Synthetic biology: advancing biological frontiers by building synthetic systems

Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field

Stream Fusion, to Completeness

Stream processing is mainstream (again): Widely-used stream libraries are now available for virtually all modern OO and functional languages, from Java to C# to Scala to OCaml to Haskell. Yet expressivity and performance are still lacking. For instance, the popular, well-optimized Java 8 streams do not support the zip operator and are still an order of magnitude slower than hand-written loops. We present the first approach that represents the full generality of stream processing and eliminates overheads, via the use of staging. It is based on an unusually rich semantic model of stream interaction. We support any combination of zipping, nesting (or flat-mapping), sub-ranging, filtering, mapping-of finite or infinite streams. Our model captures idiosyncrasies that a programmer uses in optimizing stream pipelines, such as rate differences and the choice of a "for" vs. "while" loops. Our approach delivers hand-written-like code, but automatically. It explicitly avoids the reliance on black-box optimizers and sufficiently-smart compilers, offering highest, guaranteed and portable performance. Our approach relies on high-level concepts that are then readily mapped into an implementation. Accordingly, we have two distinct implementations: an OCaml stream library, staged via MetaOCaml, and a Scala library for the JVM, staged via LMS. In both cases, we derive libraries richer and simultaneously many tens of times faster than past work. We greatly exceed in performance the standard stream libraries available in Java, Scala and OCaml, including the well-optimized Java 8 streams

WEBGOP : collaborative Web services based on graph-oriented programming

2005-2006 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Staged Compilation with Two-Level Type Theory

The aim of staged compilation is to enable metaprogramming in a way such that we have guarantees about the well-formedness of code output, and we can also mix together object-level and meta-level code in a concise and convenient manner. In this work, we observe that two-level type theory (2LTT), a system originally devised for the purpose of developing synthetic homotopy theory, also serves as a system for staged compilation with dependent types. 2LTT has numerous good properties for this use case: it has a concise specification, well-behaved model theory, and it supports a wide range of language features both at the object and the meta level. First, we give an overview of 2LTT's features and applications in staging. Then, we present a staging algorithm and prove its correctness. Our algorithm is "staging-by-evaluation", analogously to the technique of normalization-by-evaluation, in that staging is given by the evaluation of 2LTT syntax in a semantic domain. The staging algorithm together with its correctness constitutes a proof of strong conservativity of 2LLT over the object theory. To our knowledge, this is the first description of staged compilation which supports full dependent types and unrestricted staging for types

A Practical Unification of Multi-stage Programming and Macros

Program generation is indispensable. We propose a novel unification of two existing metaprogramming techniques: multi-stage programming and hygienic generative macros. The former supports runtime code generation and execution in a type-safe manner while the latter offers compile-time code generation. In this work we draw upon a long line of research on metaprogramming, starting with Lisp, MetaML and MetaOCaml. We provide direct support for quotes, splices and top-level splices, all regulated uniformly by a level-counting Phase Consistency Principle. Our design enables the construction and combination of code values for both expressions and types. Moreover, code generation can happen either at runtime à la MetaML or at compile time, in a macro fashion, à la MacroML. We provide an implementation of our design in Scala and we present two case studies. The first implements the Hidden Markov Model, Shonan Challenge for HPC. The second implements the staged streaming library Strymonas

Sequences and consequences

The conversion of data into knowledge constitutes a great challenge for future biological research. The new science of Systems Biology claims to be able to solve the problem but I contend that this approach will fail because deducing models of function from the behaviour of a complex system is an inverse problem that is impossible to solve. In addition, one cannot easily escape into high-level holistic approaches, since the essence of all biological systems is that they are encoded as molecular descriptions in their genes and since genes are molecules and exert their functions through other molecules, the molecular explanation must constitute the core of understanding biological systems. We then solve the forward problem of computing the behaviour of the system from its components and their interactions. I propose that the correct level of abstraction is the cell and provide an outline of Cellmap, a design for a system to organize biological information

Inductive Definition and Domain Theoretic Properties of Fully Abstract

A construction of fully abstract typed models for PCF and PCF^+ (i.e., PCF + "parallel conditional function"), respectively, is presented. It is based on general notions of sequential computational strategies and wittingly consistent non-deterministic strategies introduced by the author in the seventies. Although these notions of strategies are old, the definition of the fully abstract models is new, in that it is given level-by-level in the finite type hierarchy. To prove full abstraction and non-dcpo domain theoretic properties of these models, a theory of computational strategies is developed. This is also an alternative and, in a sense, an analogue to the later game strategy semantics approaches of Abramsky, Jagadeesan, and Malacaria; Hyland and Ong; and Nickau. In both cases of PCF and PCF^+ there are definable universal (surjective) functionals from numerical functions to any given type, respectively, which also makes each of these models unique up to isomorphism. Although such models are non-omega-complete and therefore not continuous in the traditional terminology, they are also proved to be sequentially complete (a weakened form of omega-completeness), "naturally" continuous (with respect to existing directed "pointwise", or "natural" lubs) and also "naturally" omega-algebraic and "naturally" bounded complete -- appropriate generalisation of the ordinary notions of domain theory to the case of non-dcpos.Comment: 50 page

Conceptual Model-Based Systems Biology: Mapping Knowledge and Discovering Gaps in the mRNA Transcription Cycle

We propose a Conceptual Model-based Systems Biology framework for qualitative modeling, executing, and eliciting knowledge gaps in molecular biology systems. The framework is an adaptation of Object-Process Methodology (OPM), a graphical and textual executable modeling language. OPM enables concurrent representation of the system's structure—the objects that comprise the system, and behavior—how processes transform objects over time. Applying a top-down approach of recursively zooming into processes, we model a case in point—the mRNA transcription cycle. Starting with this high level cell function, we model increasingly detailed processes along with participating objects. Our modeling approach is capable of modeling molecular processes such as complex formation, localization and trafficking, molecular binding, enzymatic stimulation, and environmental intervention. At the lowest level, similar to the Gene Ontology, all biological processes boil down to three basic molecular functions: catalysis, binding/dissociation, and transporting. During modeling and execution of the mRNA transcription model, we discovered knowledge gaps, which we present and classify into various types. We also show how model execution enhances a coherent model construction. Identification and pinpointing knowledge gaps is an important feature of the framework, as it suggests where research should focus and whether conjectures about uncertain mechanisms fit into the already verified model

Graph Search as a Feature in Imperative/Procedural Programming Languages

abstract: Graph theory is a critical component of computer science and software engineering, with algorithms concerning graph traversal and comprehension powering much of the largest problems in both industry and research. Engineers and researchers often have an accurate view of their target graph, however they struggle to implement a correct, and efficient, search over that graph. To facilitate rapid, correct, efficient, and intuitive development of graph based solutions we propose a new programming language construct - the search statement. Given a supra-root node, a procedure which determines the children of a given parent node, and optional definitions of the fail-fast acceptance or rejection of a solution, the search statement can conduct a search over any graph or network. Structurally, this statement is modelled after the common switch statement and is put into a largely imperative/procedural context to allow for immediate and intuitive development by most programmers. The Go programming language has been used as a foundation and proof-of-concept of the search statement. A Go compiler is provided which implements this construct.Dissertation/ThesisMasters Thesis Software Engineering 201