Processing of laser Doppler flowmetry signals from healthy subjects and patients with varicose veins: information categorization approach based on intrinsic mode functions and entropy computation

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A natural structural variant of the mouse TCR beta-chain displays intrinsic receptor function and antigen specificity.

The Cbeta0 alternate cassette exon is located between the Jbeta1 and Cbeta1 genes in the mouse TCR beta-locus. In T cells with a VDJbeta1 rearrangement, the Cbeta0 exon may be included in TCRbeta transcripts (herein called TCRbeta-Cbeta0 transcripts), potentially inserting an additional 24 aa between the V and C domains of the TCR beta-chain. These TCRbeta splice isoforms may be differentially regulated after Ag activation, because we detected TCRbeta-Cbeta0 transcripts in a high proportion (>60%) of immature and mature T cells having VDJbeta1 rearrangements but found a substantially reduced frequency (<35%) of TCRbeta-Cbeta0 expression among CD8 T cells selected by Ag in vivo. To study the potential activity of the TCRbeta-Cbeta0 splice variant, we cloned full-length TCR cDNAs by single-cell RT-PCR into retroviral expression vectors. We found that the TCRbeta-Cbeta0 splice isoform can function during an early stage of T cell development normally dependent on TCR beta-chain expression. We also demonstrate that T hybridoma-derived cells expressing a TCRbeta-Cbeta0 isoform together with the clonally associated TCR alpha-chain recognize the same cognate peptide-MHC ligand as the corresponding normal alphabetaTCR. This maintenance of receptor function and specificity upon insertion of the Cbeta0 peptide cassette signifies a remarkable adaptability for the TCR beta-chain, and our findings open the possibility that this splice isoform may function in vivo.

On the HHT, its problems, and some solutions

Mechanical Systems and Signal Processing, Vol.22, Number 6

Empirical mode decomposition: a novel technique for the study of tremor time series

Tremor is a clinical feature characterized by oscillations of a part of the body. The detection and study of tremor is an important step in investigations seeking to explain underlying control strategies of the central nervous system under natural (or physiological) and pathological conditions. It is well established that tremorous activity is composed of deterministic and stochastic components. For this reason, the use of digital signal processing techniques (DSP) which take into account the nonlinearity and nonstationarity of such signals may bring new information into the signal analysis which is often obscured by traditional linear techniques (e.g. Fourier analysis). In this context, this paper introduces the application of the empirical mode decomposition (EMD) and Hilbert spectrum (HS), which are relatively new DSP techniques for the analysis of nonlinear and nonstationary time-series, for the study of tremor. Our results, obtained from the analysis of experimental signals collected from 31 patients with different neurological conditions, showed that the EMD could automatically decompose acquired signals into basic components, called intrinsic mode functions (IMFs), representing tremorous and voluntary activity. The identification of a physical meaning for IMFs in the context of tremor analysis suggests an alternative and new way of detecting tremorous activity. These results may be relevant for those applications requiring automatic detection of tremor. Furthermore, the energy of IMFs was visualized as a function of time and frequency by means of the HS. This analysis showed that the variation of energy of tremorous and voluntary activity could be distinguished and characterized on the HS. Such results may be relevant for those applications aiming to identify neurological disorders. In general, both the HS and EMD demonstrated to be very useful to perform objective analysis of any kind of tremor and can therefore be potentially used to perform functional assessment.

Use of intrinsic modes in biology: Examples of indicial response of pulmonary blood pressure to ± step hypoxia

Recently, a new method to analyze biological nonstationary stochastic variables has been presented. The method is especially suitable to analyze the variation of one biological variable with respect to changes of another variable. Here, it is illustrated by the change of the pulmonary blood pressure in response to a step change of oxygen concentration in the gas that an animal breathes. The pressure signal is resolved into the sum of a set of oscillatory intrinsic mode functions, which have zero “local mean,” and a final nonoscillatory mode. With this device, we obtain a set of “mean trends,” each of which represents a “mean” in a definitive sense, and together they represent the mean trend systematically with different degrees of oscillatory content. Correspondingly, the oscillatory content of the signal about any mean trend can be represented by a set of partial sums of intrinsic mode functions. When the concept of “indicial response function” is used to describe the change of one variable in response to a step change of another variable, we now have a set of indicial response functions of the mean trends and another set of indicial response functions to describe the energy or intensity of oscillations about each mean trend. Each of these can be represented by an analytic function whose coefficients can be determined by a least-squares curve-fitting procedure. In this way, experimental results are stated sharply by analytic functions.

Independent component analysis of climate data: A new look at EOF rotation

The complexity inherent in climate data makes it necessary to introduce more than one statistical tool to the researcher to gain insight into the climate system. Empirical orthogonal function (EOF) analysis is one of the most widely used methods to analyze weather/climate modes of variability and to reduce the dimensionality of the system. Simple structure rotation of EOFs can enhance interpretability of the obtained patterns but cannot provide anything more than temporal uncorrelatedness. In this paper, an alternative rotation method based on independent component analysis (ICA) is considered. The ICA is viewed here as a method of EOF rotation. Starting from an initial EOF solution rather than rotating the loadings toward simplicity, ICA seeks a rotation matrix that maximizes the independence between the components in the time domain. If the underlying climate signals have an independent forcing, one can expect to find loadings with interpretable patterns whose time coefficients have properties that go beyond simple noncorrelation observed in EOFs. The methodology is presented and an application to monthly means sea level pressure (SLP) field is discussed. Among the rotated (to independence) EOFs, the North Atlantic Oscillation (NAO) pattern, an Arctic Oscillation–like pattern, and a Scandinavian-like pattern have been identified. There is the suggestion that the NAO is an intrinsic mode of variability independent of the Pacific.

EMG signal filtering based on Empirical Mode Decomposition

This paper introduces a procedure for filtering electromyographic (EMG) signals. Its key element is the Empirical Mode Decomposition, a novel digital signal processing technique that can decompose my time-series into a set of functions designated as intrinsic mode functions. The procedure for EMG signal filtering is compared to a related approach based on the wavelet transform. Results obtained from the analysis of synthetic and experimental EMG signals show that Our method can be Successfully and easily applied in practice to attenuation of background activity in EMG signals. (c) 2006 Elsevier Ltd. All rights reserved.

Direct effects of colchicine on myocardial function - Studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm(2) [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, K-cs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus; SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Direct effects of colchicine on myocardial function: studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm2 [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, Kcs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Atenuação de ruídos coerentes utilizando decomposição em modos empíricos

The seismic processing technique has the main objective to provide adequate picture of geological structures from subsurface of sedimentary basins. Among the key steps of this process is the enhancement of seismic reflections by filtering unwanted signals, called seismic noise, the improvement of signals of interest and the application of imaging procedures. The seismic noise may appear random or coherent. This dissertation will present a technique to attenuate coherent noise, such as ground roll and multiple reflections, based on Empirical Mode Decomposition method. This method will be applied to decompose the seismic trace into Intrinsic Mode Functions. These functions have the properties of being symmetric, with local mean equals zero and the same number of zero-crossing and extremes. The developed technique was tested on synthetic and real data, and the results were considered encouraging

Estimates for the Poisson kernel and Hardy spaces on compact manifolds

We study Hardy spaces on the boundary of a smooth open subset or R-n and prove that they can be defined either through the intrinsic maximal function or through Poisson integrals, yielding identical spaces. This extends to any smooth open subset of R-n results already known for the unit ball. As an application, a characterization of the weak boundary values of functions that belong to holomorphic Hardy spaces is given, which implies an F. and M. Riesz type theorem. (C) 2004 Elsevier B.V. All rights reserved.

Immunevasion des murinen Cytomegalovirus: Regulatoren der MHC-Klasse-I vermittelten Antigenpräsentation

Zu den Immunevasionsmechanismen des murinen Cytomegalovirus, die sich im Laufe der Koevolution von Virus und Wirt entwickelt haben, gehört die Interferenz von drei viralen Regulatoren mit der Antigenpräsentation über MHC-Klasse-I-Moleküle, wodurch die Aktivierung von zytotoxischen CD8 T-Zellen beeinflusst wird: Während m152/gp40 peptidbeladene MHC-Klasse-I-Komplexe im cis-Golgi-Kompartiment akkumuliert, führt m06/gp48 diese Komplexe der lysosomalen Degradation zu. Im Gegensatz dazu vermittelt m04/gp34 deren Transport an die Zelloberfläche, wurde in der Literatur bisher aber trotzdem als Inhibitor der CD8 T-Zellaktivierung beschrieben. Ziel der vorliegenden Arbeit war es, den Einfluss dieser viralen Proteine auf die Peptidpräsentation bzw. die T-Zellaktivierung zu untersuchen. Dazu wurde ein Set von Viren verwendet, das neben mCMV-WT aus mCMV-Deletionsmutanten besteht, die jedes der regulatorischen Proteine einzeln bzw. in allen möglichen Kombinationen exprimieren, einschließlich einer Mutante, die keines der Proteine besitzt. Entgegen der bisher gültigen Annahme konnte in der vorliegenden Arbeit gezeigt werden, dass m04/gp34 die Antigenpräsentation nicht inhibiert. Wird es allein exprimiert, bleibt die T-Zellaktivierung unbeeinflusst. Wird es zusammen mit m152/gp40 exprimiert, stellt es die T-Zellaktivierung wieder her, indem es den herunter regulierenden Effekt von m152/gp40 antagonisiert. Dieser positiv regulierende Effekt von m04/gp34 wird wiederum durch m06/gp48 aufgehoben. Es konnte ebenfalls gezeigt werden, wie die verschiedenen Effekte dieser Virusproteine in vivo das Überleben im infizierten Wirt steuern. So wird im adoptiven Transfermodell die Infektion mit der Deletionsmutante, die m152/gp40 alleine exprimiert, schlechter kontrolliert als die Infektion mit der m152/gp40 und m04/gp34 exprimierenden Mutante. Dieser die CD8 T-Zellkontrolle verbessernde Effekt von m04/gp34 wird durch m06/gp48 wieder aufgehoben. Dass ein viraler Erreger nicht nur negative Regulatoren der Antigenpräsentation exprimiert, sondern auch einen positiven Regulator, der den Effekt eines negativen Regulators wieder aufhebt, ist in der Literatur beispiellos. Durch differentielle Expression dieser Regulatoren eröffnet sich damit dem Virus die Möglichkeit, die Antigenpräsentation gezielt zu modulieren.

