Detecting separate time scales in genetic expression data.

BACKGROUND: Biological processes occur on a vast range of time scales, and many of them occur concurrently. As a result, system-wide measurements of gene expression have the potential to capture many of these processes simultaneously. The challenge however, is to separate these processes and time scales in the data. In many cases the number of processes and their time scales is unknown. This issue is particularly relevant to developmental biologists, who are interested in processes such as growth, segmentation and differentiation, which can all take place simultaneously, but on different time scales. RESULTS: We introduce a flexible and statistically rigorous method for detecting different time scales in time-series gene expression data, by identifying expression patterns that are temporally shifted between replicate datasets. We apply our approach to a Saccharomyces cerevisiae cell-cycle dataset and an Arabidopsis thaliana root developmental dataset. In both datasets our method successfully detects processes operating on several different time scales. Furthermore we show that many of these time scales can be associated with particular biological functions. CONCLUSIONS: The spatiotemporal modules identified by our method suggest the presence of multiple biological processes, acting at distinct time scales in both the Arabidopsis root and yeast. Using similar large-scale expression datasets, the identification of biological processes acting at multiple time scales in many organisms is now possible.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Transcriptional activation of immediate-early gene ETR101 by human T-cell leukaemia virus type I Tax

Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular gene expression through interactions with multiple cellular transcription pathways. This study describes the finding of immediate-early gene ETR101 expression in HTLV-I-infected cells and its regulation by Tax. ETR101 was persistently expressed in HTLV-I-infected cells but not in HTLV-I uninfected cells. Expression of ETR101 was dependent upon Tax expression in the inducible Tax-expressing cell line JPX-9 and also in Jurkat cells transiently transfected with Tax-expressing vectors. Tax transactivated the ETR101 gene promoter in a transient transfection assay. A series of deletion and mutation analyses of the ETR101 gene promoter indicated that a 35 bp region immediately upstream of the TATA-box sequence, which contains a consensus cAMP response element (CRE) and a G+C-rich sequence, is the critical responsive element for Tax activation. Site-directed mutagenesis analysis of the 35 bp region suggested that both the consensus CRE motif and its upstream G+C-rich sequence were critical for Tax transactivation. Electrophoretic mobility shift analysis (EMSA) using the 35 bp sequence as probe showed the formation of a specific protein-DNA complex in HTLV-I-infected cell lines. EMSA with specific antibodies confirmed that the CREB transcription factor was responsible for formation of this specific protein-DNA complex. These results suggested that Tax directly transactivated ETR101 gene expression, mainly through a CRE sequence via the CREB transcription pathway.published_or_final_versio

Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model

<p>Abstract</p> <p>Background</p> <p>Infantile hemangiomas (IH) are the most common benign tumors of infancy. The typical clinical course consists of rapid growth during the first year of life, followed by natural and gradual involution over a multi-year time span through unknown cellular mechanisms. Some tumors respond to medical treatment with corticosteroids or beta-blockers, however, when this therapy fails or is incomplete, surgical extirpation may be necessary. Noninvasive therapies to debulk or eliminate these tumors would be an important advance. The development of an <it>in vitro </it>cell culture system and an animal model would allow new insights into the biological processes involved in the development and pathogenesis of IH.</p> <p>Results</p> <p>We observed that proliferative stage IH specimens contain significantly more SALL4+ and CD133+ cells than involuting tumors, suggesting a possible stem cell origin. A tumor sphere formation assay was adapted to culture IH cells <it>in vitro</it>. Cells in IH tumor spheres express GLUT1, indicative of an IH cell of origin, elevated levels of VEGF, and various stem/progenitor cell markers such as SALL4, KDR, Oct4, Nanog and CD133. These cells were able to self-renew and differentiate to endothelial lineages, both hallmarks of tumor stem cells. Treatment with Rapamycin, a potent mTOR/VEGF inhibitor, dramatically suppressed IH cell growth <it>in vitro</it>. Subcutaneous injection of cells from IH tumor spheres into immunodeficient NOD-SCID mice produced GLUT1 and CD31 positive tumors with the same cellular proliferation, differentiation and involution patterns as human hemangiomas.</p> <p>Conclusions</p> <p>The ability to propagate large numbers of IH stem cells <it>in vitro </it>and the generation of an <it>in vivo </it>mouse model provides novel avenues for testing IH therapeutic agents in the future.</p

Climbing the Jaynes-Cummings Ladder and Observing its Sqrt(n) Nonlinearity in a Cavity QED System

The already very active field of cavity quantum electrodynamics (QED), traditionally studied in atomic systems, has recently gained additional momentum by the advent of experiments with semiconducting and superconducting systems. In these solid state implementations, novel quantum optics experiments are enabled by the possibility to engineer many of the characteristic parameters at will. In cavity QED, the observation of the vacuum Rabi mode splitting is a hallmark experiment aimed at probing the nature of matter-light interaction on the level of a single quantum. However, this effect can, at least in principle, be explained classically as the normal mode splitting of two coupled linear oscillators. It has been suggested that an observation of the scaling of the resonant atom-photon coupling strength in the Jaynes-Cummings energy ladder with the square root of photon number n is sufficient to prove that the system is quantum mechanical in nature. Here we report a direct spectroscopic observation of this characteristic quantum nonlinearity. Measuring the photonic degree of freedom of the coupled system, our measurements provide unambiguous, long sought for spectroscopic evidence for the quantum nature of the resonant atom-field interaction in cavity QED. We explore atom-photon superposition states involving up to two photons, using a spectroscopic pump and probe technique. The experiments have been performed in a circuit QED setup, in which ultra strong coupling is realized by the large dipole coupling strength and the long coherence time of a superconducting qubit embedded in a high quality on-chip microwave cavity.Comment: ArXiv version of manuscript published in Nature in July 2008, 5 pages, 5 figures, hi-res version at http://www.finkjohannes.com/SqrtNArxivPreprint.pd

