Measurement of the Ratios of Branching Fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) and B(Bs -> Ds pi) / B(Bd -> Dd pi)

Using 355 pb^-1 of data collected by the CDF II detector in \ppbar collisions at sqrt{s} = 1.96 TeV at the Fermilab Tevatron, we study the fully reconstructed hadronic decays B -> D pi and B -> D pi pi pi. We present the first measurement of the ratio of branching fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) = 1.05 pm 0.10 (stat) pm 0.22 (syst). We also update our measurement of B(Bs -> Ds pi) / B(Bd -> Dd pi) to 1.13 pm 0.08 (stat) pm 0.23 (syst) improving the statistical uncertainty by more than a factor of two. We find B(Bs -> Ds pi) = [3.8 pm 0.3 (stat) pm 1.3 (syst)] \times 10^{-3} and B(Bs -> Ds pi pi pi) = [8.4 pm 0.8 (stat) pm 3.2 (syst)] \times 10^{-3}.Comment: 7 pages, 2 figure

Cross Section Measurements of High-pTp_T Dilepton Final-State Processes Using a Global Fitting Method

We present a new method for studying high-$p_T$ dilepton events ($e^{\pm}e^{\mp}$, $\mu^{\pm}\mu^{\mp}$, $e^{\pm}\mu^{\mp}$) and simultaneously extracting the production cross sections of $p\bar{p} \to t\bar{t}$, $p\bar{p} \to W^+W^-$, and p\bar{p} \to \ztt at a center-of-mass energy of $\sqrt{s} = 1.96$ TeV. We perform a likelihood fit to the dilepton data in a parameter space defined by the missing transverse energy and the number of jets in the event. Our results, which use $360 {\rm pb^{-1}}$ of data recorded with the CDF II detector at the Fermilab Tevatron Collider, are $\sigma(t\bar{t}) = 8.5_{-2.2}^{+2.7}$ pb, $\sigma(W^+W^-) = 16.3^{+5.2}_{-4.4}$ pb, and \sigma(\ztt) =291^{+50}_{-46} pb.Comment: 20 pages, 2 figures, to be submitted to PRD-R

Search for New Physics in Lepton + Photon + X Events with L=305 pb-1 of ppbar Collisions at roots=1.96 TeV

We present results of a search for anomalous production of events containing a charged lepton (either electron or muon) and a photon, both with high transverse momentum, accompanied by additional signatures, X, including missing transverse energy (MET) and additional leptons and photons. We use the same kinematic selection criteria as in a previous CDF search, but with a substantially larger data set, 305 pb-1, a ppbar collision energy of 1.96 TeV, and the upgraded CDF II detector. We find 42 Lepton+Photon+MET events versus a standard model expectation of 37.3 +- 5.4 events. The level of excess observed in Run I, 16 events with an expectation of 7.6 +- 0.7 events (corresponding to a 2.7 sigma effect), is not supported by the new data. In the signature of Multi-Lepton+Photon+X we observe 31 events versus an expectation of 23.0 +- 2.7 events. In this sample we find no events with an extra photon or MET and so find no events like the one ee+gg+MET event observed in Run I.Comment: 7 pages, 3 figures, 1 table. Accepted to PR

Measurement of the Lambda_b Lifetime in Lambda_b --> J/psi Lambda0 in p-pbar Collisions at sqrt(s)=1.96 TeV

We report a measurement of the Lambda_b lifetime in the exclusive decay Lambda_b --> J/psi Lambda0 in p-pbar collisions at sqrt(s) = 1.96 TeV using an integrated luminosity of 1.0 fb^{-1} of data collected by the CDF II detector at the Fermilab Tevatron. Using fully reconstructed decays, we measure tau(Lambda_b) = 1.593 ^{+0.083}_{-0.078} (stat.) +- 0.033 (syst.) ps. This is the single most precise measurement of tau(Lambda_b) and is 3.2 sigma higher than the current world average.Comment: 7 Pages, 2 Figures, 1 Table. Submitted to Phys. Rev. Let

