Model-based testing with UML applied to a roaming algorithm for bluetooth devices

In late 2001, the Object Management Group issued a Request for Proposal to develop a testing profile for UML 2.0. In June 2003, the work on the UML 2.0 Testing Profile was finally adopted by the OMG. Since March 2004, it has become an official standard of the OMG. The UML 2.0 Testing Profile provides support for UML based model-driven testing. This paper introduces a methodology on how to use the testing profile in order to modify and extend an existing UML design model for test issues. The application of the methodology will be explained by applying it to an existing UML Model for a Bluetooth device.     

Membrane biology and signal transduction

Posters

Membrane biology and signal transduction     

Internalization of cationic peptides: the road less (or more?) traveled

Facilitating the entry of molecules into mammalian cells is of great interest to fields as diverse as cell biology and drug delivery. The discovery of natural protein transduction domains and the development of artificial ones, including polyarginine, provides a means to achieve this goal. Here, we comment on key chemical and biological aspects of cationic peptide internalization, including the physiological relevance of this process. Received 13 April 2006; received after revision 21 May 2006; accepted 2 June 2006     

Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion

Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events.     

The waking brain: an update

Wakefulness and consciousness depend on perturbation of the cortical soliloquy. Ascending activation of the cerebral cortex is characteristic for both waking and paradoxical (REM) sleep. These evolutionary conserved activating systems build a network in the brainstem, midbrain, and diencephalon that contains the neurotransmitters and neuromodulators glutamate, histamine, acetylcholine, the catecholamines, serotonin, and some neuropeptides orchestrating the different behavioral states. Inhibition of these waking systems by GABAergic neurons allows sleep. Over the past decades, a prominent role became evident for the histaminergic and the orexinergic neurons as a hypothalamic waking center.     

Forecasting temporally aggregated vector ARMA processes

If interest centres on forecasting a temporally aggregated multiple time series and the generation process of the disaggregate series is a known vector ARMA (autoregressive moving average) process then forecasting the disaggregate series and temporally aggregating the forecasts is at least as efficient, under a mean squared error measure, as forecasting the aggregated series directly. Necessary and sufficient conditions for equality of the two forecasts are given. In practice the data generation process is usually unknown and has to be determined from the available data. Using asymptotic theory it is shown that also in this case aggregated forecasts from the disaggregate process will usually be superior to forecasts obtained from the aggregated process.     

Asymmetric cell divisions promote stratification and differentiation of mammalian skin

The epidermis is a stratified squamous epithelium forming the barrier that excludes harmful microbes and retains body fluids. To perform these functions, proliferative basal cells in the innermost layer periodically detach from an underlying basement membrane of extracellular matrix, move outward and eventually die. Once suprabasal, cells stop dividing and enter a differentiation programme to form the barrier. The mechanism of stratification is poorly understood. Although studies in vitro have led to the view that stratification occurs through the delamination and subsequent movement of epidermal cells, most culture conditions favour keratinocytes that lack the polarity and cuboidal morphology of basal keratinocytes in tissue. These features could be important in considering an alternative mechanism, that stratification occurs through asymmetric cell divisions in which the mitotic spindle orients perpendicularly to the basement membrane. Here we show that basal epidermal cells use their polarity to divide asymmetrically, generating a committed suprabasal cell and a proliferative basal cell. We further demonstrate that integrins and cadherins are essential for the apical localization of atypical protein kinase C, the Par3-LGN-Inscuteable complex and NuMA-dynactin to align the spindle.     

Mice in the world of stem cell biology

The ability of embryos to diversify and of some adult tissues to regenerate throughout life is directly attributable to stem cells. These cells have the capacity to self-renew-that is, to divide and to create additional stem cells-and to differentiate along a specific lineage. The differentiation of pluripotent embryonic stem cells along specific cell lineages has been used to understand the molecular mechanisms involved in tissue development. The often endless capacity of embryonic stem cells to generate differentiated cell types positions the field of stem cells at the nexus between developmental biologists, who are fascinated by the properties of these cells, and clinicians, who are excited about the prospects of bringing stem cells from bench to bedside to treat degenerative disorders and injuries for which there are currently no cures. Here we highlight the importance of mice in stem cell biology and in bringing the world one step closer to seeing these cells brought to fruition in modern medicine.