Persistent TFIIH binding to non-excised DNA damage causes cell and developmental failure

Congenital nucleotide excision repair (NER) deficiency gives rise to several cancer-prone and/or progeroid disorders. It is not understood how defects in the same DNA repair pathway cause different disease features and severity. Here, we show that the absence of functional ERCC1-XPF or XPG endonucleases leads to stable and prolonged binding of the transcription/DNA repair factor TFIIH to DNA damage, which correlates with disease severity and induces senescence features in human cells. In vivo, in C. elegans, this prolonged TFIIH binding to non-excised DNA damage causes developmental arrest and neuronal dysfunction, in a manner dependent on transcription-coupled NER. NER factors XPA and TTDA both promote stable TFIIH DNA binding and their depletion therefore suppresses these severe phenotypical consequences. These results identify stalled NER intermediates as pathogenic to cell functionality and organismal development, which can in part explain why mutations in XPF or XPG cause different disease features than mutations in XPA or TTDA.</p

HappyHier: hoe gelukkig is men waar? : Gegevensverzameling en bepaling van de invloed van het type grondgebruik, deel I

This study set out to measure what influence the type of environment has on how happy people say they feel at a certain moment in time, with the aim of formulating rules for quantifying the effect of spatial changes on wellbeing. A smartphone app was developed for use by a broad sample population in the Netherlands, with push notifications prompting people to report how they felt at a certain moment. From 1 May to 28 July of 2016, 4318 unique participants made use of this HappyHier app, filling in at least one questionnaire on location. The results show that people are happier outdoors than indoors. And when they are outdoors, they are happier in predominantly natural surroundings than in more built-up areas. Moreover, from the ratings given to the surroundings, it can be concluded that they have a more positive effect when the participants found them more restful or stimulating. People’s impressions of the beauty of their surroundings had less influenc

Search for Charginos with a Small Mass Difference with the Lightest Supersymmetric Particle at \sqrt{s} = 189 GeV

A search for charginos nearly mass-degenerate with the lightest supersymmetric particle is performed using the 176 pb^-1 of data collected at 189 GeV in 1998 with the L3 detector. Mass differences between the chargino and the lightest supersymmetric particle below 4 GeV are considered. The presence of a high transverse momentum photon is required to single out the signal from the photon-photon interaction background. No evidence for charginos is found and upper limits on the cross section for chargino pair production are set. For the first time, in the case of heavy scalar leptons, chargino mass limits are obtained for any \tilde{\chi}^{+-}_1 - \tilde{\chi}^0_1 mass difference

Measurements of Cross Sections and Forward-Backward Asymmetries at the Z Resonance and Determination of Electroweak Parameters

We report on measurements of hadronic and leptonic cross sections and leptonic forward-backward asymmetries performed with the L3 detector in the years 1993-95. A total luminosity of 103 pb^-1 was collected at centre-of-mass energies \sqrt{s} ~ m_Z and \sqrt{s} ~ m_Z +/- 1.8 GeV which corresponds to 2.5 million hadronic and 245 thousand leptonic events selected. These data lead to a significantly improved determination of Z parameters. From the total cross sections, combined with our measurements in 1990-92, we obtain the final results: m_Z = 91189.8 +/- 3.1 MeV, Gamma_Z = 2502.4 +/- 4.2 MeV, Gamma_had = 1741.1 +/- 3.8 MeV, Gamma_l = 84.14 +/- 0.17 MeV. An invisible width of Gamma_inv = 499.1 +/- 2.9 MeV is derived which in the Standard Model yields for the number of light neutrino species N_nu = 2.978 +/- 0.014. Adding our results on the leptonic forward-backward asymmetries and the tau polarisation, the effective vector and axial-vector coupling constants of the neutral weak current to charged leptons are determined to be \bar{g}_V^l = -0.0397 +/- 0.0017 and \bar{g}_A^l = -0.50153 +/- 0.00053.Including our measurements of the Z -> b \bar{b} forward-backward and quark charge asymmetries a value for the effective electroweak mixing angle of sin^2\bar{\theta}_W = 0.23093 +/- 0.00066 is derived. All these measurements are in good agreement with the Standard Model of electroweak interactions. Using all our measurements of electroweak observables an upper limit on the mass of the Standard Model Higgs boson of m_H < 133 GeV is set at 95% confidence level.Comment: 97 pages, 37 figure

