15 research outputs found

    Applications of Wavelet Transforms to the Suppression of Coherent Noise from Seismic Data in the Pre-Stack Domain

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    The wavelet transform, a relatively new mathematical technique, allows the analysis of non-stationary signals by using basis functions which are compact in time and frequency. The variables in the wavelet domain, scale (a frequency range), and translation (a temporal increment) can be associated with time-frequency, and so in the wavelet transform we have the potential to filter seismic signals in a pseudo time-frequency sense. The one dimensional discrete multiresolution form of the wavelet transform can be effectively used to suppress low frequency coherent noise on seismic shot records. This process, achieved by the muting or weighting of coefficients in the wavelet transform domain, is demonstrated by suppressing low velocity, low frequency ground roll from land- based seismic data, the benefits of which are visible at both the shot and stack stages of the seismic processing stream. The extension of this technique to the suppression of higher frequency coherent noise is limited by the octave band splitting of frequency space by the transform. The wavelet packet transform, an extension of the wavelet transform, allows a more adaptable tiling of the time frequency domain which in turn allows the suppression of noise containing high frequencies whilst minimising signal distortion. This technique is demonstrated to be effective in suppressing airblast from land based common receiver gathers, whilst minimising the distortion of reflected signals. These filtering techniques can be extended to two dimensions, filtering data in the two dimensional wavelet and wavelet packet domains. This technique involves muting the transform coefficients in the wavelet/wavelet packet transform space which has four variables: temporal translation, offset translation, frequency scale and wavenumber scale. As for the one-dimensional case the two dimensional wavelet transform suffers from poor resolution due to the octave splitting of f-k space, but when used in combination with a velocity based shift such as normal moveout, can be used to filter data with minimal distortion to the residual signal. Extending the process to using the two-dimensional wavelet packet transform eliminates the shift requirement and leads to more effective filtering in the four variable transform space. The wavelet packet filtering technique is effective in suppressing low velocity noise from land based seismic records showing visible improvement in both the common shot records and resultant stack. The non-stationary properties of the wavelet transform allows the filtering across geophone arrays (that is, the common shot record) by the application of the transform in the offset domain. Filtering of the wavelet coefficients, in combination with a linear or hyperbolic shift applied before and removed after filtering, allows discrimination against linear noise on common shot records associated with first breaks and hyperbolic events on common midpoint records such as multiples. The use of a simple muting technique in the wavelet domain effectively suppresses these forms of coherent noise. Where the velocity contrast between signal and noise is high, noise suppression is possible whilst preserving reflector amplitudes. Where the velocity contrast is smaller, weighting of the wavelet coefficients (based on transforms of the input signal after translation) allows noise suppression whilst preserving the amplitude versus offset relationships of the primary signal. This is shown to be effective on synthetic, marine and land based data, with improvements observed on common shot records and resultant stacks. The results of all these wavelet transform based filtering techniques are sensitive to the choice of wavelet transform kernel wavelet. The suitability of a kernel wavelet for filtering can be related to the frequency spectra of the kernel wavelet. A fast rate of frequency amplitude fall-off at the edge of a given scale of basis wavelet minimises frequency overlap between neighbouring kernel wavelet scales and so minimises contamination by noise associated with aliasing in the filtered signal, a process that is inherent in the transform process. A flat amplitude response across the frequency range of a given scale also leads to improved filtering results

    Age and diet shape the genetic architecture of body weight in diversity outbred mice.

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    Understanding how genetic variation shapes a complex trait relies on accurately quantifying both the additive genetic and genotype-environment interaction effects in an age-dependent manner. We used a linear mixed model to quantify diet-dependent genetic contributions to body weight measured through adulthood in diversity outbred female mice under five diets. We observed that heritability of body weight declined with age under all diets, except the 40% calorie restriction diet. We identified 14 loci with age-dependent associations and 19 loci with age- and diet-dependent associations, with many diet-dependent loci previously linked to neurological function and behavior in mice or humans. We found their allelic effects to be dynamic with respect to genomic background, age, and diet, identifying several loci where distinct alleles affect body weight at different ages. These results enable us to more fully understand and predict the effectiveness of dietary intervention on overall health throughout age in distinct genetic backgrounds

    Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart.

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    Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12, and 18 mo to characterize molecular changes that occur in the aging heart. Transcripts and proteins reveal activation of pathways related to exocytosis and cellular transport with age, whereas processes involved in protein folding decrease with age. Additional changes are apparent only in the protein data including reduced fatty acid oxidation and increased autophagy. For proteins that form complexes, we see a decline in correlation between their component subunits with age, suggesting age-related loss of stoichiometry. The most affected complexes are themselves involved in protein homeostasis, which potentially contributes to a cycle of progressive breakdown in protein quality control with age. Our findings highlight the important role of post-transcriptional regulation in aging. In addition, we identify genetic loci that modulate age-related changes in protein homeostasis, suggesting that genetic variation can alter the molecular aging process

    Healthcare systems data in the context of clinical trials - A comparison of cardiovascular data from a clinical trial dataset with routinely collected data

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    BACKGROUND: Routinely-collected healthcare systems data (HSD) are proposed to improve the efficiency of clinical trials. A comparison was undertaken between cardiovascular (CVS) data from a clinical trial database with two HSD resources. METHODS: Protocol-defined and clinically reviewed CVS events (heart failure (HF), acute coronary syndrome (ACS), thromboembolic stroke, venous and arterial thromboembolism) were identified within the trial data. Data (using pre-specified codes) was obtained from NHS Hospital Episode Statistics (HES) and National Institute for Cardiovascular Outcomes Research (NICOR) HF and myocardial ischaemia audits for trial participants recruited in England between 2010 and 2018 who had provided consent. The primary comparison was trial data versus HES inpatient (APC) main diagnosis (Box-1). Correlations are presented with descriptive statistics and Venn diagrams. Reasons for non-correlation were explored. RESULTS: From 1200 eligible participants, 71 protocol-defined clinically reviewed CVS events were recorded in the trial database. 45 resulted in a hospital admission and therefore could have been recorded by either HES APC/ NICOR. Of these, 27/45 (60%) were recorded by HES inpatient (Box-1) with an additional 30 potential events also identified. HF and ACS were potentially recorded in all 3 datasets; trial data recorded 18, HES APC 29 and NICOR 24 events respectively. 12/18 (67%) of the HF/ACS events in the trial dataset were recorded by NICOR. CONCLUSION: Concordance between datasets was lower than anticipated and the HSD used could not straightforwardly replace current trial practices, nor directly identify protocol-defined CVS events. Further work is required to improve the quality of HSD and consider event definitions when designing clinical trials incorporating HSD

    WJMSC-Derived Small Extracellular Vesicle Enhance T Cell Suppression Through PD-L1

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    © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles Both mesenchymal stem cells (MSCs) and their corresponding small extracellular vesicles (sEVs, commonly referred to as exosomes) share similar immunomodulatory properties that are potentially beneficial for the treatment of acute graft versus host disease (aGvHD). We report that clinical grade Wharton\u27s Jelly-derived MSCs (WJMSCs) secrete sEVs enriched in programmed death-ligand 1 (PD-L1), an essential ligand for an inhibitory immune checkpoint. A rapid increase in circulating sEV-associated PD-L1 was observed in patients with aGvHD and was directly associated with the infusion time of clinical grade WJMSCs. In addition, in vitro inhibitory antibody mediated blocking of sEV-associated PD-L1 restored T cell activation (TCA), suggesting a functional inhibitory role of sEVs-PD-L1. PD-L1-deficient sEVs isolated from WJMSCs following CRISPR-Cas9 gene editing fail to inhibit TCA. Furthermore, we found that PD-L1 is essential for WJMSC-derived sEVs to modulate T cell receptors (TCRs). Our study reveals an important mechanism by which therapeutic WJMSCs modulate TCR-mediated TCA through sEVs or sEV-carried immune checkpoints. In addition, our clinical data suggest that sEV-associated PD-L1 may be not only useful in predicting the outcomes from WJMSC clinical administration, but also in developing cell-independent therapy for aGvHD patients

    Healthcare systems data in the context of clinical trials ? A comparison of cardiovascular data from a clinical trial dataset with routinely collected data

