Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study

BACKGROUND: Nuclear alterations are a well-known manifestation of cancer. However, little is known about the early, microscopically-undetectable stages of malignant transformation. Based on the phenomenon of field cancerization, the tissue in the field of a tumor can be used to identify and study the initiating events of carcinogenesis. Morphological changes in nuclear organization have been implicated in the field of colorectal cancer (CRC), and we hypothesize that characterization of chromatin alterations in the early stages of CRC will provide insight into cancer progression, as well as serve as a biomarker for early detection, risk stratification and prevention. METHODS: For this study we used transmission electron microscopy (TEM) images of nuclei harboring pre-neoplastic CRC alterations in two models: a carcinogen-treated animal model of early CRC, and microscopically normal-appearing tissue in the field of human CRC. We quantify the chromatin arrangement using approaches with two levels of complexity: 1) binary, where chromatin is separated into areas of dense heterochromatin and loose euchromatin, and 2) grey-scale, where the statistics of continuous mass-density distribution within the nucleus is quantified by its spatial correlation function. RESULTS: We established an increase in heterochromatin content and clump size, as well as a loss of its characteristic peripheral positioning in microscopically normal pre-neoplastic cell nuclei. Additionally, the analysis of chromatin density showed that its spatial distribution is altered from a fractal to a stretched exponential. CONCLUSIONS: We characterize quantitatively and qualitatively the nanoscale structural alterations preceding cancer development, which may allow for the establishment of promising new biomarkers for cancer risk stratification and diagnosis. The findings of this study confirm that ultrastructural changes of chromatin in field carcinogenesis represent early neoplastic events leading to the development of well-documented, microscopically detectable hallmarks of cancer

Measurements of Charmless Hadronic b->s Penguin Decays in the pi+pi-K+pi- Final State and First Observation of B0 -> rho0K+pi-

We report measurements of charmless hadronic B^0 decays into the pi+pi-K+pi+ final state. The analysis uses a sample of 657x10^6 BBbar pairs collected with the Belle detector at the KEKB asymmetric-energy e+e- collider at the Y(4S) resonance. The decay B^0 -> rho0 Kpi is observed for the first time; the significance is 5.0sigma and the corresponding partial branching fraction for M_Kpi in (0.75,1.20) GeV/c^2 is [2.8 +- 0.5(stat) +-0.5(syst)] x 10^{-6}. We also obtain the first evidence for B^0 -> f0Kpi with 3.5sigma significance and for B^0 -> pi+pi-K*0 with 4.5sigma significance. For the two-body decays B^0 -> rho0K*0 and B^0 -> f0K*0, the significances are 2.7sigma and 2.5sigma, respectively, and the upper limits on the branching fractions are 3.4x10^{-6} and 2.2x10^{-6} at 90% confidence level.Comment: 6 pages, 3 figures. accepted by PRD(RC

Evidence of time-dependent CP violation in the decay B0 to D*+D*-

We report a measurement of the CP-odd fraction and the time-dependent CP violation in B0 to D*+D*- decays, using 657.10^6 BBbar events collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. We measure a CP-odd fraction of Rperp=0.125+/-0.043(stat)+/-0.023(syst). From the distributions of the proper-time intervals between a B0to D*+D*- decay and the other B meson in the event, we obtain evidence of CP violation with measured parameters AD*+D*-=0.15+/-0.13(stat)+/-0.04(syst) and SD*+D*-=-0.96+/-0.25(stat)-0.16+0.13(syst).Comment: Published in PR

Observation of B+ -> Dbar*0 tau+ nu_tau and Evidence for B+ -> Dbar^0 tau+ nu_tau at Belle

We present measurements of B+ -> Dbar*0 tau+ nu_tau and B+ -> Dbar^0 tau+ nu_tau decays in a data sample of 657 x 10^6 BBbar pairs collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. We find 446^{+58}_{-56} events of the decay B+ -> Dbar*0 tau+ nu_tau with a significance of 8.1 standard deviations, and 146^{+42}_{-41} events of the decay B+ -> Dbar0 tau+ nu_tau with a significance of 3.5 standard deviations. The latter signal provides the first evidence for this decay mode. The measured branching fractions are B(B+ -> Dbar*0 tau+ nu_tau)=(2.12^{+0.28}_{-0.27} (stat) +- 0.29 (syst)) % and B(B+ -> Dbar0 tau+ nu_tau)=(0.77 +- 0.22 (stat) +- 0.12 (syst)) %.Comment: 6 pages, 4 figures, submitted to Phys. Rev. Let

Performance studies of the Belle II Silicon Vertex Detector with data taken at the DESY test beam in April 2016

Belle II is a multipurpose detector currently under construction which will be operated at the next generation B-factory SuberKEKB in Japan. Its main devices for the vertex reconstruction are the Silicon Vertex Detector (SVD) and the Pixel Detector (PXD). In April 2016 a sector of the Belle II SVD and PXD have been tested in a beam of high energetic electrons at the test beam facility at DESY Hamburg (Germany). We report here the results for the hit efficiency estimation and the measurement of the resolution for the Belle II silicon vertex etector. We find that the hit efficiencies are on average above 99.5% and that the measured resolution is within the expectations

