Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer.

Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. However, functional studies show a strikingly constrained tumorigenic pathway underlying heterogeneous genetic variants. These results suggest that although the mutation-specific routes that cells take during oncogenesis are stochastic, genetic trajectories may be constrained by selection for functional convergence on key signaling pathways. Our findings highlight the robust evolutionary pressures that simultaneously shape the expansion and constraint of genomic diversity, a principle that holds important implications for understanding tumor evolution and optimizing therapeutic strategies.Across cancer types tumor heterogeneity has been observed, but how this relates to tumor evolution is unclear. Here, the authors sequence multiple synchronous lung cancers, highlighting the evolutionary pressures that simultaneously shape the expansion and constraint of genomic heterogeneity

A Field Guide to Genetic Programming

xiv, 233 p. : il. ; 23 cm.Libro ElectrónicoA Field Guide to Genetic Programming (ISBN 978-1-4092-0073-4) is an introduction to genetic programming (GP). GP is a systematic, domain-independent method for getting computers to solve problems automatically starting from a high-level statement of what needs to be done. Using ideas from natural evolution, GP starts from an ooze of random computer programs, and progressively refines them through processes of mutation and sexual recombination, until solutions emerge. All this without the user having to know or specify the form or structure of solutions in advance. GP has generated a plethora of human-competitive results and applications, including novel scientific discoveries and patentable inventions. The authorsIntroduction -- Representation, initialisation and operators in Tree-based GP -- Getting ready to run genetic programming -- Example genetic programming run -- Alternative initialisations and operators in Tree-based GP -- Modular, grammatical and developmental Tree-based GP -- Linear and graph genetic programming -- Probalistic genetic programming -- Multi-objective genetic programming -- Fast and distributed genetic programming -- GP theory and its applications -- Applications -- Troubleshooting GP -- Conclusions.Contents xi 1 Introduction 1.1 Genetic Programming in a Nutshell 1.2 Getting Started 1.3 Prerequisites 1.4 Overview of this Field Guide I Basics 2 Representation, Initialisation and GP 2.1 Representation 2.2 Initialising the Population 2.3 Selection 2.4 Recombination and Mutation Operators in Tree-based 3 Getting Ready to Run Genetic Programming 19 3.1 Step 1: Terminal Set 19 3.2 Step 2: Function Set 20 3.2.1 Closure 21 3.2.2 Sufficiency 23 3.2.3 Evolving Structures other than Programs 23 3.3 Step 3: Fitness Function 24 3.4 Step 4: GP Parameters 26 3.5 Step 5: Termination and solution designation 27 4 Example Genetic Programming Run 4.1 Preparatory Steps 29 4.2 Step-by-Step Sample Run 31 4.2.1 Initialisation 31 4.2.2 Fitness Evaluation Selection, Crossover and Mutation Termination and Solution Designation Advanced Genetic Programming 5 Alternative Initialisations and Operators in 5.1 Constructing the Initial Population 5.1.1 Uniform Initialisation 5.1.2 Initialisation may Affect Bloat 5.1.3 Seeding 5.2 GP Mutation 5.2.1 Is Mutation Necessary? 5.2.2 Mutation Cookbook 5.3 GP Crossover 5.4 Other Techniques 32 5.5 Tree-based GP 39 6 Modular, Grammatical and Developmental Tree-based GP 47 6.1 Evolving Modular and Hierarchical Structures 47 6.1.1 Automatically Defined Functions 48 6.1.2 Program Architecture and Architecture-Altering 50 6.2 Constraining Structures 51 6.2.1 Enforcing Particular Structures 52 6.2.2 Strongly Typed GP 52 6.2.3 Grammar-based Constraints 53 6.2.4 Constraints and Bias 55 6.3 Developmental Genetic Programming 57 6.4 Strongly Typed Autoconstructive GP with PushGP 59 7 Linear and Graph Genetic Programming 61 7.1 Linear Genetic Programming 61 7.1.1 Motivations 61 7.1.2 Linear GP Representations 62 7.1.3 Linear GP Operators 64 7.2 Graph-Based Genetic Programming 65 7.2.1 Parallel Distributed GP (PDGP) 65 7.2.2 PADO 67 7.2.3 Cartesian GP 67 7.2.4 Evolving Parallel Programs using Indirect Encodings 68 8 Probabilistic Genetic Programming 8.1 Estimation of Distribution Algorithms 69 8.2 Pure EDA GP 71 8.3 Mixing Grammars and Probabilities 74 9 Multi-objective Genetic Programming 75 9.1 Combining Multiple Objectives into a Scalar Fitness Function 75 9.2 Keeping the Objectives Separate 76 9.2.1 Multi-objective Bloat and Complexity Control 77 9.2.2 Other Objectives 78 9.2.3 Non-Pareto Criteria 80 9.3 Multiple Objectives via Dynamic and Staged Fitness Functions 80 9.4 Multi-objective Optimisation via Operator Bias 81 10 Fast and Distributed Genetic Programming 83 10.1 Reducing Fitness Evaluations/Increasing their Effectiveness 83 10.2 Reducing Cost of Fitness with Caches 86 10.3 Parallel and Distributed GP are Not Equivalent 88 10.4 Running GP on Parallel Hardware 89 10.4.1 Master–slave GP 89 10.4.2 GP Running on GPUs 90 10.4.3 GP on FPGAs 92 10.4.4 Sub-machine-code GP 93 10.5 Geographically Distributed GP 93 11 GP Theory and its Applications 97 11.1 Mathematical Models 98 11.2 Search Spaces 99 11.3 Bloat 101 11.3.1 Bloat in Theory 101 11.3.2 Bloat Control in Practice 104 III Practical Genetic Programming 12 Applications 12.1 Where GP has Done Well 12.2 Curve Fitting, Data Modelling and Symbolic Regression 12.3 Human Competitive Results – the Humies 12.4 Image and Signal Processing 12.5 Financial Trading, Time Series, and Economic Modelling 12.6 Industrial Process Control 12.7 Medicine, Biology and Bioinformatics 12.8 GP to Create Searchers and Solvers – Hyper-heuristics xiii 12.9 Entertainment and Computer Games 127 12.10The Arts 127 12.11Compression 128 13 Troubleshooting GP 13.1 Is there a Bug in the Code? 13.2 Can you Trust your Results? 13.3 There are No Silver Bullets 13.4 Small Changes can have Big Effects 13.5 Big Changes can have No Effect 13.6 Study your Populations 13.7 Encourage Diversity 13.8 Embrace Approximation 13.9 Control Bloat 13.10 Checkpoint Results 13.11 Report Well 13.12 Convince your Customers 14 Conclusions Tricks of the Trade A Resources A.1 Key Books A.2 Key Journals A.3 Key International Meetings A.4 GP Implementations A.5 On-Line Resources 145 B TinyGP 151 B.1 Overview of TinyGP 151 B.2 Input Data Files for TinyGP 153 B.3 Source Code 154 B.4 Compiling and Running TinyGP 162 Bibliography 167 Inde

