Search results for: tumor visualization
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1315

Search results for: tumor visualization

115 Association of Genetically Proxied Cholesterol-Lowering Drug Targets and Head and Neck Cancer Survival: A Mendelian Randomization Analysis

Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

Procedia PDF Downloads 93
114 Test Rig Development for Up-to-Date Experimental Study of Multi-Stage Flash Distillation Process

Authors: Marek Vondra, Petr Bobák

Abstract:

Vacuum evaporation is a reliable and well-proven technology with a wide application range which is frequently used in food, chemical or pharmaceutical industries. Recently, numerous remarkable studies have been carried out to investigate utilization of this technology in the area of wastewater treatment. One of the most successful applications of vacuum evaporation principal is connected with seawater desalination. Since 1950’s, multi-stage flash distillation (MSF) has been the leading technology in this field and it is still irreplaceable in many respects, despite a rapid increase in cheaper reverse-osmosis-based installations in recent decades. MSF plants are conveniently operated in countries with a fluctuating seawater quality and at locations where a sufficient amount of waste heat is available. Nowadays, most of the MSF research is connected with alternative heat sources utilization and with hybridization, i.e. merging of different types of desalination technologies. Some of the studies are concerned with basic principles of the static flash phenomenon, but only few scientists have lately focused on the fundamentals of continuous multi-stage evaporation. Limited measurement possibilities at operating plants and insufficiently equipped experimental facilities may be the reasons. The aim of the presented study was to design, construct and test an up-to-date test rig with an advanced measurement system which will provide real time monitoring options of all the important operational parameters under various conditions. The whole system consists of a conventionally designed MSF unit with 8 evaporation chambers, versatile heating circuit for different kinds of feed water (e.g. seawater, waste water), sophisticated system for acquisition and real-time visualization of all the related quantities (temperature, pressure, flow rate, weight, conductivity, pH, water level, power input), access to a wide spectrum of operational media (salt, fresh and softened water, steam, natural gas, compressed air, electrical energy) and integrated transparent features which enable a direct visual control of selected physical mechanisms (water evaporation in chambers, water level right before brine and distillate pumps). Thanks to the adjustable process parameters, it is possible to operate the test unit at desired operational conditions. This allows researchers to carry out statistical design and analysis of experiments. Valuable results obtained in this manner could be further employed in simulations and process modeling. First experimental tests confirm correctness of the presented approach and promise interesting outputs in the future. The presented experimental apparatus enables flexible and efficient research of the whole MSF process.

Keywords: design of experiment, multi-stage flash distillation, test rig, vacuum evaporation

Procedia PDF Downloads 382
113 Fuzzy Optimization for Identifying Anticancer Targets in Genome-Scale Metabolic Models of Colon Cancer

Authors: Feng-Sheng Wang, Chao-Ting Cheng

Abstract:

Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

Procedia PDF Downloads 70
112 Epidemiology of Gestational Choriocarcinoma: A Systematic Review

Authors: Farah Amalina Mohamed Affandi, Redhwan Ahmad Al-Naggar, Seok Mui Wang, Thanikasalam Kathiresan

Abstract:

Gestational choriocarcinoma is a condition in which there is an abnormal growth or a tumor inside the women’s uterus after conception. It is a type of gestational trophoblastic disease which is relatively rare and malignant. The current epidemiological data of this disease are inadequate. The purposes of this study are to examine the epidemiology of choriocarcinoma and their risk factors based on all available population-based and hospital-based data of the disease. In this study, we searched The MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases using the keywords ‘choriocarcinoma’, ‘gestational’, ‘gestational choriocarcinoma’ and ‘epidemiology’. We included only human studies published in English between 1995 and 2015 to ensure up to date evidence. Case studies, case reports, animal studies, letters to the editor, news, and review articles were excluded. Retrieved articles were screened in three phases. In the first phase, any articles that did not match the inclusion criteria based solely on titles were excluded. In the second phase, the abstracts of remaining articles were screened thoroughly; any articles that did not meet our inclusion criteria were excluded. In the final phase, full texts of the remaining articles were read and assessed to exclude articles that did not meet the inclusion criteria or any articles that fulfilled the exclusion criteria. Duplicates articles were also removed. Systematic reviews and meta-analysis were excluded. Extracted data were summarized in table and figures descriptively. The reference lists of included studies were thoroughly reviewed in search for other relevant studies. A total of ten studies met all the selection criteria. Nine were retrospective studies and one was cohort study. Total numbers of 4563 cases of choriocarcinoma were reviewed from several countries which are Korea, Japan, South Africa, USA, New Mexico, Finland, Turkey, China, Brazil and The Netherlands. Different studies included different range of age with their mean age of 28.5 to 30.0 years. All studies investigated on the disease’s incidence rate, only two studies examined on the risk factors or associations of the disease. Approximately 20% of the studies showed a reduction in the incidence of choriocarcinoma while the other 80% showed inconsistencies in rate. Associations of age, fertility age, occupations and socio-demographic with the status remains unclear. There is limited information on the epidemiological aspects of gestational choriocarcinoma. The observed results indicated there was a decrease in the incidence rate of gestational choriocarcinoma globally. These could be due to the reduction in the incidence of molar pregnancy and the efficacy of the treatment, mainly by chemotherapy.

Keywords: epidemiology, gestational choriocarcinoma, incidence, prevalence, risk factor

Procedia PDF Downloads 324
111 Identification of Hub Genes in the Development of Atherosclerosis

Authors: Jie Lin, Yiwen Pan, Li Zhang, Zhangyong Xia

Abstract:

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and extracellular matrix in the arterial walls. This pathological process can lead to the formation of plaques that can obstruct blood flow and trigger various cardiovascular diseases such as heart attack and stroke. The underlying molecular mechanisms still remain unclear, although many studies revealed the dysfunction of endothelial cells, recruitment and activation of monocytes and macrophages, and the production of pro-inflammatory cytokines and chemokines in atherosclerosis. This study aimed to identify hub genes involved in the progression of atherosclerosis and to analyze their biological function in silico, thereby enhancing our understanding of the disease’s molecular mechanisms. Through the analysis of microarray data, we examined the gene expression in media and neo-intima from plaques, as well as distant macroscopically intact tissue, across a cohort of 32 hypertensive patients. Initially, 112 differentially expressed genes (DEGs) were identified. Subsequent immune infiltration analysis indicated a predominant presence of 27 immune cell types in the atherosclerosis group, particularly noting an increase in monocytes and macrophages. In the Weighted gene co-expression network analysis (WGCNA), 10 modules with a minimum of 30 genes were defined as key modules, with blue, dark, Oliver green and sky-blue modules being the most significant. These modules corresponded respectively to monocyte, activated B cell, and activated CD4 T cell gene patterns, revealing a strong morphological-genetic correlation. From these three gene patterns (modules morphology), a total of 2509 key genes (Gene Significance >0.2, module membership>0.8) were extracted. Six hub genes (CD36, DPP4, HMOX1, PLA2G7, PLN2, and ACADL) were then identified by intersecting 2509 key genes, 102 DEGs with lipid-related genes from the Genecard database. The bio-functional analysis of six hub genes was estimated by a robust classifier with an area under the curve (AUC) of 0.873 in the ROC plot, indicating excellent efficacy in differentiating between the disease and control group. Moreover, PCA visualization demonstrated clear separation between the groups based on these six hub genes, suggesting their potential utility as classification features in predictive models. Protein-protein interaction (PPI) analysis highlighted DPP4 as the most interconnected gene. Within the constructed key gene-drug network, 462 drugs were predicted, with ursodeoxycholic acid (UDCA) being identified as a potential therapeutic agent for modulating DPP4 expression. In summary, our study identified critical hub genes implicated in the progression of atherosclerosis through comprehensive bioinformatic analyses. These findings not only advance our understanding of the disease but also pave the way for applying similar analytical frameworks and predictive models to other diseases, thereby broadening the potential for clinical applications and therapeutic discoveries.

Keywords: atherosclerosis, hub genes, drug prediction, bioinformatics

Procedia PDF Downloads 58
110 Demonstrating the Efficacy of a Low-Cost Carbon Dioxide-Based Cryoablation Device in Veterinary Medicine for Translation to Third World Medical Applications

Authors: Grace C. Kuroki, Yixin Hu, Bailey Surtees, Rebecca Krimins, Nicholas J. Durr, Dara L. Kraitchman

Abstract:

The purpose of this study was to perform a Phase I veterinary clinical trial with a low-cost, carbon-dioxide-based, passive thaw cryoablation device as proof-of-principle for application in pets and translation to third-world treatment of breast cancer. This study was approved by the institutional animal care and use committee. Client-owned dogs with subcutaneous masses, primarily lipomas or mammary cancers, were recruited for the study. Inclusion was based on clinical history, lesion location, preanesthetic blood work, and fine needle aspirate or biopsy confirmation of mass. Informed consent was obtained from the owners for dogs that met inclusion criteria. Ultrasound assessment of mass extent was performed immediately prior to mass cryoablation. Dogs were placed under general anesthesia and sterilely prepared. A stab incision was created to insert a custom 4.19 OD x 55.9 mm length cryoablation probe (Kubanda Cryotherapy) into the mass. Originally designed for treating breast cancer in low resource settings, this device has demonstrated potential in effectively necrosing subcutaneous masses. A dose escalation study of increasing freeze-thaw cycles (5/4/5, 7/5/7, and 10/7/10 min) was performed to assess the size of the iceball/necrotic extent of cryoablation. Each dog was allowed to recover for ~1-2 weeks before surgical removal of the mass. A single mass was treated in seven dogs (2 mammary masses, a sarcoma, 4 lipomas, and 1 adnexal mass) with most masses exceeding 2 cm in any dimension. Mass involution was most evident in the malignant mammary and adnexal mass. Lipomas showed minimal shrinkage prior to surgical removal, but an area of necrosis was evident along the cryoablation probe path. Gross assessment indicated a clear margin of cryoablation along the cryoprobe independent of tumor type. Detailed histopathology is pending, but complete involution of large lipomas appeared to be unlikely with a 10/7/10 protocol. The low-cost, carbon dioxide-based cryotherapy device permits a minimally invasive technique that may be useful for veterinary applications but is also informative of the unlikely resolution of benign adipose breast masses that may be encountered in third world countries.

Keywords: cryoablation, cryotherapy, interventional oncology, veterinary technology

Procedia PDF Downloads 128
109 Networked Media, Citizen Journalism and Political Participation in Post-Revolutionary Tunisia: Insight from a European Research Project

Authors: Andrea Miconi

Abstract:

The research will focus on the results of the Tempus European Project eMEDia dedicated to Cross-Media Journalism. The project is founded by the European Commission as it involves four European partners - IULM University, Tampere University, University of Barcelona, and the Mediterranean network Unimed - and three Tunisian Universities – IPSI La Manouba, Sfax and Sousse – along with the Tunisian Ministry for Higher Education and the National Syndicate of Journalists. The focus on Tunisian condition is basically due to the role played by digital activists in its recent history. The research is dedicated to the relationship between political participation, news-making practices and the spread of social media, as it is affecting Tunisian society. As we know, Tunisia during the Arab Spring had been widely considered as a laboratory for the analysis the use of new technologies for political participation. Nonetheless, the literature about the Arab Spring actually fell short in explaining the genesis of the phenomenon, on the one hand by isolating technologies as a casual factor in the spread of demonstrations, and on the other by analyzing North-African condition through a biased perspective. Nowadays, it is interesting to focus on the consolidation of the information environment three years after the uprisings. And what is relevant, only a close, in-depth analysis of Tunisian society is able to provide an explanation of its history, and namely of the part of digital media in the overall evolution of political system. That is why the research is based on different methodologies: desk stage, interviews, and in-depth analysis of communication practices. Networked journalism is the condition determined by the technological innovation on news-making activities: a condition upon which professional journalist can no longer be considered the only player in the information arena, and a new skill must be developed. Along with democratization, nonetheless, the so-called citizen journalism is also likely to produce some ambiguous effects, such as the lack of professional standards and the spread of information cascades, which may prove to be particularly dangerous in an evolving media market as the Tunisian one. This is why, according to the project, a new profile must be defined, which is able to manage this new condition, and which can be hardly reduced to the parameters of traditional journalistic work. Rather than simply using new devices for news visualization, communication professionals must also be able to dialogue with all new players and to accept the decentralized nature of digital environments. This networked nature of news-making seemed to emerge during the Tunisian revolution, when bloggers, journalists, and activists used to retweet each other. Nonetheless, this intensification of communication exchange was inspired by the political climax of the uprising, while all media, by definition, are also supposed to bring some effects on people’s state of mind, culture and daily life routines. That is why it is worth analyzing the consolidation of these practices in a normal, post-revolutionary situation.

Keywords: cross-media, education, Mediterranean, networked journalism, social media, Tunisia

Procedia PDF Downloads 192
108 ReactorDesign App: An Interactive Software for Self-Directed Explorative Learning

Authors: Chia Wei Lim, Ning Yan

Abstract:

The subject of reactor design, dealing with the transformation of chemical feedstocks into more valuable products, constitutes the central idea of chemical engineering. Despite its importance, the way it is taught to chemical engineering undergraduates has stayed virtually the same over the past several decades, even as the chemical industry increasingly leans towards the use of software for the design and daily monitoring of chemical plants. As such, there has been a widening learning gap as chemical engineering graduates transition from university to the industry since they are not exposed to effective platforms that relate the fundamental concepts taught during lectures to industrial applications. While the success of technology enhanced learning (TEL) has been demonstrated in various chemical engineering subjects, TELs in the teaching of reactor design appears to focus on the simulation of reactor processes, as opposed to arguably more important ideas such as the selection and optimization of reactor configuration for different types of reactions. This presents an opportunity for us to utilize the readily available easy-to-use MATLAB App platform to create an educational tool to aid the learning of fundamental concepts of reactor design and to link these concepts to the industrial context. Here, interactive software for the learning of reactor design has been developed to narrow the learning gap experienced by chemical engineering undergraduates. Dubbed the ReactorDesign App, it enables students to design reactors involving complex design equations for industrial applications without being overly focused on the tedious mathematical steps. With the aid of extensive visualization features, the concepts covered during lectures are explicitly utilized, allowing students to understand how these fundamental concepts are applied in the industrial context and equipping them for their careers. In addition, the software leverages the easily accessible MATLAB App platform to encourage self-directed learning. It is useful for reinforcing concepts taught, complementing homework assignments, and aiding exam revision. Accordingly, students are able to identify any lapses in understanding and clarify them accordingly. In terms of the topics covered, the app incorporates the design of different types of isothermal and non-isothermal reactors, in line with the lecture content and industrial relevance. The main features include the design of single reactors, such as batch reactors (BR), continuously stirred tank reactors (CSTR), plug flow reactors (PFR), and recycle reactors (RR), as well as multiple reactors consisting of any combination of ideal reactors. A version of the app, together with some guiding questions to aid explorative learning, was released to the undergraduates taking the reactor design module. A survey was conducted to assess its effectiveness, and an overwhelmingly positive response was received, with 89% of the respondents agreeing or strongly agreeing that the app has “helped [them] with understanding the unit” and 87% of the respondents agreeing or strongly agreeing that the app “offers learning flexibility”, compared to the conventional lecture-tutorial learning framework. In conclusion, the interactive ReactorDesign App has been developed to encourage self-directed explorative learning of the subject and demonstrate the industrial applications of the taught design concepts.

Keywords: explorative learning, reactor design, self-directed learning, technology enhanced learning

Procedia PDF Downloads 90
107 Magnetic Navigation of Nanoparticles inside a 3D Carotid Model

Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis

Abstract:

Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.