Limits on Anomalous Triple Gauge Couplings in ppbar Collisions at sqrt{s}=1.96 TeV

We present a search for anomalous triple gauge couplings (ATGC) in WW and WZ boson production. The boson pairs are produced in ppbar collisions at sqrt{s}=1.96 TeV, and the data sample corresponds to 350 pb-1 of integrated luminosity collected with the CDF II detector at the Fermilab Tevatron. In this search one W decays to leptons, and the other boson (W or Z) decays hadronically. Combining with a previously published CDF measurement of Wgamma boson production yields ATGC limits of -0.18 < lambda < 0.17 and -0.46 < Delta kappa < 0.39 at the 95% confidence level, using a cut-off scale Lambda=1.5 TeV.Comment: 7 pages, 3 figures. Submitted to Phys. Rev.

Measurement of the Top Quark Mass with the Dynamical Likelihood Method using Lepton plus Jets Events with b-tags in ppbar Collisions at s**(1/2) = 1.96 TeV

This report describes a measurement of the top quark mass, M_{top}, with the dynamical likelihood method (DLM) using the CDF II detector at the Fermilab Tevatron. The Tevatron produces top/anti-top pairs in protons and anti-protons collisions at a center-of-mass energy of 1.96 TeV. The data sample used in this analysis was accumulated from March 2002 through August 2004, which corresponds to an integrated luminosity of 318 pb^{-1}. We use the top/anti-top candidates in the ``lepton+jets'' decay channel, requiring at least one jet identified as a b quark by finding a displaced secondary vertex. The DLM defines a likelihood for each event based on the differential cross section as a function of M_{top} per unit phase space volume of the final partons, multiplied by the transfer functions from jet to parton energies. The method takes into account all possible jet combinations in an event, and the likelihood is multiplied event by event to derive the top quark mass by the maximum likelihood method. Using 63 top quark candidates observed in the data, with 9.2 events expected from background, we measure the top quark mass to be 173.2 +2.6/-2.4 (stat.) +/- 3.2 (syst.) GeV/c^2, or 173.2 +4.1/-4.0 GeV/c^2.Comment: 66 pages, 26 figures, 4 table

Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cells

Bone-marrow-derived mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and differentiation into multiple cell types. Accumulating preclinical and clinical evidence indicates that MSCs are good candidates to use as cell therapy in many degenerative diseases. For MSC clinical applications, an adequate number of cells are necessary so an extensive expansion is required. However, spontaneous immortalization and malignant transformation of MSCs after culture expansion have been reported in human and mouse, while very few data are present for rat MSCs (rMSCs). In this study, we monitored the chromosomal status of rMSCs at several passages in vitro, also testing the influence of four different cell culture conditions. We first used the conventional traditional cytogenetic techniques, in order to have the opportunity to observe even minor structural abnormalities and to identify low-degree mosaic conditions. Then, a more detailed genomic analysis was conducted by array comparative genomic hybridization. We demonstrated that, irrespective of culture conditions, rMSCs manifested a markedly aneuploid karyotype and a progressive chromosomal instability in all the passages we analyzed and that they are anything but stable during in vitro culture. Despite the fact that the risk of neoplastic transformation associated with this genomic instability needs to be further addressed and considering the apparent genomic stability reported for in vitro cultured human MSCs (hMSCs), our findings underline the fact that rMSCs may not in fact be a good model for effectively exploring the full clinical therapeutic potential of hMSCs

Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation

Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. / Methods: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. / Results: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. / Conclusions: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF

Identification of the cathelicidin peptide LL-37 as agonist for the type I insulin-like growth factor receptor