Multimedia and Audience: Implications for Executive Summaries

In an effort to put technical reports into a multimedia format, this thesis explored audience analysis and multimedia issues related to executive summaries. While multimedia has been shown to be effective at conveying complex information in certain environments, little research has been done to apply this technology to technical reporting. This thesis concentrates on the executive summary audience because the executive summary is the most read and most important section of a report. To analyze the audience, I conducted telephone interviews with report readers using an interview form I developed based on Mathes and Stevenson\u27s guidelines for conducting an audience analysis. I included a section to assess the readers\u27 perceptions of the usefulness of four forms of multimedia--sound, video, hypertext, and CD-ROM--for effectively retrieving information from an executive summary. The data results show on average a well educated, middle aged group of readers with considerable experience in their jobs. In the multimedia assessment, hypertext was rated the most useful at retrieving information from an executive summary, with video, CD-ROM, and sound following in that order. For report writers, then, the data helps to narrow down the type of information to include and what multimedia format to consider when preparing an executive summary

Migration Research in a Digitized World: Using Innovative Technology to Tackle Methodological Challenges

This open access book explores implications of the digital revolution for migration scholars’ methodological toolkit. New information and communication technologies hold considerable potential to improve the quality of migration research by originating previously non-viable solutions to a myriad of methodological challenges in this field of study. Combining cutting-edge migration scholarship and methodological expertise, the book addresses a range of crucial issues related to both researcher-designed data collections and the secondary use of “big data”, highlighting opportunities as well as challenges and limitations. A valuable source for students and scholars engaged in migration research, the book will also be of keen interest to policymakers

Migration Research in a Digitized World

This open access book explores implications of the digital revolution for migration scholars’ methodological toolkit. New information and communication technologies hold considerable potential to improve the quality of migration research by originating previously non-viable solutions to a myriad of methodological challenges in this field of study. Combining cutting-edge migration scholarship and methodological expertise, the book addresses a range of crucial issues related to both researcher-designed data collections and the secondary use of “big data”, highlighting opportunities as well as challenges and limitations. A valuable source for students and scholars engaged in migration research, the book will also be of keen interest to policymakers

