418 research outputs found
Establishment of an In Vitro Assay for Assessing the Effects of Drugs on the Liver Stages of Plasmodium vivax Malaria
Plasmodium vivax (Pv) is the second most important human malaria parasite. Recent data indicate that the impact of Pv malaria on the health and economies of the developing world has been dramatically underestimated. Pv has a unique feature in its life cycle. Uninucleate sporozoites (spz), after invasion of human hepatocytes, either proceed to develop into tens of thousands of merozoites within the infected hepatocytes or remain as dormant forms called hypnozoites, which cause relapses of malaria months to several years after the primary infection. Elimination of malaria caused by Pv will be facilitated by developing a safe, highly effective drug that eliminates Pv liver stages, including hypnozoites. Identification and development of such a drug would be facilitated by the development of a medium to high throughput assay for screening drugs against Pv liver stages. We undertook the present pilot study to (1) assess the feasibility of producing large quantities of purified, vialed, cryopreserved Pv sporozoites and (2) establish a system for culturing the liver stages of Pv in order to assess the effects of drugs on the liver stages of Pv. We used primaquine (PQ) to establish this assay model, because PQ is the only licensed drug known to clear all Pv hepatocyte stages, including hypnozoites, and the effect of PQ on Pv hepatocyte stage development in vitro has not previously been reported. We report that we have established the capacity to reproducibly infect hepatoma cells with purified, cyropreserved Pv spz from the same lot, quantitate the primary outcome variable of infected hepatoma cells and demonstrate the inhibitory activity of primaquine on the infected hepatoma cells. We have also identified small parasite forms that may be hypnozoites. These data provide the foundation for finalizing a medium throughput, high content assay to identify new drugs for the elimination of all Pv liver stages
The influence of tumor size and environment on gene expression in commonly used human tumor lines
BACKGROUND: The expression profiles of solid tumor models in rodents have been only minimally studied despite their extensive use to develop anticancer agents. We have applied RNA expression profiling using Affymetrix U95A GeneChips to address fundamental biological questions about human tumor lines. METHODS: To determine whether gene expression changed significantly as a tumor increased in size, we analyzed samples from two human colon carcinoma lines (Colo205 and HCT-116) at three different sizes (200 mg, 500 mg and 1000 mg). To investigate whether gene expression was influenced by the strain of mouse, tumor samples isolated from C.B-17 SCID and Nu/Nu mice were also compared. Finally, the gene expression differences between tissue culture and in vivo samples were investigated by comparing profiles from lines grown in both environments. RESULTS: Multidimensional scaling and analysis of variance demonstrated that the tumor lines were dramatically different from each other and that gene expression remained constant as the tumors increased in size. Statistical analysis revealed that 63 genes were differentially expressed due to the strain of mouse the tumor was grown in but the function of the encoded proteins did not link to any distinct biological pathways. Hierarchical clustering of tissue culture and xenograft samples demonstrated that for each individual tumor line, the in vivo and in vitro profiles were more similar to each other than any other profile. We identified 36 genes with a pattern of high expression in xenograft samples that encoded proteins involved in extracellular matrix, cell surface receptors and transcription factors. An additional 17 genes were identified with a pattern of high expression in tissue culture samples and encoded proteins involved in cell division, cell cycle and RNA production. CONCLUSIONS: The environment a tumor line is grown in can have a significant effect on gene expression but tumor size has little or no effect for subcutaneously grown solid tumors. Furthermore, an individual tumor line has an RNA expression pattern that clearly defines it from other lines even when grown in different environments. This could be used as a quality control tool for preclinical oncology studies
Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron
We study the underlying event in proton-antiproton collisions by examining
the behavior of charged particles (transverse momentum pT > 0.5 GeV/c,
pseudorapidity |\eta| < 1) produced in association with large transverse
momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the
Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV
center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan
production) or the leading jet (in high-pT jet production) in each event to
define three regions of \eta-\phi space; toward, away, and transverse, where
\phi is the azimuthal scattering angle. For Drell-Yan production (excluding the
leptons) both the toward and transverse regions are very sensitive to the
underlying event. In high-pT jet production the transverse region is very
sensitive to the underlying event and is separated into a MAX and MIN
transverse region, which helps separate the hard component (initial and
final-state radiation) from the beam-beam remnant and multiple parton
interaction components of the scattering. The data are corrected to the
particle level to remove detector effects and are then compared with several
QCD Monte-Carlo models. The goal of this analysis is to provide data that can
be used to test and improve the QCD Monte-Carlo models of the underlying event
that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.
Study of CP violation in Dalitz-plot analyses of B0 --> K+K-KS, B+ --> K+K-K+, and B+ --> KSKSK+
We perform amplitude analyses of the decays , , and , and measure CP-violating
parameters and partial branching fractions. The results are based on a data
sample of approximately decays, collected with the
BABAR detector at the PEP-II asymmetric-energy factory at the SLAC National
Accelerator Laboratory. For , we find a direct CP asymmetry
in of , which differs
from zero by . For , we measure the
CP-violating phase .
For , we measure an overall direct CP asymmetry of
. We also perform an angular-moment analysis of
the three channels, and determine that the state can be described
well by the sum of the resonances , , and
.Comment: 35 pages, 68 postscript figures. v3 - minor modifications to agree
with published versio
Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay
We reconstruct the rare decays , , and in a data sample
corresponding to collected in collisions at
by the CDF II detector at the Fermilab Tevatron
Collider. Using and decays we report the branching ratios. In addition, we report
the measurement of the differential branching ratio and the muon
forward-backward asymmetry in the and decay modes, and the
longitudinal polarization in the decay mode with respect to the squared
dimuon mass. These are consistent with the theoretical prediction from the
standard model, and most recent determinations from other experiments and of
comparable accuracy. We also report the first observation of the {\mathcal{B}}(B^0_s \to
\phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}27 \pm 6B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let
Measurement of the Production Cross Section and Search for Anomalous and Couplings in Collisions at TeV
This Letter describes the current most precise measurement of the boson
pair production cross section and most sensitive test of anomalous
and couplings in collisions at a center-of-mass energy of 1.96
TeV. The candidates are reconstructed from decays containing two charged
leptons and two neutrinos, where the charged leptons are either electrons or
muons. Using data collected by the CDF II detector from 3.6 fb of
integrated luminosity, a total of 654 candidate events are observed with an
expected background contribution of events. The measured total
cross section is pb, which is in good agreement
with the standard model prediction. The same data sample is used to place
constraints on anomalous and couplings.Comment: submitted to Phys. Rev. Let
Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons
We report measurements of the resonance properties of Lambda_c(2595)+ and
Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as
Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+
pi+/- final states. These measurements are performed using data corresponding
to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV,
collected with the CDF II detector at the Fermilab Tevatron. Exploiting the
largest available charmed baryon sample, we measure masses and decay widths
with uncertainties comparable to the world averages for Sigma_c states, and
significantly smaller uncertainties than the world averages for excited
Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17
pages, 15 figure
Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV
We present a search for a new heavy charged vector boson decaying
to an electron-neutrino pair in collisions at a center-of-mass
energy of 1.96\unit{TeV}. The data were collected with the CDF II detector
and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No
significant excess above the standard model expectation is observed and we set
upper limits on . Assuming standard
model couplings to fermions and the neutrino from the boson decay to
be light, we exclude a boson with mass less than
1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR
Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-
We report a measurement of time-integrated CP-violation asymmetries in the
resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II
data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar
collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come
from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production
flavor of the charm meson is determined by the charge of the accompanying pion.
We apply a Dalitz-amplitude analysis for the description of the dynamic decay
structure and use two complementary approaches, namely a full Dalitz-plot fit
employing the isobar model for the contributing resonances and a
model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We
find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57
(stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry,
consistent with the standard model prediction.Comment: 15 page
Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-
We report the first observation of the baryonic flavor-changing neutral
current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a
statistical significance of 5.8 Gaussian standard deviations. This measurement
uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV
collected by the CDF II detector at the Tevatron collider. The total and
differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We
find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}.
We also report the first measurement of the differential branching ratio of B_s
-> phi mu+ mu- using 49 signal events. In addition, we report branching ratios
for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let
- …