Co-Evolution of quasispecies: B-cell mutation rates maximize viral error catastrophes

Co-evolution of two coupled quasispecies is studied, motivated by the competition between viral evolution and adapting immune response. In this co-adaptive model, besides the classical error catastrophe for high virus mutation rates, a second ``adaptation-'' catastrophe occurs, when virus mutation rates are too small to escape immune attack. Maximizing both regimes of viral error catastrophes is a possible strategy for an optimal immune response, reducing the range of allowed viral mutation rates to a minimum. From this requirement one obtains constraints on B-cell mutation rates and receptor lengths, yielding an estimate of somatic hypermutation rates in the germinal center in accordance with observation.Comment: 4 pages RevTeX including 2 figure

Characteristics of tropospheric ozone depletion events in the Arctic spring: analysis of the ARCTAS, ARCPAC, and ARCIONS measurements and satellite BrO observations

Arctic ozone depletion events (ODEs) are caused by halogen catalyzed ozone loss. In situ chemistry, advection of ozone-poor air mass, and vertical mixing in the lower troposphere are important factors affecting ODEs. To better characterize the ODEs, we analyze the combined set of surface, ozonesonde, and aircraft in situ measurements of ozone and bromine compounds during the Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS), the Aerosol, Radiation, and Cloud Processes affecting Arctic Climate (ARCPAC), and the Arctic Intensive Ozonesonde Network Study (ARCIONS) experiments (April 2008). Tropospheric BrO columns retrieved from satellite measurements and back trajectory calculations are also used to investigate the characteristics of observed ODEs. In situ observations from these field experiments are inadequate to validate tropospheric BrO columns derived from satellite measurements. In view of this difficulty, we construct an ensemble of tropospheric column BrO estimates from two satellite (OMI and GOME-2) measurements and with three independent methods of calculating stratospheric BrO columns. Furthermore, we select analysis methods that do not depend on the absolute magnitude of column BrO, such as time-lagged correlation analysis of ozone and tropospheric column BrO, to understand characteristics of ODEs. Time-lagged correlation analysis between in situ (surface and ozonesonde) measurements of ozone and satellite derived tropospheric BrO columns indicates that the ODEs are due to either local halogen-driven ozone loss or short-range (∼1 day) transport from nearby regions with ozone depletion. The effect of in situ ozone loss is also evident in the diurnal variation difference between low (10th and 25th percentiles) and higher percentiles of surface ozone concentrations at Alert, Canada. Aircraft observations indicate low-ozone air mass transported from adjacent high-BrO regions. Correlation analyses of ozone with potential temperature and time-lagged tropospheric BrO column show that the vertical extent of local ozone loss is surprisingly deep (1–2 km) at Resolute and Churchill, Canada. The unstable boundary layer during ODEs at Churchill could potentially provide a source of free-tropospheric BrO through convective transport and explain the significant negative correlation between free-tropospheric ozone and tropospheric BrO column at this site

Whole brain radiotherapy (WBRT) after local treatment of brain metastases in melanoma patients: Statistical Analysis Plan

Background: The WBRTMel trial is a multinational, open-label, phase III randomised controlled trial comparing whole brain radiotherapy (WBRT) to observation following local treatment of one to three melanoma brain metastases with surgery and/or stereotactic irradiation. The primary trial endpoint was to determine the effect of adding WBRT to local treatment on distant intracranial control, and the secondary endpoints were neurocognitive function, quality of life (QoL), performance status, overall survival, death from intracranial causes, death from melanoma and cost-effectiveness. Objective: The objective of this update is to outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis. Methods: The SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical and QoL outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data. Results: The resulting SAP is consistent with best practice and will allow open and transparent reporting. Conclusion: We have developed a SAP for the WBRTMel trial which will be followed to ensure high-quality standards of internal validity to minimise analysis bias

A Proposal for a Three Detector Short-Baseline Neutrino Oscillation Program in the Fermilab Booster Neutrino Beam

A Short-Baseline Neutrino (SBN) physics program of three LAr-TPC detectors located along the Booster Neutrino Beam (BNB) at Fermilab is presented. This new SBN Program will deliver a rich and compelling physics opportunity, including the ability to resolve a class of experimental anomalies in neutrino physics and to perform the most sensitive search to date for sterile neutrinos at the eV mass-scale through both appearance and disappearance oscillation channels. Using data sets of 6.6e20 protons on target (P.O.T.) in the LAr1-ND and ICARUS T600 detectors plus 13.2e20 P.O.T. in the MicroBooNE detector, we estimate that a search for muon neutrino to electron neutrino appearance can be performed with ~5 sigma sensitivity for the LSND allowed (99% C.L.) parameter region. In this proposal for the SBN Program, we describe the physics analysis, the conceptual design of the LAr1-ND detector, the design and refurbishment of the T600 detector, the necessary infrastructure required to execute the program, and a possible reconfiguration of the BNB target and horn system to improve its performance for oscillation searches.Comment: 209 pages, 129 figure

Search for Doubly-Charged Higgs Boson Production at HERA

A search for the single production of doubly-charged Higgs bosons H^{\pm \pm} in ep collisions is presented. The signal is searched for via the Higgs decays into a high mass pair of same charge leptons, one of them being an electron. The analysis uses up to 118 pb^{-1} of ep data collected by the H1 experiment at HERA. No evidence for doubly-charged Higgs production is observed and mass dependent upper limits are derived on the Yukawa couplings h_{el} of the Higgs boson to an electron-lepton pair. Assuming that the doubly-charged Higgs only decays into an electron and a muon via a coupling of electromagnetic strength h_{e \mu} = \sqrt{4 \pi \alpha_{em}} = 0.3, a lower limit of 141 GeV on the H^{\pm\pm} mass is obtained at the 95% confidence level. For a doubly-charged Higgs decaying only into an electron and a tau and a coupling h_{e\tau} = 0.3, masses below 112 GeV are ruled out.Comment: 15 pages, 3 figures, 1 tabl