Search for neutral charmless B decays at LEP

A search for rare charmless decays of \Bd and \Bs mesons has been performed in the exclusive channels \Bd_{(\mathrm s)}\ra\eta\eta, \Bd_{(\mathrm s)}\ra\eta\pio and \Bd_{(\mathrm s)}\ra\pio\pio. The data sample consisted of three million hadronic \Zo decays collected by the L3 experiment at LEP from 1991 through 1994. No candidate event has been observed and the following upper limits at 90\% confidence level on the branching ratios have been set \begin{displaymath} \mathrm{Br}(\Bd\ra\eta\eta)<4.1\times 10^{-4},\,\, \mathrm{Br}(\Bs\ra\eta\eta)<1.5\times 10^{-3},\,\, \end{displaymath} \begin{displaymath} \mathrm{Br}(\Bd\ra\eta\pio)<2.5\times 10^{-4},\,\, \mathrm{Br}(\Bs\ra\eta\pio)<1.0\times 10^{-3},\,\, \end{displaymath} \begin{displaymath} \mathrm{Br}(\Bd\ra\pio\pio)<6.0\times 10^{-5},\,\, \mathrm{Br}(\Bs\ra\pio\pio)<2.1\times 10^{-4}. \end{displaymath} These are the first experimental limits on \Bd\ra\eta\eta and on the \Bs neutral charmless modes

Search for neutral B meson decays to two charged leptons

The decays $\mathrm{B_d^0,\,B_s^0 \rightarrow e^+e^-,\,\mu^+\mu^-,\, e^\pm\mu^\mp}$ are searched for in 3.5 million hadronic ${\mathrm{Z}}$ events, which constitute the full LEP I data sample collected by the L3 detector. No signals are observed, therefore upper limits at the 90\%(95\%) confidence levels are set on the following branching fractions: % \begin{center}% {\setlength{\tabcolsep}{2pt} \begin{tabular}{lccccclcccc}% % Br$({\mathrm{B_d^0 \rightarrow {\mathrm{e^+e^-}}}})$ & $<$ & $1.4(1.8)$ & $\times$ & $10^{-5}$; & \hspace*{5mm} & Br$({\mathrm{B_s^0 \rightarrow {\mathrm{e^+e^-}}}})$ & $<$ & $5.4(7.0)$ & $\times$ & $10^{-5}$; \\% Br$({\mathrm{B_d^0 \rightarrow \mu^+\mu^-}})$ & $<$ & $1.0(1.4)$ & $\times$ & $10^{-5}$; & \hspace*{5mm} & Br$({\mathrm{B_s^0 \rightarrow \mu^+\mu^-}})$ & $<$ & $3.8(5.1)$ & $\times$ & $10^{-5}$; \\% Br$({\mathrm{B_d^0 \rightarrow {\mathrm{e^\pm\mu^\mp}}}})$ & $<$ & $1.6(2.0)$ & $\times$ & $10^{-5}$; & \hspace*{5mm} & Br$({\mathrm{B_s^0 \rightarrow {\mathrm{e^\pm\mu^\mp}}}})$ & $<$ & $4.1(5.3)$ & $\times$ & $10^{-5}$. \\% % \end{tabular}% } \end{center}% % The results for ${\mathrm{B_s^0\rightarrow{\mathrm{e^+e^-}}}}$ and ${\mathrm{B_s^0 \rightarrow {\mathrm{e^\pm\mu^\mp}}}}$ are the first limits set on these decay modes