`The frozen accident' as an evolutionary adaptation: A rate distortion theory perspective on the dynamics and symmetries of genetic coding mechanisms

We survey some interpretations and related issues concerning the frozen hypothesis due to F. Crick and how it can be explained in terms of several natural mechanisms involving error correction codes, spin glasses, symmetry breaking and the characteristic robustness of genetic networks. The approach to most of these questions involves using elements of Shannon's rate distortion theory incorporating a semantic system which is meaningful for the relevant alphabets and vocabulary implemented in transmission of the genetic code. We apply the fundamental homology between information source uncertainty with the free energy density of a thermodynamical system with respect to transcriptional regulators and the communication channels of sequence/structure in proteins. This leads to the suggestion that the frozen accident may have been a type of evolutionary adaptation

Without magic bullets: the biological basis for public health interventions against protein folding disorders

Protein folding disorders of aging like Alzheimer's and Parkinson's diseases currently present intractable medical challenges. 'Small molecule' interventions - drug treatments - often have, at best, palliative impact, failing to alter disease course. The design of individual or population level interventions will likely require a deeper understanding of protein folding and its regulation than currently provided by contemporary 'physics' or culture-bound medical magic bullet models. Here, a topological rate distortion analysis is applied to the problem of protein folding and regulation that is similar in spirit to Tlusty's (2010a) elegant exploration of the genetic code. The formalism produces large-scale, quasi-equilibrium 'resilience' states representing normal and pathological protein folding regulation under a cellular-level cognitive paradigm similar to that proposed by Atlan and Cohen (1998) for the immune system. Generalization to long times produces diffusion models of protein folding disorders in which epigenetic or life history factors determine the rate of onset of regulatory failure, in essence, a premature aging driven by familiar synergisms between disjunctions of resource allocation and need in the context of socially or physiologically toxic exposures and chronic powerlessness at individual and group scales. Application of an HPA axis model is made to recent observed differences in Alzheimer's onset rates in White and African American subpopulations as a function of an index of distress-proneness

Improving Model-Based Software Synthesis: A Focus on Mathematical Structures

Computer hardware keeps increasing in complexity. Software design needs to keep up with this. The right models and abstractions empower developers to leverage the novelties of modern hardware. This thesis deals primarily with Models of Computation, as a basis for software design, in a family of methods called software synthesis. We focus on Kahn Process Networks and dataflow applications as abstractions, both for programming and for deriving an efficient execution on heterogeneous multicores. The latter we accomplish by exploring the design space of possible mappings of computation and data to hardware resources. Mapping algorithms are not at the center of this thesis, however. Instead, we examine the mathematical structure of the mapping space, leveraging its inherent symmetries or geometric properties to improve mapping methods in general. This thesis thoroughly explores the process of model-based design, aiming to go beyond the more established software synthesis on dataflow applications. We starting with the problem of assessing these methods through benchmarking, and go on to formally examine the general goals of benchmarks. In this context, we also consider the role modern machine learning methods play in benchmarking. We explore different established semantics, stretching the limits of Kahn Process Networks. We also discuss novel models, like Reactors, which are designed to be a deterministic, adaptive model with time as a first-class citizen. By investigating abstractions and transformations in the Ohua language for implicit dataflow programming, we also focus on programmability. The focus of the thesis is in the models and methods, but we evaluate them in diverse use-cases, generally centered around Cyber-Physical Systems. These include the 5G telecommunication standard, automotive and signal processing domains. We even go beyond embedded systems and discuss use-cases in GPU programming and microservice-based architectures

Modelling the evolution of biological complexity with a two-dimensional lattice self-assembly process

Self-assembling systems are prevalent across numerous scales of nature, lying at the heart of diverse physical and biological phenomena. Individual protein subunits self-assembling into complexes is often a vital first step of biological processes. Errors during protein assembly, due to mutations or misfolds, can have devastating effects and are responsible for an assortment of protein diseases, known as proteopathies. With proteins exhibiting endless layers of complexity, building any all-encompassing model is unrealistic. Coarse-grained models, despite not faithfully capturing every detail of the original system, have massive potential to assist understanding complex phenomenon. A principal actor in self-assembly is the binding interactions between subunits, and so geometric constraints, polarity, kinetic forces, etc. can often be marginalised. This work explores how self-assembly and its outcomes are inextricably tied to the involved interactions through the use of a two-dimensional lattice polyomino model. %Armed with this tractable model, we can probe how dynamics acting on evolution are reflected in interaction properties. First, this thesis addresses how the interaction characteristics of self-assembly building blocks determine what structures they form. Specifically, if the same structures are consistently produced and remain finite in size. Assembly graphs store subunit interaction information and are used in classifying these two properties, the determinism and boundedness respectively. Arbitrary sets of building blocks are classified without the costly overhead of repeated stochastic assembling, improving both the analysis speed and accuracy. Furthermore, assembly graphs naturally integrate combinatorial and graph techniques, enabling a wider range of future polyomino studies. The second part narrows in on implications of nondeterministic assembly on interaction strength evolution. Generalising subunit binding sites with mutable binary strings introduces such interaction strengths into the polyomino model. Deterministic assemblies obey analytic expectations. Conversely, interactions in nondeterministic assemblies rapidly diverge from equilibrium to minimise assembly inconsistency. Optimal interaction strengths during assembly are also reflected in evolution. Transitions between certain polyominoes are strongly forbidden when interaction strengths are misaligned. The third aspect focuses on genetic duplication, an evolutionary event observed in organisms across all taxa. Through polyomino evolutions, a duplication-heteromerisation pathway emerges as an efficient process. This pathway exploits the advantages of both self-interactions and pairwise-interactions, and accelerates evolution by avoiding complexity bottlenecks. Several simulation predictions are successfully validated against a large data set of protein complexes. These results focus on coarse-grained models rather than quantified biological insight. Despite this, they reinforce existing observations of protein complexes, as well as posing several new mechanisms for the evolution of biological complexity

Optimization and Applications of Modern Wireless Networks and Symmetry

Due to the future demands of wireless communications, this book focuses on channel coding, multi-access, network protocol, and the related techniques for IoT/5G. Channel coding is widely used to enhance reliability and spectral efficiency. In particular, low-density parity check (LDPC) codes and polar codes are optimized for next wireless standard. Moreover, advanced network protocol is developed to improve wireless throughput. This invokes a great deal of attention on modern communications

Landscapes and Effective Fitness

The concept of a fitness landscape arose in theoretical biology, while that of effective fitness has its origin in evolutionary computation. Both have emerged as useful conceptual tools with which to understand the dynamics of evolutionary processes, especially in the presence of complex genotype-phenotype relations. In this contribution we attempt to provide a unified discussion of these two approaches, discussing both their advantages and disadvantages in the context of some simple models. We also discuss how fitness and effective fitness change under various transformations of the configuration space of the underlying genetic model, concentrating on coarse-graining transformations and on a particular coordinate transformation that provides an appropriate basis for illuminating the structure and consequences of recombination