To understand the origins of the fragile X syndrome and factors predisposing alleles to instability and hyperexpansion, we have compared the haplotype (using markers FRAXAC1, FRAXAC2, and DXS548) and AGG interspersion patterns of the FMR1 CGG repeat for 214 normal and 16 premutation chromosomes. Association testing between interspersion pattern and haplotype reveals a highly significant (P < 0....

Triplet repeat expansions in the Fragile X mental retardation 1 (FMR1) gene cause either intellectual disability and autism, or adult-onset neurodegeneration, with poorly understood variability in presentation. Previous studies have identified several long noncoding RNAs (lncRNAs) at the FMR1 locus, including FMR4. Similarly to FMR1, FMR4 is silenced by large-repeat expansions that result in en...

Improved modularity and separation of concerns do not only intend to aid initial development, but are conceived such that developers can better manage software complexity, evolution and reuse [9]. Paradoxically, the essential techniques that AOSD proposes to improve software modularity seem to restrict the evolvability of that software. More specifically, the pointcuts that state when and where...

Infection of human cells with adenovirus serotype 12 (Ad12) induces metaphase fragility of four, and apparently only four, chromosomal loci. Surprisingly, each of these four loci corresponds to a cluster of genes encoding a small abundant structural RNA: the RNU1 and RNU2 loci contain tandemly repeated genes encoding U1 and U2 small nuclear RNAs (snRNAs), respectively; the PSU1 locus is a clust...

Robustness, a long-recognized property of living systems, allows function in the face of uncertainty while fragility, i.e., extreme sensitivity, can potentially lead to catastrophic failure following seemingly innocuous perturbations. Carlson and Doyle hypothesized that highly-evolved networks, e.g., those involved in cell-cycle regulation, can be resistant to some perturbations while highly se...

Can memories be unlearned, or is unlearning a form of acquiring a new memory that competes with the old, effectively masking it? We considered motor memories that were acquired when people learned to use a novel tool. We trained people to reach with tool A and quantified recall in error-clamp trials, i.e., trials in which the memory was reactivated but error-dependent learning was minimized. We...

It happens increasingly often that experts need to collaborate in order to exchange ideas, views and opinions on their path towards understanding. However, every collaboration process is inherently fragile and involves a large set of human subjective aspects, including social interaction, personality, and emotions. In this paper we present Pogat, an a↵ective virtual agent designed to support th...

In 1866, Carl Ludwig together with Elias Cyon created the first isolated perfused frog heart preparation. Perfusion systems for the isolated mammalian heart were developed by H. Newell Martin in 1883 and by Oscar Langendorff in 1895. In its working mode, the isolated perfused rat heart was established in the 1960s.