Role of MALDI-MSI in combination with 3D tissue models for early stage efficacy and safety testing of drugs and toxicants

Introduction: Three-dimensional (3D) cell cultures have become increasingly important materials to investigate biological processes and drug efficacy and toxicity. The ability of 3D cultures to mimic the physiology of primary tissues and organs in the human body enables further insight into cellular behavior and is hence highly desirable in early-stage drug development. Analyzing the spatial distribution of drug compounds and endogenous molecules provides an insight into the efficacy of a drug whilst simultaneously giving information on biological responses. Areas Covered: In this review we will examine the main 3D cell culture systems employed and applications, which describe their integration with mass spectrometry imaging (MSI). Expert Opinion: MSI is a powerful technique that can map a vast range of molecules simultaneously in tissues without the addition of labels that can provide insights into the efficacy and safety of a new drug. The combination of MSI and 3D cell cultures has emerged as a promising tool in early-stage drug analysis. However, the most common administration route for pharmaceutical drugs is via oral delivery. The use of MSI in combination with models of the GI tract is an area that has been little explored to date, the reasons for this are discussed

Neutral winds in the polar thermosphere as measured from dynamics explorer

Remote sensing measurements of the meridional thermospheric neutral wind using the Fabry-Perot Interferometer on Dynamics Explorer have been combined with measurements of the zonal component using the Wind and Temperature Spectrometer on the same spacecraft. The two data sets with appropriate spatial phasing and averaging determine the vector wind along the track of the polar orbiting spacecraft. A study of fifty-eight passes over the Southern (sunlit) pole has enabled the average Universal Time dependence of the wind field to be determined for essentially a single solar local time cut. The results show the presence of a "back-ground" wind field driven by solar EUV heating upon which is superposed a circulating wind field driven by high latitude momentum and energy sources.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24099/1/0000356.pd

Moments of the Hadronic Invariant Mass Spectrum in B --> X_c l nu Decays at Belle

We present a measurement of the hadronic invariant mass squared (M^2_X) spectrum in charmed semileptonic B meson decays B --> X_c l nu based on 140 fb^-1 of Belle data collected near the Y(4S) resonance. We determine the first, the second central and the second non-central moments of this spectrum for lepton energy thresholds ranging between 0.7 and 1.9 GeV. Full correlations between these measurements are evaluated.Comment: published version of the paper (one figure added, minor changes in the text); 16 pages, 3 figures, 10 table

Improved measurement of CP-violating parameters in rho+rho- decays

We present a measurement of the CP-violating asymmetry in rho+rho- decays using 535 million BBbar pairs collected with the Belle detector at the KEKB e+e- collider. We measure CP-violating coefficients A = 0.16 +- 0.21(stat) +- 0.07 (syst) and S = 0.19 +- 0.30(stat) +- 0.07 (syst}. These values are used to determine the unitarity triangle angle phi_2 using an isospin analysis; the solution consistent with Standard Model lies in the range 53 < phi_2 < 114 deg. at 90 C.L.Comment: 6 pages, 4 figures, presented at JPS/DPF 2006 (Added KEK, BELLE preprint numbers, submitted to PRD(RC)

Researcher as Artist/Artist as Researcher

This is a postmodern article that is nontraditional in its form, content, and mode of representation. Upon recognizing that we share interests and common experiences as artists, we decided to collect life history information from each other about our artistic experiences. Thus we have become, simultaneously, "the researched" and "the re searcher." In these conversations, we explore the ways in which we were each guided by our past, very strong aesthetic and artistic experiences. We also include the voices of other researchers and artists in our conversations as we explore the influences of art in the formation of our worldviews.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68774/2/10.1177_107780049500100107.pd

Measurement of the ratio B(D0->pi+pi-pi0)/B(D0->K-pi+pi0) and the time-integrated CP asymmetry in D0->pi+pi-pi0

We report a high-statistics measurement of the relative branching fraction B(D0->pi+pi-pi0)/B(D0->K-pi+pi0) using a 532 fb^{-1} data sample collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. The measured value of the relative branching fraction is B(D0->pi+pi-pi0)/B(D0->K-pi+pi0) = (10.12 +/- 0.04(stat) +/- 0.18(syst))x10^{-2} which has an accuracy comparable to the world average. We also present a measurement of the time-integrated CP asymmetry in D0->pi+pi-pi0 decay. The result, A_{CP} = (0.43 +/- 1.30)%, shows no significant CP violation.Comment: 15 pages, 11 figures, submitted to Physics Letters

Search for B -> h(*) nu nubar Decays at Belle

We present a search for the rare decays B -> h(*) nu nubar, where h(*) stands for a light meson. A data sample of 535 million BBbar pairs collected with the Belle detector at the KEKB e+e- collider is used. Signal candidates are required to have an accompanying B meson fully reconstructed in a hadronic mode and signal-side particles consistent with a single h(*) meson. No significant signal is observed and we set upper limits on the branching fractions at 90% confidence level. The limits on B0 -> K*0 nu nubar and B+ -> K+ nu nubar decays are more stringent than the previous constraints, while the first searches for B0 -> K0 nu nubar, pi0 nu nubar, rho0 nu nubar, phi nu nubar and B+ -> K*+ nu nubar, rho+ nu nubar are reported.Comment: 6 pages, 2 figures, submit to PR

Demonstration of a novel technique to measure two-photon exchange effects in elastic e±pe^\pm p scattering

The discrepancy between proton electromagnetic form factors extracted using unpolarized and polarized scattering data is believed to be a consequence of two-photon exchange (TPE) effects. However, the calculations of TPE corrections have significant model dependence, and there is limited direct experimental evidence for such corrections. We present the results of a new experimental technique for making direct $e^\pm p$ comparisons, which has the potential to make precise measurements over a broad range in $Q^2$ and scattering angles. We use the Jefferson Lab electron beam and the Hall B photon tagger to generate a clean but untagged photon beam. The photon beam impinges on a converter foil to generate a mixed beam of electrons, positrons, and photons. A chicane is used to separate and recombine the electron and positron beams while the photon beam is stopped by a photon blocker. This provides a combined electron and positron beam, with energies from 0.5 to 3.2 GeV, which impinges on a liquid hydrogen target. The large acceptance CLAS detector is used to identify and reconstruct elastic scattering events, determining both the initial lepton energy and the sign of the scattered lepton. The data were collected in two days with a primary electron beam energy of only 3.3 GeV, limiting the data from this run to smaller values of $Q^2$ and scattering angle. Nonetheless, this measurement yields a data sample for $e^\pm p$ with statistics comparable to those of the best previous measurements. We have shown that we can cleanly identify elastic scattering events and correct for the difference in acceptance for electron and positron scattering. The final ratio of positron to electron scattering: $R=1.027\pm0.005\pm0.05$ for $=0.206$ GeV$^2$ and $0.830\leq \epsilon\leq 0.943$

Spectra of prompt electrons from decays of B+ and B0 mesons and ratio of inclusive semielectronic branching fractions

We present spectra of prompt electrons from decays of neutral and charged B mesons. The results are based on 140 /fb of data collected by the Belle detector on the Upsilon(4S) resonance at the KEKB e+e- asymmetric collider. We tag Upsilon(4S) -> B \bar{B} events by reconstructing a B meson in one of several hadronic decay modes; the semileptonic decay of the other B meson is inferred from the presence of an identified electron. We obtain for charged and neutral B mesons the partial rates of semileptonic decay, to electrons with momentum greater than 0.6 GeV/c in the B rest frame, and their ratio b_+/b_0 = 1.08 +- 0.05 +- 0.02, where the first and second errors are statistical and systematic, respectively.Comment: 16 pages, 2 figure files, submitted to Phys. Lett.

Observation of the Decays B0->K+pi-pi0 and B0->rho-K+

We report the observation of B^0 decays to the K^+pi^-pi^0 final state using a data sample of 78 fb^-1 collected by the Belle detector at the KEKB e^+e^- collider. With no assumptions about intermediate states in the decay, the branching fraction is measured to be (36.6^{+4.2}_{-4.3}+- 3.0)*10^-6.We also search for B decays to intermediate two-body states with the same K^+pi^-pi^0 final state. Significant B signals are observed in the rho(770)^- K^+ and K^*(892)^+pi^- channels, with branching fractions of (15.1^{+3.4+1.4+2.0}_{-3.3-1.5-2.1})* 10^-6 and (14.8^{+4.6+1.5+2.4}_{-4.4-1.0-0.9})* 10^-6, respectively. The first error is statistical, the second is systematic and the third is due to the largest possible interference. Contributions from other possible two-body states will be discussed. No CP asymmetry is found in the inclusive K^+pi^-pi^0 or rho^-K^+ modes, and we set 90% confidence level bounds on the asymmetry of -0.12<A_{CP}<0.26 and -0.18<A_{CP}<0.64, respectively.Comment: 18 pages, 7 figure