Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo

After activation, Langerhans cells (LC), a distinct subpopulation of epidermis-resident dendritic cells, migrate from skin to lymph nodes where they regulate the magnitude and quality of immune responses initiated by epicutaneously applied antigens. Modulation of LC-keratinocyte adhesion is likely to be central to regulation of LC migration. LC express high levels of epithelial cell adhesion molecule (EpCAM; CD326), a cell-surface protein that is characteristic of some epithelia and many carcinomas and that has been implicated in intercellular adhesion and metastasis. To gain insight into EpCAM function in a physiologic context in vivo, we generated conditional knockout mice with EpCAM-deficient LC and characterized them. Epidermis from these mice contained increased numbers of LC with normal levels of MHC and costimulatory molecules and T-cell-stimulatory activity in vitro. Migration of EpCAM-deficient LC from skin explants was inhibited, but chemotaxis of dissociated LC was not. Correspondingly, the ability of contact allergen-stimulated, EpCAM-deficient LC to exit epidermis in vivo was delayed, and strikingly fewer hapten-bearing LC subsequently accumulated in lymph nodes. Attenuated migration of EpCAM-deficient LC resulted in enhanced contact hypersensitivity responses as previously described in LC-deficient mice. Intravital microscopy revealed reduced translocation and dendrite motility in EpCAM-deficient LC in vivo in contact allergen-treated mice. These results conclusively link EpCAM expression to LC motility/migration and LC migration to immune regulation. EpCAM appears to promote LC migration from epidermis by decreasing LC-keratinocyte adhesion and may modulate intercellular adhesion and cell movement within in epithelia during development and carcinogenesis in an analogous fashion

Predicting survival from colorectal cancer histology slides using deep learning: A retrospective multicenter study

BACKGROUND: For virtually every patient with colorectal cancer (CRC), hematoxylin-eosin (HE)-stained tissue slides are available. These images contain quantitative information, which is not routinely used to objectively extract prognostic biomarkers. In the present study, we investigated whether deep convolutional neural networks (CNNs) can extract prognosticators directly from these widely available images. METHODS AND FINDINGS: We hand-delineated single-tissue regions in 86 CRC tissue slides, yielding more than 100,000 HE image patches, and used these to train a CNN by transfer learning, reaching a nine-class accuracy of >94% in an independent data set of 7,180 images from 25 CRC patients. With this tool, we performed automated tissue decomposition of representative multitissue HE images from 862 HE slides in 500 stage I-IV CRC patients in the The Cancer Genome Atlas (TCGA) cohort, a large international multicenter collection of CRC tissue. Based on the output neuron activations in the CNN, we calculated a "deep stroma score," which was an independent prognostic factor for overall survival (OS) in a multivariable Cox proportional hazard model (hazard ratio [HR] with 95% confidence interval [CI]: 1.99 [1.27-3.12], p = 0.0028), while in the same cohort, manual quantification of stromal areas and a gene expression signature of cancer-associated fibroblasts (CAFs) were only prognostic in specific tumor stages. We validated these findings in an independent cohort of 409 stage I-IV CRC patients from the "Darmkrebs: Chancen der Verhütung durch Screening" (DACHS) study who were recruited between 2003 and 2007 in multiple institutions in Germany. Again, the score was an independent prognostic factor for OS (HR 1.63 [1.14-2.33], p = 0.008), CRC-specific OS (HR 2.29 [1.5-3.48], p = 0.0004), and relapse-free survival (RFS; HR 1.92 [1.34-2.76], p = 0.0004). A prospective validation is required before this biomarker can be implemented in clinical workflows. CONCLUSIONS: In our retrospective study, we show that a CNN can assess the human tumor microenvironment and predict prognosis directly from histopathological images

epsilon'/epsilon at the NLO: 10 Years Later

During the last four years several parameters relevant for the analysis of the CP-violating ratio epsilon'/epsilon improved and/or changed significantly. In particular, the experimental value of epsilon'/epsilon and the strange quark mass decreased, the uncertainty in the CKM factor has been reduced, and for a value of the hadronic matrix element of the dominant electroweak penguin operator Q_8, some consensus has been reached among several theory groups. In view of this situation, ten years after the first analyses of epsilon'/epsilon at the next-to-leading order, we reconsider the analysis of epsilon'/epsilon within the SM and investigate what can be said about the hadronic Q_6 matrix element of the dominant QCD penguin operator on the basis of the present experimental value of epsilon'/epsilon and todays values of all other parameters. Employing a conservative range for the reduced electroweak penguin matrix element R_8=1.0+-0.2 from lattice QCD, and present values for all other input parameters, on the basis of the current world average for epsilon'/epsilon, we obtain the reduced hadronic matrix element of the dominant QCD penguin operator R_6=1.23+-0.16 implying _0^NDR(m_c) ~ -0.8 _2^NDR(m_c). We compare these results with those obtained in large-N_c approaches in which generally R_6 ~ R_8 and _0^NDR(m_c) is chirally suppressed relatively to _2^NDR(m_c). We present the correlation between R_6 and R_8 that is implied by the data on epsilon'/epsilon provided new physics contributions to epsilon'/epsilon can be neglected.Comment: 18 pages, 1 eps figure, version to appear in JHE

