Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Design of an RFID-based inventory control and management system : a case study

Author name used in this publication: Jacky S. L. Ting2011-2012 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Using social network analysis to combat counterfeiting

2013-2014 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Separating Stimulus-Induced and Background Components of Dynamic Functional Connectivity in Naturalistic fMRI

We consider the challenges in extracting stimulus-related neural dynamics from other intrinsic processes and noise in naturalistic functional magnetic resonance imaging (fMRI). Most studies rely on inter-subject correlations (ISC) of low-level regional activity and neglect varying responses in individuals. We propose a novel, data-driven approach based on low-rank plus sparse (L+S) decomposition to isolate stimulus-driven dynamic changes in brain functional connectivity (FC) from the background noise, by exploiting shared network structure among subjects receiving the same naturalistic stimuli. The time-resolved multi-subject FC matrices are modeled as a sum of a low-rank component of correlated FC patterns across subjects, and a sparse component of subject-specific, idiosyncratic background activities. To recover the shared low-rank subspace, we introduce a fused version of principal component pursuit (PCP) by adding a fusion-type penalty on the differences between the columns of the low-rank matrix. The method improves the detection of stimulus-induced group-level homogeneity in the FC profile while capturing inter-subject variability. We develop an efficient algorithm via a linearized alternating direction method of multipliers to solve the fused-PCP. Simulations show accurate recovery by the fused-PCP even when a large fraction of FC edges are severely corrupted. When applied to natural fMRI data, our method reveals FC changes that were time-locked to auditory processing during movie watching, with dynamic engagement of sensorimotor systems for speech-in-noise. It also provides a better mapping to auditory content in the movie than ISC

A financial data mining model for extracting customer behavior

Author name used in this publication: George T. S. Ho2011-2012 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Hybrid risk management methodology : a case study

Author name used in this publication: Jacky Siu-Lun TingAuthor name used in this publication: Albert Hing-Choi Tsang2008-2009 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809

Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c

Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder, in which language function can be severely affected. We demonstrate that in the mouse striatum, the gene Foxp2 negatively interacts with the synapse suppressor gene Mef2c. We present causal evidence that Mef2c inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2c suppresses corticostriatal synapse formation and striatal spinogenesis, but can itself be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2c, and both intrastriatal and global decrease of Mef2c rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders.National Institutes of Health (U.S.) (Grant R37 HD028341)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Award R37 HD028341