Migration Research in a Digitized World: Using Innovative Technology to Tackle Methodological Challenges

This book explores implications of the digital revolution for migration scholars' methodological toolkit. New information and communication technologies hold considerable potential to improve the quality of migration research by originating previously non-viable solutions to a myriad of methodological challenges in this field of study. Combining cutting-edge migration scholarship and methodological expertise, the book addresses a range of crucial issues related to both researcher-designed data collections and the secondary use of "big data", highlighting opportunities as well as challenges and limitations. A valuable source for students and scholars engaged in migration research, the book will also be of keen interest to policymakers

The Influence Of Knowing Web 2.0 Risks And Controls On Web 2.0 Usage And Security Practices Of Online Users

Significant changes have taken place on the internet in recent years. The most prominent is the introduction of Web 2.0 technologies (Web 2.0), which promotes sharing and collaboration. This study investigates the usage patterns, and awareness levels of the risks and controls associated with Web 2.0 by educated and uneducated users. Accounting students (as a proxy for educated users) are taught about the risks and controls of Web 2.0 as part of their studies, whereas Business Strategy students’ (as a proxy for uneducated users) exposure is limited to popular media and their own research. The results indicate that the use of Web 2.0 is popular among South African students irrespective of which course they major in. The Web 2.0 awareness levels of both populations were relatively high with no significant differences. Contrary to expectation, the level of usage; types of Web 2.0 technologies; types of risks; and the manner and frequency of sharing of information by the two populations were not found to differ significantly. The research highlights that although Accounting students are taught about the risks and controls in Web 2.0, they do not take these risks and controls into consideration in their personal life when interacting with Web 2.0. Contrary to expectation, it appears that being formally educated on Web 2.0 does not have a larger impact on user behaviour than awareness gained from popular media. It also indicates how user behaviour influences the effectiveness of online controls

Sustainable faculty development: issues in technology for teacher education

This dissertation centers around research and development on faculty preparation for integration of technology for teacher education. Chapter 1 is the general introduction in which the background and the significance of the research topics are addressed. Chapter 2, Chapter 3, and Chapter 4 consist of three published or publishable papers. Chapter 5 is the general conclusion. Chapter 2 summarizes the literature related to one-on-one technology mentoring programs in higher education and K--12 institutions nation wide, and identifies themes contributing to a successful mentoring program. Chapter 3 describes the pedagogical shift of an exemplary technology-using teacher educator through her eight-year journey with a one-on-one technology mentoring program. A grounded theory approach was used to relate and integrate the stages experienced by an exemplary technology-using teacher educator who moved from limited knowledge and use of technology to learning to apply basic applications in the classroom and on to integrating innovative technology. In Chapter 4, results from an online survey on the issues of sustainability of faculty\u27s use and integration of technology in teacher education programs are presented. Based on the findings of a pilot case study, the survey was developed to gather quantitative data from 60 teacher education faculty members from 31 higher education institutions. The purpose of the survey study was to investigate how to encourage faculty members who have made significant use of technology to continue to use technology in their teacher preparation courses and to sustain efforts in making technology an essential component across the curriculum in teacher education programs. In addition, the survey results helped to identify effective faculty development practices and provided information on breaking down barriers to faculty\u27s continued technology integration.;Taken together, the three studies in this dissertation provided insights in effective faculty development practice for supporting faculty integration of technology into their teaching. Results from all three studies suggested the importance of forming a community of faculty members working to integrate technology. In addition, all three studies provided evidence for the effectiveness of the one-one-one mentoring approach to faculty development in this area

Algorithmic Pricing:The Current State of Affairs from a Law and Economics Perspective

The rise of algorithmic pricing has transformed perfect price discrimination from a theoretical concept into a real possibility. Through self-learning pricingalgorithms, a strategy can be developed that approximates consumers’ reservation prices with ever-improving accuracy. This paper analyzes algorithmic pricing from a law and economics perspective to identify the efficiency and equity effects that the practice could cause and determine to which extent it is regulated under the current legal framework. This paper finds that under competitive market conditions, algorithmic pricing could be welcomed from an efficiency perspective, but from an equity and ethical perspective serious concerns need to be raised. If these concerns are to be taken seriously, the legal framework provides only a partially functional approach to address algorithmic pricing. Additional appropriate remedies are, therefore, needed to protect consumers adequately and effectively against exploitation that reduces their welfare