IFN stimulated gene expression in the liver is a better predictor of treatment response in chronic hepatitis c than the IL28b (IFN lambda 3) genotype

Background: Therapy of chronic hepatitis C (CHC) with pegIFNa/ribavirin achieves sustained virologic response (SVR) in ~55%. Pre-activation of the endogenous interferon system in the liver is associated non-response (NR). Recently, genome-wide association studies described associations of allelic variants near the IL28B (IFNλ3) gene with treatment response and with spontaneous clearance of the virus. We investigated if the IL28B genotype determines the constitutive expression of IFN stimulated genes (ISGs) in the liver of patients with CHC. Methods: We genotyped 93 patients with CHC for 3 IL28B single nucleotide polymorphisms (SNPs, rs12979860, rs8099917, rs12980275), extracted RNA from their liver biopsies and quantified the expression of IL28B and of 8 previously identified classifier genes which discriminate between SVR and NR (IFI44L, RSAD2, ISG15, IFI22, LAMP3, OAS3, LGALS3BP and HTATIP2). Decision tree ensembles in the form of a random forest classifier were used to calculate the relative predictive power of these different variables in a multivariate analysis. Results: The minor IL28B allele (bad risk for treatment response) was significantly associated with increased expression of ISGs, and, unexpectedly, with decreased expression of IL28B. Stratification of the patients into SVR and NR revealed that ISG expression was conditionally independent from the IL28B genotype, i.e. there was an increased expression of ISGs in NR compared to SVR irrespective of the IL28B genotype. The random forest feature score (RFFS) identified IFI27 (RFFS = 2.93), RSAD2 (1.88) and HTATIP2 (1.50) expression and the HCV genotype (1.62) as the strongest predictors of treatment response. ROC curves of the IL28B SNPs showed an AUC of 0.66 with an error rate (ERR) of 0.38. A classifier with the 3 best classifying genes showed an excellent test performance with an AUC of 0.94 and ERR of 0.15. The addition of IL28B genotype information did not improve the predictive power of the 3-gene classifier. Conclusions: IL28B genotype and hepatic ISG expression are conditionally independent predictors of treatment response in CHC. There is no direct link between altered IFNλ3 expression and pre-activation of the endogenous system in the liver. Hepatic ISG expression is by far the better predictor for treatment response than IL28B genotype

CROO: A universal infrastructure and protocol to detect identity fraud

Identity fraud (IDF) may be defined as unauthorized exploitation of credential information through the use of false identity. We propose CROO, a universal (i.e. generic) infrastructure and protocol to either prevent IDF (by detecting attempts thereof), or limit its consequences (by identifying cases of previously undetected IDF). CROO is a capture resilient one-time password scheme, whereby each user must carry a personal trusted device used to generate one-time passwords (OTPs) verified by online trusted parties. Multiple trusted parties may be used for increased scalability. OTPs can be used regardless of a transaction’s purpose (e.g. user authentication or financial payment), associated credentials, and online or on-site nature; this makes CROO a universal scheme. OTPs are not sent in cleartext; they are used as keys to compute MACs of hashed transaction information, in a manner allowing OTP-verifying parties to confirm that given user credentials (i.e. OTP-keyed MACs) correspond to claimed hashed transaction details. Hashing transaction details increases user privacy. Each OTP is generated from a PIN-encrypted non-verifiable key; this makes users’ devices resilient to off-line PIN-guessing attacks. CROO’s credentials can be formatted as existing user credentials (e.g. credit cards or driver’s licenses)

Classe de Mathématiques, réalité et communication

This study focuses on an inquiry-based teaching experience in mathematics, with 5th grade students in which we have established a strong connection with reality and intensified student’s ability to communicate, while promoting problem solving and mathematical reasoning. Mathematics lessons are organized into four phases: (i) Launching the task for students; (ii) Development of the task; (iii) Discussion of the task; and (iv) Systematization of mathematical learning. To prepare task discussion, the teacher implements a “gallery of tasks” through which students have their first contact with their colleague’s resolutions: they can ask questions and make comments in the presented sheets. This article presents the results of a lesson on percentages, in which students worked on the task entitled “Discount at Bit- @ - Byte”. The analysis of this task and the results of similar tasks of reality made throughout the school year shows that the inquiry-based teaching allows improvements in mathematics, namely learning concepts and capabilities such as reasoning, communication and problem solving

Measurement of the Tau Branching Fractions into Leptons

Using data collected with the L3 detector near the Z resonance, corresponding to an integrated luminosity of 150pb-1, the branching fractions of the tau lepton into electron and muon are measured to be B(tau->e nu nu) = (17.806 +- 0.104 (stat.) +- 0.076 (syst.)) %, B(tau->mu nu nu) = (17.342 +- 0.110 (stat.) +- 0.067 (syst.)) %. From these results the ratio of the charged current coupling constants of the muon and the electron is determined to be g_mu/g_e = 1.0007 +- 0.0051. Assuming electron-muon universality, the Fermi constant is measured in tau lepton decays as G_F = (1.1616 +- 0.0058) 10^{-5} GeV^{-2}. Furthermore, the coupling constant of the strong interaction at the tau mass scale is obtained as alpha_s(m_tau^2) = 0.322 +- 0.009 (exp.) +- 0.015 (theory)

Higgs Candidates in e+e- Interactions at root(s) = 206.6 GeV

In a search for the Standard Model Higgs boson, carried out on 212.5 pb-1 of data collected by the L3 detector at the highest LEP centre-of-mass energies, including 116.5 pb-1 above root(s) = 206GeV, an excess of candidates for the process e+e- -> Z* -> HZ is found for Higgs masses near 114.5GeV. We present an analysis of our data and the characteristics of our strongest candidates.Comment: Footnote added, matches the version to be published in Physics Letters

Search for a Higgs Boson Decaying to Weak Boson Pairs at LEP

A Higgs particle produced in association with a Z boson and decaying into weak boson pairs is searched for in 336.4 1/pb of data collected by the L3 experiment at LEP at centre-of-mass energies from 200 to 209 GeV. Limits on the branching fraction of the Higgs boson decay into two weak bosons as a function of the Higgs mass are derived. These results are combined with the L3 search for a Higgs boson decaying to photon pairs. A Higgs produced with a Standard Model e+e- --> Zh cross section and decaying only into electroweak boson pairs is excluded at 95% CL for a mass below 107 GeV

Search for Heavy Neutral and Charged Leptons in e+ e- Annihilation at LEP

A search for exotic unstable neutral and charged heavy leptons as well as for stable charged heavy leptons is performed with the L3 detector at LEP. Sequential, vector and mirror natures of heavy leptons are considered. No evidence for their existence is found and lower limits on their masses are set

Inclusive D* Production in Two-Photon Collisions at LEP

Inclusive D^{*+-} production in two-photon collisions is studied with the L3 detector at LEP, using 683 pb^{-1} of data collected at centre-of-mass energies from 183 to 208 GeV. Differential cross sections are determined as functions of the transverse momentum and pseudorapidity of the D^{*+-} mesons in the kinematic region 1 GeV < P_T < 12 GeV and |eta| < 1.4. The cross sections sigma(e^+e^- -> e^+e^-D^{*+-}X) in this kinematical region is measured and the sigma(e^+e^- -> e^+e^- cc{bar}X) cross section is derived. The measurements are compared with next-to-leading order perturbative QCD calculations

Search for Doubly-Charged Higgs Bosons at LEP

Doubly-charged Higgs bosons are searched for in e^+e^- collision data collected with the L3 detector at LEP at centre-of-mass energies up to 209 GeV. Final states with four leptons are analysed to tag the pair-production of doubly charged Higgs bosons. No significant excess is found and lower limits at 95% confidence level on the doubly-charged Higgs boson mass are derived. They vary from 95.5 GeV to 100.2 GeV, depending on the decay mode. Doubly-charged Higgs bosons which couple to electrons would modify the cross section and forward-backward asymmetry of the e^+e^- -> e^+e^- process. The measurements of these quantities do not deviate from the Standard Model expectations and doubly-charged Higgs bosons with masses up to the order of a TeV are excluded

Standard Model Higgs Boson with the L3 Experiment at LEP

Final results of the search for the Standard Model Higgs boson are presented for the data collected by the L3 detector at LEP at centre-of-mass energies up to about 209 GeV. These data are compared with the expectations of Standard Model processes for Higgs boson masses up to 120 GeV. A lower limit on the mass of the Standard Model Higgs boson of 112.0 GeV is set at the 95 % confidence level. The most significant high mass candidate is a Hnunu event. It has a reconstructed Higgs mass of 115 GeV and it was recorded at root(s)=206.4 GeV