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    Background Routinely-collected healthcare systems data (HSD) are proposed to improve the efficiency of clinical trials. A comparison was undertaken between cardiovascular (CVS) data from a clinical trial database with two HSD resources. Methods Protocol-defined and clinically reviewed CVS events (heart failure (HF), acute coronary syndrome (ACS), thromboembolic stroke, venous and arterial thromboembolism) were identified within the trial data. Data (using pre-specified codes) was obtained from NHS Hospital Episode Statistics (HES) and National Institute for Cardiovascular Outcomes Research (NICOR) HF and myocardial ischaemia audits for trial participants recruited in England between 2010 and 2018 who had provided consent. The primary comparison was trial data versus HES inpatient (APC) main diagnosis (Box-1). Correlations are presented with descriptive statistics and Venn diagrams. Reasons for non-correlation were explored. Results From 1200 eligible participants, 71 protocol-defined clinically reviewed CVS events were recorded in the trial database. 45 resulted in a hospital admission and therefore could have been recorded by either HES APC/ NICOR. Of these, 27/45 (60%) were recorded by HES inpatient (Box-1) with an additional 30 potential events also identified. HF and ACS were potentially recorded in all 3 datasets; trial data recorded 18, HES APC 29 and NICOR 24 events respectively. 12/18 (67%) of the HF/ACS events in the trial dataset were recorded by NICOR. Conclusion Concordance between datasets was lower than anticipated and the HSD used could not straightforwardly replace current trial practices, nor directly identify protocol-defined CVS events. Further work is required to improve the quality of HSD and consider event definitions when designing clinical trials incorporating HSD

    Life-long dietary restrictions have negligible or damaging effects on late-life cognitive performance: A key role for genetics in outcomes.

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    Several studies report that caloric restriction (CR) or intermittent fasting (IF) can improve cognition, while others report limited or no cognitive benefits. Here, we compare the effects of 20% CR, 40% CR, 1-day IF, and 2-day IF feeding paradigms to ad libitum controls on Y-maze working memory (WM) and contextual fear memory (CFM) in a large population of Diversity Outbred mice that model the genetic diversity of humans. While CR and IF interventions improve lifespan, we observed no enhancement of working memory or CFM in mice on these feeding paradigms, and report 40% CR to be damaging to recall of CFM. Using Quantitative Trait Loci mapping, we identified the gene Slc16a7 to be associated with CFM outcomes in aged mice on lifespan promoting feeding paradigms. Limited utility of dieting and fasting on memory in mice that recapitulate genetic diversity in the human population highlights the need for anti-aging therapeutics that promote cognitive function, with the neuronal monocarboxylate transporter MCT2 encoded by Slc16a7 highlighted as novel target

    Intermittent fasting and caloric restriction interact with genetics to shape physiological health in mice.

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    Dietary interventions can dramatically affect physiological health and organismal lifespan. The degree to which organismal health is improved depends upon genotype and the severity of dietary intervention, but neither the effects of these factors, nor their interaction, have been quantified in an outbred population. Moreover, it is not well understood what physiological changes occur shortly after dietary change and how these may affect the health of an adult population. In this article, we investigated the effect of 6-month exposure of either caloric restriction (CR) or intermittent fasting (IF) on a broad range of physiological traits in 960 1-year old Diversity Outbred mice. We found CR and IF affected distinct aspects of physiology and neither the magnitude nor the direction (beneficial or detrimental) of effects were concordant with the severity of the intervention. In addition to the effects of diet, genetic variation significantly affected 31 of 36 traits (heritabilities ranged from 0.04 to 0.65). We observed significant covariation between many traits that was due to both diet and genetics and quantified these effects with phenotypic and genetic correlations. We genetically mapped 16 diet-independent and 2 diet-dependent significant quantitative trait loci, both of which were associated with cardiac physiology. Collectively, these results demonstrate the degree to which diet and genetics interact to shape the physiological health of adult mice following 6 months of dietary intervention

    Emirates Mars Mission Characterization of Mars Atmosphere Dynamics and Processes

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    International audienceThe Emirates Mars Mission (EMM) - Hope Probe - was developed to understand Mars atmospheric circulation, dynamics, and processes through characterization of the Mars atmosphere layers and its interconnections enabled by a unique high-altitude (19,970 km periapse and 42,650 km apoapse) low inclination orbit that will offer an unprecedented local and seasonal time coverage over most of the planet. EMM has three scientific objectives to (A) characterize the state of the Martian lower atmosphere on global scales and its geographic, diurnal and seasonal variability, (B) correlate rates of thermal and photochemical atmospheric escape with conditions in the collisional Martian atmosphere, and (C) characterize the spatial structure and variability of key constituents in the Martian exosphere. The EMM data products include a variety of spectral and imaging data from three scientific instruments measuring Mars at visible, ultraviolet, and infrared wavelengths and contemporaneously and globally sampled on both diurnal and seasonal timescale. Here, we describe our strategies for addressing each objective with these data in addition to the complementary science data, tools, and physical models that will facilitate our understanding. The results will also fill a unique role by providing diagnostics of the physical processes driving atmospheric structure and dynamics, the connections between the lower and upper atmospheres, and the influences of these on atmospheric escape
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