An upper bound on the Kaon B-parameter and Re(epsilon_K)

New precise data in B physics and theoretical developments in K physics lead us to reconsider the weak K^0-\bar{K}^0 transition from a large-N_c viewpoint, N_c being the number of colors. In this framework, we infer an upper limit on \hat{B}_K and the Kaon indirect CP violation.Comment: 11 pages, 4 figures. V2 : Minor corrections, final version accepted for publication in JHE

On the Particle Data Group evaluation of Psi' and chi_c Branching Ratios

I propose a new evaluation of $\psi'(2S)$ and $\chi_c(1P)$ branching ratios which avoids the correlations affecting the current Particle Data Group evaluation. These correlations explain the apparent technique-dependent discrepancies between the available determinations of the ${\cal B}(\chi_c(1P)\to p\bar p)$ and $\Gamma(\chi_c(1P)\to \gamma\gamma)$ under the hypotesis that the current values of the $\psi'(2S)\to\chi_c(1P)\gamma$ branching ratios are overestimated. In the process I also noticed that Particle Data Group has not restated many of the older measurements, when necessary, for the new value of ${\cal B}(J/\psi\to l^+l^-)$, which significantly affects the evaluation of some relevant $\psi'(2S)$ and $\chi_c(1P)$ exclusive branching ratios.Comment: 13 pages. Revised version. Submitted to Phys. Rev.

Improved Measurements of Branching Fractions for B->Kpi, pipi and KK Decays

We report improved measurements of branching fractions for $B\to K\pi$, $\pi^+\pi^-$, $\pi^+\pi^0$ and $K\bar{K}$ decays based on a data sample of 85.0 million $B\bar{B}$ pairs collected at the $\Upsilon (4S)$ resonance with the Belle detector at the KEKB $e^+e^-$ storage ring. This data sample is almost three times larger than the sample previously used. We observe clear signals for $B\to K\pi$, $\pi^+\pi^-$ and $\pi^+\pi^0$ decays and set upper limits on $B\to K\bar{K}$ decays. The results can be used to give model-dependent constraints on the CKM angle $\phi_3$, as well as limits on the hadronic uncertainty in the time-dependent analysis of the angle $\phi_2$.Comment: 10 pages, 1 figure, 4 tables. Submitted to Phys. Rev. D Rapid Communications. Several corrections were mad

Charmed quark component of the photon wave function

We determine the c-anti-c component of the photon wave function on the basis of (i) the data on the transitions e+ e- -> J/psi(3096), psi(3686), psi(4040), psi(4415), (ii) partial widths of the two-photon decays eta_{c0}(2979), chi_{c0}(3415), chi_{c2}(3556) -> gamma-gamma, and (iii) wave functions of the charmonium states obtained by solving the Bethe-Salpeter equation for the c-anti-c system. Using the obtained c-anti-c component of the photon wave function we calculate the gamma-gamma decay partial widths for radial excitation 2S state, eta_{c0}(3594) -> gamma-gamma, and 2P states chi_{c0}(3849), chi_{c2}(3950) -> gamma-gamma.Comment: 20 pages, 8 figure

Theory and applications of atomic and ionic polarizabilities

Atomic polarization phenomena impinge upon a number of areas and processes in physics. The dielectric constant and refractive index of any gas are examples of macroscopic properties that are largely determined by the dipole polarizability. When it comes to microscopic phenomena, the existence of alkaline-earth anions and the recently discovered ability of positrons to bind to many atoms are predominantly due to the polarization interaction. An imperfect knowledge of atomic polarizabilities is presently looming as the largest source of uncertainty in the new generation of optical frequency standards. Accurate polarizabilities for the group I and II atoms and ions of the periodic table have recently become available by a variety of techniques. These include refined many-body perturbation theory and coupled-cluster calculations sometimes combined with precise experimental data for selected transitions, microwave spectroscopy of Rydberg atoms and ions, refractive index measurements in microwave cavities, ab initio calculations of atomic structures using explicitly correlated wave functions, interferometry with atom beams, and velocity changes of laser cooled atoms induced by an electric field. This review examines existing theoretical methods of determining atomic and ionic polarizabilities, and discusses their relevance to various applications with particular emphasis on cold-atom physics and the metrology of atomic frequency standards.Comment: Review paper, 44 page

Measurement of the B --> K^* gamma Branching Fractions and Asymmetries

We report measurements of the radiative decay B --> K^*\gamma. The analysis is based on a data sample containing 85.0*10^6 B meson pairs collected by the Belle detector at the KEKB storage ring. We measure branching fractions of Br(B^0 --> K^{*0}\gamma) = (4.01 \pm 0.21 \pm 0.17)*10^{-5} and Br(B^+ --> K^{*+}\gamma) = (4.25 \pm 0.31 \pm 0.24)*10^{-5}, where the first and second errors are statistical and systematic, respectively. The isospin asymmetry between B^0 and B^+ decay widths is measured to be \Delta_{0+} = +0.012 \pm 0.044 \pm 0.026. We search for a partial rate asymmetry between CP conjugate modes, and find A_{cp}(B --> K^*\gamma) = =0.015 \pm 0.044 \pm 0.012.Comment: 10 pages, 5 figures, submitted to Phys. Rev.