Computational Cancer Biology: An Evolutionary Perspective

ISSN:1553-734XISSN:1553-735

Coalition theories: empirical evidence for dutch municipalities

The paper analyzes coalition formation in Dutch municipalities. After discussing the main features of the institutional setting, several theories are discussed, which are classified as size oriented, policy oriented and actor oriented models. A test statistic is proposed to determine the predictive power of these models. The empirical analysis shows that strategic positions as well as some of the distinguished preferences are important in the setting of Dutch municipalities. Especially, the dominant minimum number principle yields highly significant results for coalition formations in the period 1978–1986

On cycles in the transcription network of Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>We investigate the cycles in the transcription network of <it>Saccharomyces cerevisiae</it>. Unlike a similar network of <it>Escherichia coli</it>, it contains many cycles. We characterize properties of these cycles and their place in the regulatory mechanism of the cell.</p> <p>Results</p> <p>Almost all cycles in the transcription network of <it>Saccharomyces cerevisiae </it>are contained in a single <it>strongly connected component</it>, which we call LSCC (L for "largest"), except for a single cycle of two transcription factors. The fact that LSCC includes almost all cycles is well explained by the properties of a random graph with the same in- and out-degrees of the nodes.</p> <p>Among different physiological conditions, cell cycle has the most significant relationship with LSCC, as the set of 64 transcription interactions that are active in all phases of the cell cycle has overlap of 27 with the interactions of LSCC (of which there are 49).</p> <p>Conversely, if we remove the interactions that are active in all phases of the cell cycle (25% of interactions to transcription factors), the LSCC would have only three nodes and 5 edges, many fewer than expected. This subgraph of the transcription network consists mostly of interactions that are active only in the stress response subnetwork.</p> <p>We also characterize the role of LSCC in the topology of the network. We show that LSCC can be used to define a natural hierarchy in the network and that in every physiological subnetwork LSCC plays a pivotal role.</p> <p>Conclusion</p> <p>Apart from those well-defined conditions, the transcription network of <it>Saccharomyces cerevisiae </it>is devoid of cycles. It was observed that two conditions that were studied and that have no cycles of their own are <it>exogenous</it>: diauxic shift and DNA repair, while cell cycle and sporulation are <it>endogenous</it>. We claim that in a certain sense (slow recovery) stress response is <it>endogenous </it>as well.</p

Top of the Pods - In search of a podcasting “podagogy” for language learning

The popularization of portable media players such as the iPod, and the delivery of audio and video content through content management software such as iTunes mean that there is a wealth of language learning resources freely available to users who may download them and use them anywhere at any time. These resources vary greatly in quality and follow different approaches to learning. This paper provides a taxonomy of podcast resources, reviews materials in the light of Second Language Acquisition theories, argues for better design, and outlines directions for future research

Elasticity and Petri nets

Digital electronic systems typically use synchronous clocks and primarily assume fixed duration of their operations to simplify the design process. Time elastic systems can be constructed either by replacing the clock with communication handshakes (asynchronous version) or by augmenting the clock with a synchronous version of a handshake (synchronous version). Time elastic systems can tolerate static and dynamic changes in delays (asynchronous case) or latencies (synchronous case) of operations that can be used for modularity, ease of reuse and better power-delay trade-off. This paper describes methods for the modeling, performance analysis and optimization of elastic systems using Marked Graphs and their extensions capable of describing behavior with early evaluation. The paper uses synchronous elastic systems (aka latency-tolerant systems) for illustrating the use of Petri nets, however, most of the methods can be applied without changes (except changing the delay model associated with events of the system) to asynchronous elastic systems.Peer ReviewedPostprint (author's final draft

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Efficient Evaluation of Low Degree Multivariate Polynomials in Ring-LWE Homomorphic Encryption Schemes

Homomorphic encryption schemes allow to perform computations over encrypted data. In schemes based on RLWE assumption the plaintext data is a ring polynomial. In many use cases of homomorphic encryption only the degree-0 coefficient of this polynomial is used to encrypt data. In this context any computation on encrypted data can be performed. It is trickier to perform generic computations when more than one coefficient per ciphertext is used. In this paper we introduce a method to efficiently evaluate low-degree multivariate polynomials over encrypted data. The main idea is to encode several messages in the coefficients of a plaintext space polynomial. Using ring homomorphism operations and multiplications between ciphertexts, we compute multivariate monomials up to a given degree. Afterwards, using ciphertext additions we evaluate the input multivariate polynomial. We perform extensive experimentations of the proposed evaluation method. As example, evaluating an arbitrary multivariate degree-3 polynomial with 100 variables over Boolean space takes under 13 seconds

The Integrated Genomic Landscape of Thymic Epithelial Tumors

Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy