Informatique

Automatic analysis of programs with preprocessing directives
and conditional compilation is challenging. The
difficulties range from parsing to program understanding.
Symbolic evaluation offers a fundamental and general approach
to solve these difficulties. It finds, for every line of
code, the Boolean expression under which it is compiled or
reached. It can also find all the possible values of preprocessing
variables (macros) for each line of code. Conditional
values have been shown an effective representation
to do fast practical symbolic evaluation of preprocessing;
but their interaction with macro expansion and evaluation
has not been formally investigated. We present convergent
rewrite systems over conditional values that can interact
with macro expansion and evaluation and transform them
into Boolean expressions. Once transformed, well known
simplification techniques for Boolean expressions can be
applied. This entails a more complete solution to the efficient
symbolic evaluation of C-preprocessing using conditional
values.

List Comprehension is a succinct syntactic form to describe
lists in functional languages. It uses nested generators (i.e.,
iterators) and filters (i.e., Boolean expressions). The former
generates lists, whereas the latter restricts the contents
of these lists. List Comprehension translation is commonly
based on Wadler’s rules that emit code based on recursive
functions. This code often results either in stack overflow or
in inefficient execution for many Common Lisp implementations.
We present a very simple technique to compile List Comprehension
in the Loop Facility of Common Lisp, resulting
in efficient code that avoids stack overflow. Our translation
code is also very short, with an emitted code very close to
the user-specified list comprehension.
We also present a translation into more fundamental constructs
of Common Lisp that often results in even more efficient
code, although this translation is more complex than
using the Loop Facility.
The author has used the first translation technique for
compiling a new language called BioVelo, which is part of
bioinformatics software called Pathway Tools [2].

In reverse engineering, parsing may be partially done
to extract lightweight source models. Parsing code con-
taining preprocessing directives, syntactical errors and
embedded languages is a difficult task using context-free
grammars. Several researchers have proposed some form
of lexical analyzer to parse such code. We present a
lightweight tool, called RegReg, based on a hierarchy of
lexers described by tagged regular expressions. By us-
ing tags, the automatically generated parse tree can be
easily manipulated. The ability to control the matching
rulemechanismfor each regular expression increases effi-
ciency and disambiguation choices. RegReg is lightweight
as it uses aminimal number of features and its implemen-
tation uses only deterministic automaton. It has been im-
plemented in Scheme which allows extending the tool in a
functional programming style. We demonstrate how Re-
gReg can be used to implement island and fuzzy parsing.
RegReg is publicly available under a BSD-like license.

We show that masquerade detection, based on se-
quences of commands executed by the users, can be
eectively and eciently done by the construction of
a customized grammar representing the normal be-
havior of a user. More specically, we use the Se-
quitur algorithm to generate a context-free grammar
which eciently extracts repetitive sequences of com-
mands executed by one user { which is mainly used
to generate a prole of the user. This technique iden-
ties also the common scripts implicitly or explicitly
shared between users { a useful set of data for re-
ducing false positives. During the detection phase,
a block of commands is classied as either normal
or a masquerade based on its decomposition in sub-
strings using the grammar of the alleged user. Based
on experimental results using the Schonlau datasets,
this approach shows a good detection rates across all
false positive rates { they are the highest among all
published results known to the author.

The notion of recognition of a language by a finite semigroup
can be generalized to recognition by finite groupoids, i.e. sets equipped with a binary operation ‘·’ which is not necessarily associative. It is well known that L can be recognized by a groupoid iff L is context-free. But it is also known that some subclasses of groupoids can only recognize regular languages. For example, loops recognize exactly the regular open languages and Beaudry et al. described the largest class of groupoids known to recognize only regular languages. A groupoid H is said to be conservative if a·b is in {a, b} for all a, b in H. The main result of this paper is that conservative groupoids can only recognize regular languages. This class is incomparable with the one of Beaudry et al. so we are exhibiting a new sense in which a groupoid can be too weak to have context-free capabilities.

We show that, when the images formed, the frontal part of the Shroud of Turin laid on a body in the same position as when the bloodstains formed by contact. In other words, after the Shroud was laid on top of a body, no forceful flattening occurred before the images formed. Moreover, the argument that the top half of
the Shroud could not have been draping a real body when the images formed, to avoid prominent image distortions, is shown to be incorrect. If a cloth is appropriately laid on the front part of a
body, and a body image forms by a vertical projection on the cloth, no major image distortions occur. Small image distortions
are to be expected, and indeed we can observe some on the Shroud. These two aspects, the Shroud was not forcefully flattened before the images formed and no major image distortions occur due to the way the Shroud was laid on the body,
give the simplest scenario for the formation of the images. There is no need to claim a special even that would have flattened the Shroud before the images formed. Our analysis is based on precise length measurements on digital images, the bloodstain locations, and geometry.