Keywords: artery, drug, nanoparticles, navigation

Procedia PDF Downloads 102
106 Seafloor and Sea Surface Modelling in the East Coast Region of North America

Authors: Magdalena Idzikowska, Katarzyna Pająk, Kamil Kowalczyk

Abstract:

Seafloor topography is a fundamental issue in geological, geophysical, and oceanographic studies. Single-beam or multibeam sonars attached to the hulls of ships are used to emit a hydroacoustic signal from transducers and reproduce the topography of the seabed. This solution provides relevant accuracy and spatial resolution. Bathymetric data from ships surveys provides National Centers for Environmental Information – National Oceanic and Atmospheric Administration. Unfortunately, most of the seabed is still unidentified, as there are still many gaps to be explored between ship survey tracks. Moreover, such measurements are very expensive and time-consuming. The solution is raster bathymetric models shared by The General Bathymetric Chart of the Oceans. The offered products are a compilation of different sets of data - raw or processed. Indirect data for the development of bathymetric models are also measurements of gravity anomalies. Some forms of seafloor relief (e.g. seamounts) increase the force of the Earth's pull, leading to changes in the sea surface. Based on satellite altimetry data, Sea Surface Height and marine gravity anomalies can be estimated, and based on the anomalies, it’s possible to infer the structure of the seabed. The main goal of the work is to create regional bathymetric models and models of the sea surface in the area of the east coast of North America – a region of seamounts and undulating seafloor. The research includes an analysis of the methods and techniques used, an evaluation of the interpolation algorithms used, model thickening, and the creation of grid models. Obtained data are raster bathymetric models in NetCDF format, survey data from multibeam soundings in MB-System format, and satellite altimetry data from Copernicus Marine Environment Monitoring Service. The methodology includes data extraction, processing, mapping, and spatial analysis. Visualization of the obtained results was carried out with Geographic Information System tools. The result is an extension of the state of the knowledge of the quality and usefulness of the data used for seabed and sea surface modeling and knowledge of the accuracy of the generated models. Sea level is averaged over time and space (excluding waves, tides, etc.). Its changes, along with knowledge of the topography of the ocean floor - inform us indirectly about the volume of the entire water ocean. The true shape of the ocean surface is further varied by such phenomena as tides, differences in atmospheric pressure, wind systems, thermal expansion of water, or phases of ocean circulation. Depending on the location of the point, the higher the depth, the lower the trend of sea level change. Studies show that combining data sets, from different sources, with different accuracies can affect the quality of sea surface and seafloor topography models.

Keywords: seafloor, sea surface height, bathymetry, satellite altimetry

Procedia PDF Downloads 74
105 Real-Time Neuroimaging for Rehabilitation of Stroke Patients

Authors: Gerhard Gritsch, Ana Skupch, Manfred Hartmann, Wolfgang Frühwirt, Hannes Perko, Dieter Grossegger, Tilmann Kluge

Abstract:

Rehabilitation of stroke patients is dominated by classical physiotherapy. Nowadays, a field of research is the application of neurofeedback techniques in order to help stroke patients to get rid of their motor impairments. Especially, if a certain limb is completely paralyzed, neurofeedback is often the last option to cure the patient. Certain exercises, like the imagination of the impaired motor function, have to be performed to stimulate the neuroplasticity of the brain, such that in the neighboring parts of the injured cortex the corresponding activity takes place. During the exercises, it is very important to keep the motivation of the patient at a high level. For this reason, the missing natural feedback due to a movement of the effected limb may be replaced by a synthetic feedback based on the motor-related brain function. To generate such a synthetic feedback a system is needed which measures, detects, localizes and visualizes the motor related µ-rhythm. Fast therapeutic success can only be achieved if the feedback features high specificity, comes in real-time and without large delay. We describe such an approach that offers a 3D visualization of µ-rhythms in real time with a delay of 500ms. This is accomplished by combining smart EEG preprocessing in the frequency domain with source localization techniques. The algorithm first selects the EEG channel featuring the most prominent rhythm in the alpha frequency band from a so-called motor channel set (C4, CZ, C3; CP6, CP4, CP2, CP1, CP3, CP5). If the amplitude in the alpha frequency band of this certain electrode exceeds a threshold, a µ-rhythm is detected. To prevent detection of a mixture of posterior alpha activity and µ-activity, the amplitudes in the alpha band outside the motor channel set are not allowed to be in the same range as the main channel. The EEG signal of the main channel is used as template for calculating the spatial distribution of the µ - rhythm over all electrodes. This spatial distribution is the input for a inverse method which provides the 3D distribution of the µ - activity within the brain which is visualized in 3D as color coded activity map. This approach mitigates the influence of lid artifacts on the localization performance. The first results of several healthy subjects show that the system is capable of detecting and localizing the rarely appearing µ-rhythm. In most cases the results match with findings from visual EEG analysis. Frequent eye-lid artifacts have no influence on the system performance. Furthermore, the system will be able to run in real-time. Due to the design of the frequency transformation the processing delay is 500ms. First results are promising and we plan to extend the test data set to further evaluate the performance of the system. The relevance of the system with respect to the therapy of stroke patients has to be shown in studies with real patients after CE certification of the system. This work was performed within the project ‘LiveSolo’ funded by the Austrian Research Promotion Agency (FFG) (project number: 853263).

Keywords: real-time EEG neuroimaging, neurofeedback, stroke, EEG–signal processing, rehabilitation

Procedia PDF Downloads 379
104 Temperature-Dependent Post-Mortem Changes in Human Cardiac Troponin-T (cTnT): An Approach in Determining Postmortem Interval

Authors: Sachil Kumar, Anoop Kumar Verma, Wahid Ali, Uma Shankar Singh

Abstract:

Globally approximately 55.3 million people die each year. In the India there were 95 lakh annual deaths in 2013. The number of deaths resulted from homicides, suicides and unintentional injuries in the same period was about 5.7 lakh. The ever-increasing crime rate necessitated the development of methods for determining time since death. An erroneous time of death window can lead investigators down the wrong path or possibly focus a case on an innocent suspect. In this regard a research was carried out by analyzing the temperature dependent degradation of a Cardiac Troponin-T protein (cTnT) in the myocardium postmortem as a marker for time since death. Cardiac tissue samples were collected from (n=6) medico-legal autopsies, (in the Department of Forensic Medicine and Toxicology, King George’s Medical University, Lucknow India) after informed consent from the relatives and studied post-mortem degradation by incubation of the cardiac tissue at room temperature (20±2 OC), 12 0C, 25 0C and 37 0C for different time periods ((~5, 26, 50, 84, 132, 157, 180, 205, and 230 hours). The cases included were the subjects of road traffic accidents (RTA) without any prior history of disease who died in the hospital and their exact time of death was known. The analysis involved extraction of the protein, separation by denaturing gel electrophoresis (SDS-PAGE) and visualization by Western blot using cTnT specific monoclonal antibodies. The area of the bands within a lane was quantified by scanning and digitizing the image using Gel Doc. The data shows a distinct temporal profile corresponding to the degradation of cTnT by proteases found in cardiac muscle. The disappearance of intact cTnT and the appearance of lower molecular weight bands are easily observed. Western blot data clearly showed the intact protein at 42 kDa, two major (27 kDa, 10kDa) fragments, two additional minor fragments (32 kDa) and formation of low molecular weight fragments as time increases. At 12 0C the intensity of band (intact cTnT) decreased steadily as compared to RT, 25 0C and 37 0C. Overall, both PMI and temperature had a statistically significant effect where the greatest amount of protein breakdown was observed within the first 38 h and at the highest temperature, 37 0C. The combination of high temperature (37 0C) and long Postmortem interval (105.15 hrs) had the most drastic effect on the breakdown of cTnT. If the percent intact cTnT is calculated from the total area integrated within a Western blot lane, then the percent intact cTnT shows a pseudo-first order relationship when plotted against the log of the time postmortem. These plots show a good coefficient of correlation of r = 0.95 (p=0.003) for the regression of the human heart at different temperature conditions. The data presented demonstrates that this technique can provide an extended time range during which Postmortem interval can be more accurately estimated.

