Clinical Implications of Evolutionary Modeling of Cancer Progression

Evolutionary theory of cancer was developed in 1976 by cancer research Peter Nowell and has illuminated the path toward increasing safety and efficacy of clinical treatment strategies. Major foundations that makeup the complexity in Darwinian framework of cancer includes clonal evolution, clonal expansion, and competition. Due to these characteristics, virtually all types of cancer have evolutionary capabilities to reject or adapt and become resistant to pharmaceutical therapies. Despite compelling evidence of these process, evolutionary modeling of cancer continues to be underutilized in clinical settings. Contributions to this include the complex adaptive mechanisms that tools fail to detect or are unable to be targeted effectively, lack of studies regarding quantity and relevance, and the perception of evolutionary theory. As a result, failure to clinically adopt evolutionary modeling has delayed development of new cancer therapy strategies, particularly for cancer recurrence. Drug resistance and relapse are devastating and compelling pieces of evidence that should compel researchers and clinicians to integrate evolutionary modeling into cancer treatment. Evolutionary modeling provides key insight into developing treatments that are as dynamic as cancer biology, including personalized medicine, Adaptive Therapy (AT), and to make systemic cancer treatments obsolete

On 3-D inelastic analysis methods for hot section components (base program)

A 3-D Inelastic Analysis Method program is described. This program consists of a series of new computer codes embodying a progression of mathematical models (mechanics of materials, special finite element, boundary element) for streamlined analysis of: (1) combustor liners, (2) turbine blades, and (3) turbine vanes. These models address the effects of high temperatures and thermal/mechanical loadings on the local (stress/strain)and global (dynamics, buckling) structural behavior of the three selected components. Three computer codes, referred to as MOMM (Mechanics of Materials Model), MHOST (Marc-Hot Section Technology), and BEST (Boundary Element Stress Technology), have been developed and are briefly described in this report

Development of utility system simulation model

"Worked preformed for Commonwealth Edison Company, Chicago, Illinois."Includes bibliographical references (leaf 28)MIT DSR Project 7210

Regional Development Modeling: Theory and Practice

This volume contains a collection of papers presented at IIASA's conference on "Theoretical and Practical Aspects of Regional Development Modelling". Of the 50 papers presented , 26 were selected for publication, in such a way as to strike a balance between theory and application of regional systems analysis. The book is divided into seven parts. After an introduction, the second and third parts contain overviews of current modelling practice and planned economies. In the next two parts, the focus shifts to the theoretical problems encountered in structural and multi-objective analysis of regional systems. The final two sections contain examples of regional development models currently ready for use or in operation and analyze the success of these models in clarifying regional planning and policy problems

Simulation Modeling

The book presents some recent specialized works of a theoretical and practical nature in the field of simulation modeling, which is being addressed to a large number of specialists, mathematicians, doctors, engineers, economists, professors, and students. The book comprises 11 chapters that promote modern mathematical algorithms and simulation modeling techniques, in practical applications, in the following thematic areas: mathematics, biomedicine, systems of systems, materials science and engineering, energy systems, and economics. This project presents scientific papers and applications that emphasize the capabilities of simulation modeling methods, helping readers to understand the phenomena that take place in the real world, the conditions of their development, and their effects, at a high scientific and technical level. The authors have published work examples and case studies that resulted from their researches in the field. The readers get new solutions and answers to questions related to the emerging applications of simulation modeling and their advantages

Sterilization Assembly Development Laboratory - Monitoring plan

Monitoring plan with test requirements and procedures for sterilization assembly development laborator

Study and development of a solidification model using CFD

Aquesta tesis de màster estableix un estat de l'art sobre diferents models de congelació de l'aigua utilitzant tècniques numèriques per donar resposta a un problema industrial. Mecanismes de transferència de calor com la convecció i la conducció són estudiats per dur a terme la implementació d'aquests models en un solver de CFD . La part final d'aquesta tesis estarà enfocada a produir un solver basat en la transferència de calor conjugada en un marc de multi-regió entre un sòlid i un liquid sotmès a canvi de fase.Esta tesis de màster establece un estado del arte sobre diferentes modelos de congelación de agua usando técnicas numéricas. Mecanismos de transferencia de calor como convección y conducción son estudiados para llevar a cabo la implementación de estos modelos en un solver de CFD. La parte final de esta tesis estará enfocada en producir un solver basado en la transferencia de calor conjugada en un marco de multi-región entre un sólido y un líquido sometido a cambio de fase.This master's thesis establishes a comprehensive state of the art of some water solification models by using numerical techniques. Heat transfer mechanisms as convection and conduction are studied so as to carry out the implementation of such models within a CFD solver framework. The final part of this thesis is devoted to produce a new solver based on the conjugate heat transfer in a multi-region environment between a solid and a two-phase liquid

Thermal analysis of anti-icing systems in aeronautical velocity sensors and structures

This work reviews theoretical–experimental studies undertaken at COPPE/UFRJ on conjugated heat transfer problems associated with the transient thermal behavior of heated aeronautical Pitot tubes and wing sections with anti-icing systems. One of the main objectives is to demonstrate the importance of accounting for the conduction–convection conjugation in more complex models that attempt to predict the thermal behavior of the anti-icing system under adverse atmospheric conditions. The experimental analysis includes flight tests validation of a Pitot tube thermal behavior with the military aircraft A4 Skyhawk (Brazilian Navy) and wind tunnel runs (INMETRO and NIDF/COPPE/UFRJ, both in Brazil), including the measurement of spatial and temporal variations of surface temperatures along the probe through infrared thermography. The theoretical analysis first involves the proposition of an improved lumped-differential model for heat conduction along a Pitot probe, approximating the radial temperature gradients within the metallic and ceramic (electrical insulator) walls. The convective heat transfer problem in the external fluid is solved using the boundary layer equations for compressible flow, applying the Illingsworth variables transformation considering a locally similar flow. The nonlinear partial differential equations are solved using the Generalized Integral Transform Technique in the Mathematica platform. In addition, a fully local differential conjugated problem model was proposed, including both the dynamic and thermal boundary layer equations for laminar, transitional, and turbulent flow, coupled to the heat conduction equation at the sensor or wing section walls. With the aid of a single-domain reformulation of the problem, which is rewritten as one set of equations for the whole spatial domain, through space variable physical properties and coefficients, the GITT is again invoked to provide hybrid numerical–analytical solutions to the velocity and temperature fields within both the fluid and solid regions. Then, a modified Messinger model is adopted to predict ice formation on either wing sections or Pitot tubes, which allows for critical comparisons between the simulation and the actual thermal response of the sensor or structure. Finally, an inverse heat transfer problem is formulated aimed at estimating the heat transfer coefficient at the leading edge of Pitot tubes, in order to detect ice accretion, and estimating the relative air speed in the lack of a reliable dynamic pressure reading. Due to the intrinsic dynamical behavior of the present inverse problem, it is solved within the Bayesian framework by using particle filter.Indisponível

Tracking Cancer Evolution through the Disease Course.

During cancer evolution, constituent tumor cells compete under dynamic selection pressures. Phenotypic variation can be observed as intratumor heterogeneity, which is propagated by genome instability leading to mutations, somatic copy-number alterations, and epigenomic changes. TRACERx was set up in 2014 to observe the relationship between intratumor heterogeneity and patient outcome. By integrating multiregion sequencing of primary tumors with longitudinal sampling of a prospectively recruited patient cohort, cancer evolution can be tracked from early- to late-stage disease and through therapy. Here we review some of the key features of the studies and look to the future of the field. SIGNIFICANCE: Cancers evolve and adapt to environmental challenges such as immune surveillance and treatment pressures. The TRACERx studies track cancer evolution in a clinical setting, through primary disease to recurrence. Through multiregion and longitudinal sampling, evolutionary processes have been detailed in the tumor and the immune microenvironment in non-small cell lung cancer and clear-cell renal cell carcinoma. TRACERx has revealed the potential therapeutic utility of targeting clonal neoantigens and ctDNA detection in the adjuvant setting as a minimal residual disease detection tool primed for translation into clinical trials