Structured Multi-Level Feature Interaction Identification

This is a conference paper.Features are an established means of adding non-geometric information and extra geometric semantics to conventional CAD systems. It has been already realised that although feature-based modelling is necessary for the next generation of integrated design and manufacturing systems, inherent feature interactions pose a difficulty in representing and manipulating geometric design. This paper presents a structured multi-level geometric feature interaction classification scheme implemented within a Design-by Feature (DbF) system for representation validation analysis. Various feature interaction definitions and classification methods are first surveyed. The elements and the tests used for the identification process are presented. The classification encompasses existing feature interference cases found in the literature, uses a clear structure for the classification and, is applied at three different levels

DNA methylation, the early-life social environment and behavioral disorders

One of the outstanding questions in behavioral disorders is untangling the complex relationship between nurture and nature. Although epidemiological data provide evidence that there is an interaction between genetics (nature) and the social and physical environments (nurture) in a spectrum of behavioral disorders, the main open question remains the mechanism. Emerging data support the hypothesis that DNA methylation, a covalent modification of the DNA molecule that is a component of its chemical structure, serves as an interface between the dynamic environment and the fixed genome. We propose that modulation of DNA methylation in response to environmental cues early in life serves as a mechanism of life-long genome adaptation. Under certain contexts, this adaptation can turn maladaptive resulting in behavioral disorders. This hypothesis has important implications on understanding, predicting, preventing, and treating behavioral disorders including autism that will be discussed

HEATR2 Plays a Conserved Role in Assembly of the Ciliary Motile Apparatus

Cilia are highly conserved microtubule-based structures that perform a variety of sensory and motility functions during development and adult homeostasis. In humans, defects specifically affecting motile cilia lead to chronic airway infections, infertility and laterality defects in the genetically heterogeneous disorder Primary Ciliary Dyskinesia (PCD). Using the comparatively simple Drosophila system, in which mechanosensory neurons possess modified motile cilia, we employed a recently elucidated cilia transcriptional RFX-FOX code to identify novel PCD candidate genes. Here, we report characterization of CG31320/HEATR2, which plays a conserved critical role in forming the axonemal dynein arms required for ciliary motility in both flies and humans. Inner and outer arm dyneins are absent from axonemes of CG31320 mutant flies and from PCD individuals with a novel splice-acceptor HEATR2 mutation. Functional conservation of closely arranged RFX-FOX binding sites upstream of HEATR2 orthologues may drive higher cytoplasmic expression of HEATR2 during early motile ciliogenesis. Immunoprecipitation reveals HEATR2 interacts with DNAI2, but not HSP70 or HSP90, distinguishing it from the client/chaperone functions described for other cytoplasmic proteins required for dynein arm assembly such as DNAAF1-4. These data implicate CG31320/HEATR2 in a growing intracellular pre-assembly and transport network that is necessary to deliver functional dynein machinery to the ciliary compartment for integration into the motile axoneme