Ownerships for reasoning about parallelism : type system and semantics

Technical Report to accompany Ownership for Reasoning About Parallelism. Documents type system which captures effects and the operational semantics for the language which is presented as part of the paper.

Pinned fronts in heterogeneous media of jump type

In this paper, we analyse the impact of a (small) heterogeneity of jump type on the most simple localized solutions of a 3-component FitzHugh–Nagumo-type system. We show that the heterogeneity can pin a 1-front solution, which travels with constant (non-zero) speed in the homogeneous setting, to a fixed, explicitly determined, distance from the heterogeneity. Moreover, we establish the stability of this heterogeneous pinned 1-front solution. In addition, we analyse the pinning of 1-pulse, or 2-front, solutions. The paper is concluded with simulations in which we consider the dynamics and interactions of N-front patterns in domains with M heterogeneities of jump type (N = 3, 4, M ≥ 1).

Leveraging managed frameworks from modular languages

Managed execution frameworks, such as the.NET Common Language Runtime or the Java Virtual Machine, provide a rich environment for the creation of application programs. These execution environments are ideally suited for languages that depend on type-safety and the declarative control of feature access. Furthermore, such frameworks typically provide a rich collection of library primitives specialized for almost every domain of application programming. Thus, when a new language is implemented on one of these frameworks it becomes necessary to provide some kind of mapping from the new language to the libraries of the framework. The design of such mappings is challenging since the type-system of the new language may not span the domain exposed in the library application programming interfaces (APIs). The nature of these design considerations was clarified in the implementation of the Gardens Point Component Pascal (gpcp) compiler. In this paper we describe the issues, and the solutions that we settled on in this case. The problems that were solved have a wider applicability than just our example, since they arise whenever any similar language is hosted in such an environment.

Using Ownership to Reason About Inherent Parallelism in Object-Oriented Programs

With the emergence of multi-cores into the mainstream, there is a growing need for systems to allow programmers and automated systems to reason about data dependencies and inherent parallelismin imperative object-oriented languages. In this paper we exploit the structure of object-oriented programs to abstract computational side-effects. We capture and validate these effects using a static type system. We use these as the basis of sufficient conditions for several different data and task parallelism patterns. We compliment our static type system with a lightweight runtime system to allow for parallelization in the presence of complex data flows. We have a functioning compiler and worked examples to demonstrate the practicality of our solution.

On model typing

Where object-oriented languages deal with objects as described by classes, model-driven development uses models, as graphs of interconnected objects, described by metamodels. A number of new languages have been and continue to be developed for this model- based paradigm, both for model transformation and for general programming using models. Many of these use single-object approaches to typing, derived from solutions found in object-oriented systems, while others use metamodels as model types, but without a clear notion of polymorphism. Both of these approaches lead to brittle and overly restrictive reuse characteristics. In this paper we propose a simple extension to object-oriented typing to better cater for a model-oriented context, including a simple strategy for typing models as a collection of interconnected objects. We suggest extensions to existing type system formalisms to support these concepts and their manipulation. Using a simple example we show how this extended approach permits more flexible reuse, while preserving type safety.

Automatic generation of assertions to detect potential security vulnerabilities in C programs that use union and pointer types

Type unions, pointer variables and function pointers are a long standing source of subtle security bugs in C program code. Their use can lead to hard-to-diagnose crashes or exploitable vulnerabilities that allow an attacker to attain privileged access over classified data. This paper describes an automatable framework for detecting such weaknesses in C programs statically, where possible, and for generating assertions that will detect them dynamically, in other cases. Exclusively based on analysis of the source code, it identifies required assertions using a type inference system supported by a custom made symbol table. In our preliminary findings, our type system was able to infer the correct type of unions in different scopes, without manual code annotations or rewriting. Whenever an evaluation is not possible or is difficult to resolve, appropriate runtime assertions are formed and inserted into the source code. The approach is demonstrated via a prototype C analysis tool.

A framework for reasoning about inherent parallelism in modern object-oriented languages

