A Note on Zipf's Law, Natural Languages, and Noncoding DNA regions

In Phys. Rev. Letters (73:2, 5 Dec. 94), Mantegna et al. conclude on the basis of Zipf rank frequency data that noncoding DNA sequence regions are more like natural languages than coding regions. We argue on the contrary that an empirical fit to Zipf's ``law'' cannot be used as a criterion for similarity to natural languages. Although DNA is a presumably an ``organized system of signs'' in Mandelbrot's (1961) sense, an observation of statistical features of the sort presented in the Mantegna et al. paper does not shed light on the similarity between DNA's ``grammar'' and natural language grammars, just as the observation of exact Zipf-like behavior cannot distinguish between the underlying processes of tossing an $M$ sided die or a finite-state branching process.Comment: compressed uuencoded postscript file: 14 page

LRRK2: an éminence grise of Wnt-mediated neurogenesis?

The importance of Leucine-Rich Repeat Kinase 2 (LRRK2) to mature neurons is well-established, since mutations in PARK8, the gene encoding LRRK2, are the most common known cause of Parkinson’s disease. Nonetheless, despite the LRRK2 knockout mouse having no overt neurodevelopmental defect, numerous lines of in vitro data point towards a central role for this protein in neurogenesis. Roles for LRRK2 have been described in many key processes, including neurite outgrowth and the regulation of microtubule dynamics. Moreover, LRRK2 has been implicated in cell cycle control, suggesting additional roles in neurogenesis that precede terminal differentiation. However, we contend that the suggested function of LRRK2 as a scaffolding protein at the heart of numerous Wnt signaling cascades provides the most tantalizing link to neurogenesis in the developing brain. Numerous lines of evidence show a critical requirement for multiple Wnt pathways in the development of certain brain regions, not least the dopaminergic neurons of the ventral mid-brain. In conclusion, these observations indicate a function of LRRK2 as a subtle yet critical mediator of the action of Wnt ligands on developing neurons. We suggest that LRRK2 loss- or gain-of-function are likely modifiers of developmental phenotypes seen in animal models of Wnt signaling deregulation, a hypothesis that can be tested by cross-breeding relevant genetically modified experimental strains

Formalizing Triggers: A Learning Model for Finite Spaces

In a recent seminal paper, Gibson and Wexler (1993) take important steps to formalizing the notion of language learning in a (finite) space whose grammars are characterized by a finite number of parameters. They introduce the Triggering Learning Algorithm (TLA) and show that even in finite space convergence may be a problem due to local maxima. In this paper we explicitly formalize learning in finite parameter space as a Markov structure whose states are parameter settings. We show that this captures the dynamics of TLA completely and allows us to explicitly compute the rates of convergence for TLA and other variants of TLA e.g. random walk. Also included in the paper are a corrected version of GW's central convergence proof, a list of "problem states" in addition to local maxima, and batch and PAC-style learning bounds for the model

LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6

Mutations in PARK8, encoding leucine-rich repeat kinase 2 (LRRK2), are a frequent cause of Parkinson's disease (PD). Nonetheless, the physiological role of LRRK2 remains unclear. Here, we demonstrate that LRRK2 participates in canonical Wnt signaling as a scaffold. LRRK2 interacts with key Wnt signaling proteins of the β-catenin destruction complex and dishevelled proteins in vivo and is recruited to membranes following Wnt stimulation, where it binds to the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) in cellular models. LRRK2, therefore, bridges membrane and cytosolic components of Wnt signaling. Changes in LRRK2 expression affects pathway activity, while pathogenic LRRK2 mutants reduce both signal strength and the LRRK2-LRP6 interaction. Thus, decreased LRRK2-mediated Wnt signaling caused by reduced binding to LRP6 may underlie the neurodegeneration observed in PD. Finally, a newly developed LRRK2 kinase inhibitor disrupted Wnt signaling to a similar extent as pathogenic LRRK2 mutations. The use of LRRK2 kinase inhibition to treat PD may therefore need reconsideration

Recent results on GaAs detectors - 137

The present understanding of the charge collection in GaAs detectors with respect to the materials used and its processing are discussed. The radiation induced degradation of the charge collection efficiency and the leakage current of the detectors are summarised. The status of strip and pixel detectors for the ATLAS experiment are reported along with the latest results from GaAs X-ray detectors for non-high energy physics applications.Comment: 7 pages. 4 postscript figures + 1 postscript preprint logo + 1 LaTeX file + 1 style file. Also available at http://ppewww.ph.gla.ac.uk/preprints/97/05