scholarly journals Connecting the Microenvironmental Niche to Treatment Response in Ovarian Cancer

2018 ◽  
Author(s):  
Maximilian Strobl ◽  
Matthew Wicker ◽  
Vikram Adhikarla ◽  
W. Andrew Shockey ◽  
Eszter Lakatos ◽  
...  

AbstractOvarian cancer has the highest mortality rate of all gynecologic cancers, which may be attributed to an often late stage diagnosis, when the cancer is already metastatic, and rapid development of treatment resistance. We propose that the metastatic disease could be better characterized by observing interactions within the microenvironmental niche of the primary site that shapes the tumor’s early phenotypic progression. We present a mechanistic mathematical model of ovarian cancer that considers spatial interactions between tumor cells and several key stromal components. We demonstrate how spatial biomarker imaging data from the primary tumor can be analyzed to define a patient-specific microenvironment in the mathematical model. We then show preliminary results, using this model, that demonstrate how differences in the niche composition of a tumor affects phenotypic evolution and treatment response.

2019 ◽  
Vol 5 (6) ◽  
pp. a004648 ◽  
Author(s):  
Deep Pandya ◽  
Sandra Catalina Camacho ◽  
Maria M. Padron ◽  
Olga Camacho-Vanegas ◽  
Jean-Noel Billaud ◽  
...  

2018 ◽  
Vol 63 (3) ◽  
pp. 279-290
Author(s):  
Vytautas Ostasevicius ◽  
Yahor Tretsyakou-Savich ◽  
Mantas Venslauskas ◽  
Agne Bertasiene ◽  
Vladimir Minchenya ◽  
...  

Abstract Time-consuming design and manufacturing processes are a serious disadvantage when adapting human cardiovascular implants as they cause unacceptable delays after the decision to intervene surgically has been made. An ideal cardiovascular implant should have a broad range of characteristics such as strength, viscoelasticity and blood compatibility. The present research proposes the sequence of the geometrical adaptation procedures and presents their results. The adaptation starts from the identification of a person’s current health status while performing abdominal aortic aneurysm (AAA) imaging, which is a point of departure for the mathematical model of a cardiovascular implant. The computerized tomography scan shows the patient-specific geometry parameters of AAA and helps to create a model using COMSOL Multiphysics software. The initial parameters for flow simulation are taken from the results of a patient survey. The simulation results allow choosing the available shape of an implant which ensures a non-turbulent flow. These parameters are essential for the design and manufacturing of an implant prototype which should be tested experimentally for the assurance that the mathematical model is adequate to a physical one. The article gives a focused description of competences and means that are necessary to achieve the shortest possible preparation of the adapted cardiovascular implant for the surgery.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi63-vi64
Author(s):  
Daniel Glazar ◽  
Rene Brady ◽  
Rachel Howard ◽  
Daniel Grass ◽  
John Arrington ◽  
...  

Abstract PURPOSE/OBJECTIVES We set out to predict response and progression risk in recurrent high-grade glioma patients treated with hypofractionated stereotactic radiation plus pembrolizumab and bevacizumab (NCT02313272). At present RANO criteria define progression as 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement (either at baseline or best response) or significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids. To this extent, a predictive model is needed to adaptively learn and forecast individual response to therapy. We evaluate if early tumor volume evolution can train a mathematical model to predict subsequent response to therapy. MATERIALS/METHODS We develop a mathematical model that describes patient-uniform tumor growth rate and initial pembrolizumab and bevacizumab responses, and patient-specific treatment response dynamics. A total of 154 radiology scans were delineated to derive longitudinal tumor volumes of 26 patients. In a leave-one-out study, patient-uniform model parameters are derived and then applied to the left-out patient to adaptively learn treatment response dynamics to forecast tumor volume evolution and progression risk. Model prediction performance is evaluated based on classification accuracy, including sensitivity and specificity. RESULTS Patient-uniform glioma growth rate and initial treatment response rates are estimated to achieve acceptable fits to the longitudinal data of all untrained patients with R2 = 0.81 [0.75, 0.89]. Response dynamics are predicted with high accuracy (0.78 [0.76, 0.79]), with positive and negative predictive values of 0.90 [0.86, 0.92] and 0.81 [0.78, 0.86], and sensitivity and specificity of 0.71 [0.69, 0.73] and 0.88 [0.83, 0.91] respectively. CONCLUSIONS Two patient-specific parameters in a mathematical model can be adaptively learned from early tumor volume evolution to predict subsequent response to therapy and progression risk for individual patients. Future validation is required in an independent dataset and prospective evaluation in another clinical trial.


Author(s):  
Olexandr Pavlenko ◽  
Serhii Dun ◽  
Maksym Skliar

In any economy there is a need for the bulky goods transportation which cannot be divided into smaller parts. Such cargoes include building structures, elements of industrial equipment, tracked or wheeled construction and agricultural machinery, heavy armored military vehicles. In any case, tractor-semitrailer should provide fast delivery of goods with minimal fuel consumption. In order to guarantee the goods delivery, tractor-semitrailers must be able to overcome the existing roads broken grade and be capable to tow a semi-trailer in off-road conditions. These properties are especially important for military equipment transportation. The important factor that determines a tractor-semitrailer mobility is its gradeability. The purpose of this work is to improve a tractor-semitrailer mobility with tractor units manufactured at PJSC “AutoKrAZ” by increasing the tractor-semitrailer gradeability. The customer requirements for a new tractor are determined by the maximizing the grade to 18°. The analysis of the characteristics of modern tractor-semitrailers for heavy haulage has shown that the highest rate of this grade is 16.7°. The factors determining the limiting gradeability value were analyzed, based on the tractor-semitrailer with a KrAZ-6510TE tractor and a semi-trailer with a full weight of 80 t. It has been developed a mathematical model to investigate the tractor and semi-trailer axles vertical reactions distribution on the tractor-semitrailer friction performances. The mathematical model has allowed to calculate the gradeability value that the tractor-semitrailer can overcome in case of wheels and road surface friction value and the tractive force magnitude from the engine. The mathematical model adequacy was confirmed by comparing the calculations results with the data of factory tests. The analysis showed that on a dry road the KrAZ-6510TE tractor with a 80 t gross weight semitrailer is capable to climb a gradient of 14,35 ° with its coupling mass full use condition. The engine's maximum torque allows the tractor-semitrailer to overcome a gradient of 10.45° It has been determined the ways to improve the design of the KrAZ-6510TE tractor to increase its gradeability. Keywords: tractor, tractor-semitrailer vehicle mobility, tractor-semitrailer vehicle gradeability.


Author(s):  
Oleksii Timkov ◽  
Dmytro Yashchenko ◽  
Volodymyr Bosenko

The article deals with the development of a physical model of a car equipped with measuring, recording and remote control equipment for experimental study of car properties. A detailed description of the design of the physical model and of the electronic modules used is given, links to application libraries and the code of the first part of the program for remote control of the model are given. Atmega microcontroller on the Arduino Uno platform was used to manage the model and register the parameters. When moving the car on the memory card saved such parameters as speed, voltage on the motor, current on the motor, the angle of the steered wheel, acceleration along three coordinate axes are recorded. Use of more powerful microcontrollers will allow to expand the list of the registered parameters of movement of the car. It is possible to measure the forces acting on the elements of the car and other parameters. In the future, it is planned to develop a mathematical model of motion of the car and check its adequacy in conducting experimental studies on maneuverability on the physical model. In addition, it is possible to conduct studies of stability and consumption of electrical energy. The physical model allows to quickly change geometric dimensions and mass parameters. In the study of highway trains, this approach will allow to investigate the various layout schemes of highway trains in the short term. It is possible to make two-axle road trains and saddle towed trains, three-way hitched trains of different layout. The results obtained will allow us to improve not only the mathematical model, but also the experimental physical model, and move on to further study the properties of hybrid road trains with an active trailer link. This approach allows to reduce material and time costs when researching the properties of cars and road trains. Keywords: car, physical model, experiment, road trains, sensor, remote control, maneuverability, stability.


Author(s):  
Serhii Kovbasenko ◽  
Andriy Holyk ◽  
Serhii Hutarevych

The features of an advanced mathematical model of motion of a truck with a diesel engine operating on the diesel and diesel gas cycles are presented in the article. As a result of calculations using the mathematical model, a decrease in total mass emissions as a result of carbon monoxide emissions is observed due to a decrease in emissions of nitrogen oxides and emissions of soot in the diesel gas cycle compared to the diesel cycle. The mathematical model of a motion of a truck on a city driving cycle according to GOST 20306-90 allows to study the fuel-economic, environmental and energy indicators of a diesel and diesel gas vehicle. The results of the calculations on the mathematical model will make it possible to conclude on the feasibility of converting diesel vehicles to using compressed natural gas. Object of the study – the fuel-economic, environmental and energy performance diesel engine that runs on dual fuel system using CNG. Purpose of the study – study of changes in fuel, economic, environmental and energy performance of vehicles with diesel engines operating on diesel and diesel gas cycles, according to urban driving cycle modes. Method of the study – calculations on a mathematical model and comparison of results with road tests. Bench and road tests, results of calculations on the mathematical model of motion of a truck with diesel, working on diesel and diesel gas cycles, show the improvement of environmental performance of diesel vehicles during the converting to compressed natural gas in operation. Improvement of environmental performance is obtained mainly through the reduction of soot emissions and nitrogen oxides emissions from diesel gas cycle operations compared to diesel cycle operations. The results of the article can be used to further develop dual fuel system using CNG. Keywords: diesel engine, diesel gas engine, CNG


1998 ◽  
Vol 2 ◽  
pp. 23-30
Author(s):  
Igor Basov ◽  
Donatas Švitra

Here a system of two non-linear difference-differential equations, which is mathematical model of self-regulation of the sugar level in blood, is investigated. The analysis carried out by qualitative and numerical methods allows us to conclude that the mathematical model explains the functioning of the physiological system "insulin-blood sugar" in both normal and pathological cases, i.e. diabetes mellitus and hyperinsulinism.


2001 ◽  
Vol 6 (1) ◽  
pp. 9-19 ◽  
Author(s):  
A. Buikis ◽  
J. Cepitis ◽  
H. Kalis ◽  
A. Reinfelds ◽  
A. Ancitis ◽  
...  

The mathematical model of wood drying based on detailed transport phenomena considering both heat and moisture transfer have been offered in article. The adjustment of this model to the drying process of papermaking is carried out for the range of moisture content corresponding to the period of drying in which vapour movement and bound water diffusion in the web are possible. By averaging as the desired models are obtained sequence of the initial value problems for systems of two nonlinear first order ordinary differential equations. 


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