Showing papers by "Simon Jones published in 2008"

'Diagnostic overshadowing': worse physical health care for people with mental illness.

Abstract: It is now well established that people with mental illness die prematurely and have significantly higher medical co-morbidity compared with the general population (1), and that there are a number of possible reasons for this as discussed by Leucht et al. in the November issue 2007 of the Acta Psychiatrica Scandinavica (2). One of these may be diagnostic overshadowing , a process by which physical symptoms are misattributed to mental illness. This concept has received little attention in the psychiatric literature but mental health service users have reported its widespread occurrence (3) and its potential impact has been emphasized in two recent reports (4, 5).

Composable memory transactions

Abstract: Writing concurrent programs is notoriously difficult and is of increasing practical importance. A particular source of concern is that even correctly implemented concurrency ions cannot be composed together to form larger ions. In this paper we present a concurrency model, based on transactional memory, that offers far richer composition. All the usual benefits of transactional memory are present (e.g., freedom from low-level deadlock), but in addition we describe modular forms of blocking and choice that were inaccessible in earlier work.

Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition

Abstract: In human gene therapy applications, lentiviral vectors may have advantages over γ-retroviral vectors in several areas, including the ability to transduce nondividing cells, resistance to gene silencing and a potentially safer integration site profile. However, unlike γ-retroviral vectors it has been problematic to drive the expression of multiple genes efficiently and coordinately with approaches such as internal ribosome entry sites or dual promoters. Using different 2A peptides, lentiviral vectors expressing two-gene T-cell receptors directed against the melanoma differentiation antigens gp100 and MART-1 were constructed. We demonstrated that addition of amino-acid spacer sequences (GSG or SGSG) before the 2A sequence is a prerequisite for efficient synthesis of biologically active T-cell receptors and that addition of a furin cleavage site followed by a V5 peptide tag yielded optimal T-cell receptor gene expression. Furthermore, we determined that the furin cleavage site was recognized in lymphocytes and accounted for removal of residual 2A peptides at the post-translational level with an efficiency of 20–30%, which could not be increased by addition of multiple furin cleavage sites. The novel bicistronic lentiviral vector developed herein afforded robust anti-melanoma activities to engineered peripheral blood lymphocytes, including cytokine secretion, cell proliferation and lytic activity. Such optimal vectors may have immediate applications in cancer gene therapy.

Type checking with open type functions

Abstract: We report on an extension of Haskell with open type-level functions and equality constraints that unifies earlier work on GADTs, functional dependencies, and associated types. The contribution of the paper is that we identify and characterise the key technical challenge of entailment checking; and we give a novel, decidable, sound, and complete algorithm to solve it, together with some practically-important variants. Our system is implemented in GHC, and is already in active use.

State of the art metrics for nursing: a rapid appraisal

Abstract: Health. We thank the members of the Nursing Outcome Measures task and finish group chaired by Professor Anne Marie Rafferty and convened by Professor Dame Christine Beasley, the Chief Nursing Officer for England. These experts' insights and experiences informed us as we undertook this review to support their work. The work presented here is our appraisal of the literature and is not intended to represent the full breadth of work undertaken by that group. We particularly thank members of the group and others who provided support and comments, and Janice Sigsworth, the Deputy Chief Nursing Officer who was directly responsible for commissioning this report.

Harnessing the Multicores: Nested Data Parallelism in Haskell

Abstract: If you want to program a parallel computer, a purely functional language like Haskell is a promising starting point. Since the language is pure, it is by-default safe for parallel evaluation, whereas imperative languages are by-default unsafe. But that doesn\'t make it easy! Indeed it has proved quite difficult to get robust, scalable performance increases through parallel functional programming, especially as the number of processors increases. A particularly promising and well-studied approach to employing large numbers of processors is data parallelism. Blelloch\'s pioneering work on NESL showed that it was possible to combine a rather flexible programming model (nested data parallelism) with a fast, scalable execution model (flat data parallelism). In this paper we describe Data Parallel Haskell, which embodies nested data parallelism in a modern, general-purpose language, implemented in a state-of-the-art compiler, GHC. We focus particularly on the vectorisation transformation, which transforms nested to flat data parallelism.

