Capmatinib for patients with non-small cell lung cancer with MET exon 14 skipping mutations: a review of preclinical and clinical studies

The mesenchymal-epithelial transition (MET) receptor tyrosine kinase binds the hepatocyte growth factor to activate downstream cell signaling pathways involved in cell proliferation, survival, and migration. Several genetic mechanisms can result in an aberrant activation of this receptor in cancer cells. One such activating mechanism involves the acquisition of gene mutations that cause MET exon 14 skipping (METex14) during mRNA splicing. Mutations leading to METex14 are found in approximately 3?4% of patients with non-small cell lung cancer (NSCLC). Accumulating evidence suggests that METex14 is a true, independent oncogenic driver in NSCLC, as well as being an independent prognostic factor for poorer survival in patients with NSCLC. The successes of target therapies have relied on improved understanding of the genetic alterations that lead to the dysregulation of the molecular pathways and more advanced molecular diagnostics. Multiple efforts have been made to target the MET pathway in cancer; however, real clinical progress has only occurred since the emergence of METex14 as a valid biomarker for MET inhibition. Capmatinib is a highly potent and selective type Ib inhibitor of MET. Following preclinical demonstration of activity against MET-dependent cancer cell line growth and METdriven tumor growth in xenograft models, data from a phase 1 clinical trial showed an acceptable safety profile of capmatinib and preliminary evidence of efficacy in patients with MET-dysregulated NSCLC. The multicohort GEOMETRY mono-1 phase 2 trial reported objective response rates of 68% and 41% in treatment-na?ve and in pre-treated patients with METex14 advanced NSCLC, respectively. These results have supported the approval of capmatinib by the US Food and Drug Administration for patients with metastatic NSCLC harboring METex14.Pathogenesis and treatment of chronic pulmonary disease

Heavy-to-light transition form factors and their relations in light-cone QCD sum rules

The improved light-cone QCD sum rules by using chiral current correlator is systematically reviewed and applied to the calculation of all the heavy-to-light form factors, including all the semileptonic and penguin ones. By choosing suitable chiral currents, the light-cone sum rules for all the form factors are greatly simplified and depend mainly on one leading twist distribution amplitude of the light meson. As a result, relations between these form factors arise naturally. At the considered accuracy these relations reproduce the results obtained in the literature. Moreover, since the explicit dependence on the leading twist distribution amplitudes is preserved, these relations may be more useful to simulate the experimental data and extract the information on the distribution amplitude.Comment: 1+16 pages, no figure

A passive micromachined device for alignment of arrays of single-mode fibers for hermetic photonic packaging - the CLASP concept

A micro-machined fiber alignment device, called CLASP (Capture and Locking Alignment Spring Positioner) has been fabricated. It uses a nickel leaf spring to passively capture vertical arrays of single-mode fibers with {approximately} 2 {mu}m accuracy

Analysis of Various Polarization Asymmetries In The Inclusive b→sℓ+ℓ−b\to s \ell^+ \ell^- Decay In The Fourth-Generation Standard Model

In this study a systematical analysis of various polarization asymmetries in inclusive b \rar s \ell^+ \ell^- decay in the standard model (SM) with four generation of quarks is carried out. We found that the various asymmetries are sensitive to the new mixing and quark masses for both of the $\mu$ and $\tau$ channels. Sizeable deviations from the SM values are obtained. Hence, b \rar s \ell^+ \ell^- decay is a valuable tool for searching physics beyond the SM, especially in the indirect searches for the fourth-generation of quarks ($t', b')$.Comment: 19 Pages, 10 Figures, 3 Table

Rare Decays of \Lambda_b->\Lambda + \gamma and \Lambda_b ->\Lambda + l^{+} l^{-} in the Light-cone Sum Rules