Keywords: degradation, postmortem interval, proteolysis, temperature, troponin

Procedia PDF Downloads 382
103 Posttraumatic Stress Disorder and Associated Factors among Patients with Prostate Cancer

Authors: Meral Huri, Sedef Şahin

Abstract:

Post-traumatic stress disorder (PTSD) is characterized by psychiatric symptoms and triggered by a terrifying experience which may immediately effect cognitive, affective, behavioral and social skills of the individual. One of the most common noncutaneous cancer among men is prostate cancer. The incidence of psychological stress is quite common in men with prostate cancer. The aim of the study was to explore the PTSD frequency among prostate cancer and define the relationship between occupational participation, coping skills and level of perceived social support among patients with prostate cancer. Forty patients diagnosed with prostate cancer were included in the study. After dividing the patients into two groups ( study/ control) according to type of tumor, we recorded their characteristics and evaluations differences. We evaluated the demographic information form, Structured Clinical Interview for DSM-IV (SCID- I)- Clinical Version for PTSD, Multidimensional Scale of Perceived Social Support, Styles of Coping Inventory and Canadian Occupational Performance Measure (COPM) before and after 1 month from surgery. The mean age of the study group (n:18) was 65.85.6 years (range: 61-79 years). The mean age of the control group (n: 22) was a little bit higher than the study group with mean age 71.3±6.9 years (range: 60-85 years). There was no statistically significant difference between the groups for age and the other characteristics. According to the results of the study, statistically significant difference was found between the level of PTSD of study and the control group. 22% of study group showed PTSD while 13% of the control group showed PTSD (r: 0.02, p<0.001). The scores of study group and control group showed statistically significant difference in five sub-categories of Styles of Coping Inventory. Patients with prostate cancer showed decreased scores in optimistic, seeking social supports and self-confident approach, while increased scores in helpless and submissive sub-categories than the control group (p<0.001). The scores of Multidimensional Scale of Perceived Social Supports of study group and control group showed statistically significant difference. The total perceived social supports score of the study group was 71.34 ± 0.75 while it was 75.34 ± 0.64 for the control group. Total and the sub-category scores of study group were statistically significant lower than the control group. According to COPM, mean scores of occupational participation of study group for occupational performance were 4.32±2.24 and 7.01±1.52 for the control group, respectively). Mean Satisfaction scores were 3,22±2.31 and 7.45±1.74 for the study and control group, respectively. The patients with prostate cancer and benign prostate hyperplasia (BPH) did not show any statistically difference in activity performance (r:0.87) while patients with prostate cancer showed statistically lower scores than the patients with BPH in activity satisfaction (r:0.02, p<0.001).Psycho-social occupational therapy interventions might help to decrease the prevalence of PTSD by increasing associated factors such as the social support perception, using coping skills and activity participation of patients with prostate cancer.

Keywords: activity performance, occupational therapy, posttraumatic stress disorder, prostate cancer

Procedia PDF Downloads 139
102 Immersive and Non-Immersive Virtual Reality Applied to the Cervical Spine Assessment

Authors: Pawel Kiper, Alfonc Baba, Mahmoud Alhelou, Giorgia Pregnolato, Michela Agostini, Andrea Turolla

Abstract:

Impairment of cervical spine mobility is often related to pain triggered by musculoskeletal disorders or direct traumatic injuries of the spine. To date, these disorders are assessed with goniometers and inclinometers, which are the most popular devices used in clinical settings. Nevertheless, these technologies usually allow measurement of no more than two-dimensional range of motion (ROM) quotes in static conditions. Conversely, the wide use of motion tracking systems able to measure 3 to 6 degrees of freedom dynamically, while performing standard ROM assessment, are limited due to technical complexities in preparing the setup and high costs. Thus, motion tracking systems are primarily used in research. These systems are an integral part of virtual reality (VR) technologies, which can be used for measuring spine mobility. To our knowledge, the accuracy of VR measure has not yet been studied within virtual environments. Thus, the aim of this study was to test the reliability of a protocol for the assessment of sensorimotor function of the cervical spine in a population of healthy subjects and to compare whether using immersive or non-immersive VR for visualization affects the performance. Both VR assessments consisted of the same five exercises and random sequence determined which of the environments (i.e. immersive or non-immersive) was used as first assessment. Subjects were asked to perform head rotation (right and left), flexion, extension and lateral flexion (right and left side bending). Each movement was executed five times. Moreover, the participants were invited to perform head reaching movements i.e. head movements toward 8 targets placed along a circular perimeter each 45°, visualized one-by-one in random order. Finally, head repositioning movement was obtained by head movement toward the same 8 targets as for reaching and following reposition to the start point. Thus, each participant performed 46 tasks during assessment. Main measures were: ROM of rotation, flexion, extension, lateral flexion and complete kinematics of the cervical spine (i.e. number of completed targets, time of execution (seconds), spatial length (cm), angle distance (°), jerk). Thirty-five healthy participants (i.e. 14 males and 21 females, mean age 28.4±6.47) were recruited for the cervical spine assessment with immersive and non-immersive VR environments. Comparison analysis demonstrated that: head right rotation (p=0.027), extension (p=0.047), flexion (p=0.000), time (p=0.001), spatial length (p=0.004), jerk target (p=0.032), trajectory repositioning (p=0.003), and jerk target repositioning (p=0.007) were significantly better in immersive than non-immersive VR. A regression model showed that assessment in immersive VR was influenced by height, trajectory repositioning (p<0.05), and handedness (p<0.05), whereas in non-immersive VR performance was influenced by height, jerk target (p=0.002), head extension, jerk target repositioning (p=0.002), and by age, head flex/ext, trajectory repositioning, and weight (p=0.040). The results of this study showed higher accuracy of cervical spine assessment when executed in immersive VR. The assessment of ROM and kinematics of the cervical spine can be affected by independent and dependent variables in both immersive and non-immersive VR settings.

Keywords: virtual reality, cervical spine, motion analysis, range of motion, measurement validity

Procedia PDF Downloads 157
101 Investigation of FOXM1 Gene Expression in Breast Cancer and Its Relationship with Mir-216B-5P Expression Level

Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

Abstract:

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

Procedia PDF Downloads 65
100 Quantitative Comparisons of Different Approaches for Rotor Identification

Authors: Elizabeth M. Annoni, Elena G. Tolkacheva

Abstract:

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that is a known prognostic marker for stroke, heart failure and death. Reentrant mechanisms of rotor formation, which are stable electrical sources of cardiac excitation, are believed to cause AF. No existing commercial mapping systems have been demonstrated to consistently and accurately predict rotor locations outside of the pulmonary veins in patients with persistent AF. There is a clear need for robust spatio-temporal techniques that can consistently identify rotors using unique characteristics of the electrical recordings at the pivot point that can be applied to clinical intracardiac mapping. Recently, we have developed four new signal analysis approaches – Shannon entropy (SE), Kurtosis (Kt), multi-scale frequency (MSF), and multi-scale entropy (MSE) – to identify the pivot points of rotors. These proposed techniques utilize different cardiac signal characteristics (other than local activation) to uncover the intrinsic complexity of the electrical activity in the rotors, which are not taken into account in current mapping methods. We validated these techniques using high-resolution optical mapping experiments in which direct visualization and identification of rotors in ex-vivo Langendorff-perfused hearts were possible. Episodes of ventricular tachycardia (VT) were induced using burst pacing, and two examples of rotors were used showing 3-sec episodes of a single stationary rotor and figure-8 reentry with one rotor being stationary and one meandering. Movies were captured at a rate of 600 frames per second for 3 sec. with 64x64 pixel resolution. These optical mapping movies were used to evaluate the performance and robustness of SE, Kt, MSF and MSE techniques with respect to the following clinical limitations: different time of recordings, different spatial resolution, and the presence of meandering rotors. To quantitatively compare the results, SE, Kt, MSF and MSE techniques were compared to the “true” rotor(s) identified using the phase map. Accuracy was calculated for each approach as the duration of the time series and spatial resolution were reduced. The time series duration was decreased from its original length of 3 sec, down to 2, 1, and 0.5 sec. The spatial resolution of the original VT episodes was decreased from 64x64 pixels to 32x32, 16x16, and 8x8 pixels by uniformly removing pixels from the optical mapping video.. Our results demonstrate that Kt, MSF and MSE were able to accurately identify the pivot point of the rotor under all three clinical limitations. The MSE approach demonstrated the best overall performance, but Kt was the best in identifying the pivot point of the meandering rotor. Artifacts mildly affect the performance of Kt, MSF and MSE techniques, but had a strong negative impact of the performance of SE. The results of our study motivate further validation of SE, Kt, MSF and MSE techniques using intra-atrial electrograms from paroxysmal and persistent AF patients to see if these approaches can identify pivot points in a clinical setting. More accurate rotor localization could significantly increase the efficacy of catheter ablation to treat AF, resulting in a higher success rate for single procedures.

Keywords: Atrial Fibrillation, Optical Mapping, Signal Processing, Rotors

Procedia PDF Downloads 318
99 Geographic Information Systems and a Breath of Opportunities for Supply Chain Management: Results from a Systematic Literature Review

Authors: Anastasia Tsakiridi

Abstract:

Geographic information systems (GIS) have been utilized in numerous spatial problems, such as site research, land suitability, and demographic analysis. Besides, GIS has been applied in scientific fields like geography, health, and economics. In business studies, GIS has been used to provide insights and spatial perspectives in demographic trends, spending indicators, and network analysis. To date, the information regarding the available usages of GIS in supply chain management (SCM) and how these analyses can benefit businesses is limited. A systematic literature review (SLR) of the last 5-year peer-reviewed academic literature was conducted, aiming to explore the existing usages of GIS in SCM. The searches were performed in 3 databases (Web of Science, ProQuest, and Business Source Premier) and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The analysis resulted in 79 papers. The results indicate that the existing GIS applications used in SCM were in the following domains: a) network/ transportation analysis (in 53 of the papers), b) location – allocation site search/ selection (multiple-criteria decision analysis) (in 45 papers), c) spatial analysis (demographic or physical) (in 34 papers), d) combination of GIS and supply chain/network optimization tools (in 32 papers), and e) visualization/ monitoring or building information modeling applications (in 8 papers). An additional categorization of the literature was conducted by examining the usage of GIS in the supply chain (SC) by the business sectors, as indicated by the volume of the papers. The results showed that GIS is mainly being applied in the SC of the biomass biofuel/wood industry (33 papers). Other industries that are currently utilizing GIS in their SC were the logistics industry (22 papers), the humanitarian/emergency/health care sector (10 papers), the food/agro-industry sector (5 papers), the petroleum/ coal/ shale gas sector (3 papers), the faecal sludge sector (2 papers), the recycle and product footprint industry (2 papers), and the construction sector (2 papers). The results were also presented by the geography of the included studies and the GIS software used to provide critical business insights and suggestions for future research. The results showed that research case studies of GIS in SCM were conducted in 26 countries (mainly in the USA) and that the most prominent GIS software provider was the Environmental Systems Research Institute’s ArcGIS (in 51 of the papers). This study is a systematic literature review of the usage of GIS in SCM. The results showed that the GIS capabilities could offer substantial benefits in SCM decision-making by providing key insights to cost minimization, supplier selection, facility location, SC network configuration, and asset management. However, as presented in the results, only eight industries/sectors are currently using GIS in their SCM activities. These findings may offer essential tools to SC managers who seek to optimize the SC activities and/or minimize logistic costs and to consultants and business owners that want to make strategic SC decisions. Furthermore, the findings may be of interest to researchers aiming to investigate unexplored research areas where GIS may improve SCM.

Keywords: supply chain management, logistics, systematic literature review, GIS

Procedia PDF Downloads 127
98 Application of Laser-Induced Breakdown Spectroscopy for the Evaluation of Concrete on the Construction Site and in the Laboratory

Authors: Gerd Wilsch, Tobias Guenther, Tobias Voelker

Abstract:

In view of the ageing of vital infrastructure facilities, a reliable condition assessment of concrete structures is becoming of increasing interest for asset owners to plan timely and appropriate maintenance and repair interventions. For concrete structures, reinforcement corrosion induced by penetrating chlorides is the dominant deterioration mechanism affecting the serviceability and, eventually, structural performance. The determination of the quantitative chloride ingress is required not only to provide valuable information on the present condition of a structure, but the data obtained can also be used for the prediction of its future development and associated risks. At present, wet chemical analysis of ground concrete samples by a laboratory is the most common test procedure for the determination of the chloride content. As the chloride content is expressed by the mass of the binder, the analysis should involve determination of both the amount of binder and the amount of chloride contained in a concrete sample. This procedure is laborious, time-consuming, and costly. The chloride profile obtained is based on depth intervals of 10 mm. LIBS is an economically viable alternative providing chloride contents at depth intervals of 1 mm or less. It provides two-dimensional maps of quantitative element distributions and can locate spots of higher concentrations like in a crack. The results are correlated directly to the mass of the binder, and it can be applied on-site to deliver instantaneous results for the evaluation of the structure. Examples for the application of the method in the laboratory for the investigation of diffusion and migration of chlorides, sulfates, and alkalis are presented. An example for the visualization of the Li transport in concrete is also shown. These examples show the potential of the method for a fast, reliable, and automated two-dimensional investigation of transport processes. Due to the better spatial resolution, more accurate input parameters for model calculations are determined. By the simultaneous detection of elements such as carbon, chlorine, sodium, and potassium, the mutual influence of the different processes can be determined in only one measurement. Furthermore, the application of a mobile LIBS system in a parking garage is demonstrated. It uses a diode-pumped low energy laser (3 mJ, 1.5 ns, 100 Hz) and a compact NIR spectrometer. A portable scanner allows a two-dimensional quantitative element mapping. Results show the quantitative chloride analysis on wall and floor surfaces. To determine the 2-D distribution of harmful elements (Cl, C), concrete cores were drilled, split, and analyzed directly on-site. Results obtained were compared and verified with laboratory measurements. The results presented show that the LIBS method is a valuable addition to the standard procedures - the wet chemical analysis of ground concrete samples. Currently, work is underway to develop a technical code of practice for the application of the method for the determination of chloride concentration in concrete.

Keywords: chemical analysis, concrete, LIBS, spectroscopy

Procedia PDF Downloads 102
97 Monoallelic and Biallelic Deletions of 13q14 in a Group of 36 CLL Patients Investigated by CGH Haematological Cancer and SNP Array (8x60K)

Authors: B. Grygalewicz, R. Woroniecka, J. Rygier, K. Borkowska, A. Labak, B. Nowakowska, B. Pienkowska-Grela

Abstract:

Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. Hemizygous and or homozygous loss at 13q14 occur in more than half of cases and constitute the most frequent chromosomal abnormality in CLL. It is believed that deletions 13q14 play a role in CLL pathogenesis. Two microRNA genes miR-15a and miR- 16-1 are targets of 13q14 deletions and plays a tumor suppressor role by targeting antiapoptotic BCL2 gene. Deletion size, as a single change detected in FISH analysis, has haprognostic significance. Patients with small deletions, without RB1 gene involvement, have the best prognosis and the longest overall survival time (OS 133 months). In patients with bigger deletion region, containing RB1 gene, prognosis drops to intermediate, like in patients with normal karyotype and without changes in FISH with overall survival 111 months. Aim: Precise delineation of 13q14 deletions regions in two groups of CLL patients, with mono- and biallelic deletions and qualifications of their prognostic significance. Methods: Detection of 13q14 deletions was performed by FISH analysis with CLL probe panel (D13S319, LAMP1, TP53, ATM, CEP-12). Accurate deletion size detection was performed by CGH Haematological Cancer and SNP array (8x60K). Results: Our investigated group of CLL patients with the 13q14 deletion, detected by FISH analysis, comprised two groups: 18 patients with monoallelic deletions and 18 patients with biallelic deletions. In FISH analysis, in the monoallelic group the range of cells with deletion, was 43% to 97%, while in biallelic group deletion was detected in 11% to 94% of cells. Microarray analysis revealed precise deletion regions. In the monoallelic group, the range of size was 348,12 Kb to 34,82 Mb, with median deletion size 7,93 Mb. In biallelic group discrepancy of total deletions, size was 135,27 Kb to 33,33 Mb, with median deletion size 2,52 Mb. The median size of smaller deletion regions on one copy chromosome 13 was 1,08 Mb while the average region of bigger deletion on the second chromosome 13 was 4,04 Mb. In the monoallelic group, in 8/18 deletion region covered RB1 gene. In the biallelic group, in 4/18 cases, revealed deletion on one copy of biallelic deletion and in 2/18 showed deletion of RB1 gene on both deleted 13q14 regions. All minimal deleted regions included miR-15a and miR-16-1 genes. Genetic results will be correlated with clinical data. Conclusions: Application of CGH microarrays technique in CLL allows accurately delineate the size of 13q14 deletion regions, what have a prognostic value. All deleted regions included miR15a and miR-16-1, what confirms the essential role of these genes in CLL pathogenesis. In our investigated groups of CLL patients with mono- and biallelic 13q14 deletions, patients with biallelic deletion presented smaller deletion sizes (2,52 Mb vs 7,93 Mb), what is connected with better prognosis.

Keywords: CLL, deletion 13q14, CGH microarrays, SNP array

Procedia PDF Downloads 252
96 CSPG4 Molecular Target in Canine Melanoma, Osteosarcoma and Mammary Tumors for Novel Therapeutic Strategies

Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

Abstract:

Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

Procedia PDF Downloads 166
95 Analysis of Flow Dynamics of Heated and Cooled Pylon Upstream to the Cavity past Supersonic Flow with Wall Heating and Cooling

Authors: Vishnu Asokan, Zaid M. Paloba

Abstract:

Flow over cavities is an important area of research due to the significant change in flow physics caused by cavity aspect ratio, free stream Mach number and the nature of upstream boundary layer approaching the cavity leading edge. Cavity flow finds application in aircraft wheel well, weapons bay, combustion chamber of scramjet engines, etc. These flows are highly unsteady, compressible and turbulent and it involves mass entrainment coupled with acoustics phenomenon. Variation of flow dynamics in an angled cavity with a heated and cooled pylon upstream to the cavity with spatial combinations of heat flux addition and removal to the wall studied numerically. The goal of study is to investigate the effect of energy addition, removal to the cavity walls and pylon cavity flow dynamics. Preliminary steady state numerical simulations on inclined cavities with heat addition have shown that wall pressure profiles, as well as the recirculation, are influenced by heat transfer to the compressible fluid medium. Such a hybrid control of cavity flow dynamics in the form of heat transfer and pylon geometry can open out greater opportunities in enhancement of mixing and flame holding requirements of supersonic combustors. Addition of pylon upstream to the cavity reduces the acoustic oscillations emanating from the geometry. A numerical unsteady analysis of supersonic flow past cavities exposed to cavity wall heating and cooling with heated and cooled pylon helps to get a clear idea about the oscillation suppression in the cavity. A Cavity of L/D 4 and aft wall angle 22 degree with an upstream pylon of h/D=1.5 mm with a wall angle 29 degree exposed to supersonic flow of Mach number 2 and heat flux of 40 W/cm² and -40 W/cm² modeled for the above study. In the preliminary study, the domain is modeled and validated numerically with a turbulence model of SST k-ω using an HLLC implicit scheme. Both qualitative and quantitative flow data extracted and analyzed using advanced CFD tools. Flow visualization is done using numerical Schlieren method as the fluid medium gives the density variation. The heat flux addition to the wall increases the secondary vortex size of the cavity and removal of energy leads to the reduction in vortex size. The flow field turbulence seems to be increasing at higher heat flux. The shear layer thickness increases as heat flux increases. The steady state analysis of wall pressure shows that there is variation on wall pressure as heat flux increases. Shift in frequency of unsteady wall pressure analysis is an interesting observation for the above study. The time averaged skin friction seems to be reducing at higher heat flux due to the variation in viscosity of fluid inside the cavity.

Keywords: energy addition, frequency shift, Numerical Schlieren, shear layer, vortex evolution

Procedia PDF Downloads 139
94 Anti-Phospholipid Antibody Syndrome Presenting with Seizure, Stroke and Atrial Mass: A Case Report

Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

Abstract:

Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

Procedia PDF Downloads 109
93 Investigating Selected Traditional African Medicinal Plants for Anti-fibrotic Potential: Identification and Characterization of Bioactive Compounds Through Fourier-Transform Infrared Spectroscopy and Gas Chromatography-Mass Spectrometry Analysis

Authors: G. V. Manzane, S. J. Modise

Abstract:

Uterine fibroids, also known as leiomyomas or myomas, are non-cancerous growths that develop in the muscular wall of the uterus during the reproductive years. The cause of uterine fibroids includes hormonal, genetic, growth factors, and extracellular matrix factors. Common symptoms of uterine fibroids include heavy and prolonged menstrual bleeding which can lead to a high risk of anemia, lower abdominal pains, pelvic pressure, infertility, and pregnancy loss. The growth of this tumor is a concern because of its negative impact on women’s health and the increase in their economic burden. Traditional medicinal plants have long been used in Africa for their potential therapeutic effects against various ailments. In this study, we aimed to identify and characterize bioactive compounds from selected African medicinal plants with potential anti-fibrotic properties using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GCMS) analysis. Two medicinal plant species known for their traditional use in fibrosis-related conditions were selected for investigation. Aqueous extracts were prepared from the plant materials, and FTIR analysis was conducted to determine the functional groups present in the extracts. GCMS analysis was performed to identify the chemical constituents of the extracts. The FTIR analysis revealed the presence of various functional groups, such as phenols, flavonoids, terpenoids, and alkaloids, known for their potential therapeutic activities. These functional groups are associated with antioxidant, anti-inflammatory, and anti-fibrotic properties. The GCMS analysis identified several bioactive compounds, including flavonoids, alkaloids, terpenoids, and phenolic compounds, which are known for their pharmacological activities. The discovery of bioactive compounds in African medicinal plants that exhibit anti-fibrotic effects, opens up promising avenues for further research and development of potential treatments for fibrosis. This suggests the potential of these plants as a valuable source of novel therapeutic agents for treating fibrosis-related conditions. In conclusion, our study identified and characterized bioactive compounds from selected African medicinal plants using FTIR and GCMS analysis. The presence of compounds with known antifibrotic properties suggests that these plants hold promise as a potential source of natural products for the development of novel anti-fibrotic therapies.

Keywords: uterine fibroids, african medicinal plants, bioactive compounds, identify and characterized

Procedia PDF Downloads 89
92 Scenario of Some Minerals and Impact of Promoter Hypermethylation of DAP-K Gene in Gastric Carcinoma Patients of Kashmir Valley

Authors: Showkat Ahmad Bhat, Iqra Reyaz, Falaque ul Afshan, Ahmad Arif Reshi, Muneeb U. Rehman, Manzoor R. Mir, Sabhiya Majid, Sonallah, Sheikh Bilal, Ishraq Hussain

Abstract:

Background: Gastric cancer is the fourth most common cancer and the second leading cause of worldwide cancer-related deaths, with a wide variation in incidence rates across different geographical areas. The current view of cancer is that a malignancy arises from a transformation of the genetic material of a normal cell, followed by successive mutations and by chain of alterations in genes such as DNA repair genes, oncogenes, Tumor suppressor genes. Minerals are necessary for the functioning of several transcriptional factors, proteins that recognize certain DNA sequences and have been found to play a role in gastric cancer. Material Methods:The present work was a case control study and its aim was to ascertain the role of minerals and promoter hypermethylation of CpG islands of DAP-K gene in Gastric cancer patients among the Kashmiri population. Serum was extracted from all the samples and mineral estimation was done by AAS from serum, DNA was also extracted and was modified using bisulphite modification kit. Methylation-specific PCR was used for the analysis of the promoter hypermethylation status of DAP-K gene. The epigenetic analysis revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of DAP-K gene and has different mineral profile. Results: In our study mean serum copper levels were significantly different for the two genders (p<0.05), while as no significant differences were observed for iron and zinc levels. In Methylation-specific PCR the methylation status of the promoter region of DAP-K gene was as 67.50% (27/40) of the gastric cancer tissues showed methylated DAP-K promoter and 32.50% (13/40) of the cases however showed unmethylated DAP-K promoter. Almost all 85% (17/20) of the histopathologically confirmed normal tissues showed unmethylated DAP-K promoter except only in 3 cases where DAP-K promoter was found to be methylated. The association of promoter hypermethylation with gastric cancer was evaluated by χ2 (Chi square) test and was found to be significant (P=0.0006). Occurrence of DAP-K methylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant (P =0.7635, Odds ratio=1.368 and 95% C.I=0.4197 to 4.456). When the frequency of DAP-K promoter methylation was compared with clinical staging of the disease, DAP-K promoter methylation was found to be certainly higher in Stage III/IV (85.71%) compared to Stage I/ II (57.69%) but the difference was not statistically significant (P =0.0673). These results suggest that DAP-K aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in Gastric cancer and is reportedly one of the commonest epigenetic changes in the development of Gastric cancer.

Keywords: gastric cancer, minerals, AAS, hypermethylation, CpG islands, DAP-K gene

Procedia PDF Downloads 511
91 Aloe vera Prevents Injuries Induced by Whole Body X-ray Irradiation in Rodents

Authors: Shashi Bala, Neha A. Chugh, Subhash C. Bansal, Mohal L. Garg, Ashwani Koul

Abstract:

Purpose: The present study was designed to evaluate the radioprotective efficacy of Aloe vera from whole body X-ray exposure in rodents. Materials and Methods: For this purpose, after on week’s acclimatization, male balb/c mice procured from Central Animal House, Panjab University, Chandigarh (India), were divided into four groups: Group I mice served as control. Group II mice were orally administrated Aloe vera pulp extract (50 mg/ kg body weight) on alternate days for 30 days. Group III mice were subjected to whole body X-ray irradiation to cumulative dose of 2Gy (0.258Gy twice a day for four days in the last week). Group IV animals were pretreated with Aloe vera pulp extract on alternate days as in Group II and in the last week of the study, they were exposed to X-ray as in Group III. Results: Spleen of X-ray irradiated mice showed histopathological alterations accompanied with enhanced activity of lactate dehydrogenase (LDH) in serum. Elevated levels of reactive oxygen species (ROS), lipid peroxidation (LPO), enhanced activities in Glutathione based enzymes such as Glutathione peroxidase (GSH-Px), Glutathione reductase (GR), Catalase (CAT), Superoxide dismutase (SOD) associated with depletion in reduced Glutathione (GSH) concentration were observed after X-ray exposure in blood plasma and spleen.. Pro-inflammatory cytokines like tumor necrosis factors (TNF-α) and Inteleukin-6 (IL-6) levels were also found to be enhanced in serum of irradiated mice. Irradiation-induced significant elevation in Total leucocyte counts (TLC), neutrophil counts and decline in platelet counts, associated with unaltered levels of red blood cell counts (RBC’s) and haemoglobin (Hb) in various treatment groups. Clastogenic damage and apoptosis was also found to be increase in splenic tissue of X-ray exposed mice as assessed by micronucleus and TUNEL assay. However, X-ray irradiated animals administered with Aloe vera revealed significant improvement in levels of ROS/ LPO, LDH activity, and antioxidant mechanism. Aloe vera pretreated animals exhibited less severe damage, and early recovery in micronucleated cells, hematological parameters, apoptotic cells and inflammatory markers as compared to X-ray exposed mice. Conclusion: These results indicate that the radioprotective potential of Aloe vera against X-ray induced damage. This may be due to its free radical scavenging, antioxidant, anti-apoptotic and anti-inflammatory properties.

Keywords: aloe vera, antioxidant defense system, lactate dehydrogenase (LDH), micronucleus assay, x-ray

Procedia PDF Downloads 187
90 Manufacturing the Authenticity of Dokkaebi’s Visual Representation in Tourist Marketing

Authors: Mikyung Bak

Abstract:

The dokkaebi, a beloved icon of Korean culture, is represented as an elf, goblin, monster, dwarf, or any similar creature in different media, such as animated shows, comics, soap operas, and movies. It is often described as a mythical creature with a horn or horns and long teeth, wearing tiger-skin pants or a grass skirt, and carrying a magic stick. Many Korean researchers agree on the similarity of the image of the Korean dokkaebi with that of the Japanese oni, a view that is regard as negative from an anti-colonial or nationalistic standpoint. They cite such similarity between the two mythical creatures as evidence that Japanese colonialism persists in Korea. The debate on the originality of dokkaebi’s visual representation is an issue that must be addressed urgently. This research demonstrates through a diagram the plurality of interpretations of dokkaebi’s visual representations in what are considered ‘authentic’ images of dokkaebi in Korean art and culture. This diagram presents the opinions of four major groups in the debate, namely, the scholars of Korean literature and folklore, art historians, authors, and artists. It also shows the creation of new dokkaebi visual representations in popular media, including those influenced by the debate. The diagram further proves that dokkaebi’s representations varied, which include the typical persons or invisible characters found in Korean literature, original Korean folk characters in traditional art, and even universal spirit characters. They are also visually represented by completely new creatures as well as oni-based mythical beings and the actual oni itself. The earlier dokkaebi representations were driven by the creation of a national ideology or national cultural paradigm and, thus, were more uniform and protected. In contrast, the more recent representations are influenced by the Korean industrial strategy of ‘cultural economics,’ which is concerned with the international rather than the domestic market. This recent Korean cultural strategy emphasizes diversity and commonality with the global culture rather than originality and locality. It employs traditional cultural resources to construct a global image. Consequently, dokkaebi’s recent representations have become more common and diverse, thereby incorporating even oni’s characteristics. This argument has rendered the grounds of the debate irrelevant. The dokkaebi has been used recently for tourist marketing purposes, particularly in revitalizing interest in regions considered the cradle of various traditional dokkaebi tales. These campaign strategies include the Jeju-do Dokkaebi Park, Koksung Dokkaebi Land, as well as the Taebaek and Sokri-san Dokkaebi Festivals. Almost dokkaebi characters are identical to the Japanese oni in tourist marketing. However, the pursuit for dokkaebi’s authentic visual representation is less interesting and fruitful than the appreciation of the entire spectrum of dokkaebi images that have been created. Thus, scholars and stakeholders must not exclude the possibilities for a variety of potentials within the visual culture. The same sentiment applies to traditional art and craft. This study aims to contribute to a new visualization of the dokkaebi that embraces the possibilities of both folk craft and art, which continue to be uncovered by diverse and careful researchers in a still-developing field.

Keywords: Dokkaebi, post-colonial period, representation, tourist marketing

Procedia PDF Downloads 270
89 The Physiological Effect of Cold Atmospheric Pressure Plasma on Cancer Cells, Cancer Stem Cells, and Adult Stem Cells

Authors: Jeongyeon Park, Yeo Jun Yoon, Jiyoung Seo, In Seok Moon, Hae Jun Lee, Kiwon Song

Abstract:

Cold Atmospheric Pressure Plasma (CAPP) is defined as a partially ionized gas with electrically charged particles at room temperature and atmospheric pressure. CAPP generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has potential as a new apoptosis-promoting cancer therapy. With an annular type dielectric barrier discharge (DBD) CAPP-generating device combined with a helium (He) gas feeding system, we showed that CAPP selectively induced apoptosis in various cancer cells while it promoted proliferation of the adipose tissue-derived stem cell (ASC). The apoptotic effect of CAPP was highly selective toward p53-mutated cancer cells. The intracellular ROS was mainly responsible for apoptotic cell death in CAPP-treated cancer cells. CAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of CAPP as a potent cancer therapy. With the same device and exposure conditions to cancer cells, CAPP stimulated proliferation of the ASC, a kind of mesenchymal stem cell that is capable of self-renewing and differentiating into adipocytes, chondrocytes, osteoblasts and neurons. CAPP-treated ASCs expressed the stem cell markers and differentiated into adipocytes as untreated ASCs. The increase of proliferation by CAPP in ASCs was offset by a NO scavenger but was not affected by ROS scavengers, suggesting that NO generated by CAPP is responsible for the activated proliferation in ASCs. Usually, cancer stem cells are reported to be resistant to known cancer therapies. When we applied CAPP of the same device and exposure conditions to cancer cells to liver cancer stem cells (CSCs) that express CD133 and epithelial cell adhesion molecule (EpCAM) cancer stem cell markers, apoptotic cell death was not examined. Apoptotic cell death of liver CSCs was induced by the CAPP generated from a device with an air-based flatten type DBD. An exposure of liver CSCs to CAPP decreased the viability of liver CSCs to a great extent, suggesting plasma be used as a promising anti-cancer treatment. To validate whether CAPP can be a promising anti-cancer treatment or an adjuvant modality to eliminate remnant tumor in cancer surgery of vestibular schwannoma, we applied CAPP to mouse schwannoma cell line SC4 Nf2 ‑/‑ and human schwannoma cell line HEI-193. A CAPP treatment leads to anti-proliferative effect in both cell lines. We are currently studying the molecular mechanisms of differential physiological effect of CAPP; the proliferation of ASCs and apoptosis of various cancer cells and CSCs.

Keywords: cold atmospheric pressure plasma, apoptosis, proliferation, cancer cells, adult stem cells

Procedia PDF Downloads 277
88 Evaluation of Role of Surgery in Management of Pediatric Germ Cell Tumors According to Risk Adapted Therapy Protocols

Authors: Ahmed Abdallatif

Abstract:

Background: Patients with malignant germ cell tumors have age distribution in two peaks, with the first one during infancy and the second after the onset of puberty. Gonadal germ cell tumors are the most common malignant ovarian tumor in females aged below twenty years. Sacrococcygeal and retroperitoneal abdominal tumors usually presents in a large size before the onset of symptoms. Methods: Patients with pediatric germ cell tumors presenting to Children’s Cancer Hospital Egypt and National Cancer Institute Egypt from January 2008 to June 2011 Patients underwent stratification according to risk into low, intermediate and high risk groups according to children oncology group classification. Objectives: Assessment of the clinicopathologic features of all cases of pediatric germ cell tumors and classification of malignant cases according to their stage, and the primary site to low, intermediate and high risk patients. Evaluation of surgical management in each group of patients focusing on surgical approach, the extent of surgical resection according to each site, ability to achieve complete surgical resection and perioperative complications. Finally, determination of the three years overall and disease-free survival in different groups and the relation to different prognostic factors including the extent of surgical resection. Results: Out of 131 cases surgically explored only 26 cases had re exploration with 8 cases explored for residual disease 9 cases for remote recurrence or metastatic disease and the other 9 cases for other complications. Patients with low risk kept under follow up after surgery, out of those of low risk group (48 patients) only 8 patients (16.5%) shifted to intermediate risk. There were 20 patients (14.6%) diagnosed as intermediate risk received 3 cycles of compressed (Cisplatin, Etoposide and Bleomycin) and all high risk group patients 69patients (50.4%) received chemotherapy. Stage of disease was strongly and significantly related to overall survival with a poorer survival in late stages (stage IV) as compared to earlier stages. Conclusion: Overall survival rate at 3 three years was (76.7% ± 5.4, 3) years EFS was (77.8 % ±4.0), however 3 years DFS was much better (89.8 ± 3.4) in whole study group with ovarian tumors had significantly higher Overall survival (90% ± 5.1). Event Free Survival analysis showed that Male gender was 3 times likely to have bad events than females. Patients who underwent incomplete resection were 4 times more than patients with complete resection to have bad events. Disease free survival analysis showed that Patients who underwent incomplete surgery were 18.8 times liable for recurrence compared to those who underwent complete surgery, and patients who were exposed to re-excision were 21 times more prone to recurrence compared to other patients.

Keywords: extragonadal, germ cell tumors, gonadal, pediatric

Procedia PDF Downloads 214
87 Molecular Docking Analysis of Flavonoids Reveal Potential of Eriodictyol for Breast Cancer Treatment

Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

Abstract:

Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

Procedia PDF Downloads 76
86 Low Cost LiDAR-GNSS-UAV Technology Development for PT Garam’s Three Dimensional Stockpile Modeling Needs

Authors: Mohkammad Nur Cahyadi, Imam Wahyu Farid, Ronny Mardianto, Agung Budi Cahyono, Eko Yuli Handoko, Daud Wahyu Imani, Arizal Bawazir, Luki Adi Triawan

Abstract:

Unmanned aerial vehicle (UAV) technology has cost efficiency and data retrieval time advantages. Using technologies such as UAV, GNSS, and LiDAR will later be combined into one of the newest technologies to cover each other's deficiencies. This integration system aims to increase the accuracy of calculating the volume of the land stockpile of PT. Garam (Salt Company). The use of UAV applications to obtain geometric data and capture textures that characterize the structure of objects. This study uses the Taror 650 Iron Man drone with four propellers, which can fly for 15 minutes. LiDAR can classify based on the number of image acquisitions processed in the software, utilizing photogrammetry and structural science principles from Motion point cloud technology. LiDAR can perform data acquisition that enables the creation of point clouds, three-dimensional models, Digital Surface Models, Contours, and orthomosaics with high accuracy. LiDAR has a drawback in the form of coordinate data positions that have local references. Therefore, researchers use GNSS, LiDAR, and drone multi-sensor technology to map the stockpile of salt on open land and warehouses every year, carried out by PT. Garam twice, where the previous process used terrestrial methods and manual calculations with sacks. Research with LiDAR needs to be combined with UAV to overcome data acquisition limitations because it only passes through the right and left sides of the object, mainly when applied to a salt stockpile. The UAV is flown to assist data acquisition with a wide coverage with the help of integration of the 200-gram LiDAR system so that the flying angle taken can be optimal during the flight process. Using LiDAR for low-cost mapping surveys will make it easier for surveyors and academics to obtain pretty accurate data at a more economical price. As a survey tool, LiDAR is included in a tool with a low price, around 999 USD; this device can produce detailed data. Therefore, to minimize the operational costs of using LiDAR, surveyors can use Low-Cost LiDAR, GNSS, and UAV at a price of around 638 USD. The data generated by this sensor is in the form of a visualization of an object shape made in three dimensions. This study aims to combine Low-Cost GPS measurements with Low-Cost LiDAR, which are processed using free user software. GPS Low Cost generates data in the form of position-determining latitude and longitude coordinates. The data generates X, Y, and Z values to help georeferencing process the detected object. This research will also produce LiDAR, which can detect objects, including the height of the entire environment in that location. The results of the data obtained are calibrated with pitch, roll, and yaw to get the vertical height of the existing contours. This study conducted an experimental process on the roof of a building with a radius of approximately 30 meters.

Keywords: LiDAR, unmanned aerial vehicle, low-cost GNSS, contour

Procedia PDF Downloads 84