Nonequilibrium mechanism of transcription termination from observations of single RNA polymerase molecules

Cessation of transcription at specific terminator DNA sequences is used by viruses, bacteria, and eukaryotes to regulate the expression of downstream genes, but the mechanisms of transcription termination are poorly characterized. To elucidate the kinetic mechanism of termination at the intrinsic terminators of enteric bacteria, we observed, by using single-molecule light microscopy techniques, the behavior of surface-immobilized Escherichia coli RNA polymerase (RNAP) molecules in vitro. An RNAP molecule remains at a canonical intrinsic terminator for ≈64 s before releasing DNA, implying the formation of an elongation-incompetent (paused) intermediate by transcription complexes that terminate but not by those that read through the terminator. Analysis of pause lifetimes establishes a complete minimal mechanism of termination in which paused intermediate formation is both necessary and sufficient to induce release of RNAP at the terminator. The data suggest that intrinsic terminators function by a nonequilibrium process in which terminator effectiveness is determined by the relative rates of nucleotide addition and paused state entry by the transcription complex.

Roles of SecG in ATP- and SecA-dependent protein translocation

SecA, the translocation ATPase in Escherichia coli, undergoes cycles of conformational changes (insertion/deinsertion) in response to ATP and a preprotein. The membrane-embedded portion of protein translocase, SecYEG, has crucial roles in the SecA-driven preprotein translocation reaction. We previously identified a secY mutation (secY205) that did not allow an ATP- and preprotein-dependent (productive) insertion of SecA as well as secA mutations that suppressed the secY205 translocation defect. One of the suppressor mutations, secA36, also suppressed the cold-sensitive phenotype of the secG deletion mutant. In vitro experiments at 20°C showed that inverted membrane vesicles lacking SecG were almost inactive in combination with the wild-type SecA protein in translocation of proOmpA as well as in the accompanying ATP hydrolysis. In contrast, the SecA36 mutant protein was found to be able to execute the translocation activity fully at this temperature, even in the absence of SecG. A SecG requirement and its alleviation by the SecA36 alteration also were shown for the SecA insertion reaction. The finding that the SecA36 protein no longer requires assistance from SecG in its insertion and in its catalysis of protein translocation agrees with the idea that SecG normally assists in the functioning of SecA. In agreement with this notion, when the intrinsic SecA function was compromised by a lowered ATP concentration, SecG became essential even at 37°C and even for the SecA36 protein. We propose that in the normal translocase, SecG cooperates with SecA to facilitate efficient movement of preprotein in each catalytic cycle of SecA.

Sparse time-frequency data analysis : a multi-scale approach

In this work, we further extend the recently developed adaptive data analysis method, the Sparse Time-Frequency Representation (STFR) method. This method is based on the assumption that many physical signals inherently contain AM-FM representations. We propose a sparse optimization method to extract the AM-FM representations of such signals. We prove the convergence of the method for periodic signals under certain assumptions and provide practical algorithms specifically for the non-periodic STFR, which extends the method to tackle problems that former STFR methods could not handle, including stability to noise and non-periodic data analysis. This is a significant improvement since many adaptive and non-adaptive signal processing methods are not fully capable of handling non-periodic signals. Moreover, we propose a new STFR algorithm to study intrawave signals with strong frequency modulation and analyze the convergence of this new algorithm for periodic signals. Such signals have previously remained a bottleneck for all signal processing methods. Furthermore, we propose a modified version of STFR that facilitates the extraction of intrawaves that have overlaping frequency content. We show that the STFR methods can be applied to the realm of dynamical systems and cardiovascular signals. In particular, we present a simplified and modified version of the STFR algorithm that is potentially useful for the diagnosis of some cardiovascular diseases. We further explain some preliminary work on the nature of Intrinsic Mode Functions (IMFs) and how they can have different representations in different phase coordinates. This analysis shows that the uncertainty principle is fundamental to all oscillating signals.