Within the Standard Model, we investigate the weak decays of $\Lambda_b \to \Lambda + \gamma$ and $\Lambda_b \to \Lambda + l^{+} l^{-}$ with the light-cone sum rules approach. The higher twist distribution amplitudes of $\Lambda$ baryon to the leading conformal spin are included in the sum rules for transition form factors. Our results indicate that the higher twist distribution amplitudes almost have no influences on the transition form factors retaining the heavy quark spin symmetry, while such corrections can result in significant impacts on the form factors breaking the heavy quark spin symmetry. Two phenomenological models (COZ and FZOZ) for the wave function of $\Lambda$ baryon are also employed in the sum rules for a comparison, which can give rise to the form factors approximately 5 times larger than that in terms of conformal expansion. Utilizing the form factors calculated in LCSR, we then perform a careful study on the decay rate, polarization asymmetry and forward-backward asymmetry, with respect to the decays of $\Lambda_b \to \Lambda \gamma$, $\Lambda l^{+}l^{-}$.Comment: 38 pages, 15 figures, some typos are corrected and more references are adde

Vector and pseudoscalar charm meson radiative decays

Combining heavy quark effective theory and the chiral Lagrangian approach we investigate radiative decays of pseudoscalar $D$ mesons. We first reanalyse $D^{*} \rightarrow D \gamma$ decays within the effective Lagrangian approach using heavy quark spin symmetry, chiral symmetry Lagrangian, but including also the light vector mesons. We then investigate $D \rightarrow V \gamma$ decays and calculate the $D^0 \rightarrow \bar{K}^{*0} \gamma$ and $D^{s+} \rightarrow \rho^+ \gamma$ partial widths and branching ratios.Comment: 21 pages Latex, no figures, IJS-TP-94/19, TUM-31-62/94, NUHEP-TH-94-

Hubble expansion and structure formation in the "running FLRW model" of the cosmic evolution

A new class of FLRW cosmological models with time-evolving fundamental parameters should emerge naturally from a description of the expansion of the universe based on the first principles of quantum field theory and string theory. Within this general paradigm, one expects that both the gravitational Newton's coupling, G, and the cosmological term, Lambda, should not be strictly constant but appear rather as smooth functions of the Hubble rate. This scenario ("running FLRW model") predicts, in a natural way, the existence of dynamical dark energy without invoking the participation of extraneous scalar fields. In this paper, we perform a detailed study of these models in the light of the latest cosmological data, which serves to illustrate the phenomenological viability of the new dark energy paradigm as a serious alternative to the traditional scalar field approaches. By performing a joint likelihood analysis of the recent SNIa data, the CMB shift parameter, and the BAOs traced by the Sloan Digital Sky Survey, we put tight constraints on the main cosmological parameters. Furthermore, we derive the theoretically predicted dark-matter halo mass function and the corresponding redshift distribution of cluster-size halos for the "running" models studied. Despite the fact that these models closely reproduce the standard LCDM Hubble expansion, their normalization of the perturbation's power-spectrum varies, imposing, in many cases, a significantly different cluster-size halo redshift distribution. This fact indicates that it should be relatively easy to distinguish between the "running" models and the LCDM cosmology using realistic future X-ray and Sunyaev-Zeldovich cluster surveys.Comment: Version published in JCAP 08 (2011) 007: 1+41 pages, 6 Figures, 1 Table. Typos corrected. Extended discussion on the computation of the linearly extrapolated density threshold above which structures collapse in time-varying vacuum models. One appendix, a few references and one figure adde

Nonresonant Three-body Decays of D and B Mesons

Nonresonant three-body decays of D and B mesons are studied. It is pointed out that if heavy meson chiral perturbation theory (HMChPT) is applied to the heavy-light strong and weak vertices and assumed to be valid over the whole kinematic region, then the predicted decay rates for nonresonant charmless 3-body B decays will be too large and especially B^- --> pi^- K^+ K^- greatly exceeds the current experimental limit. This can be understood as chiral symmetry has been applied there twice beyond its region of validity. If HMChPT is applied only to the strong vertex and the weak transition is accounted for by the form factors, the dominant B^* pole contribution to the tree-dominated direct three-body B decays will become small and the branching ratio will be of order 10^{-6}. The decay modes B^- --> (K^- h^+ h^-)_{NR} and bar{B}^0 --> (bar{K}^0 h^+h^-)_{NR} for h = pi, K are penguin dominated. We apply HMChPT in two different cases to study the direct 3-body D decays and compare the results with experiment. Theoretical uncertainties are discussed.Comment: 24 pages, 2 figures. New experimental results of direct 3-body D decays as Reported at ICHEP2002 are included. To appear in Phys. Re

Hadronic B Decays Involving Even Parity Charmed Mesons

Hadronic B decays containing an parity-even charmed meson in the final state are studied. Specifically we focus on the Cabibbo-allowed decays $\bar B\to D^{**} \pi(\rho), D^{**}\bar D_s^{(*)}, \bar D^{**}_sD^{(*)}$ and $\bar B_s\to D_s^{**}\pi(\rho)$, where $D^{**}$ denotes generically a p-wave charmed meson. The $B\to D^{**}$ transition form factors are studied in the improved version of the Isgur-Scora-Grinstein-Wise quark model. We apply heavy quark effective theory and chiral symmetry to study the strong decays of p-wave charmed mesons and determine the magnitude of the $D_1^{1/2}-D_1^{3/2}$ mixing angle. Except the decay to $D_1(2427)^0\pi^-$ the predictions for $B^-\to D^{**0}\pi^-$ agree with experiment. The sign of $D_1^{1/2}-D_1^{3/2}$ mixing angle is found to be positive in order to avoid a severe suppression on the production of $D_1(2427)^0\pi^-$. The interference between color-allowed and color-suppressed tree amplitudes is expected to be destructive in the decay $B^-\to D_1(2427)^0\pi^-$. Hence, an observation of the ratio $D_1(2427)^0\pi^-/D_1(2427)^+\pi^-$ can be used to test the relative signs of various form factors as implied by heavy quark symmetry. Although the predicted $B^-\to D_1(2420)^0\rho^-$ at the level of $3\times 10^{-3}$ exceeds the present upper limit, it leads to the ratio $D_1(2420)\rho^-/D_1(2420)\pi^-\approx 2.6$ as expected from the factorization approach and from the ratio $f_\rho/f_\pi\approx 1.6$ . Therefore, it is crucial to have a measurement of this mode to test the factorization hypothesis. For $\bar B\to \bar D_s^{**}D$ decays, it is expected that \bar D_{s0}^*D\gsim \bar D_{s1}D as the decay constants of the multiplet $(D_{s0}^*,D_{s1})$ become the same in the heavy quark limit.Comment: 27 pages, Belle's new data on DD_s^{**} productions in B decays and on the radiative decay D_{s1}-> D_s\gamma are updated and discussed. Add two reference

Nonfactorizable contributions in B decays to charmonium: the case of B−→K−hcB^- \to K^- h_c

Nonleptonic $B$ to charmonium decays generally show deviations from the factorization predictions. For example, the mode $B^- \to K^- \chi_{c0}$ has been experimentally observed with sizeable branching fraction while its factorized amplitude vanishes. We investigate the role of rescattering effects mediated by intermediate charmed meson production in this class of decay modes, and consider $B^- \to K^- h_c$ with $h_c$ the $J^{PC}=1^{+-}$ $\bar c c$ meson. Using an effective lagrangian describing interactions of pairs of heavy-light $Q{\bar q}$ mesons with a quarkonium state, we relate this mode to the analogous mode with $\chi_{c0}$ in the final state. We find ${\cal B}(B^- \to K^- h_c)$ large enough to be measured at the $B$ factories, so that this decay mode could be used to study the poorly known $h_c$.Comment: RevTex, 16 pages, 2 eps figure