QuaSI: Quantile Sparse Image Prior for Spatio-Temporal Denoising of Retinal OCT Data

Optical coherence tomography (OCT) enables high-resolution and non-invasive 3D imaging of the human retina but is inherently impaired by speckle noise. This paper introduces a spatio-temporal denoising algorithm for OCT data on a B-scan level using a novel quantile sparse image (QuaSI) prior. To remove speckle noise while preserving image structures of diagnostic relevance, we implement our QuaSI prior via median filter regularization coupled with a Huber data fidelity model in a variational approach. For efficient energy minimization, we develop an alternating direction method of multipliers (ADMM) scheme using a linearization of median filtering. Our spatio-temporal method can handle both, denoising of single B-scans and temporally consecutive B-scans, to gain volumetric OCT data with enhanced signal-to-noise ratio. Our algorithm based on 4 B-scans only achieved comparable performance to averaging 13 B-scans and outperformed other current denoising methods.Comment: submitted to MICCAI'1

Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study.

Limited data exist regarding treatment patterns and outcomes in elderly patients with HER2-positive metastatic breast cancer (MBC). registHER is an observational study of patients (N = 1,001) with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up 27 months). Outcomes were analyzed by age at MBC diagnosis: younger (<65 years), older (65-74 years), elderly (≥75 years). For progression-free survival (PFS) and overall survival (OS) analyses of first-line trastuzumab versus nontrastuzumab, older and elderly patients were combined. Cox regression analyses were adjusted for baseline characteristics and treatments. Estrogen receptor/progesterone receptor status was similar across age groups. Underlying cardiovascular disease was most common in elderly patients. In patients receiving trastuzumab-based first-line treatment, elderly patients were less likely to receive chemotherapy. In trastuzumab-treated patients, incidence of left ventricular dysfunction (LVD) and congestive heart failure (CHF) (grades ≥ 3) were highest in elderly patients (LVD: elderly 4.8 %, younger 2.8 %, older 1.5 %; CHF: elderly 3.2 %, younger 1.9 %, older 1.5 %). Unadjusted median PFS (months) was significantly higher in patients treated with first-line trastuzumab than those who were not (<65 years: 11.0 vs. 3.4, respectively; ≥65 years: 11.7 vs. 4.8, respectively). In patients <65 years, unadjusted median OS (months) was significantly higher in trastuzumab-treated patients; in patients ≥65 years, median OS was similar (<65 years: 40.4 vs. 25.9; ≥65 years: 31.2 vs. 28.5). In multivariate analyses, first-line trastuzumab use was associated with significant improvement in PFS across age. For OS, significant improvement was observed for patients <65 years and nonsignificant improvement for patients ≥65 years. Elderly patients with HER2-positive MBC had higher rates of underlying cardiovascular disease than their younger counterparts and received less aggressive treatment, including less first-line trastuzumab. These real-world data suggest improved PFS across all age groups and similar trends for OS

Identification of Interdependent Variables that Influence Coreceptor Switch in R5 SHIVSF162P3N_{SF162P3N}-Infected Macaques

Background: We previously reported that adoption of an “open” envelope glycoprotein (Env) to expose the CD4 binding site for efficient receptor binding and infection of cell targets such as macrophages that express low levels of the receptor represents an early event in the process of coreceptor switch in two rapidly progressing (RP) R5 SHIV$_{SF162P3N}$-infected rhesus macaques, releasing or reducing Env structural constraints that have been suggested to limit the pathways available for a change in coreceptor preference. Here we extended these studies to two additional RP monkeys with coreceptor switch and three without to confirm and identify additional factors that facilitated the process of phenotypic conversion. Results: We found that regardless of coreceptor switching, R5 viruses in SHIV$_{SF162P3N}$-infected RP macaques evolved over time to infect macrophages more efficiently; this was accompanied by increased sCD4 sensitivity, with structural changes in the CD4 binding site, the V3 loop and/or the fusion domain of their Envs that are suggestive of better CD4 contact, CCR5 usage and/or virus fusion. However, sCD4-sensitive variants with improved CD4 binding were observed only in RPs with coreceptor switch. Furthermore, cumulative viral load was higher in RPs with than in those without phenotypic switch, with the latter maintaining a longer period of seroconversion. Conclusions: Our data suggest that the increased virus replication in the RPs with R5-to-X4 conversion increased the rate of virus evolution and reduction in the availability of target cells with optimal CD4 expression heightened the competition for binding to the receptor. In the absence of immunological restrictions, variants that adopt an “open” Env to expose the CD4 binding site for better CD4 use are selected, allowing structural changes that confer CXCR4-use to be manifested. Viral load, change in target cell population during the course of infection and host immune response therefore are interdependent variables that influence R5 virus evolution and coreceptor switch in SHIV$_{SF162P3N}$-infected rhesus macaques. Because an "open" Env conformation also renders the virus more susceptible to antibody neutralization, our findings help to explain the infrequent and late appearance of X4 virus in HIV-1 infection when the immune system deteriorates

