369 research outputs found
Study of Causal Component Placement in an Active Sound Cancellation System
In a feedforward Active Sound Cancellation (ASC) system, the acoustic delay between a primary source and an error microphone must be greater than the delay between the measurement of that source by the reference microphone and the arrival of the secondary source\u27s wave at the error microphone. Such a configuration is called a causal configuration. For periodic disturbances, cancellation can still be achieved in non-causal configuration. Since the waveform is periodic, each cycle of the waveform is identical, and the cycle being canceled is not the measured part of the waveform, but a subsequent cycle in the waveform. Non-periodic sources cannot be cancelled by a non-causal ASC system, and convergence of the Least Mean Squares algorithm is not as effective in a non-causal configuration as in a causal configuration. The ASC system was implemented to create a local zone of silence inside a reverberant enclosure. The primary source was a 125 Hz sinusoid generated outside of the enclosure. System delays were calculated and a causal component configuration was chosen. System performance under both causal and non-causal component configurations was examined. The system was able to create a maximum attenuation of \u3e18 dB in both the causal and non-causal configurations. However, it was discovered that in the non-causal configuration, the computation of the optimal inverse signal was much slower than in the causal configuration
Differential transcriptional modulation of duplicated fatty acid-binding protein genes by dietary fatty acids in zebrafish (Danio rerio): evidence for subfunctionalization or neofunctionalization of duplicated genes
<p>Abstract</p> <p>Background</p> <p>In the Duplication-Degeneration-Complementation (DDC) model, subfunctionalization and neofunctionalization have been proposed as important processes driving the retention of duplicated genes in the genome. These processes are thought to occur by gain or loss of regulatory elements in the promoters of duplicated genes. We tested the DDC model by determining the transcriptional induction of fatty acid-binding proteins (Fabps) genes by dietary fatty acids (FAs) in zebrafish. We chose zebrafish for this study for two reasons: extensive bioinformatics resources are available for zebrafish at zfin.org and zebrafish contains many duplicated genes owing to a whole genome duplication event that occurred early in the ray-finned fish lineage approximately 230-400 million years ago. Adult zebrafish were fed diets containing either fish oil (12% lipid, rich in highly unsaturated fatty acid), sunflower oil (12% lipid, rich in linoleic acid), linseed oil (12% lipid, rich in linolenic acid), or low fat (4% lipid, low fat diet) for 10 weeks. FA profiles and the steady-state levels of <it>fabp </it>mRNA and heterogeneous nuclear RNA in intestine, liver, muscle and brain of zebrafish were determined.</p> <p>Result</p> <p>FA profiles assayed by gas chromatography differed in the intestine, brain, muscle and liver depending on diet. The steady-state level of mRNA for three sets of duplicated genes, <it>fabp1a/fabp1b.1/fabp1b.2</it>, <it>fabp7a/fabp7b</it>, and <it>fabp11a</it>/<it>fabp11b</it>, was determined by reverse transcription, quantitative polymerase chain reaction (RT-qPCR). In brain, the steady-state level of <it>fabp7b </it>mRNAs was induced in fish fed the linoleic acid-rich diet; in intestine, the transcript level of <it>fabp1b.1 </it>and <it>fabp7b </it>were elevated in fish fed the linolenic acid-rich diet; in liver, the level of <it>fabp7a </it>mRNAs was elevated in fish fed the low fat diet; and in muscle, the level of <it>fabp7a </it>and <it>fabp11a </it>mRNAs were elevated in fish fed the linolenic acid-rich or the low fat diets. In all cases, induction of the steady-state level of <it>fabp </it>mRNAs by dietary FAs correlated with induced levels of hnRNA for a given <it>fabp </it>gene. As such, up-regulation of the steady-state level of <it>fabp </it>mRNAs by FAs occurred at the level of initiation of transcription. None of the sister duplicates of these <it>fabp </it>genes exhibited an increase in their steady-state transcript levels in a specific tissue following feeding zebrafish any of the four experimental diets.</p> <p>Conclusion</p> <p>Differential induction of only one of the sister pair of duplicated <it>fabp </it>genes by FAs provides evidence to support the DDC model for retention of duplicated genes in the zebrafish genome by either subfunctionalization or neofunctionalization.</p
Nonparametric Methods for the Exploration and Analysis of Survival Data
Traditional survival analysis methods are primarily those of Kaplan-Meier curves, the log-rank test and Cox's Proportional Hazards model. Only the first of these techniques is routinely used to provide a graphical representation of the data. The idea of a regression curve is used to describe the relationship between survival time and a continuous covariate is rarely considered. This is presumably due to the complexity of estimating a mean when there are censored observations. Median survival times are often quoted for a set of analysed data and extending this to a median curve across a continuous covariate would provide an intuitive description of the effect of this covariate on survival time. In this thesis, a combination of two nonparametric procedures using kernel estimates provides a doubly-smooth quantile estimator for the pth (0 ≤ p ≤ 1) quantile of survival time given a covariate. Similar