Performance studies of the Belle II Silicon Vertex Detector with data taken at the DESY test beam in April 2016

Belle II is a multipurpose detector currently under construction which will be operated at the next generation B-factory SuberKEKB in Japan. Its main devices for the vertex reconstruction are the Silicon Vertex Detector (SVD) and the Pixel Detector (PXD). In April 2016 a sector of the Belle II SVD and PXD have been tested in a beam of high energetic electrons at the test beam facility at DESY Hamburg (Germany). We report here the results for the hit efficiency estimation and the measurement of the resolution for the Belle II silicon vertex etector. We find that the hit efficiencies are on average above 99.5% and that the measured resolution is within the expectations

The Belle II SVD detector

The Silicon Vertex Detector (SVD) is one of the main detectors in the Belle II experiment at KEK, Japan. In combination with a pixel detector, the SVD determines precise decay vertex and low-momentum track reconstruction. The SVD ladders are being developed at several institutes. For the development of the tracking algorithm as well as the performance estimation of the ladders, beam tests for the ladders were performed. We report an overview of the SVD development, its performance measured in the beam test, and the prospect of its assembly and commissioning until installation

Observation of Bs0→J/ψf0(980)B_s^0\to J/\psi f_0(980) and Evidence for Bs0→J/ψf0(1370)B_s^0\to J/\psi f_0(1370)

We report the first observation of $B_s^0\to J/\psi f_0(980)$ and first evidence for $B_s^0\to J/\psi f_0(1370)$, which are CP eigenstate decay modes. These results are obtained from $121.4\;\mathrm{fb}^{-1}$ of data collected at the $\Upsilon(5S)$ resonance with the Belle detector at the KEKB $e^+e^-$ collider. We measure the branching fractions $\mathcal{B}(B_s^0\to J/\psi f_0(980);f_0(980)\to\pi^+\pi^-)=(1.16^{+0.31}_{-0.19}(\mathrm{stat.})^{+0.15}_{-0.17}(\mathrm{syst.})^{+0.26}_{-0.18}(N_{B_s^{(*)}\bar B_s^{(*)}})) \times 10^{-4}$ with a significance of $8.4\sigma$, and $\mathcal{B}(B_s^0\to J/\psi f_0(1370);f_0(1370)\to\pi^+\pi^-)=(0.34^{+0.11}_{-0.14}(\mathrm{stat.})^{+0.03}_{-0.02}(\mathrm{syst.})^{+0.08}_{-0.05}(N_{B_s^{(*)}\bar B_s^{(*)}})) \times 10^{-4}$ with a significance of $4.2\sigma$. The last error listed is due to uncertainty in the number of produced $B_s^{(*)}\bar B_s^{(*)}$ pairs.Comment: 5 pages, 2 figures, 2 tables, published in PR

Measurement of the CP-violation Parameter sin2ϕ1\phi_1 with a New Tagging Method at the Υ(5S)\Upsilon(5S) Resonance

We report a measurement of the CP-violation parameter sin2$\phi_1$ at the $\Upsilon(5S)$ resonance using a new tagging method, called "$B$-$\pi$ tagging." In $\Upsilon(5S)$ decays containing a neutral $B$ meson, a charged $B$, and a charged pion, the neutral $B$ is reconstructed in the $J/\psi K_S^0$ CP-eigenstate decay channel. The initial flavor of the neutral $B$ meson at the moment of the $\Upsilon(5S)$ decay is opposite to that of the charged $B$ and may thus be inferred from the charge of the pion without reconstructing the charged $B$. From the asymmetry between $B$-$\pi^+$ and $B$-$\pi^-$ tagged $J/\psi K_S^0$ yields, we determine sin2$\phi_1$ = 0.57 $\pm$ 0.58(stat) $\pm$ 0.06(syst). The results are based on 121 fb$^{-1}$ of data recorded by the Belle detector at the KEKB $e^+ e^-$ collider.Comment: 6 pages, 3 figures (submitted to PRL

Observation of B0→pΛˉD(∗)−B^{0} \rightarrow p\bar{\Lambda} D^{(*)-}

We report the first observation of the decays $B^0 \rightarrow p\bar{\Lambda} D^{(*)-}$. The data sample of $711$ fb$^{-1}$ used in this analysis corresponds to $772$ million $B\bar{B}$ pairs, collected at the $\Upsilon(4S)$ resonance by the Belle detector at the KEKB asymmetric-energy $e^{+}e^{-}$ collider. We observe $19.8\sigma$ and $10.8\sigma$ excesses of events for the two decay modes and measure the branching fractions of $B^0 \rightarrow p\bar{\Lambda} D^{-}$ and $B^0 \rightarrow p\bar{\Lambda} D^{*-}$ to be $(25.1\pm2.6\pm3.5)\times10^{-6}$ and $(33.6\pm6.3\pm4.4)\times10^{-6}$, respectively, where the first uncertainties are statistical and the second are systematic. These results are not compatible with the predictions based on the generalized factorization approach. In addition, a threshold enhancement in the di-baryon ($p\bar{\Lambda}$) system is observed, consistent with that observed in similar $B$ decays.Comment: 16 pages, 3 figures and 3 tables, submitted to PR