Harnessing the Multicores: Nested Data Parallelism in Haskell

Abstract: If you want to program a parallel computer, a purely functional language like Haskell is a promising starting point. Since the language is pure, it is by-default safe for parallel evaluation, whereas imperative languages are by-default unsafe. But that doesn't make it easy! Indeed it has proved quite difficult to get robust, scalable performance increases through parallel functional programming, especially as the number of processors increases. A particularly promising and well-studied approach to employing large numbers of processors is to use data parallelism. Blelloch's pioneering work on NESL showed that it was possible to combine a rather flexible programming model (nested data parallelism) with a fast, scalable execution model (flat data parallelism). In this talk I will describe Data Parallel Haskell, which embodies nested data parallelism in a modern, general-purpose language, implemented in a state-of-the-art compiler, GHC. I will focus particularly on the vectorisation transformation, which transforms nested to flat data parallelism, and I hope to present performance numbers.

Parallel generational-copying garbage collection with a block-structured heap

Abstract: We present a parallel generational-copying garbage collector implemented for the Glasgow Haskell Compiler. We use a block-structured memory allocator, which provides a natural granularity for dividing the work of GC between many threads, leading to a simple yet effective method for parallelising copying GC. The results are encouraging: we demonstrate wall-clock speedups of on average a factor of 2 in GC time on a commodity 4-core machine with no programmer intervention, compared to our best sequential GC.

Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response.

Abstract: Sepsis, an overwhelming inflammatory response to infection, is a major cause of morbidity and mortality worldwide and has no specific therapy. Phospholipid metabolites, such as lysophospholipids, have been shown to regulate inflammatory responses in sepsis, although their mechanism of action is not well understood. The phospholipid-metabolizing enzymes, lysophospholipid acyltransferases, control membrane phospholipid composition, function, and the inflammatory responses of innate immune cells. Here, we show that lysophosphatidylcholine acyltransferase (LPCAT) regulates inflammatory responses to LPS and other microbial stimuli. Specific inhibition of LPCAT down-regulated inflammatory cytokine production in monocytes and epithelial cells by preventing translocation of TLR4 into membrane lipid raft domains. Our observations demonstrate a new regulatory mechanism that facilitates the innate immune responses to microbial molecular patterns and provide a basis for the anti-inflammatory activity observed in many phospholipid metabolites. This provides the possibility of the development of new classes of anti-inflammatory and antisepsis agents.

A tutorial on parallel and concurrent programming in Haskell

Abstract: This practical tutorial introduces the features available in Haskell for writing parallel and concurrent programs. We first describe how to write semi-explicit parallel programs by using annotations to express opportunities for parallelism and to help control the granularity of parallelism for effective execution on modern operating systems and processors. We then describe the mechanisms provided by Haskell for writing explicitly parallel programs with a focus on the use of software transactional memory to help share information between threads. Finally, we show how nested data parallelism can be used to write deterministically parallel programs which allows programmers to use rich data types in data parallel programs which are automatically transformed into flat data parallel versions for efficient execution on multi-core processors.

FPH: first-class polymorphism for Haskell

Abstract: Languages supporting polymorphism typically have ad-hoc restrictions on where polymorphic types may occur. Supporting "firstclass" polymorphism, by lifting those restrictions, is obviously desirable, but it is hard to achieve this without sacrificing type inference. We present a new type system for higher-rank and impredicative polymorphism that improves on earlier proposals: it is an extension of Damas-Milner; it relies only on System F types; it has a simple, declarative specification; it is robust to program transformations; and it enjoys a complete and decidable type inference algorithm.

A support device for receiving a refuse sack

Abstract: There is provided a support device (10) comprising a peripheral region (14), in the form of a closed loop and arranged to receive a receptacle, such as a synthetic plastics bag or refuse sack; a lid (12) being hinged to said peripheral region (14) and arranged to close over said region (14) when desired; at least one clip adapted to engage with the peripheral region (14) so as to retain the receptacle in a position; and a handle (16) for carrying the support device (10).

Partial Vectorisation of Haskell Programs

Abstract: Vectorisation for functional programs, also called the flattening transformation, relies on drastically reordering computations and restructuring the representation of data types. As a result, it only applies to the purely functional core of a fully-fledged functional language, such as Haskell or ML. A concrete implementation needs to apply vectorisation selectively and integrate vectorised with unvectorised code. This is challenging, as vectorisation alters the data representation, which must be suitably converted between vectorised and unvectorised code. In this paper, we present an approach to partial vectorisation that selectively vectorises sub-expressions and data types, and also, enables linking vectorised with unvectorised modules.