The human cathelicidin antimicrobial protein-18 and its C terminal peptide, LL-37, displays broad antimicrobial activity that is mediated through direct contact with the microbial cell membrane. In addition, recent studies reveal that LL-37 is involved in diverse biological processes such as immunomodulation, apoptosis, angiogenesis and wound healing. An intriguing role for LL-37 in carcinogenesis is also beginning to emerge and the aim of this paper was to explore if and how LL-37 contributes to the signaling involved in tumor development. To this end, we investigated the putative interaction between LL-37 and growth factor receptors known to be involved in tumor growth and progression. Among several receptors tested, LL-37 bound with the highest affinity to insulin-like growth factor 1 receptor (IGF-1R), a receptor that is strongly linked to malignant cellular transformation. Furthermore, this interaction resulted in a dose-dependent phosphorylation and ubiquitination of IGF-1R, with downstream signaling confined to the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)-pathway but not affecting phosphatidylinositol 3 kinase/Akt signaling. We found that signaling induced by LL-37 was dependent on the recruitment of β-arrestin to the fully functional IGF-1R and by using mutant receptors we demonstrated that LL-37 signaling is dependent on β-arrestin-1 binding to the C-terminus of IGF-1R. When analyzing the biological consequences of increased ERK activation induced by LL-37, we found that it resulted in enhanced migration and invasion of malignant cells in an IGF-1R/β-arrestin manner, but did not affect cell proliferation. These results indicate that LL-37 may act as a partial agonist for IGF-1R, with subsequent intra-cellular signaling activation driven by the binding of β-arrestin-1 to the IGF-1R. Functional experiments show that LL-37-dependent activation of the IGF-1R signaling resulted in increased migratory and invasive potential of malignant cells

Tumor-specific expression of αvβ3 integrin promotes spontaneous metastasis of breast cancer to bone

INTRODUCTION: Studies in xenograft models and experimental models of metastasis have implicated several β3 integrin-expressing cell populations, including endothelium, platelets and osteoclasts, in breast tumor progression. Since orthotopic human xenograft models of breast cancer are poorly metastatic to bone and experimental models bypass the formation of a primary tumor, however, the precise contribution of tumor-specific αvβ3 to the spontaneous metastasis of breast tumors from the mammary gland to bone remains unclear. METHODS: We used a syngeneic orthotopic model of spontaneous breast cancer metastasis to test whether exogenous expression of αvβ3 in a mammary carcinoma line (66cl4) that metastasizes to the lung, but not to bone, was sufficient to promote its spontaneous metastasis to bone from the mammary gland. The tumor burden in the spine and the lung following inoculation of αvβ3-expressing 66cl4 (66cl4beta3) tumor cells or control 66cl4pBabe into the mammary gland was analyzed by real-time quantitative PCR. The ability of these cells to grow and form osteolytic lesions in bone was determined by histology and tartrate-resistant acid phosphatase staining of bone sections following intratibial injection of tumor cells. The adhesive, migratory and invasive properties of 66cl4pBabe and 66cl4beta3 cells were evaluated in standard in vitro assays. RESULTS: The 66cl4beta3 tumors showed a 20-fold increase in metastatic burden in the spine compared with 66cl4pBabe. A similar trend in lung metastasis was observed. αvβ3 did not increase the proliferation of 66cl4 cells in vitro or in the mammary gland in vivo. Similarly, αvβ3 is not required for the proliferation of 66cl4 cells in bone as both 66cl4pBabe and 66cl4beta3 proliferated to the same extent when injected directly into the tibia. 66cl4beta3 tumor growth in the tibia, however, increased osteoclast recruitment and bone resorption compared with 66cl4 tumors. Moreover, αvβ3 increased 66cl4 tumor cell adhesion and αvβ3-dependent haptotactic migration towards bone matrix proteins, as well as their chemotactic response to bone-derived soluble factors in vitro. CONCLUSION: These results demonstrate for the first time that tumor-specific αvβ3 contributes to spontaneous metastasis of breast tumors to bone and suggest a critical role for this receptor in mediating chemotactic and haptotactic migration towards bone factors