Background

Flux Balance Analysis (FBA) is a genome-scale computational technique for modeling the steady-state fluxes of an organism’s reaction network. When the organism’s reaction network needs to be completed to obtain growth using FBA, without relying on the genome, the completion process is called reaction gap-filling. Currently, computational techniques used to gap-fill a reaction network compute the minimum set of reactions using Mixed-Integer Linear Programming (MILP). Depending on the number of candidate reactions used to complete the model, MILP can be computationally demanding.

Results

We present a computational technique, called FastGapFilling, that efficiently completes a reaction network by using only Linear Programming, not MILP. FastGapFilling creates a linear program with all candidate reactions, an objective function based on their weighted fluxes, and a variable weight on the biomass reaction: no integer variable is used. A binary search is performed by modifying the weight applied to the flux of the biomass reaction, and solving each corresponding linear program, to try reducing the number of candidate reactions to add to the network to generate a working model. We show that this method has proved effective on a series of incomplete E. coli and yeast models with, in some cases, a three orders of magnitude execution speedup compared with MILP. We have implemented FastGapFilling in MetaFlux as part of Pathway Tools (version 17.5), which is freely available to academic users, and for a fee to commercial users. Download from: biocyc.org/download.shtml.

Conclusions

The computational technique presented is very efficient allowing interactive completion of reaction networks of FBA models. Computational techniques based on MILP cannot offer such fast and interactive completion.

Keywords:
Flux Balance Analysis (FBA); Gap-filling; Systems biology; Reaction network; Linear Programming (LP); Mixed-Integer Linear Programming (MILP)

OPEN ACCESS PAPER

The complete atom mapping of a chemical reaction is a bijection of the reactant atoms to the product atoms that specifies the terminus of each reactant atom. Atom mapping of biochemical reactions is useful for many applications of systems biology, in particular for metabolic engineering where synthesizing new biochemical pathways has to take into account for the number of carbon atoms from a source compound that are conserved in the synthesis of a target compound. Rapid, accurate computation of the atom mapping(s) of a biochemical reaction remains elusive despite significant work on this topic. In particular, past researchers did not validate the accuracy of mapping algorithms. We introduce a new method for computing atom mappings called the minimum weighted edit-distance (MWED) metric. The metric is based on bond propensity to react and computes biochemically valid atom mappings for a large percentage of biochemical reactions. MWED models can be formulated efficiently as Mixed-Integer Linear Programs (MILPs). We have demonstrated this approach on 7501 reactions of the MetaCyc database for which 87% of the models could be solved in less than 10 s. For 2.1% of the reactions, we found multiple optimal atom mappings. We show that the error rate is 0.9% (22 reactions) by comparing these atom mappings to 2446 atom mappings of the manually curated Kyoto Encyclopedia of Genes and Genomes (KEGG) RPAIR database. To our knowledge, our computational atom-mapping approach is the most accurate and among the fastest published to date. The atom-mapping data will be available in the MetaCyc database later in 2012; the atom-mapping software will be available within the Pathway Tools software later in 2012.

C/C++ code relying on preprocessing can be quite complex to analyze. This is often due to free preprocessing variables set at compile time. In general, preprocessing selectively compile parts of the source code based on the values of preprocessing variables which may be free. In this case, the relations between these parts can only be represented by conditional expressions using the free variables. Traditional symbolic evaluation can be used to infer these expressions, but its best case time complexity is exponential.

We present a new approach for symbolic evaluation that can efficiently compute these conditions by binding variables to conditional values and avoiding the path feasibility analysis of traditional symbolic evaluation. It infers the exact conditional expressions for which the lines of code are compiled and the (conditional) values of preprocessing variables at each point of the source code. Our prototype shows the approach as practical and scaleable to large C/C++software

Component-based software manufacturing has the potential to bring division-of-labor benefits to the world of software engineering. In order to make a market of software components viable, however, producers and consumers must agree on enforceable software contracts.

