Specific "scientific" data structures, and their processing

Programming physicists use, as all programmers, arrays, lists, tuples, records, etc., and this requires some change in their thought patterns while converting their formulae into some code, since the "data structures" operated upon, while elaborating some theory and its consequences, are rather: power series and Pad\'e approximants, differential forms and other instances of differential algebras, functionals (for the variational calculus), trajectories (solutions of differential equations), Young diagrams and Feynman graphs, etc. Such data is often used in a [semi-]numerical setting, not necessarily "symbolic", appropriate for the computer algebra packages. Modules adapted to such data may be "just libraries", but often they become specific, embedded sub-languages, typically mapped into object-oriented frameworks, with overloaded mathematical operations. Here we present a functional approach to this philosophy. We show how the usage of Haskell datatypes and - fundamental for our tutorial - the application of lazy evaluation makes it possible to operate upon such data (in particular: the "infinite" sequences) in a natural and comfortable manner.Comment: In Proceedings DSL 2011, arXiv:1109.032

Extraction of Transcript Diversity from Scientific Literature

Transcript diversity generated by alternative splicing and associated mechanisms contributes heavily to the functional complexity of biological systems. The numerous examples of the mechanisms and functional implications of these events are scattered throughout the scientific literature. Thus, it is crucial to have a tool that can automatically extract the relevant facts and collect them in a knowledge base that can aid the interpretation of data from high-throughput methods. We have developed and applied a composite text-mining method for extracting information on transcript diversity from the entire MEDLINE database in order to create a database of genes with alternative transcripts. It contains information on tissue specificity, number of isoforms, causative mechanisms, functional implications, and experimental methods used for detection. We have mined this resource to identify 959 instances of tissue-specific splicing. Our results in combination with those from EST-based methods suggest that alternative splicing is the preferred mechanism for generating transcript diversity in the nervous system. We provide new annotations for 1,860 genes with the potential for generating transcript diversity. We assign the MeSH term “alternative splicing” to 1,536 additional abstracts in the MEDLINE database and suggest new MeSH terms for other events. We have successfully extracted information about transcript diversity and semiautomatically generated a database, LSAT, that can provide a quantitative understanding of the mechanisms behind tissue-specific gene expression. LSAT (Literature Support for Alternative Transcripts) is publicly available at http://www.bork.embl.de/LSAT/

Archiving scientific data

We present an archiving technique for hierarchical data with key structure. Our approach is based on the notion of timestamps whereby an element appearing in multiple versions of the database is stored only once along with a compact description of versions in which it appears. The basic idea of timestamping was discovered by Driscoll et. al. in the context of persistent data structures where one wishes to track the sequences of changes made to a data structure. We extend this idea to develop an archiving tool for XML data that is capable of providing meaningful change descriptions and can also efficiently support a variety of basic functions concerning the evolution of data such as retrieval of any specific version from the archive and querying the temporal history of any element. This is in contrast to diff-based approaches where such operations may require undoing a large number of changes or significant reasoning with the deltas. Surprisingly, our archiving technique does not incur any significant space overhead when contrasted with other approaches. Our experimental results support this and also show that the compacted archive file interacts well with other compression techniques. Finally, another useful property of our approach is that the resulting archive is also in XML and hence can directly leverage existing XML tools

Functional and biophysical characterization of an HLA-A*6801-restricted HIV-specific T cell receptor

HLA-A*6801 exhibits several unusual features. First, it is known to bind weakly to CD8 due to the presence of an A245V substitution in the α3 domain. Second, it is able to accommodate unusually long peptides as a result of peptide ‘kinking’ in the binding groove. Third, CD8+ cytotoxic T lymphocytes that recognise HLA-A*6801-restricted antigens can tolerate substantial changes in the peptide sequence without apparent loss of recognition. In addition, it has been suggested that HLA-A68-restricted TCR might bind with higher affinity than other TCR due to their selection in the presence of a decreased contribution from CD8. Here we (1) examine monoclonal T cell recognition of an HLA-A*6801-restricted HIV-1 Tat-derived 11-amino acid peptide (ITKGLGISYGR) and natural variant sequences thereof; (2) measure the affinity and kinetics of a TCR/pHLA-A68 interaction biophysically for the first time, showing that equilibrium binding occurs within the range previously determined for non-HLA-A68-restricted TCR (KD approx. 7 μM); and (3) show that “normalization” of the non-canonical HLA-A*6801 CD8-binding domain enhances recognition of agonist peptides without inducing non-specific activation. This latter effect may provide a fundamental new mechanism with which to enhance T cell immunity to specific antigens

A Domain-Specific Language and Editor for Parallel Particle Methods

Domain-specific languages (DSLs) are of increasing importance in scientific high-performance computing to reduce development costs, raise the level of abstraction and, thus, ease scientific programming. However, designing and implementing DSLs is not an easy task, as it requires knowledge of the application domain and experience in language engineering and compilers. Consequently, many DSLs follow a weak approach using macros or text generators, which lack many of the features that make a DSL a comfortable for programmers. Some of these features---e.g., syntax highlighting, type inference, error reporting, and code completion---are easily provided by language workbenches, which combine language engineering techniques and tools in a common ecosystem. In this paper, we present the Parallel Particle-Mesh Environment (PPME), a DSL and development environment for numerical simulations based on particle methods and hybrid particle-mesh methods. PPME uses the meta programming system (MPS), a projectional language workbench. PPME is the successor of the Parallel Particle-Mesh Language (PPML), a Fortran-based DSL that used conventional implementation strategies. We analyze and compare both languages and demonstrate how the programmer's experience can be improved using static analyses and projectional editing. Furthermore, we present an explicit domain model for particle abstractions and the first formal type system for particle methods.Comment: Submitted to ACM Transactions on Mathematical Software on Dec. 25, 201