Scrap Your Type Applications

Abstract: System F is ubiquitous in logic, theorem proving, language meta-theory, compiler intermediate languages, and elsewhere. Along with its type abstractions come type applications, but these often appear redundant. This redundancy is both distracting and costly for type-directed compilers. We introduce System IF , for implicitSystem F , in which many type applications can be made implicit. It supports decidable type checking and strong normalisation. Experiments with Haskell suggest that it could be used to reduce the amount of intermediate code in compilers that employ System F . System IF constitutes a first foray into a new area in the design space of typed lambda calculi, that is interesting in its own right and may prove useful in practice.

A new synthesis of the F5 furan fatty acid and a first synthesis of the F6 furan fatty acid

Abstract: Total syntheses have been achieved of the two furan fatty acids F5 and F6 1, in which the central step features generation of the furan ring using either iodine or silver-induced 5-endo-dig cyclisations of suitably functionalized 3-alkyne-1,2-diols.

The STG runtime system (revised)

Abstract: 1 Overview 2 1.1 New features compared to GHC 3.xx . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.2 Wish list . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.3 Configuration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.4 Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.5 Subtle Dependencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Pyrrolidines as catalyst compounds

Abstract: The present invention relates to compounds for use as catalysts, methods for producing said compounds and the use of said compounds as catalysts in catalytic processes including, but not limited to, the asymmetric reduction of imine and enamine compounds and/or the reductive animation of ketone compounds. A compound for use as a catalyst has the formula (I) wherein: R1, R2, R3, R4 and R5 are each separately selected from the group consisting of hydrogen, alkyl and aryl; X is oxygen or sulfur; and Z has the formula (II) wherein: R6 and R7 are each separately selected from the group consisting of hydrogen, alkoxy, nitro, halogen, alkyl and aryl, or R6 and R7 are linked to form a cyclic group; and Y is oxygen, sulfur or NR10 in which R10 is selected from the group consisting of hydrogen, alkyl and aryl.

N,N′‐Bis(phenylmethylene)‐1,2‐Ethanediamine

Abstract: [[104-71-2] C16H16N2 (MW 236.32) InChI = 1S/C16H16N2/c1-3-7-15(8-4-1)13-17-11-12-18-14-16-9-5-2-6-10-16/h1-10,13-14H,11-12H2 InChIKey = QBAKBJNOARBSGP-UHFFFAOYSA-N (used as a ligand for enyne isomerizations as well as cycloadditions) Physical Data: mp 52–54 °C; bp 175–177 °C (2 Torr); d 0.97 g cm−3. Solubility: soluble in CH2Cl2, benzene, H2O, EtOH, MeOH. Form Supplied in: light yellow to yellow crystalline powder. Available from Aldrich and AcrosOrganics as a 99.5% pure solid. Handling, Storage, and Precautions: wash hands thoroughly after handling. Store in a cool, dry place. Compound is stable under normal temperatures and pressures, is incompatible with strong oxidizing agents and releases irritating and toxic fumes upon decomposition. Toxic to aquatic organisms.

Kinetic Resolution of Racemic Pyrrolidine-2,5-diones Using Chiral Oxazaborolidine Catalysts.

Abstract: Kinetic resolution of racemic C-3 substituted pyrrolidine-2,5-diones has been achieved for the first time using highly efficient oxazaborolidine catalysts derived from cis-1-amino-indan-2-ol.

FPH: First-class Polymorphism for Haskell Declarative, Constraint-free Type Inference for Impredicative Polymorphism

Abstract: Languages supporting polymorphism typically have ad-hoc restrictions on where polymorphic types may occur. Supporting “firstclass” polymorphism, by lifting those restrictions, is obviously desirable, but it is hard to achieve this without sacrificing type inference. We present a new type system for higher-rank and impredicative polymorphism that improves on earlier proposals: it is an extension of Damas-Milner; it relies only on System F types; it has a simple, declarative specification; it is robust to program transformations; and it enjoys a complete and decidable type inference algorithm.