In this paper, we show how to enforce contracts if components are manufactured from class and interface hierarchies. In particular, we focus on one style of contract: pre-and post-conditions. Programmers annotate class and interface methods with pre-and post-conditions and the run-time system checks these conditions during evaluation. These contracts guarantee that methods are called properly and provide appropriate results.

In procedural languages, the use of pre-and post-condition contracts is well-established and studies have demonstrated its value. In object-oriented languages, however, assigning blame for pre- and post-condition failures poses subtle and complex problems. Specifically, assigning blame for malformed class and interface hierarchies is so difficult that none of the existing contract monitoring tools correctly assign blame for these failures. In this paper, we show how to overcome these problems in the context of Java. Our work is based on the notion of behavioral subtyping.

This paper describes a new approach for debugging lazy functional languages. It rests on the fact that a functional program is the transformation of an expression; one debugs a program by investigating the syntactic form of the expression and by stopping the reduction process at given points. We show what problems are involved and our approach to solving them in a prototype implementation.

The BioCyc database collection at BioCyc.org integrates genome and cellular network information for more than 1,100 organisms. This method chapter describes Web-based tools for browsing metabolic and regulatory networks within BioCyc. These tools allow visualization of complete metabolic and regulatory networks, and allow the user to zoom-in on regions of the network of interest. The user can find objects of interest such as genes and metabolites within the networks, and can selectively examine the connectivity of the network. The EcoCyc database within the BioCyc collection has been extensively curated. The descriptions within EcoCyc of the Escherichia coli metabolic network and regulatory network were derived from thousands of publications. Other BioCyc databases received moderate levels of curation, or no curation at all. Those databases receiving no curation contain metabolic networks that were computationally inferred from the annotated genome sequences of each organism.

The notion of recognition of a language by a finite semigroup can be generalized to recognition by finite groupoids, i.e. sets equipped with a binary operation ‘⋅’ which is not necessarily associative. It is well known that L can be recognized by a groupoid iff L is context-free. However it is also known that some subclasses of groupoids can only recognize regular languages.

A groupoid H  is said to be conservative if a⋅b ∈ {a,b} for all a,b ∈ H. The first result of this paper is that conservative groupoids can only recognize regular languages. This class of groupoids is incomparable with the ones identified so far which share this property, so we are exhibiting a new way in which a groupoid can be too weak to recognize non-regular languages.

We also study the class L_cons of regular languages that can be recognized in this way and explain how it fits within the well-known Straubing–Thérien hierarchy. In particular we show that L_cons contains depth 1/2 of the hierarchy and is entirely contained in depth 3/2.

Le Saint Suaire de Besançon fut très populaire pendant près de trois siècles, attirant des foules considérables dès ses premières ostensions au 16e siècle. Sa popularité est si grande qu'en 1705 le roi Louis XIV ordonne la suspension des ostensions pour éviter que les soldats allemands s'emparent de la ville en se dissimulant parmi les dizaines de milliers de pèlerins étrangers. Le Suaire de Besançon disparaît en 1794 lors de la Révolution française, mais il subsiste de nombreux anciens manuscrits et publications le décrivant. Le manuscrit 826 du 18e siècle des archives de la bibliothèque de Besançon est composé de deux dissertations distinctes qui poursuivent des objectifs diamétralement opposés, la première plaidant en faveur de l'authenticité du Suaire de Besançon et la seconde soutenant le contraire. Ce livre présente une transcription inédite de la première dissertation et une version modernisée de la seconde dissertation publiée en 1831, accompagnée de commentaires. Les auteurs de ces dissertations comparent le Suaire de Besançon avec le Suaire de Turin, parfois pour déterminer lequel serait authentique. Le lecteur pourra juger de la pertinence de ces comparaisons et mieux découvrir ces deux Suaires. Il découvrira aussi des éléments modernes de la seconde dissertation et en particulier qu'un suaire authentique est plus crédible s'il produit une image tridimensionnelle, une remarque très pertinente au regard des développements scientifiques modernes sur le Suaire de Turin. Quelle est l'origine du Suaire de Besançon? Était-il aussi populaire que le Suaire de Turin? Est-ce que l'Histoire de ce Suaire a été combinée à celle du Suaire de Turin? Le chevalier Othon de la Roche est-il réellement à l'origine du Suaire de Besançon ou peut-être est-il plutôt à l'origine de celui de Turin? Voilà quelques-unes des questions fascinantes abordées dans ce livre.