Biomarker discovery for colon cancer using a 761 gene RT-PCR assay

<p>Abstract</p> <p>Background</p> <p>Reverse transcription PCR (RT-PCR) is widely recognized to be the gold standard method for quantifying gene expression. Studies using RT-PCR technology as a discovery tool have historically been limited to relatively small gene sets compared to other gene expression platforms such as microarrays. We have recently shown that TaqMan^®RT-PCR can be scaled up to profile expression for 192 genes in fixed paraffin-embedded (FPE) clinical study tumor specimens. This technology has also been used to develop and commercialize a widely used clinical test for breast cancer prognosis and prediction, the Onco <it>type</it>DX™ assay. A similar need exists in colon cancer for a test that provides information on the likelihood of disease recurrence in colon cancer (prognosis) and the likelihood of tumor response to standard chemotherapy regimens (prediction). We have now scaled our RT-PCR assay to efficiently screen 761 biomarkers across hundreds of patient samples and applied this process to biomarker discovery in colon cancer. This screening strategy remains attractive due to the inherent advantages of maintaining platform consistency from discovery through clinical application.</p> <p>Results</p> <p>RNA was extracted from formalin fixed paraffin embedded (FPE) tissue, as old as 28 years, from 354 patients enrolled in NSABP C-01 and C-02 colon cancer studies. Multiplexed reverse transcription reactions were performed using a gene specific primer pool containing 761 unique primers. PCR was performed as independent TaqMan^®reactions for each candidate gene. Hierarchal clustering demonstrates that genes expected to co-express form obvious, distinct and in certain cases very tightly correlated clusters, validating the reliability of this technical approach to biomarker discovery.</p> <p>Conclusion</p> <p>We have developed a high throughput, quantitatively precise multi-analyte gene expression platform for biomarker discovery that approaches low density DNA arrays in numbers of genes analyzed while maintaining the high specificity, sensitivity and reproducibility that are characteristics of RT-PCR. Biomarkers discovered using this approach can be transferred to a clinical reference laboratory setting without having to re-validate the assay on a second technology platform.</p

Ultra-High Energy Cosmic Rays in a Structured and Magnetized Universe

We simulate propagation of cosmic ray nucleons above 10^{19} eV in scenarios where both the source distribution and magnetic fields within about 50 Mpc from us are obtained from an unconstrained large scale structure simulation. We find that consistency of predicted sky distributions with current data above 4 x 10^{19} eV requires magnetic fields of ~0.1 microGauss in our immediate environment, and a nearby source density of ~10^{-4}-10^{-3} Mpc^{-3}. Radio galaxies could provide the required sources, but only if both high and low-luminosity radio galaxies are very efficient cosmic ray accelerators. Moreover, at ~10^{19} eV an additional isotropic flux component, presumably of cosmological origin, should dominate over the local flux component by about a factor three in order to explain the observed isotropy. This argues against the scenario in which local astrophysical sources of cosmic rays above ~10^{19} eV reside in strongly magnetized (B~0.1 microGauss) and structured intergalactic medium. Finally we discuss how future large scale full-sky detectors such as the Pierre Auger project will allow to put much more stringent constraints on source and magnetic field distributions.Comment: 11 revtex pages, 10 postscript figures included, final version to appear in PR

UV Circular Polarisation in Star Formation Regions : The Origin of Homochirality?

Ultraviolet circularly polarised light has been suggested as the initial cause of the homochirality of organic molecules in terrestrial organisms, via enantiomeric selection of prebiotic molecules by asymmetric photolysis. We present a theoretical investigation of mechanisms by which ultraviolet circular polarisation may be produced in star formation regions. In the scenarios considered here, light scattering produces only a small percentage of net circular polarisation at any point in space, due to the forward throwing nature of the phase function in the ultraviolet. By contrast, dichroic extinction can produce a fairly high percentage of net circular polarisation (∼10%) and may therefore play a key role in producing an enantiomeric excessPeer reviewe

Measurement of \cal{B}(D^+ --> mu^+ nu) and the Pseudoscalar Decay Constant fD+f_{D^+}

In 60 pb-1 of data taken on the psi(3770) resonance with the CLEO-c detector, we find 8 D+ to mu+ nu event candidates that are mostly signal, containing only 1 estimated background. Using this statistically compelling sample, we measure preliminary values of B(D+ to mu+ nu) = (3.5 +- 1.4 +- 0.6)*10^{-4}, and determine f_{D+} =(201+- 41+- 17) MeV.Comment: 17 pages postscript, also available through http://www.lns.cornell.edu/public/CONF/2004/, Presented at ICHEP Aug 16-22,2004, Beijing, Chin

Study of Charmless Hadronic B Meson Decays to Pseudoscalar-Vector Final States

We report results of searches for charmless hadronic B meson decays to pseudoscalar(pi^+-,K^+-,Pi^0 or Ks^0)-vector(Rho, K* or Omega) final states. Using 9.7 million BBbar pairs collected with the CLEO detector, we report first observation of B^- --> Pi^-Rho^0, B^0 --> Pi^+-Rho^-+ and B^- --> Pi^-Omega, which are expected to be dominated by hadronic b --> u transitions. The measured branching fractions are (10.4+3.3-3.4+-2.1)x10^-6, (27.6+8.4-7.4+-4.2)x10^-6 and (11.3+3.3-2.9+-1.4)x10^-6, respectively. Branching fraction upper limits are set for all the other decay modes investigated.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Update of the measurement of the cross section for e^+e^- -> psi(3770) -> hadrons

We have updated our measurement of the cross section for e^+e^- -> psi(3770) -> hadrons, our publication "Measurement of sigma(e^+e^- -> psi(3770) -> hadrons) at E_{c.m.} = 3773 MeV", arXiv:hep-ex/0512038, Phys.Rev.Lett.96, 092002 (2006). Simultaneous with this arXiv update, we have published an erratum in Phys.Rev.Lett.104, 159901 (2010). There, and in this update, we have corrected a mistake in the computation of the error on the difference of the cross sections for e^+e^- -> psi(3770) -> hadrons and e^+e^- -> psi(3770) -> DDbar. We have also used a more recent CLEO measurement of cross section for e^+e^- -> psi(3770) -> DDbar. From this, we obtain an upper limit on the branching fraction for psi(3770) -> non-DDbar of 9% at 90% confidence level.Comment: 3 pages, 0 figures. This is an erratum to Phys.Rev.Lett.96:092002,2006. Added a reference

Measurement of the Decay Constant fDS+f_D{_S^+} using $D_S^+ --> ell^+ nu

We measure the decay constant fDs using the Ds -> l+ nu channel, where the l+ designates either a mu+ or a tau+, when the tau+ -> pi+ nu. Using both measurements we find fDs = 274 +-13 +- 7 MeV. Combining with our previous determination of fD+, we compute the ratio fDs/fD+ = 1.23 +- 0.11 +- 0.04. We compare with theoretical estimates.Comment: 6 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2007

Measurement of higher cumulants of net-charge multiplicity distributions in Au++Au collisions at sNN=7.7−200\sqrt{s_{_{NN}}}=7.7-200 GeV

We report the measurement of cumulants ($C_n, n=1\ldots4$) of the net-charge distributions measured within pseudorapidity ($|\eta|<0.35$) in Au$+$Au collisions at $\sqrt{s_{_{NN}}}=7.7-200$ GeV with the PHENIX experiment at the Relativistic Heavy Ion Collider. The ratios of cumulants (e.g. $C_1/C_2$, $C_3/C_1$) of the net-charge distributions, which can be related to volume independent susceptibility ratios, are studied as a function of centrality and energy. These quantities are important to understand the quantum-chromodynamics phase diagram and possible existence of a critical end point. The measured values are very well described by expectation from negative binomial distributions. We do not observe any nonmonotonic behavior in the ratios of the cumulants as a function of collision energy. The measured values of $C_1/C_2 = \mu/\sigma^2$ and $C_3/C_1 = S\sigma^3/\mu$ can be directly compared to lattice quantum-chromodynamics calculations and thus allow extraction of both the chemical freeze-out temperature and the baryon chemical potential at each center-of-mass energy.Comment: 512 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for publication in Phys. Rev. C as a Rapid Communication. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Measurement of Absolute Hadronic Branching Fractions of D Mesons and e^+ e^- --> D D-bar Cross Sections at the psi(3770)

Using 281 /pb of e^+ e^- collisions recorded at the psi(3770) resonance with the CLEO-c detector at CESR, we determine absolute hadronic branching fractions of charged and neutral D mesons using a double tag technique. Among measurements for three D^0 and six D^+ modes, we obtain reference branching fractions B(D^0 --> K^-pi^+) = (3.891 +- 0.035 +- 0.059 +- 0.035)% and B(D^+ --> K^-pi^+pi^+) = (9.14 +- 0.10 +- 0.16 +- 0.07)%, where the first uncertainty is statistical, the second is all systematic errors other than final state radiation (FSR), and the third is the systematic uncertainty due to FSR. We include FSR in these branching fractions by allowing for additional unobserved photons in the final state. Using an independent determination of the integrated luminosity, we also extract the cross sections sigma(e+e- --> D^0 D^0-bar) = (3.66+- 0.03 +- 0.06) nb and sigma(e+e- --> D^+ D^-) = (2.91+- 0.03 +- 0.05) nb at a center of mass energy, E_cm = 3774 +- 1 MeV.Comment: 47 pages, postscript also available through this http://www.lns.cornell.edu/public/CLNS/2007/, to be published in PRD, updated branching fractions using B(KS0 --> pi+ pi-) from PDG 2007, and updated text in response to the PRD reviewe

Search for Lepton Flavor Violation in Upsilon Decays

In this Letter we describe a search for lepton flavor violation (LFV) in the bottomonium system. We search for leptonic decays of Upsilon(nS)(n=1,2, and 3) into muon and tau using the data collected with the CLEO III detector. We identify the tau lepton using its leptonic decay into electron and utilize multidimensional likelihood fitting with PDF shapes measured from independent data samples. We report our estimates of 95% CL upper limits on LFV branching fractions of Upsilon mesons. We interpret our results in terms of the exclusion plot for the energy scale of a hypothetical new interaction versus its effective LFV coupling in the framework of effective field theory.Comment: 10 pages, 3 figures, available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR