3,992 research outputs found

    Sensitivity analysis and experimental design of a stiff signal transduction pathway model

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    Sensitivity analysis is normally used to analyze how sensitive a system is with respect to the change of parameters or initial conditions and is perhaps best known in systems biology via the formalism of metabolic control analysis [1, 2]. The nuclear factor B (NF-B) signalling pathway is an important cellular signalling pathway, of which protein phosphorylation is a major factor controlling the activation of further downstream events. The NF-ÎșB proteins regulate numerous genes that play important roles in inter- and intra-cellular signalling, cellular stress responses, cell growth, survival, and apoptosis. As such, its specificity and its role in the temporal control of gene expression are of crucial physiological interest

    Toward a new economy of suspended rights: sex offenders and post-sentence confinement and control

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    Giorgio Agamben has recently described the state of exception as a new ‘paradigm of government’ while Judith Butler writes of ‘the new war prison’ in which terror suspects and other ‘detainees’ face an indefinite detention suspended beyond or outside law. Less remarked upon has been the recent entry into Australian politics of a new penal form: schemes that provide for the post-sentence detention (continued imprisonment) of sex offenders who have completed a finite sentence of imprisonment and who would otherwise be returned to society as free citizens. First introduced in 2003 in Queensland, where such detention may be indefinite, three Australian states now have extended supervision and detention arrangements, while Victoria is currently drafting legislation to add continued detention to its current extended supervision provisions. This paper examines these measures that aim to excise, quarantine or exclude certain categories or groups of people from society through the lens of liberty rights. Particularly significant within the structure of justification for these measures, it will be suggested, is the status of justice rights. The focus of the paper is upon one recent case, Director of Public Prosecutions (WA) v GTR [2008], wherein key movements occurred in an emerging jurisprudence of security and architecture of control.This conference has been generously sponsored by the School of Social and Political Sciences and the Sydney Law School, University of Sydney, in collaboration with the School of Law, University of Western Sydne

    So many genes, so little time: A practical approach to divergence-time estimation in the genomic era

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    Phylogenomic datasets have been successfully used to address questions involving evolutionary relationships, patterns of genome structure, signatures of selection, and gene and genome duplications. However, despite the recent explosion in genomic and transcriptomic data, the utility of these data sources for efficient divergence-time inference remains unexamined. Phylogenomic datasets pose two distinct problems for divergence-time estimation: (i) the volume of data makes inference of the entire dataset intractable, and (ii) the extent of underlying topological and rate heterogeneity across genes makes model mis-specification a real concern. “Gene shopping”, wherein a phylogenomic dataset is winnowed to a set of genes with desirable properties, represents an alternative approach that holds promise in alleviating these issues. We implemented an approach for phylogenomic datasets (available in SortaDate) that filters genes by three criteria: (i) clock-likeness, (ii) reasonable tree length (i.e., discernible information content), and (iii) least topological conflict with a focal species tree (presumed to have already been inferred). Such a winnowing procedure ensures that errors associated with model (both clock and topology) mis-specification are minimized, therefore reducing error in divergence-time estimation. We demonstrated the efficacy of this approach through simulation and applied it to published animal (Aves, Diplopoda, and Hymenoptera) and plant (carnivorous Caryophyllales, broad Caryophyllales, and Vitales) phylogenomic datasets. By quantifying rate heterogeneity across both genes and lineages we found that every empirical dataset examined included genes with clock-like, or nearly clock-like, behavior. Moreover, many datasets had genes that were clock-like, exhibited reasonable evolutionary rates, and were mostly compatible with the species tree. We identified overlap in age estimates when analyzing these filtered genes under strict clock and uncorrelated lognormal (UCLN) models. However, this overlap was often due to imprecise estimates from the UCLN model. We find that “gene shopping” can be an efficient approach to divergence-time inference for phylogenomic datasets that may otherwise be characterized by extensive gene tree heterogeneity
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