Electronic stress tensor analysis of hydrogenated palladium clusters

We study the chemical bonds of small palladium clusters Pd_n (n=2-9) saturated by hydrogen atoms using electronic stress tensor. Our calculation includes bond orders which are recently proposed based on the stress tensor. It is shown that our bond orders can classify the different types of chemical bonds in those clusters. In particular, we discuss Pd-H bonds associated with the H atoms with high coordination numbers and the difference of H-H bonds in the different Pd clusters from viewpoint of the electronic stress tensor. The notion of "pseudo-spindle structure" is proposed as the region between two atoms where the largest eigenvalue of the electronic stress tensor is negative and corresponding eigenvectors forming a pattern which connects them.Comment: 22 pages, 13 figures, published online, Theoretical Chemistry Account

Mucosal transmissibility, disease induction and coreceptor switching of R5 SHIVSF162P3N molecular clones in rhesus macaques

Background: Mucosally transmissible and pathogenic CCR5 (R5)-tropic simian-human immunodeficiency virus (SHIV) molecular clones are useful reagents to identity neutralization escape in HIV-1 vaccine experiments and to study the envelope evolutionary process and mechanistic basis for coreceptor switch during the course of natural infection. Results: We observed progression to AIDS in rhesus macaques infected intrarectally with molecular clones of the pathogenic R5 SHIVSF162P3N isolate. Expansion to CXCR4 usage was documented in one diseased macaque that mounted a neutralizing antibody response and in another that failed to do so, with the latter displaying a rapid progressor phenotype. V3 loop envelop glycoprotein gp120 sequence changes that are predictive of a CXCR4 (X4)-using phenotype in HIV-1 subtype B primary isolates, specifically basic amino acid substations at positions 11 (S11R), 24 (G24R) and 25 (D25K) of the loop were detected in the two infected macaques. Functional assays showed that envelopes with V3 S11R or D25K mutation were dual-tropic, infecting CD4+ target cells that expressed either the CCR5 or CXCR4 coreceptor. And, consistent with findings of coreceptor switching in macaques infected with the pathogenic isolate, CXCR4-using variant was first detected in the lymph node of the chronically infected rhesus monkey several weeks prior to its presence in peripheral blood. Moreover, X4 emergence in this macaque coincided with persistent peripheral CD4+ T cell loss and a decline in neutralizing antibody titer that are suggestive of immune deterioration, with macrophages as the major virus-producing cells at the end-stage of disease. Conclusions: The data showed that molecular clones derived from the R5 SHIVSF162P3N isolate are mucosally transmissible and induced disease in a manner similar to that observed in HIV-1 infected individuals, providing a relevant and useful animal infection model for in-depth analyses of host selection pressures and the env evolutionary changes that influence disease outcome, coreceptor switching and vaccine escape

