384 research outputs found
Recombinant Trimeric HA Protein Immunogenicity of H5N1 Avian Influenza Viruses and Their Combined Use with Inactivated or Adenovirus Vaccines
[[abstract]]Background:The highly pathogenic avian influenza (HPAI) H5N1 virus continues to cause disease in poultry and humans. The hemagglutinin (HA) envelope protein is the primary target for subunit vaccine development.Methodology/Principal Findings:We used baculovirus-insect cell expression to obtain trimeric recombinant HA (rHA) proteins from two HPAI H5N1 viruses. We investigated trimeric rHA protein immunogenicity in mice via immunizations, and found that the highest levels of neutralizing antibodies resulted from coupling with a PELC/CpG adjuvant. We also found that the combined use of trimeric rHA proteins with (a) an inactivated H5N1 vaccine virus, or (b) a recombinant adenovirus encoding full-length HA sequences for prime-boost immunization, further improved antibody responses against homologous and heterologous H5N1 virus strains. Data from cross-clade prime-boost immunization regimens indicate that sequential immunization with different clade HA antigens increased antibody responses in terms of total IgG level and neutralizing antibody titers.Conclusion/Significance:Our findings suggest that the use of trimeric rHA in prime-boost vaccine regimens represents an alternative strategy for recombinant H5N1 vaccine development
Regulation of Progranulin Expression in Human Microglia and Proteolysis of Progranulin by Matrix Metalloproteinase-12 (MMP-12)
Background: The essential role of progranulin (PGRN) as a neurotrophic factor has been demonstrated by the discovery that haploinsufficiency due to GRN gene mutations causes frontotemporal lobar dementia. In addition to neurons, microglia in vivo express PGRN, but little is known about the regulation of PGRN expression by microglia. Goal: In the current study, we examined the regulation of expression and function of PGRN, its proteolytic enzyme macrophage elastase (MMP-12), as well as the inhibitor of PGRN proteolysis, secretory leukocyte protease inhibitor (SLPI), in human CNS cells. Methods: Cultures of primary human microglia and astrocytes were stimulated with the TLR ligands (LPS or poly IC), Th1 cytokines (IL-1/IFNc), or Th2 cytokines (IL-4, IL-13). Results were analyzed by Q-PCR, immunoblotting or ELISA. The roles of MMP-12 and SLPI in PGRN cleavage were also examined. Results: Unstimulated microglia produced nanogram levels of PGRN, and PGRN release from microglia was suppressed by the TLR ligands or IL-1/IFNc, but increased by IL-4 or IL-13. Unexpectedly, while astrocytes stimulated with proinflammatory factors released large amounts of SLPI, none were detected in microglial cultures. We also identified MMP-12 as a PGRN proteolytic enzyme, and SLPI as an inhibitor of MMP-12-induced PGRN proteolysis. Experiments employing PGRN siRNA demonstrated that microglial PGRN was involved in the cytokine and chemokine production following TLR3/4 activation
Search for Pair Production of Scalar Top Quarks Decaying to a tau Lepton and a b Quark in ppbar Collisions at sqrt{s}=1.96 TeV
We search for pair production of supersymmetric top quarks (~t_1), followed
by R-parity violating decay ~t_1 -> tau b with a branching ratio beta, using
322 pb^-1 of ppbar collisions at sqrt{s}=1.96 TeV collected by the CDF II
detector at Fermilab. Two candidate events pass our final selection criteria,
consistent with the standard model expectation. We set upper limits on the
cross section sigma(~t_1 ~tbar_1)*beta^2 as a function of the stop mass
m(~t_1). Assuming beta=1, we set a 95% confidence level limit m(~t_1)>153
GeV/c^2. The limits are also applicable to the case of a third generation
scalar leptoquark (LQ_3) decaying LQ_3 -> tau b.Comment: 7 pages, 2 eps figure
ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study
<p>Abstract</p> <p>Background</p> <p>Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes.</p> <p>Methods</p> <p>Six gene polymorphisms functional in drug-metabolism – <it>GSTP1 </it>Ile105Val, <it>ABCB1 </it>Ile1145Ile, <it>MTHFR </it>Ala222Val, <it>TYMS </it>double (2R) or triple (3R) tandem repeat – and DNA-repair genes – <it>ERCC2 </it>Lys751Gln and <it>XRCC1 A</it>rg399Gln – were assessed in 201 CRC patients using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique and DNA sequencing. Patients were diagnosed as either high-risk stage II (T2 and 3 N0 M0) or III (any T N1 and 2 M0) and were administered adjuvant chemotherapy regimens that included 5-fluorouracil (5FU) and leucovorin (LV). The correlations between genetic polymorphisms and patient clinicopathological features and relapses were investigated.</p> <p>Results</p> <p>In this study, the distributions of <it>GSTP1 </it>(<it>P </it>= 0.003), <it>ABCB1 </it>(<it>P </it>= 0.001), <it>TYMS </it>(<it>P </it>< 0.0001), <it>ERCC2 </it>(<it>P </it>< 0.0001) and <it>XRCC1 </it>(<it>P </it>= 0.006) genotypes in the Asian population, with the exception of <it>MTHFR </it>(<it>P </it>= 0.081), differed significantly from their distributions in a Caucasian population. However, the unfavorable genotype <it>ERCC2 </it>2251A>C (<it>P </it>= 0.006), tumor invasion depth (<it>P </it>= 0.025), lymph node metastasis (<it>P </it>= 0.011) and cancer stage (<it>P </it>= 0.008) were significantly correlated with early relapse. Patients carrying the <it>ERCC2 </it>2251AC or2251CC genotypes had a significantly increased risk of early relapse (OR = 3.294, 95% CI, 1.272–8.532).</p> <p>Conclusion</p> <p>We suggest that <it>ERCC2 </it>2251A>C alleles may be genetic predictors of early CRC relapse.</p
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.
Observation of Bs-Bsbar Oscillations
We report the observation of Bs-Bsbar oscillations from a time-dependent
measurement of the Bs-Bsbar oscillation frequency Delta ms. Using a data sample
of 1 fb^-1 of p-pbar collisions at sqrt{s}=1.96 TeV collected with the CDF II
detector at the Fermilab Tevatron, we find signals of 5600 fully reconstructed
hadronic Bs decays, 3100 partially reconstructed hadronic Bs decays, and 61500
partially reconstructed semileptonic Bs decays. We measure the probability as a
function of proper decay time that the Bs decays with the same, or opposite,
flavor as the flavor at production, and we find a signal for Bs-Bsbar
oscillations. The probability that random fluctuations could produce a
comparable signal is 8 X 10^-8, which exceeds 5 sigma significance. We measure
Delta ms = 17.77 +- 0.10 (stat) +- 0.07 (syst) ps^-1
and extract
|Vtd/Vts| = 0.2060 +- 0.0007 (exp) + 0.0081 - 0.0060 (theor).Comment: 9 pages, 5 figures, submitted to Physical Review Letter
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 Lifetime and Decay-Width Difference in B0s -> J/psi phi Decays
We measure the mean lifetime, tau=2/(Gamma_L+Gamma_H), and the width
difference, DeltaGamma=Gamma_L-Gamma_H, of the light and heavy mass eigenstates
of the B0s meson, B0sL and B0sH, in B0s -> J/psi phi decays using 1.7 fb^-1 of
data collected with the CDF II detector at the Fermilab Tevatron ppbar
collider. Assuming CP conservation, a good approximation for the B0s system in
the Standard Model, we obtain DeltaGamma = 0.076^+0.059_-0.063 (stat.) +- 0.006
(syst.) ps^-1 and tau = 1.52 +- 0.04 (stat.) +- 0.02 (syst.) ps, the most
precise measurements to date. Our constraints on the weak phase and DeltaGamma
are consistent with CP conservation.
Dedicated to the memory of our dear friend and colleague, Michael P. Schmid
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
Tunable Optical Performances on a Periodic Array of Plasmonic Bowtie Nanoantennas with Hollow Cavities
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