Dual-Domain Filtering

We propose dual-domain filtering, an image processing paradigm that couples spatial domain with frequency domain filtering. Our dual-domain defined filter removes artifacts like residual noise of other image denoising methods and compression artifacts. Moreover, iterating the filter achieves state-of-the-art image denoising results, but with a much simpler algorithm than competing approaches. The simplicity and versatility of the dual-domain filter makes it an attractive tool for image processing.

The Ras inhibitors caveolin-1 and docking protein 1 activate peroxisome proliferator-activated receptor ? through spatial relocalization at helix 7 of its ligand-binding domain

Peroxisome proliferator-activated receptor ? (PPAR?) is a transcription factor that promotes differentiation and cell survival in the stomach. PPAR? upregulates and interacts with caveolin-1 (Cav1), a scaffold protein of Ras/mitogen-activated protein kinases (MAPKs). The cytoplasmic-to-nuclear localization of PPAR? is altered in gastric cancer (GC) patients, suggesting a so-far-unknown role for Cav1 in spatial regulation of PPAR? signaling. We show here that loss of Cav1 accelerated proliferation of normal stomach and GC cells in vitro and in vivo. Downregulation of Cav1 increased Ras/MAPK-dependent phosphorylation of serine 84 in PPAR? and enhanced nuclear translocation and ligand-independent transcription of PPAR? target genes. In contrast, Cav1 overexpression sequestered PPAR? in the cytosol through interaction of the Cav1 scaffolding domain (CSD) with a conserved hydrophobic motif in helix 7 of PPAR?'s ligand-binding domain. Cav1 cooperated with the endogenous Ras/MAPK inhibitor docking protein 1 (Dok1) to promote the ligand-dependent transcriptional activity of PPAR? and to inhibit cell proliferation. Ligand-activated PPAR? also reduced tumor growth and upregulated the Ras/MAPK inhibitors Cav1 and Dok1 in a murine model of GC. These results suggest a novel mechanism of PPAR? regulation by which Ras/MAPK inhibitors act as scaffold proteins that sequester and sensitize PPAR? to ligands, limiting proliferation of gastric epithelial cells.

Spectral-domain optical coherence tomography use in macular diseases: a review

The introduction of spectral-domain optical coherence tomography (SD-OCT) has improved the clinical value for assessment of the eyes with macular disease. This article reviews the advances of SD-OCT for the diagnostic of various macular diseases. These include vitreomacular traction syndrome, cystoid macular edema/diabetic macular edema, epiretinal membranes, full-thickness macular holes, lamellar holes, pseudoholes, microholes, and schisis from myopia. Besides offering new insights into the pathogenesis of macular abnormalities, SD-OCT is a valuable tool for monitoring macular disease.

The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration

The transmembrane ligand ephrinB2 and its cognate Eph receptor tyrosine kinases are important regulators of vascular morphogenesis. EphrinB2 may have an active signaling role, resulting in bi-directional signal transduction downstream of both ephrinB2 and Eph receptors. To separate the ligand and receptor-like functions of ephrinB2 in mice, we replaced the endogenous gene by cDNAs encoding either carboxyterminally truncated (ephrinB2(DeltaC)) or, as a control, full-length ligand (ephrinB2(WT)). While homozygous ephrinB2(WT/WT) animals were viable and fertile, loss of the ephrinB2 cytoplasmic domain resulted in midgestation lethality similar to ephrinB2 null mutants (ephrinB2(KO)). The truncated ligand was sufficient to restore guidance of migrating cranial neural crest cells, but ephrinB2(DeltaC/DeltaC) embryos showed defects in vasculogenesis and angiogenesis very similar to those observed in ephrinB2(KO/KO) animals. Our results indicate distinct requirements of functions mediated by the ephrinB carboxyterminus for developmental processes in the vertebrate embryo.

Reanalysis-driven climate simulation over CORDEX North America domain using the Canadian Regional Climate Model, version 5: model performance evaluation

The performance of reanalysis-driven Canadian Regional Climate Model, version 5 (CRCM5) in reproducing the present climate over the North American COordinated Regional climate Downscaling EXperiment domain for the 1989–2008 period has been assessed in comparison with several observation-based datasets. The model reproduces satisfactorily the near-surface temperature and precipitation characteristics over most part of North America. Coastal and mountainous zones remain problematic: a cold bias (2–6 °C) prevails over Rocky Mountains in summertime and all year-round over Mexico; winter precipitation in mountainous coastal regions is overestimated. The precipitation patterns related to the North American Monsoon are well reproduced, except on its northern limit. The spatial and temporal structure of the Great Plains Low-Level Jet is well reproduced by the model; however, the night-time precipitation maximum in the jet area is underestimated. The performance of CRCM5 was assessed against earlier CRCM versions and other RCMs. CRCM5 is shown to have been substantially improved compared to CRCM3 and CRCM4 in terms of seasonal mean statistics, and to be comparable to other modern RCMs.

Frequency-domain source localization shows state-dependent diazepam effects in 47-channel EEG

The topic of this study was to evaluate state-dependent effects of diazepam on the frequency characteristics of 47-channel spontaneous EEG maps. A novel method, the FFT-Dipole-Approximation (Lehmann and Michel, 1990), was used to study effects on the strength and the topography of the maps in the different frequency bands. Map topography was characterized by the 3-dimensional location of the equivalent dipole source and map strength was defined as the spatial standard deviation (the Global Field Power) of the maps of each frequency point. The Global Field Power can be considered as a measure of the amount of energy produced by the system, while the source location gives an estimate of the center of gravity of all sources in the brain that were active at a certain frequency. State-dependency was studied by evaluating the drug effects before and after a continuous performance task of 25 min duration. Clear interactions between drug (diazepam vs. placebo) and time after drug intake (before and after the task) were found, especially in the inferior-superior location of the dipole sources. It supports the hypothesis that diazepam, like other drugs, has different effects on brain functions depending on the momentary functional state of the brain. In addition to the drug effects, clearly different source locations and Global Field Power were found for the different frequency bands, replicating earlier reports (Michel et al., 1992).

Structural rearrangements of the central region of the morbillivirus attachment protein stalk domain trigger F protein refolding for membrane fusion

It is unknown how receptor binding by the paramyxovirus attachment proteins (HN, H, or G) triggers the fusion (F) protein to fuse with the plasma membrane for cell entry. H-proteins of the morbillivirus genus consist of a stalk ectodomain supporting a cuboidal head; physiological oligomers consist of non-covalent dimer-of-dimers. We report here the successful engineering of intermolecular disulfide bonds within the central region (residues 91-115) of the morbillivirus H-stalk; a sub-domain that also encompasses the putative F-contacting section (residues 111-118). Remarkably, several intersubunit crosslinks abrogated membrane fusion, but bioactivity was restored under reducing conditions. This phenotype extended equally to H proteins derived from virulent and attenuated morbillivirus strains and was independent of the nature of the contacted receptor. Our data reveal that the morbillivirus H-stalk domain is composed of four tightly-packed subunits. Upon receptor binding, these subunits structurally rearrange, possibly inducing conformational changes within the central region of the stalk, which, in turn, promote fusion. Given that the fundamental architecture appears conserved among paramyxovirus attachment protein stalk domains, we predict that these motions may act as a universal paramyxovirus F-triggering mechanism.

Dual-Domain Image Denoising

Image denoising methods have been implemented in both spatial and transform domains. Each domain has its advantages and shortcomings, which can be complemented by each other. State-of-the-art methods like block-matching 3D filtering (BM3D) therefore combine both domains. However, implementation of such methods is not trivial. We offer a hybrid method that is surprisingly easy to implement and yet rivals BM3D in quality.

Carbon dioxide and climate impulse response functions for the computation of greenhouse gas metrics: a multi-model analysis

The responses of carbon dioxide (CO2) and other climate variables to an emission pulse of CO2 into the atmosphere are often used to compute the Global Warming Potential (GWP) and Global Temperature change Potential (GTP), to characterize the response timescales of Earth System models, and to build reduced-form models. In this carbon cycle-climate model intercomparison project, which spans the full model hierarchy, we quantify responses to emission pulses of different magnitudes injected under different conditions. The CO2 response shows the known rapid decline in the first few decades followed by a millennium-scale tail. For a 100 Gt-C emission pulse added to a constant CO2 concentration of 389 ppm, 25 ± 9% is still found in the atmosphere after 1000 yr; the ocean has absorbed 59 ± 12% and the land the remainder (16 ± 14%). The response in global mean surface air temperature is an increase by 0.20 ± 0.12 °C within the first twenty years; thereafter and until year 1000, temperature decreases only slightly, whereas ocean heat content and sea level continue to rise. Our best estimate for the Absolute Global Warming Potential, given by the time-integrated response in CO2 at year 100 multiplied by its radiative efficiency, is 92.5 × 10−15 yr W m−2 per kg-CO2. This value very likely (5 to 95% confidence) lies within the range of (68 to 117) × 10−15 yr W m−2 per kg-CO2. Estimates for time-integrated response in CO2 published in the IPCC First, Second, and Fourth Assessment and our multi-model best estimate all agree within 15% during the first 100 yr. The integrated CO2 response, normalized by the pulse size, is lower for pre-industrial conditions, compared to present day, and lower for smaller pulses than larger pulses. In contrast, the response in temperature, sea level and ocean heat content is less sensitive to these choices. Although, choices in pulse size, background concentration, and model lead to uncertainties, the most important and subjective choice to determine AGWP of CO2 and GWP is the time horizon.

Is there a common pattern of future gas-phase air pollution in Europe under diverse climate change scenarios?

Climate change alone influences future levels of tropospheric ozone and their precursors through modifications of gas-phase chemistry, transport, removal, and natural emissions. The goal of this study is to determine at what extent the modes of variability of gas-phase pollutants respond to different climate change scenarios over Europe. The methodology includes the use of the regional modeling system MM5 (regional climate model version)-CHIMERE for a target domain covering Europe. Two full-transient simulations covering from 1991–2050 under the SRES A2 and B2 scenarios driven by ECHO-G global circulation model have been compared. The results indicate that the spatial patterns of variability for tropospheric ozone are similar for both scenarios, but the magnitude of the change signal significantly differs for A2 and B2. The 1991–2050 simulations share common characteristics for their chemical behavior. As observed from the NO2 and α-pinene modes of variability, our simulations suggest that the enhanced ozone chemical activity is driven by a number of parameters, such as the warming-induced increase in biogenic emissions and, to a lesser extent, by the variation in nitrogen dioxide levels. For gas-phase pollutants, the general increasing trend for ozone found under A2 and B2 forcing is due to a multiplicity of climate factors, such as increased temperature, decreased wet removal associated with an overall decrease of precipitation in southern Europe, increased photolysis of primary and secondary pollutants as a consequence of lower cloudiness and increased biogenic emissions fueled by higher temperatures.