With the emergence of multi-core processors into the mainstream, parallel programming is no longer the specialized domain it once was. There is a growing need for systems to allow programmers to more easily reason about data dependencies and inherent parallelism in general purpose programs. Many of these programs are written in popular imperative programming languages like Java and C]. In this thesis I present a system for reasoning about side-effects of evaluation in an abstract and composable manner that is suitable for use by both programmers and automated tools such as compilers. The goal of developing such a system is to both facilitate the automatic exploitation of the inherent parallelism present in imperative programs and to allow programmers to reason about dependencies which may be limiting the parallelism available for exploitation in their applications. Previous work on languages and type systems for parallel computing has tended to focus on providing the programmer with tools to facilitate the manual parallelization of programs; programmers must decide when and where it is safe to employ parallelism without the assistance of the compiler or other automated tools. None of the existing systems combine abstraction and composition with parallelization and correctness checking to produce a framework which helps both programmers and automated tools to reason about inherent parallelism. In this work I present a system for abstractly reasoning about side-effects and data dependencies in modern, imperative, object-oriented languages using a type and effect system based on ideas from Ownership Types. I have developed sufficient conditions for the safe, automated detection and exploitation of a number task, data and loop parallelism patterns in terms of ownership relationships. To validate my work, I have applied my ideas to the C] version 3.0 language to produce a language extension called Zal. I have implemented a compiler for the Zal language as an extension of the GPC] research compiler as a proof of concept of my system. I have used it to parallelize a number of real-world applications to demonstrate the feasibility of my proposed approach. In addition to this empirical validation, I present an argument for the correctness of the type system and language semantics I have proposed as well as sketches of proofs for the correctness of the sufficient conditions for parallelization proposed.

An investigation into the use of human papillomavirus type 16 virus-like particles as a delivery vector system for foreign proteins: N- and C-terminal fusion of GFP to the L1 and L2 capsid proteins

Development of vaccine strategies against human papillomavirus (HPV), which causes cervical cancer, is a priority. We investigated the use of virus-like particles (VLPs) of the most prevalent type, HPV-16, as carriers of foreign proteins. Green fluorescent protein (GFP) was fused to the N or C terminus of both L1 and L2, with L2 chimeras being co-expressed with native L1. Purified chimaeric VLPs were comparable in size (∼55 nm) to native HPV VLPs. Conformation-specific monoclonal antibodies (Mabs) bound to the VLPs, thereby indicating that they possibly retain their antigenicity. In addition, all of the VLPs encapsidated DNA in the range of 6-8 kb. © 2007 Springer-Verlag.

Public-oriented interactive environmental decision support system

With the application of GIS methodologies to spatial data, researchers can now identify patterns of occurrence for many social problems including health-issues and crime. Further more, since this type of data also contains clues as to the underlying causes of social problems, it can be used to make well-educated and consequently, more effective policy decisions.

Implication of 3D culture system for study of prostate cancer (CaP) mediated bone metastasis

Introduction : For the past decade, three dimensional (3D) culture has served as a foundation for regenerative medicine study. With an increasing awareness of the importance of cell-cell and cell-extracellular matrix interactions which are lacking in 2D culture system, 3D culture system has been employed for many other applications namely cancer research. Through development of various biomaterials and utilization of tissue engineering technology, many in vivo physiological responses are now better understood. The cellular and molecular communication of cancer cells and their microenvironment, for instance can be studied in vitro in 3D culture system without relying on animal models alone. Predilection of prostate cancer (CaP) to bone remains obscure due to the complexity of the mechanisms and lack of proper model for the studies. In this study, we aim to investigate the interaction between CaP cells and osteoblasts simulating the natural bone metastasis. We also further investigate the invasiveness of CaP cells and response of androgen sensitve CaP cells, LNCaP to synthetic androgen.----- Method : Human osteoblast (hOB) scaffolds were prepared by seeding hOB on medical grade polycaprolactone-tricalcium phosphate (mPLC-TCP) scaffolds and induced to produce bone matrix. CaP cell lines namely wild type PC3 (PC3-N), overexpressed prostate specific antigen PC3 (PC3k3s5) and LNCaP were seeded on hOB scaffolds as co-cultures. Morphology of cells was examined by Phalloidin-DAPI and SEM imaging. Gelatin zymography was performed on the 48 hours conditioned media (CM) from co-cultures to determine matrix metalloproteinase (MMP) activity. Gene expression of hOB/LNCaP co-cultures which were treated for 48 hours with 1nM synthetic androgen R1881 were analysed by quantitative real time PCR (qRT-PCR).----- Results : Co-culture of PCC/hOB revealed that the morphology of PCCs on the tissue engineered bone matrix varied from homogenous to heterogenous clusters. Enzymatically inactive pro-MMP2 was detected in CM from hOBs and PCCs cultured on scaffolds. Elevation in MMP9 activity was found only in hOB/PC3N co-culture. hOB/LNCaP co-culture showed increase in expression of key enzymes associated with steroid production which also corresponded to an increase in prostate specific antigen (PSA) and MMP9.----- Conclusions : Upregulation of MMP9 indicates involvement of ECM degradation during cancer invasion and bone metastases. Expression of enzymes involved in CaP progression, PSA, which is not expressed in osteoblasts, demonstrates that crosstalk between PCCs and osteoblasts may play a part in the aggressiveness of CaP. The presence of steroidogenic enzymes, particularly, RDH5, in osteoblasts and stimulated expression in co-culture, may indicate osteoblast production of potent androgens, fuelling cancer cell proliferation. Based on these results, this practical 3D culture system may provide greater understanding into CaP mediated bone metastasis. This allows the role of the CaP/hOB interaction with regards to invasive property and steroidogenesis to be further explored.