Measurements of the Correlation Function of a Microwave Frequency Single Photon Source

At optical frequencies the radiation produced by a source, such as a laser, a black body or a single photon source, is frequently characterized by analyzing the temporal correlations of emitted photons using single photon counters. At microwave frequencies, however, there are no efficient single photon counters yet. Instead, well developed linear amplifiers allow for efficient measurement of the amplitude of an electromagnetic field. Here, we demonstrate how the properties of a microwave single photon source can be characterized using correlation measurements of the emitted radiation with such detectors. We also demonstrate the cooling of a thermal field stored in a cavity, an effect which we detect using a cross-correlation measurement of the radiation emitted at the two ends of the cavity.Comment: 5 pages, 4 figure

Quantification and characterization of granulocyte macrophage colony-stimulating factor activated human peripheral blood mononuclear cells by fluorine-19 cellular MRI in an immunocompromised mouse model

PURPOSE: The purpose of this study was to test fluorine-19 (19F) cellular magnetic resonance (MRI) as a non-invasive imaging modality to track therapeutic cell migration as a surrogate marker of immunotherapeutic effectiveness. MATERIALS AND METHODS: Human peripheral blood mononuclear cell- (PBMC)-derived antigen presenting cell (APC) were labeled with a 19F-perfluorocarbon (PFC) and/or activated with granulocyte macrophage colony-stimulating factor (GM-CSF). Viability, phenotype and cell lineage characterization preceded 19F cellular MRI of PFC RESULTS: A high proportion of PBMC incorporated PFC without affecting viability, phenotype or cell lineage composition. PFC CONCLUSION: 19F cellular MRI is a non-invasive imaging technique capable of detecting and quantifying in vivo cell migration in conjunction with an established APC-based immunotherapy model. 19F cellular MRI can function as a surrogate marker for assessing and improving upon the therapeutic benefit that this immunotherapy provides

Tripartite interactions between two phase qubits and a resonant cavity

The creation and manipulation of multipartite entangled states is important for advancements in quantum computation and communication, and for testing our fundamental understanding of quantum mechanics and precision measurements. Multipartite entanglement has been achieved by use of various forms of quantum bits (qubits), such as trapped ions, photons, and atoms passing through microwave cavities. Quantum systems based on superconducting circuits have been used to control pair-wise interactions of qubits, either directly, through a quantum bus, or via controllable coupling. Here, we describe the first demonstration of coherent interactions of three directly coupled superconducting quantum systems, two phase qubits and a resonant cavity. We introduce a simple Bloch-sphere-like representation to help one visualize the unitary evolution of this tripartite system as it shares a single microwave photon. With careful control and timing of the initial conditions, this leads to a protocol for creating a rich variety of entangled states. Experimentally, we provide evidence for the deterministic evolution from a simple product state, through a tripartite W-state, into a bipartite Bell-state. These experiments are another step towards deterministically generating multipartite entanglement in superconducting systems with more than two qubits

Surprises in the doping dependence of the Fermi surface in Bi(Pb)-2212

A detailed and systematic ARPES investigation of the doping-dependence of the normal state Fermi surface (FS) of modulation-free (Pb,Bi)-2212 is presented. The FS does not change in topology away from hole-like at any stage. The data reveal, in addition, a number of surprises. Firstly the FS area does not follow the usual curve describing Tc vs x for the hole doped cuprates, but is down-shifted in doping by ca. 0.05 holes per Cu site, indicating either the break-down of Luttinger's theorem or the consequences of a significant bi-layer splitting of the FS. Secondly, the strong k-dependence of the FS width is shown to be doping independent. Finally, the relative strength of the shadow FS has a doping dependence mirroring that of Tc.Comment: 5 pages, 4 figures (revtex

Computing prime factors with a Josephson phase qubit quantum processor

A quantum processor (QuP) can be used to exploit quantum mechanics to find the prime factors of composite numbers[1]. Compiled versions of Shor's algorithm have been demonstrated on ensemble quantum systems[2] and photonic systems[3-5], however this has yet to be shown using solid state quantum bits (qubits). Two advantages of superconducting qubit architectures are the use of conventional microfabrication techniques, which allow straightforward scaling to large numbers of qubits, and a toolkit of circuit elements that can be used to engineer a variety of qubit types and interactions[6, 7]. Using a number of recent qubit control and hardware advances [7-13], here we demonstrate a nine-quantum-element solid-state QuP and show three experiments to highlight its capabilities. We begin by characterizing the device with spectroscopy. Next, we produces coherent interactions between five qubits and verify bi- and tripartite entanglement via quantum state tomography (QST) [8, 12, 14, 15]. In the final experiment, we run a three-qubit compiled version of Shor's algorithm to factor the number 15, and successfully find the prime factors 48% of the time. Improvements in the superconducting qubit coherence times and more complex circuits should provide the resources necessary to factor larger composite numbers and run more intricate quantum algorithms.Comment: 5 pages, 3 figure