Coherence and phase locking in the scalp EEG and between LORETA model sources, and microstates as putative mechanisms of brain temporo-spatial functional organization

Brain electric mechanisms of temporary, functional binding between brain regions are studied using computation of scalp EEG coherence and phase locking, sensitive to time differences of few milliseconds. However, such results if computed from scalp data are ambiguous since electric sources are spatially oriented. Non-ambiguous results can be obtained using calculated time series of strength of intracerebral model sources. This is illustrated applying LORETA modeling to EEG during resting and meditation. During meditation, time series of LORETA model sources revealed a tendency to decreased left-right intracerebral coherence in the delta band, and to increased anterior-posterior intracerebral coherence in the theta band. An alternate conceptualization of functional binding is based on the observation that brain electric activity is discontinuous, i.e., that it occurs in chunks of up to about 100 ms duration that are detectable as quasi-stable scalp field configurations of brain electric activity, called microstates. Their functional significance is illustrated in spontaneous and event-related paradigms, where microstates associated with imagery- versus abstract-type mentation, or while reading positive versus negative emotion words showed clearly different regions of cortical activation in LORETA tomography. These data support the concept that complete brain functions of higher order such as a momentary thought might be incorporated in temporal chunks of processing in the range of tens to about 100 ms as quasi-stable brain states; during these time windows, subprocesses would be accepted as members of the ongoing chunk of processing.

PDZ domain-binding motif regulates cardiomyocyte compartment-specific NaV1.5 channel expression and function

BACKGROUND Sodium channel NaV1.5 underlies cardiac excitability and conduction. The last 3 residues of NaV1.5 (Ser-Ile-Val) constitute a PDZ domain-binding motif that interacts with PDZ proteins such as syntrophins and SAP97 at different locations within the cardiomyocyte, thus defining distinct pools of NaV1.5 multiprotein complexes. Here, we explored the in vivo and clinical impact of this motif through characterization of mutant mice and genetic screening of patients. METHODS AND RESULTS To investigate in vivo the regulatory role of this motif, we generated knock-in mice lacking the SIV domain (ΔSIV). ΔSIV mice displayed reduced NaV1.5 expression and sodium current (INa), specifically at the lateral myocyte membrane, whereas NaV1.5 expression and INa at the intercalated disks were unaffected. Optical mapping of ΔSIV hearts revealed that ventricular conduction velocity was preferentially decreased in the transversal direction to myocardial fiber orientation, leading to increased anisotropy of ventricular conduction. Internalization of wild-type and ΔSIV channels was unchanged in HEK293 cells. However, the proteasome inhibitor MG132 rescued ΔSIV INa, suggesting that the SIV motif is important for regulation of NaV1.5 degradation. A missense mutation within the SIV motif (p.V2016M) was identified in a patient with Brugada syndrome. The mutation decreased NaV1.5 cell surface expression and INa when expressed in HEK293 cells. CONCLUSIONS Our results demonstrate the in vivo significance of the PDZ domain-binding motif in the correct expression of NaV1.5 at the lateral cardiomyocyte membrane and underline the functional role of lateral NaV1.5 in ventricular conduction. Furthermore, we reveal a clinical relevance of the SIV motif in cardiac disease.

Full correction for spatially distributed speed-of-sound in echo ultrasound based on measuring aberration delays via transmit beam steering

Aberrations of the acoustic wave front, caused by spatial variations of the speed-of-sound, are a main limiting factor to the diagnostic power of medical ultrasound imaging. If not accounted for, aberrations result in low resolution and increased side lobe level, over all reducing contrast in deep tissue imaging. Various techniques have been proposed for quantifying aberrations by analysing the arrival time of coherent echoes from so-called guide stars or beacons. In situations where a guide star is missing, aperture-based techniques may give ambiguous results. Moreover, they are conceptually focused on aberrators that can be approximated as a phase screen in front of the probe. We propose a novel technique, where the effect of aberration is detected in the reconstructed image as opposed to the aperture data. The varying local echo phase when changing the transmit beam steering angle directly reflects the varying arrival time of the transmit wave front. This allows sensing the angle-dependent aberration delay in a spatially resolved way, and thus aberration correction for a spatially distributed volume aberrator. In phantoms containing a cylindrical aberrator, we achieved location-independent diffraction-limited resolution as well as accurate display of echo location based on reconstructing the speed-of-sound spatially resolved. First successful volunteer results confirm the clinical potential of the proposed technique.