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Biomedical subjects

Marcelo O Magnasco

Publications and source records attributed to Marcelo O Magnasco.

9 recordsLinked to original sources

Sparse time-frequency representations.

Auditory neurons preserve exquisite temporal information about sound features, but we do not know how the brain uses this information to process the rapidly changing sounds of the natural world. Simple arguments for effective use of temporal information led us to consider the reassignment class of time-frequency representations as a model of auditory processing. Reassigned time-frequency representations can track isolated simple signals with accuracy unlimited by the time-frequency uncertainty principle, but lack of a general theory has hampered their application to complex sounds. We describe the reassigned representations for white noise and show that even spectrally dense signals produce sparse reassignments: the representation collapses onto a thin set of lines arranged in a froth-like pattern. Preserving phase information allows reconstruction of the original signal. We define a notion of "consensus," based on stability of reassignment to time-scale changes, which produces sharp spectral estimates for a wide class of complex mixed signals. As the only currently known class of time-frequency representations that is always "in focus" this methodology has general utility in signal analysis. It may also help explain the remarkable acuity of auditory perception. Many details of complex sounds that are virtually undetectable in standard sonograms are readily perceptible and visible in reassignment.

Animals↗

Harshlight: a "corrective make-up" program for microarray chips.

BACKGROUND: Microscopists are familiar with many blemishes that fluorescence images can have due to dust and debris, glass flaws, uneven distribution of fluids or surface coatings, etc. Microarray scans do show similar artifacts, which might affect subsequent analysis. Although all but the starkest blemishes are hard to find by the unaided eye, particularly in high-density oligonucleotide arrays (HDONAs), few tools are available to help with the detection of those defects. RESULTS: We develop a novel tool, Harshlight, for the automatic detection and masking of blemishes in HDONA microarray chips. Harshlight uses a combination of statistic and image processing methods to identify three different types of defects: localized blemishes affecting a few probes, diffuse defects affecting larger areas, and extended defects which may invalidate an entire chip. CONCLUSION: We demonstrate the use of Harshlight can materially improve analysis of HDONA chips, especially for experiments with subtle changes between samples. For the widely used MAS5 algorithm, we show that compact blemishes cause an average of 8 gene expression values per chip to change by more than 50%, two of them by more than twofold; our masking algorithm restores about two thirds of this damage. Large-scale artifacts are successfully detected and eliminated.

Algorithms↗

Comparing independent microarray studies: the case of human embryonic stem cells.

BACKGROUND: Microarray studies of the same phenomenon in different labs often appear at variance because the published lists of regulated transcripts have disproportionately small intersections. We demonstrate that comparing studies by intersecting lists in this manner is methodologically flawed by reanalyzing three studies of the molecular signature of "stemness" in human embryonic stem cells. There are only 7 genes common to all three published lists, suggesting disagreement. RESULTS: Carefully reanalyzing all three together from the raw data we detect 111 genes upregulated and 95 downregulated in all three studies. The upregulated list was subject to rtRTPCR analysis and 75% of the genes were confirmed. CONCLUSION: Our findings show that the three studies have a substantial core of common genes, which is missed if only the published lists are examined. Combined analysis of multiple experiments can be a powerful way to distil coherent conclusions.

Cell Line↗

Bubbling and on-off intermittency in bailout embeddings.

We establish and investigate the conceptual connection between the dynamics of the bailout embedding of a Hamiltonian system and the dynamical regimes associated with the occurrence of bubbling and blowout bifurcations. The roles of the invariant manifold and the dynamics restricted to it, required in bubbling and blowout bifurcating systems, are played in the bailout embedding by the embedded Hamiltonian dynamical system. The Hamiltonian nature of the dynamics is precisely the distinctive feature of this instance of a bubbling or blowout bifurcation. The detachment of the embedding trajectories from the original ones can thus be thought of as transient on-off intermittency, and noise-induced avoidance of some regions of the embedded phase space can be recognized as Hamiltonian bubbling.

Journal Article↗

Solving the riddle of the bright mismatches: labeling and effective binding in oligonucleotide arrays.

RNA binding to high-density oligonucleotide arrays has shown tantalizing differences with solution experiments. We analyze here its sequence specificity, fitting binding affinities to sequence composition in large datasets. Our results suggest that the fluorescent labels interfere with binding, causing a catch-22. To be detected, the RNA must both glow and bind: without labels it cannot be seen even if bound, while with too many it will not bind. A simple model for the binding of labeled oligonucleotides sheds light on the interplay between binding energies and labeling probability.

Base Sequence↗

A wave traveling over a Hopf instability shapes the cochlear tuning curve.

The tuning curve of the cochlea measures how intense an input is required to elicit a given output level as a function of the frequency. It is a fundamental object of auditory theory, for it summarizes how to identify sounds on the basis of the cochlear output. A simple model is presented showing that only two elements are sufficient for establishing the cochlear tuning curve: a broadly tuned traveling wave, moving unidirectionally from high to low frequencies, and a set of mechanosensors poised at the threshold of an oscillatory (Hopf) instability. These two components generate the various frequency-response regimes needed for a cochlear tuning curve with a high slope.

Journal Article↗

Virtual gating and nuclear transport: the hole picture.

The eukaryotic nucleus is surrounded by a protective nuclear envelope, which is perforated by trafficking machines termed nuclear pore complexes (NPCs). The NPCs are the sole mediators of exchange between the nucleus and the cytoplasm. Small molecules pass through the NPCs unchallenged; however, large macromolecules are excluded unless chaperoned across by transport factors. Here, we suggest a model, termed 'virtual gating', to explain the mechanism of this rapid and selective macromolecular trafficking.

Animals↗

Bailout embeddings and neutrally buoyant particles in three-dimensional flows.

We use the bailout embeddings of three-dimensional volume-preserving maps to study qualitatively the dynamics of small spherical neutrally buoyant impurities suspended in a time-periodic incompressible fluid flow. The accumulation of impurities in tubular vortical structures, the detachment of particles from fluid trajectories near hyperbolic invariant lines, and the formation of nontrivial three-dimensional structures in the distribution of particles are predicted.

Journal Article↗

Bailout embeddings, targeting of invariant tori, and the control of Hamiltonian chaos.

We introduce a technique, which we term bailout embedding, that can be used to target orbits having particular properties out of all orbits in a flow or map. We explicitly construct a bailout embedding for Hamiltonian systems so as to target invariant tori. We show how the bailout dynamics are able to lock onto extremely small regular islands in a chaotic sea.

Journal Article↗