A comprehensive map of the mTOR signaling network

The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation. mTOR signaling is frequently dysregulated in oncogenic cells, and thus an attractive target for anticancer therapy. Using CellDesigner, a modeling support software for graphical notation, we present herein a comprehensive map of the mTOR signaling network, which includes 964 species connected by 777 reactions. The map complies with both the systems biology markup language (SBML) and graphical notation (SBGN) for computational analysis and graphical representation, respectively. As captured in the mTOR map, we review and discuss our current understanding of the mTOR signaling network and highlight the impact of mTOR feedback and crosstalk regulations on drug-based cancer therapy. This map is available on the Payao platform, a Web 2.0 based community-wide interactive process for creating more accurate and information-rich databases. Thus, this comprehensive map of the mTOR network will serve as a tool to facilitate systems-level study of up-to-date mTOR network components and signaling events toward the discovery of novel regulatory processes and therapeutic strategies for cancer

Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support

Surgical management of tetralogy of Fallot (TOF) results in anatomic and functional abnormalities in the majority of patients. Although right ventricular volume load due to severe pulmonary regurgitation can be tolerated for many years, there is now evidence that the compensatory mechanisms of the right ventricular myocardium ultimately fail and that if the volume load is not eliminated or reduced by pulmonary valve replacement the dysfunction might be irreversible. Cardiovascular magnetic resonance (CMR) has evolved during the last 2 decades as the reference standard imaging modality to assess the anatomic and functional sequelae in patients with repaired TOF. This article reviews the pathophysiology of chronic right ventricular volume load after TOF repair and the risks and benefits of pulmonary valve replacement. The CMR techniques used to comprehensively evaluate the patient with repaired TOF are reviewed and the role of CMR in supporting clinical decisions regarding pulmonary valve replacement is discussed

Evolution of Skull and Mandible Shape in Cats (Carnivora: Felidae)

The felid family consists of two major subgroups, the sabretoothed and the feline cats, to which all extant species belong, and are the most anatomically derived of all carnivores for predation on large prey with a precision killing bite. There has been much controversy and uncertainty about why the skulls and mandibles of sabretoothed and feline cats evolved to become so anatomically divergent, but previous models have focused on single characters and no unifying hypothesis of evolutionary shape changes has been formulated. Here I show that the shape of the skull and mandible in derived sabrecats occupy entirely different positions within overall morphospace from feline cats, and that the evolution of skull and mandible shape has followed very different paths in the two subgroups. When normalised for body-size differences, evolution of bite forces differ markedly in the two groups, and are much lower in derived sabrecats, and they show a significant relationship with size and cranial shape, whereas no such relationship is present in feline cats. Evolution of skull and mandible shape in modern cats has been governed by the need for uniform powerful biting irrespective of body size, whereas in sabrecats, shape evolution was governed by selective pressures for efficient predation with hypertrophied upper canines at high gape angles, and bite forces were secondary and became progressively weaker during sabrecat evolution. The current study emphasises combinations of new techniques for morphological shape analysis and biomechanical studies to formulate evolutionary hypotheses for difficult groups

Reph, a Regulator of Eph Receptor Expression in the Drosophila melanogaster Optic Lobe

Receptors of the Eph family of tyrosine kinases and their Ephrin ligands are involved in developmental processes as diverse as angiogenesis, axon guidance and cell migration. However, our understanding of the Eph signaling pathway is incomplete, and could benefit from an analysis by genetic methods. To this end, we performed a genetic modifier screen for mutations that affect Eph signaling in Drosophila melanogaster. Several dozen loci were identified on the basis of their suppression or enhancement of an eye defect induced by the ectopic expression of Ephrin during development; many of these mutant loci were found to disrupt visual system development. One modifier locus, reph (regulator of eph expression), was characterized in molecular detail and found to encode a putative nuclear protein that interacts genetically with Eph signaling pathway mutations. Reph is an autonomous regulator of Eph receptor expression, required for the graded expression of Eph protein and the establishment of an optic lobe axonal topographic map. These results reveal a novel component of the regulatory pathway controlling expression of eph and identify reph as a novel factor in the developing visual system

Multichannel Online Blind Speech Dereverberation with Marginalization of Static Observation Parameters in a Rao-Blackwellized Particle Filter

Room reverberation leads to reduced intelligibility of audio signals and spectral coloration of audio signals. Enhancement of acoustic signals is thus crucial for high-quality audio and scene analysis applications. Multiple sensors can be used to exploit statistical evidence from multiple observations of the same event to improve enhancement. Whilst traditional beamforming techniques suffer from interfering reverberant reflections with the beam path, other approaches to dereverberation often require at least partial knowledge of the room impulse response which is not available in practice, or rely on inverse filtering of a channel estimate to obtain a clean speech estimate, resulting in difficulties with non-minimum phase acoustic impulse responses. This paper proposes a multi-sensor approach to blind dereverberation in which both the source signal and acoustic channel are directly estimated from the distorted observations using their optimal estimators. The remaining model parameters are sampled from hypothesis distributions using a particle filter, thus facilitating real-time dereverberation. This approach was previously successfully applied to single-sensor blind dereverberation. In this paper, the single-channel approach is extended to multiple sensors. Performance improvements due to the use of multiple sensors are demonstrated on synthetic and baseband speech examples