavements. Three pavements are tested, and a total number of 1.800 snowplow scrapings are applied. The skid resistance of the pavements is measured periodically using two indicators on two scales: an average profile depth (macrotexture) and a longitudinal friction coefficient (microtexture). The results of these tests show a reduction in the average profile depth between 4 % and 10 %, depending on the asphalt composition. This reduction of macrotexture is correlated with the reduction of high points on surfaces due to the removal of portions of the aggregate surfaces. The longitudinal friction coefficient of pavements decreases by 4% to 10%. This reduction in microtexture is related to the polishing of the surface of the aggregate used in the pavements. These variations of skid resistance are not linear. A phenomenon of regeneration of the friction coefficient is observed for pavements composed of sand-lime aggregates after several scraping operations.

Keywords: GripTester, macrotexture, microtexture, pavement, skid resistance, snowplow, TM2, winter road maintenance

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Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino

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Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.

Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke

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Authors: Soniya Nityanand, Ekta Minocha, Manali Jain, Rohit Anthony Sinha, Chandra Prakash Chaturvedi

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Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: amniotic fluid stem cells, acute renal failure, autophagy, cisplatin

Procedia PDF Downloads 107

Authors: Edouard Ngor Sarr, Abel Diatta, Serigne Mor Toure, Ousmane Sall, Lamine Faty

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Thanks to Web 2, we are witnessing a form of democratization of the spoken word, an exponential increase in the number of users on the web, but also, and above all, the accumulation of a daily flow of content that is becoming, at times, uncontrollable. Added to this is the rise of a violent social fabric characterised by hateful and racial comments, insults, and other content that contravenes social rules and the platforms' terms of use. Consequently, managing and regulating this mass of new content is proving increasingly difficult, requiring substantial human, technical, and technological resources. Without regulation and with the complicity of anonymity, this toxic content can pollute discussions and make these online spaces highly conducive to abuse, which very often has serious consequences for certain internet users, ranging from anxiety to suicide, depression, or withdrawal. The toxicity of a comment is defined as anything that is rude, disrespectful, or likely to cause someone to leave a discussion or to take violent action against a person or a community. Two levels of measures are needed to deal with this deleterious situation. The first measures are being taken by governments through draft laws with a dual objective: (i) to punish the perpetrators of these abuses and (ii) to make online platforms accountable for the mistakes made by their users. The second measure comes from the platforms themselves. By assessing the content left by users, they can set up filters to block and/or delete content or decide to suspend the user in question for good. However, the speed of discussions and the volume of data involved mean that platforms are unable to properly monitor the moderation of content produced by Internet users. That's why they use human moderators, either through recruitment or outsourcing. Moderating comments on the web means assessing and monitoring users‘ comments on online platforms in order to strike the right balance between protection against abuse and users’ freedom of expression. It makes it possible to determine which publications and users are allowed to remain online and which are deleted or suspended, how authorised publications are displayed, and what actions accompany content deletions. In this study, we look at the problem of automatic moderation of toxic comments in the face of local African languages and, more specifically, on social network comments in Senegal. We review the state of the art, highlighting the different approaches, algorithms, and tools for moderating comments. We also study the issues and challenges of moderation in the face of web ecosystems with lesser-known languages, such as local languages.

Keywords: moderation, local languages, Senegal, toxic comments

Procedia PDF Downloads 15

Authors: Leila Rashki Ghaleno, Mohamad Amin Hajari, Leila Montazeri, Abdolhossein Shahverdi, Mojtaba Rezazadeh Valojerdi

Abstract:

Background: Spermatogonia stem cells (SSCs) exhibit pluripotency, enabling them to undergo differentiation into many cell lineages, including neurons, glia, endothelial cells, and hepatocytes when cultured in vitro. Although the specific mechanisms are not yet fully understood, it has been observed that biopolymer agents, such as hyaluronic acid (HA) and alginate (Alg), have the potential to induce transdifferentiation of SSCs. The current work aimed to examine the process of in vitro spermatogenesis and the conversion of mouse testicular cells into hepatocytes and erythrocyte-like cells utilizing the HA-Alg hydrogel. Method: After being extracted from the testes of a 5-day postpartum mouse (5 DPP), the testicular cells were separated into two enzymatic stages and then put into a composite hydrogel containing 0.5% HA and 1% alginate. On days 14 and 28 of culture, the colonies' growth, the cells' viability, and their histology were assessed. Result: Despite observing significant cell proliferation on day 14 and the development of circular-shaped organoids on day 28, it was noted that the organoids generated in the HA-Alg medium tended to maintain their circular morphology on day 28. Notably, the testicular cells underwent transdifferentiation into cell types resembling erythrocytes and hepatocytes. The hepatocyte-like cells exhibited the presence of glycogen and lipid deposits, indicating their hepatocyte-like characteristics. Interestingly, immunostaining analysis revealed the secretion of albumin and the presence of VEGFR on day 14. However, on day 28, albumin expression was not detected, while the expression of Sox9 (a marker for hepatocytes), Vegf, CD34, and C-kit (markers for erythrocytes) showed increased levels in the gene expression evaluation. Conclusion: The present findings indicated that HA-Alg could be a potent and effective agent for the transdifferentiation of testis cells into erythrocyte and hepatocyte-like cells, as recent studies have confirmed the transformation of SSCs into hepatocyte cells during in vitro culture.

Keywords: 3D culture, mouse testicular cell, hyaluronic acid, liver organoids

Procedia PDF Downloads 72

Authors: Thanyaporn Senarai, Rapeepun Vanichviriyakit, Shinji Miyata, Chihiro Sato, Prapee Sretarugsa, Wattana Weerachatyanukul, Ken Kitajima

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In this study, we characterized a region-specific 250 kDa protein that was secreted of MSD fluid, which is believed to play dual functions in forming a spermatophoric wall for sperm physical protection, and in sperm membrane modification as part of sperm maturation process. The partial amino acid sequence and N-terminal sequencing revealed that the MSD-specific 250 kDa protein showed a high similarity with a plasma-rich protein, α-2 macroglobulin (α2M), so termed pp-α2M. This protein was a large glycoprotein contained predominantly mannose and GlcNAc. The expression of pp-α2M mRNA was detected in spermatic duct (SD), androgenic gland (AG) and hematopoietic tissue, while the protein expression was rather specific to the apical cytoplasm of MSD epithelium. The secretory pp-α2M in MSD fluid was acquired onto the MSD sperm membrane and was also found within the matrix of the acrosome. Distally, pp-α2M was removed from spermathecal sperm membrane, while its level kept constant in the sperm AC. Together the results indicate that pp-α2M is a 250 kDa region-specific secretory protein which plays roles in sperm physical protection and also acts as maturation factor in the P. pelagicus sperm.

Keywords: alpha-2 macroglobulin, blue swimming crab, sperm maturation, spermatic duct

Procedia PDF Downloads 330

Authors: Yong-Hui Zheng

Abstract:

Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

Procedia PDF Downloads 74

Authors: Khairy M. A. Zoheir

Abstract:

One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid was investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells, and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid treated mice showed a significant decrease in the Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also down regulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs also found to be significantly upregulated in lipoic acid treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for therapy Rheumatoid arthritis.

Keywords: lipoic acid, chemokines, inflammatory, rheumatoid arthritis

Procedia PDF Downloads 178

Authors: Ella Tyuryumina, Alexey Neznanov

Abstract:

Finding algorithms to predict the growth of tumors has piqued the interest of researchers ever since the early days of cancer research. A number of studies were carried out as an attempt to obtain reliable data on the natural history of breast cancer growth. Mathematical modeling can play a very important role in the prognosis of tumor process of breast cancer. However, mathematical models describe primary tumor growth and metastases growth separately. Consequently, we propose a mathematical growth model for primary tumor and primary metastases which may help to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoM-IV and corresponding software. We are interested in: 1) modelling the whole natural history of primary tumor and primary metastases; 2) developing adequate and precise CoM-IV which reflects relations between PT and MTS; 3) analyzing the CoM-IV scope of application; 4) implementing the model as a software tool. The CoM-IV is based on exponential tumor growth model and consists of a system of determinate nonlinear and linear equations; corresponds to TNM classification. It allows to calculate different growth periods of primary tumor and primary metastases: 1) ‘non-visible period’ for primary tumor; 2) ‘non-visible period’ for primary metastases; 3) ‘visible period’ for primary metastases. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. Thus, the CoM-IV model and predictive software: a) detect different growth periods of primary tumor and primary metastases; b) make forecast of the period of primary metastases appearance; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of BC and facilitate optimization of diagnostic tests. The following are calculated by CoM-IV: the number of doublings for ‘nonvisible’ and ‘visible’ growth period of primary metastases; tumor volume doubling time (days) for ‘nonvisible’ and ‘visible’ growth period of primary metastases. The CoM-IV enables, for the first time, to predict the whole natural history of primary tumor and primary metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on primary tumor sizes. Summarizing: a) CoM-IV describes correctly primary tumor and primary distant metastases growth of IV (T1-4N0-3M1) stage with (N1-3) or without regional metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and manifestation of primary metastases.

Keywords: breast cancer, exponential growth model, mathematical modelling, primary metastases, primary tumor, survival

Procedia PDF Downloads 337