Enforcing P3P policies using a digital rights management system

The protection of privacy has gained considerable attention recently. In response to this, new privacy protection systems are being introduced. SITDRM is one such system that protects private data through the enforcement of licenses provided by consumers. Prior to supplying data, data owners are expected to construct a detailed license for the potential data users. A license specifies whom, under what conditions, may have what type of access to the protected data. The specification of a license by a data owner binds the enterprise data handling to the consumer’s privacy preferences. However, licenses are very detailed, may reveal the internal structure of the enterprise and need to be kept synchronous with the enterprise privacy policy. To deal with this, we employ the Platform for Privacy Preferences Language (P3P) to communicate enterprise privacy policies to consumers and enable them to easily construct data licenses. A P3P policy is more abstract than a license, allows data owners to specify the purposes for which data are being collected and directly reflects the privacy policy of an enterprise.

Protein complementation assay as a display system for screening protein libraries in the intracellular environment

A wide range of screening strategies have been employed to isolate antibodies and other proteins with specific attributes, including binding affinity, specificity, stability and improved expression. However, there remains no high-throughput system to screen for target-binding proteins in a mammalian, intracellular environment. Such a system would allow binding reagents to be isolated against intracellular clinical targets such as cell signalling proteins associated with tumour formation (p53, ras, cyclin E), proteins associated with neurodegenerative disorders (huntingtin, betaamyloid precursor protein), and various proteins crucial to viral replication (e.g. HIV-1 proteins such as Tat, Rev and Vif-1), which are difficult to screen by phage, ribosome or cell-surface display. This study used the β-lactamase protein complementation assay (PCA) as the display and selection component of a system for screening a protein library in the cytoplasm of HEK 293T cells. The colicin E7 (ColE7) and Immunity protein 7 (Imm7) *Escherichia coli* proteins were used as model interaction partners for developing the system. These proteins drove effective β-lactamase complementation, resulting in a signal-to-noise ratio (9:1 – 13:1) comparable to that of other β-lactamase PCAs described in the literature. The model Imm7-ColE7 interaction was then used to validate protocols for library screening. Single positive cells that harboured the Imm7 and ColE7 binding partners were identified and isolated using flow cytometric cell sorting in combination with the fluorescent β-lactamase substrate, CCF2/AM. A single-cell PCR was then used to amplify the Imm7 coding sequence directly from each sorted cell. With the screening system validated, it was then used to screen a protein library based the Imm7 scaffold against a proof-of-principle target. The wild-type Imm7 sequence, as well as mutants with wild-type residues in the ColE7- binding loop were enriched from the library after a single round of selection, which is consistent with other eukaryotic screening systems such as yeast and mammalian cell-surface display. In summary, this thesis describes a new technology for screening protein libraries in a mammalian, intracellular environment. This system has the potential to complement existing screening technologies by allowing access to intracellular proteins and expanding the range of targets available to the pharmaceutical industry.

Driving-related eye and head movements are changed by the type of presbyopic correction

Purpose: To investigate whether wearing different presbyopic vision corrections alters the pattern of eye and head movements when viewing dynamic driving-related traffic scenes. Methods: Participants included 20 presbyopes (mean age: 56±5.7 years) who had no experience of wearing presbyopic vision corrections (i.e. all were single vision wearers). Eye and head movements were recorded while wearing five different vision corrections: single vision lenses (SV), progressive addition spectacle lenses (PALs), bifocal spectacle lenses (BIF), monovision (MV) and multifocal contact lenses (MTF CL) in random order. Videotape recordings of traffic scenes of suburban roads and expressways (with edited targets) were presented as dynamic driving-related stimuli and digital numeric display panels included as near visual stimuli (simulating speedometer and radio). Eye and head movements were recorded using the faceLAB™ system and the accuracy of target identification was also recorded. Results: The magnitude of eye movements while viewing the driving-related traffic scenes was greater when wearing BIF and PALs than MV and MTF CL (p≤0.013). The magnitude of head movements was greater when wearing SV, BIF and PALs than MV and MTF CL (p<0.0001) and the number of saccades was significantly higher for BIF and PALs than MV (p≤0.043). Target recognition accuracy was poorer for all vision corrections when the near stimulus was located at eccentricities inferiorly and to the left, rather than directly below the primary position of gaze (p=0.008), and PALs gave better performance than MTF CL (p=0.043). Conclusions: Different presbyopic vision corrections alter eye and head movement patterns. In particular, the larger magnitude of eye and head movements and greater number of saccades associated with the spectacle presbyopic corrections, may impact on driving performance.