Музыкальный информационный поиск с запросом по напеву

In this paper the problems of Query by Humming in Music Information Retrieval systems are analyzed. A statistical approach to the problem of retrieval is presented. The processes of segmentation as well as of the extraction of pitch and duration data are described. From the extracted data the characteristic vector is formed for each segment. The method of using the vectors in melodic search if proposed

CXCR7 influences leukocyte entry into the CNS parenchyma by controlling abluminal CXCL12 abundance during autoimmunity

During CNS autoimmunity, brain endothelial cell CXCR7 internalizes CXCL12 from the perivascular space, thereby permitting leukocyte migration into the CNS parenchyma

Knocking at the brain’s door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures

Since the first applications of two-photon microscopy in immunology 10 years ago, the number of studies using this advanced technology has increased dramatically. The two-photon microscope allows long-term visualization of cell motility in the living tissue with minimal phototoxicity. Using this technique, we examined brain autoantigen-specific T cell behavior in experimental autoimmune encephalitomyelitis, the animal model of human multiple sclerosis. Even before disease symptoms appear, the autoreactive T cells arrive at their target organ. There they crawl along the intraluminal surface of central nervous system (CNS) blood vessels before they extravasate. In the perivascular environment, the T cells meet phagocytes that present autoantigens. This contact activates the T cells to penetrate deep into the CNS parenchyma, where the infiltrated T cells again can find antigen, be further activated, and produce cytokines, resulting in massive immune cell recruitment and clinical disease

Modelling the regulation of telomere length: the effects of telomerase and G-quadruplex stabilising drugs

Telomeres are guanine-rich sequences at the end of chromosomes which shorten during each replication event and trigger cell cycle arrest and/or controlled death (apoptosis) when reaching a threshold length. The enzyme telomerase replenishes the ends of telomeres and thus prolongs the life span of cells, but also causes cellular immortalisation in human cancer. G-quadruplex (G4) stabilising drugs are a potential anticancer treatment which work by changing the molecular structure of telomeres to inhibit the activity of telomerase. We investigate the dynamics of telomere length in different conformational states, namely t-loops, G-quadruplex structures and those being elongated by telomerase. By formulating deterministic differential equation models we study the effects of various levels of both telomerase and concentrations of a G4-stabilising drug on the distribution of telomere lengths, and analyse how these effects evolve over large numbers of cell generations. As well as calculating numerical solutions, we use quasicontinuum methods to approximate the behaviour of the system over time, and predict the shape of the telomere length distribution. We find those telomerase and G4-concentrations where telomere length maintenance is successfully regulated. Excessively high levels of telomerase lead to continuous telomere lengthening, whereas large concentrations of the drug lead to progressive telomere erosion. Furthermore, our models predict a positively skewed distribution of telomere lengths, that is, telomeres accumulate over lengths shorter than the mean telomere length at equilibrium. Our model results for telomere length distributions of telomerase-positive cells in drug-free assays are in good agreement with the limited amount of experimental data available

Führung eines Prozesses zur optimalen Annäherung an den vorgegebenen Sollbereich und Anwendung auf ein Grundwasserleitersystem

Behandelt wird eine Klasse von Steuerungsaufgaben, bei denen für die Regelgröße ein Sollbereich anstelle eines Sollwertes vorgegeben sein kann und bei denen dieser Sollbereich aufgrund von Stellgrößenbeschränkungen nicht realisierbar ist. Die damit unlösbare Steuerungsaufgabe wird optimal in eine lösbare Aufgabe überführt, wobei ein Abstandsmaß eingeführt und minimiert wird, das die unvermeidliche Differenz zwischen dem geforderten Sollbereich und der realisierbaren Regelgröße misst. Bestehende Freiheitsgrade werden zur Kostenminimierung genutzt. Der entwickelte Algorithmus wird zur Steuerung eines Grundwasserleiters angewendet

Early human impact on lake cyanobacteria revealed by a Holocene record of sedimentary ancient DNA

Analysis of sedimentary DNA through time in a German lake shows a spike in cyanobacteria abundance coinciding with human activity in the Bronze Age

Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy.

In experimental autoimmune encephalitis (EAE), autoimmune T cells are activated in the periphery before they home to the CNS. On their way, the T cells pass through a series of different cellular milieus where they receive signals that instruct them to invade their target tissues. These signals involve interaction with the surrounding stroma cells, in the presence or absence of autoantigens. To portray the serial signaling events, we studied a T-cell-mediated model of EAE combining in vivo two-photon microscopy with two different activation reporters, the FRET-based calcium biosensor Twitch1 and fluorescent NFAT. In vitro activated T cells first settle in secondary (2°) lymphatic tissues (e.g., the spleen) where, in the absence of autoantigen, they establish transient contacts with stroma cells as indicated by sporadic short-lived calcium spikes. The T cells then exit the spleen for the CNS where they first roll and crawl along the luminal surface of leptomeningeal vessels without showing calcium activity. Having crossed the blood-brain barrier, the T cells scan the leptomeningeal space for autoantigen-presenting cells (APCs). Sustained contacts result in long-lasting calcium activity and NFAT translocation, a measure of full T-cell activation. This process is sensitive to anti-MHC class II antibodies. Importantly, the capacity to activate T cells is not a general property of all leptomeningeal phagocytes, but varies between individual APCs. Our results identify distinct checkpoints of T-cell activation, controlling the capacity of myelin-specific T cells to invade and attack the CNS. These processes may be valuable therapeutic targets