percentile curves can be derived for both Cox's model and a smooth proportional hazards models. While these allow a more explicit form of the curve to be written down, the doubly-smooth estimator has no assumptions about the baseline hazard rate or the shape of the covariate effect and is therefore more flexible. Assessing and comparing the fits of each of these approaches can be achieved by the calculation of a form of likelihood statistic. Due to the complexity of the mathematical properties of the nonparametric method, testing procedures are carried out using resampling techniques such as bootstrapping and permutation tests. One extension of this methodology is to consider the additional effect of a binary covariate on survival time. This is analogous to an analysis of covariance in a Normal regression model and interest lies in how to characterise the behaviour of the curves from each of the two levels. As before, percentile curves can be obtained and appropriate testing procedures applied. An algorithm based on serum creatinine curves was developed to detect graft deterioration in kidney transplant patients. These diagnoses had previously only been made by the subjective, experienced opinions of physicians, whereas the algorithm provided an explicit rule for detecting these cases. Survival times were also obtained and these data were analysed using standard techniques. Percentile curves were used to provide more information where the interpretation of a co- variate effect was difficult. In the absence of censored data, a different form of nonparametric smoothing was considered to assess the development of children suffering from cerebral palsy. Percentile curves were obtained using cubic splines to describe the growth of children with this condition and to compare them with those of normal children. This not only vindicated the belief that children suffering from cerebral palsy tend to be smaller and lighter than normal children of similar age but also provided standard curves useful in monitoring the development of these children
Sustained striatal ciliary neurotrophic factor expression negatively affects behavior and gene expression in normal and R6/1 mice
Huntington's disease (HD) is a neurodegenerative disorder caused by an elongation of CAG repeats in the HD gene, which encodes a mutant copy of huntingtin with an expanded polyglutatmine repeat. Individuals who are affected by the disease suffer from motor, cognitive, and emotional impairments. Levels of certain striatal-enriched mRNAs decrease in both HD patients and transgenic HD mice prior to the development of motor symptoms and neuronal cell death. Ciliary neurotrophic factor (CNTF) has been shown to protect neurons against chemically induced toxic insults in vitro and in vivo. To test the hypothesis that CNTF might protect neurons from the negative effects of the mutant huntingtin protein in vivo, CNTF was continuously expressed following transduction of the striatum by recombinant adeno-associated viral vectors (rAAV2). Wild-type and R6/1 HD transgenic (R6/1) mice that received bilateral or unilateral intrastriatal injections of rAAV2-CNTF experienced weight loss. The CNTF-treated R6/1 HD transgenic mice experienced motor impairments at an earlier age than expected compared with age-matched control R6/1 HD transgenic animals. CNTF also caused abnormal behavior in WT mice. In addition to behavioral impairments, in situ hybridization showed that, in both WT and R6/1 mice, CNTF expression caused a significant decrease in the levels of striatal-enriched transcripts. Overall, continuous expression of striatal CNTF at the dose mediated by the expression cassette used in this study was detrimental to HD and wild-type mice. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58641/1/21636_ftp.pd
Ly6C hi Monocytes Are Metabolically Reprogrammed in the Blood during Inflammatory Stimulation and Require Intact OxPhos for Chemotaxis and Monocyte to Macrophage Differentiation
Acute inflammation is a rapid and dynamic process involving the recruitment and activation of multiple cell types in a coordinated and precise manner. Here, we investigate the origin and transcriptional reprogramming of monocytes using a model of acute inflammation, zymosan-induced peritonitis. Monocyte trafficking and adoptive transfer experiments confirmed that monocytes undergo rapid phenotypic change as they exit the blood and give rise to monocyte-derived macrophages that persist during the resolution of inflammation. Single-cell transcriptomics revealed significant heterogeneity within the surface marker-defined CD11b+Ly6G−Ly6Chi monocyte populations within the blood and at the site of inflammation. We show that two major transcriptional reprogramming events occur during the initial six hours of Ly6Chi monocyte mobilisation, one in the blood priming monocytes for migration and a second at the site of inflammation. Pathway analysis revealed an important role for oxidative phosphorylation (OxPhos) during both these reprogramming events. Experimentally, we demonstrate that OxPhos via the intact mitochondrial electron transport chain is essential for murine and human monocyte chemotaxis. Moreover, OxPhos is needed for monocyte-to-macrophage differentiation and macrophage M(IL-4) polarisation. These new findings from transcriptional profiling open up the possibility that shifting monocyte metabolic capacity towards OxPhos could facilitate enhanced macrophage M2-like polarisation to aid inflammation resolution and tissue repair
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