Sparse Modelling and Multi-exponential Analysis

The research fields of harmonic analysis, approximation theory and computer algebra are seemingly different domains and are studied by seemingly separated research communities. However, all of these are connected to each other in many ways. The connection between harmonic analysis and approximation theory is not accidental: several constructions among which wavelets and Fourier series, provide major insights into central problems in approximation theory. And the intimate connection between approximation theory and computer algebra exists even longer: polynomial interpolation is a long-studied and important problem in both symbolic and numeric computing, in the former to counter expression swell and in the latter to construct a simple data model. A common underlying problem statement in many applications is that of determining the number of components, and for each component the value of the frequency, damping factor, amplitude and phase in a multi-exponential model. It occurs, for instance, in magnetic resonance and infrared spectroscopy, vibration analysis, seismic data analysis, electronic odour recognition, keystroke recognition, nuclear science, music signal processing, transient detection, motor fault diagnosis, electrophysiology, drug clearance monitoring and glucose tolerance testing, to name just a few. The general technique of multi-exponential modeling is closely related to what is commonly known as the Padé-Laplace method in approximation theory, and the technique of sparse interpolation in the field of computer algebra. The problem statement is also solved using a stochastic perturbation method in harmonic analysis. The problem of multi-exponential modeling is an inverse problem and therefore may be severely ill-posed, depending on the relative location of the frequencies and phases. Besides the reliability of the estimated parameters, the sparsity of the multi-exponential representation has become important. A representation is called sparse if it is a combination of only a few elements instead of all available generating elements. In sparse interpolation, the aim is to determine all the parameters from only a small amount of data samples, and with a complexity proportional to the number of terms in the representation. Despite the close connections between these fields, there is a clear lack of communication in the scientific literature. The aim of this seminar is to bring researchers together from the three mentioned fields, with scientists from the varied application domains.Output Type: Meeting Repor

Aerosolized BC-819 Inhibits Primary but Not Secondary Lung Cancer Growth

Despite numerous efforts, drug based treatments for patients suffering from lung cancer remains poor. As a promising alternative, we investigated the therapeutic potential of BC-819 for the treatment of lung cancer in mouse tumor models. BC-819 is a novel plasmid DNA which encodes for the A-fragment of Diphtheria toxin and has previously been shown to successfully inhibit tumor growth in human clinical study of bladder carcinoma. In a first set of experiments, we examined in vitro efficacy of BC-819 in human lung cancer cell-lines NCI-H460, NCI-H358 and A549, which revealed >90% reduction of cell growth. In vivo efficacy was examined in an orthotopic mouse xenograft lung cancer model and in a lung metastasis model using luminescent A549-C8-luc adenocarcinoma cells. These cells resulted in peri- and intra-bronchiolar tumors upon intrabronchial application and parenchymal tumors upon intravenous injection, respectively. Mice suffering from these lung tumors were treated with BC-819, complexed to branched polyethylenimine (PEI) and aerosolized to the mice once per week for a period of 10 weeks. Using this regimen, growth of intrabronchially induced lung tumors was significantly inhibited (p = 0.01), whereas no effect could be observed in mice suffering from lung metastasis. In summary, we suggest that aerosolized PEI/BC-819 is capable of reducing growth only in tumors arising from the luminal part of the airways and are therefore directly accessible for inhaled BC-819

TechLAN: An Experimental High-Speed ATM LAN

Introduction ATM (Asynchronous Transfer Mode) is a set of international standards for sending large amounts of voice, data and video information simultaneously over a single network at speeds up to a thousand times faster than is commonplace today. It is aimed to transport virtually every electronic communications format from e-mail to phone calls to movies. ATM promises to be a true worldwide standard and the foundation for the next century networks. The most common ATM network configuration is based on one or more fast switches interconnecting the subscribers. Such switches render the entire network distance independent, namely, the same bandwidth and service can be afforded to the communicating partners whether 1 meter or 100 kilometers apart. Unfortunately, this independence comes at a fairly high cost of the switch. It appears that when the communication parties span only a small locale, different configurations can be devised that rid themselves from reliance on the costl

Myosin VI is required for structural integrity of the apical surface of sensory hair cells in zebrafish

Unconventional myosins have been associated with hearing loss in humans, mice, and zebrafish. Mutations in myosin VI cause both recessive and dominant forms of nonsyndromic deafness in humans and deafness in Snell's waltzer mice associated with abnormal fusion of hair cell stereocilia. Although myosin VI has been implicated in diverse cellular processes such as vesicle trafficking and epithelial morphogenesis, the role of this protein in the sensory hair cells remains unclear. To investigate the function of myosin VI in zebrafish, we cloned and examined the expression pattern of myosin VI, which is duplicated in the zebrafish genome. One duplicate, myo6a, is expressed in a ubiquitous pattern during early development and at later stages, and is highly expressed in the brain, gut, and kidney. myo6b, on the other hand, is predominantly expressed in the sensory epithelium of the ear and lateral line at all developmental stages examined. Both molecules have different splice variants expressed in these tissues. Using a candidate gene approach, we show that myo6b is satellite, a gene responsible for auditory/vestibular defects in zebrafish larvae. Examination of hair cells in satellite mutants revealed that stereociliary bundles are irregular and disorganized. At the ultrastructural level, we observed that the apical surface of satellite mutant hair cells abnormally protrudes above the epithelium and the membrane near the base of the stereocilia is raised. At later stages, stereocilia fused together. We conclude that zebrafish myo6b is required for maintaining the integrity of the apical surface of hair cells, suggesting a conserved role for myosin VI in regulation of actin-based interactions with the plasma membrane

Silencing of a large microRNA cluster on human chromosome 14q32 in melanoma: biological effects of mir-376a and mir-376c on insulin growth factor 1 receptor

<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma is a devastating disease with limited therapeutic options. MicroRNAs (miRNAs) are small non coding RNA molecules with important roles in post-transcriptional gene expression regulation, whose aberrant expression has been implicated in cancer.</p> <p>Results</p> <p>We show that the expression of miRNAs from a large cluster on human chromosome 14q32 is significantly down-regulated in melanoma cell lines, benign nevi and melanoma samples relative to normal melanocytes. This miRNA cluster resides within a parentally imprinted chromosomal region known to be important in development and differentiation. In some melanoma cell lines, a chromosomal deletion or loss-of-heterozygosity was observed in the cis-acting regulatory region of this cluster. In several cell lines we were able to re-express two maternally-induced genes and several miRNAs from the cluster with a combination of de-methylating agents and histone de-acetylase inhibitors, suggesting that epigenetic modifications take part in their silencing. Stable over-expression of mir-376a and mir-376c, two miRNAs from this cluster that could be re-expressed following epigenetic manipulation, led to modest growth retardation and to a significant decrease in migration in-vitro. Bioinformatic analysis predicted that both miRNAs could potentially target the 3'UTR of IGF1R. Indeed, stable expression of mir-376a and mir-376c in melanoma cells led to a decrease in IGF1R mRNA and protein, and a luciferase reporter assay indicated that the 3'UTR of IGF1R is a target of both mir-376a and mir-376c.</p> <p>Conclusions</p> <p>Our work is the first to show that the large miRNA cluster on chromosome 14q32 is silenced in melanoma. Our results suggest that down-regulation of mir-376a and mir-376c may contribute to IGF1R over-expression and to aberrant negative regulation of this signaling pathway in melanoma, thus promoting tumorigenesis and metastasis.</p