Annihilation Emission from the Galactic Black Hole

Both diffuse high energy gamma-rays and an extended electron-positron annihilation line emission have been observed in the Galactic Center (GC) region. Although X-ray observations indicate that the galactic black hole Sgr A$^*$ is inactive now, we suggest that Sgr A$^*$ can become active when a captured star is tidally disrupted and matter is accreted into the black hole. As a consequence the galactic black hole could be a powerful source of relativistic protons. We are able to explain the current observed diffuse gamma-rays and the very detailed 511 keV annihilation line of secondary positrons by $p-p$ collisions of such protons, with appropriate injection times and energy. Relativistic protons could have been injected into the ambient material if the black hole captured a 50M$_\odot$ star at several tens million years ago. An alternative possibility is that the black hole continues to capture stars with $\sim$1M$_\odot$ every hundred thousand years. Secondary positrons produced by $p-p$ collisions at energies \ga 30 MeV are cooled down to thermal energies by Coulomb collisions, and annihilate in the warm neutral and ionized phases of the interstellar medium with temperatures about several eV, because the annihilation cross-section reaches its maximum at these temperatures. It takes about ten million years for the positrons to cool down to thermal temperatures so they can diffuse into a very large extended region around the Galactic center. A much more recent star capture may be also able to account for recent TeV observations within 10 pc of the galactic center as well as for the unidentified GeV gamma-ray sources found by EGRET at GC. The spectral difference between the GeV flux and the TeV flux could be explained naturally in this model as well.Comment: Accepted by ApJ on March 24, 200

A Dual-Tropic Primary HIV-1 Isolate That Uses Fusin and the β-Chemokine Receptors CKR-5, CKR-3, and CKR-2b as Fusion Cofactors

AbstractHere, we show that the β-chemokine receptor CKR-5 serves as a cofactor for M-tropic HIV viruses. Expression of CKR-5 with CD4 enables nonpermissive cells to form syncytia with cells expressing M-tropic, but not T-tropic, HIV-1 env proteins. Expression of CKR-5 and CD4 enables entry of a M-tropic, but not a T-tropic, virus strain. A dual-tropic primary HIV-1 isolate (89.6) utilizes both Fusin and CKR-5 as entry cofactors. Cells expressing the 89.6 env protein form syncytia with QT6 cells expressing CD4 and either Fusin or CKR-5. The β-chemokine receptors CKR-3 and CKR-2b support HIV-1 89.6 env-mediated syncytia formation but do not support fusion by any of the T-tropic or M-tropic strains tested. Our results suggest that the T-tropic viruses characteristic of disease progression may evolve from purely M-tropic viruses prevalent early in virus infection through changes in the env protein that enable the virus to use multiple entry cofactors

Realistic Equations of State for the Primeval Universe

Early universe equations of state including realistic interactions between constituents are built up. Under certain reasonable assumptions, these equations are able to generate an inflationary regime prior to the nucleosynthesis period. The resulting accelerated expansion is intense enough to solve the flatness and horizon problems. In the cases of curvature parameter \kappa equal to 0 or +1, the model is able to avoid the initial singularity and offers a natural explanation for why the universe is in expansion.Comment: 32 pages, 5 figures. Citations added in this version. Accepted EPJ

Interpretation of radio continuum and molecular line observations of Sgr B2: free-free and synchrotron emission, and implications for cosmic rays

Recent ammonia (1,1) inversion line data on the Galactic star forming region Sgr B2 show that the column density is consistent with a radial Gaussian density profile with a standard deviation of 2.75 pc. Deriving a formula for the virial mass of spherical Gaussian clouds, we obtain a virial mass of 1.9 million solar masses for Sgr B2. For this matter distribution, a reasonable magnetic field and an impinging flux of cosmic rays of solar neighbourhood intensity, we predict the expected synchrotron emission from the Sgr B2 giant molecular cloud due to secondary electrons and positrons resulting from cosmic ray interactions, including effects of losses due to pion production collisions during diffusive propagation into the cloud complex. We assemble radio continuum data at frequencies between 330 MHz and 230 GHz. From the spectral energy distribution the emission appears to be thermal at all frequencies. Before using these data to constrain the predicted synchrotron flux, we first model the spectrum as free-free emission from the known ultra compact HII regions plus emission from an envelope or wind with a radial density gradient. This severely constrains the possible synchrotron emission by secondary electrons to quite low flux levels. The absence of a significant contribution by secondary electrons is almost certainly due to multi-GeV energy cosmic rays being unable to penetrate far into giant molecular clouds. This would also explain why 100 MeV--GeV gamma-rays (from neutral pion decay or bremsstrahlung by secondary electrons) were not observed from Sgr B2 by EGRET, while TeV energy gamma-rays were observed, being produced by higher energy cosmic rays which more readily penetrate giant molecular clouds.Comment: 11 pages, 10 figures. New section on diffusion of primary and secondary cosmic ray electrons into and within the Sgr B2 Giant Molecular Cloud added. Main corrections to proofs made in this versio