Weighted pooling—practical and cost-effective techniques for pooled high-throughput sequencing

Motivation: Despite the rapid decline in sequencing costs, sequencing large cohorts of individuals is still prohibitively expensive. Recently, several sophisticated pooling designs were suggested that can identify carriers of rare alleles in large cohorts with a significantly smaller number of pools, thus dramatically reducing the cost of such large-scale sequencing projects. These approaches use combinatorial pooling designs where each individual is either present or absent from a pool. One can then infer the number of carriers in a pool, and by combining information across pools, reconstruct the identity of the carriers

The BV-algebra structure of W_3 cohomology

We summarize some recent results obtained in collaboration with J. McCarthy on the spectrum of physical states in $W_3$ gravity coupled to $c=2$ matter. We show that the space of physical states, defined as a semi-infinite (or BRST) cohomology of the $W_3$ algebra, carries the structure of a BV-algebra. This BV-algebra has a quotient which is isomorphic to the BV-algebra of polyvector fields on the base affine space of $SL(3,C)$. Details have appeared elsewhere. [Published in the proceedings of "Gursey Memorial Conference I: Strings and Symmetries," Istanbul, June 1994, eds. G. Aktas et al., Lect. Notes in Phys. 447, (Springer Verlag, Berlin, 1995)]Comment: 8 pages; uses macros tables.tex and amssym.def (version 2.1 or later

Mightyl: A compositional translation from mitl to timed automata

Metric Interval Temporal Logic (MITL) was first proposed in the early 1990s as a specification formalism for real-time systems. Apart from its appealing intuitive syntax, there are also theoretical evidences that make MITL a prime real-time counterpart of Linear Temporal Logic (LTL). Unfortunately, the tool support for MITL verification is still lacking to this day. In this paper, we propose a new construction from MITL to timed automata via very-weak one-clock alternating timed automata. Our construction subsumes the well-known construction from LTL to Büchi automata by Gastin and Oddoux and yet has the additional benefits of being compositional and integrating easily with existing tools. We implement the construction in our new tool MightyL and report on experiments using Uppaal and LTSmin as back-ends

The return of the bursts: Thermonuclear flashes from Circinus X-1

We report the detection of 15 X-ray bursts with RXTE and Swift observations of the peculiar X-ray binary Circinus X-1 during its May 2010 X-ray re-brightening. These are the first X-ray bursts observed from the source after the initial discovery by Tennant and collaborators, twenty-five years ago. By studying their spectral evolution, we firmly identify nine of the bursts as type I (thermonuclear) X-ray bursts. We obtain an arcsecond location of the bursts that confirms once and for all the identification of Cir X-1 as a type I X-ray burst source, and therefore as a low magnetic field accreting neutron star. The first five bursts observed by RXTE are weak and show approximately symmetric light curves, without detectable signs of cooling along the burst decay. We discuss their possible nature. Finally, we explore a scenario to explain why Cir X-1 shows thermonuclear bursts now but not in the past, when it was extensively observed and accreting at a similar rate.Comment: Accepted for publication in The Astrophysical Journal Letters. Tables 1 & 2 merged. Minor changes after referee's comments. 5 pages, 4 Figure

Differential geometry construction of anomalies and topological invariants in various dimensions

In the model of extended non-Abelian tensor gauge fields we have found new metric-independent densities: the exact (2n+3)-forms and their secondary characteristics, the (2n+2)-forms as well as the exact 6n-forms and the corresponding secondary (6n-1)-forms. These forms are the analogs of the Pontryagin densities: the exact 2n-forms and Chern-Simons secondary characteristics, the (2n-1)-forms. The (2n+3)- and 6n-forms are gauge invariant densities, while the (2n+2)- and (6n-1)-forms transform non-trivially under gauge transformations, that we compare with the corresponding transformations of the Chern-Simons secondary characteristics. This construction allows to identify new potential gauge anomalies in various dimensions.Comment: 27 pages, references added, matches published versio

Verifying expressed transcript variants by detecting and assembling stretches of consecutive exons

We herein describe an integrated system for the high-throughput analysis of splicing events and the identification of transcript variants. The system resolves individual splicing events and elucidates transcript variants via a pipeline that combines aspects such as bioinformatic analysis, high-throughput transcript variant amplification, and high-resolution capillary electrophoresis. For the 14 369 human genes known to have transcript variants, minimal primer sets were designed to amplify all transcript variants and examine all splicing events; these have been archived in the ASprimerDB database, which is newly described herein. A high-throughput thermocycler, dubbed GenTank, was developed to simultaneously perform thousands of PCR amplifications. Following the resolution of the various amplicons by capillary gel electrophoresis, two new computer programs, AmpliconViewer and VariantAssembler, may be used to analyze the splicing events, assemble the consecutive exons embodied by the PCR amplicons, and distinguish expressed versus putative transcript variants. This novel system not only facilitates the validation of putative transcript variants and the detection of novel transcript variants, it also semi-quantitatively measures the transcript variant expression levels of each gene. To demonstrate the system’s capability, we used it to resolve transcript variants yielded by single and multiple splicing events, and to decipher the exon connectivity of long transcripts

Presentation of the 9th Edition of the Model Checking Contest.

International audience; The Model Checking Contest (MCC) is an annual competition of software tools for model checking. Tools must process an increasing benchmark gathered from the whole community and may participate in various examinations: state space generation, computation of global properties, computation of some upper bounds in the model, evaluation of reachability formulas, evaluation of CTL formulas, and evaluation of LTL formulas.For each examination and each model instance, participating tools are provided with up to 3600 s and 16 gigabyte of memory. Then, tool answers are analyzed and confronted to the results produced by other competing tools to detect diverging answers (which are quite rare at this stage of the competition, and lead to penalties).For each examination, golden, silver, and bronze medals are attributed to the three best tools. CPU usage and memory consumption are reported, which is also valuable information for tool developers

Component-wise incremental LTL model checking

Efficient symbolic and explicit-state model checking approaches have been developed for the verification of linear time temporal logic (LTL) properties. Several attempts have been made to combine the advantages of the various algorithms. Model checking LTL properties usually poses two challenges: one must compute the synchronous product of the state space and the automaton model of the desired property, then look for counterexamples that is reduced to finding strongly connected components (SCCs) in the state space of the product. In case of concurrent systems, where the phenomenon of state space explosion often prevents the successful verification, the so-called saturation algorithm has proved its efficiency in state space exploration. This paper proposes a new approach that leverages the saturation algorithm both as an iteration strategy constructing the product directly, as well as in a new fixed-point computation algorithm to find strongly connected components on-the-fly by incrementally processing the components of the model. Complementing the search for SCCs, explicit techniques and component-wise abstractions are used to prove the absence of counterexamples. The resulting on-the-fly, incremental LTL model checking algorithm proved to scale well with the size of models, as the evaluation on models of the Model Checking Contest suggests