Flavor changing single top quark production channels at e^+e^- colliders in the effective Lagrangian description

We perform a global analysis of the sensitivity of LEP2 and e^+e^- colliders with a c.m. energy in the range 500 - 2000 GeV to new flavor-changing single top quark production in the effective Lagrangian approach. The processes considered are sensitive to new flavor-changing effective vertices such as Ztc, htc, four-Fermi tcee contact terms as well as a right-handed Wtb coupling. We show that e^+ e^- colliders are most sensitive to the physics responsible for the contact tcee vertices. For example, it is found that the recent data from the 189 GeV LEP2 run can be used to rule out any new flavor physics that can generate these four-Fermi operators up to energy scales of \Lambda > 0.7 - 1.4 TeV, depending on the type of the four-Fermi interaction. We also show that a corresponding limit of \Lambda > 1.3 - 2.5 and \Lambda > 17 - 27 TeV can be reached at the future 200 GeV LEP2 run and a 1000 GeV e^+e^- collider, respectively. We note that these limits are much stronger than the typical limits which can be placed on flavor diagonal four-Fermi couplings. Similar results hold for \mu^+\mu^- colliders and for tu(bar) associated production. Finally we briefly comment on the necessity of measuring all flavor-changing effective vertices as they can be produced by different types of heavy physics.Comment: 34 pages, plain latex, 7 figures embadded in the text using epsfig. Added new references and discussions regarding their relevance to the paper. Added more comments on the comparison between flavor-changing and flavor-diagonal contact terms and on the importance of measuring the Ztc verte

Fermi-edge singularities in linear and non-linear ultrafast spectroscopy

We discuss Fermi-edge singularity effects on the linear and nonlinear transient response of an electron gas in a doped semiconductor. We use a bosonization scheme to describe the low energy excitations, which allows to compute the time and temperature dependence of the response functions. Coherent control of the energy absorption at resonance is analyzed in the linear regime. It is shown that a phase-shift appears in the coherent control oscillations, which is not present in the excitonic case. The nonlinear response is calculated analytically and used to predict that four wave-mixing experiments would present a Fermi-edge singularity when the exciting energy is varied. A new dephasing mechanism is predicted in doped samples that depends linearly on temperature and is produced by the low-energy bosonic excitations in the conduction band.Comment: long version; 9 pages, 4 figure

Molecular mechanisms of HIV Type 1 prophylaxis failure revealed by Single-genome sequencing

Trials of HIV-1 pre- and post-exposure prophylaxis show promise. Here, we describe a novel strategy for deciphering mechanisms of prophylaxis failure that could improve therapeutic outcomes. A healthcare worker began antiretroviral prophylaxis immediately after a high-risk needlestick injury but nonetheless became viremic 11 weeks later. Single genome sequencing of plasma viral RNA identified 15 drug-sensitive transmitted/founder HIV-1 genomes responsible for productive infection. Sequences emanating from these genomes exhibited extremely low diversity, suggesting virus sequestration as opposed to low-level replication as the cause of breakthrough infection. Identification of transmitted/founder viruses allows for genome-wide assessment of molecular mechanisms of prophylaxis failure

CTLA-4 and PD-1 dual blockade induces SIV reactivation without control of rebound after antiretroviral therapy interruption

The primary human immunodeficiency virus (HIV) reservoir is composed of resting memory CD4+ T cells, which often express the immune checkpoint receptors programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4), which limit T cell activation via synergistic mechanisms. Using simian immunodeficiency virus (SIV)-infected, long-term antiretroviral therapy (ART)-treated rhesus macaques, we demonstrate that PD-1, CTLA-4 and dual CTLA-4/PD-1 immune checkpoint blockade using monoclonal antibodies is well tolerated, with evidence of bioactivity in blood and lymph nodes. Dual blockade was remarkably more effective than PD-1 blockade alone in enhancing T cell cycling and differentiation, expanding effector-memory T cells and inducing robust viral reactivation in plasma and peripheral blood mononuclear cells. In lymph nodes, dual CTLA-4/PD-1 blockade, but not PD-1 alone, decreased the total and intact SIV-DNA in CD4+ T cells, and SIV-DNA and SIV-RNA in B cell follicles, a major site of viral persistence during ART. None of the tested interventions enhanced SIV-specific CD8+ T cell responses during ART or viral control after ART interruption. Thus, despite CTLA-4/PD-1 blockade inducing robust latency reversal and reducing total levels of integrated virus, the degree of reservoir clearance was still insufficient to achieve viral control. These results suggest that immune checkpoint blockade regimens targeting PD-1 and/or CTLA-4, if performed in people living with HIV with sustained aviremia, are unlikely to induce HIV remission in the absence of additional interventions

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

BACKGROUND REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. METHODS We randomly assigned, in a 1:1 ratio, participants (=12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARSCoV- 2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase- quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). RESULTS Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. CONCLUSIONS Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load

Molecular identification of transmitted/founder viruses by single genome amplification following percutaneous occupational exposure to HIV-1

Background: Occupational exposure of health care workers (HCW) to HIV-1 is an uncommon but important route of virus transmission. Single genome amplification (SGA) and sequencing of plasma vRNA during acute infection (Keele PNAS 2008) makes possible, for the first time, a precise identification of transmitted/founder (T/F) viral genomes and a molecular analysis of mechanisms of treatment failure following post-exposure prophylaxis (PEP). Methods: A 53 yo phlebotomist sustained a deep hollow-bore needle injury to the left forefinger with inadvertent blood inoculation from an advanced AIDS patient. PEP (AZT, 3TC, IND) was initiated within two hours and continued for 4 wks. 6 wks post-exposure, HIV-1 ELISA was negative. 12 wks post-exposure, HIV-1 ELISA and vRNA were positive and WB negative. SGA-direct amplicon sequencing was performed on plasma vRNA from the source patient (SP) and HCW. Results: A total of 179 full-length pol, env gp41, and 3’ half-genome sequences were determined by SGA. Sequences from the SP revealed maximum diversity of ≤4.35% in gp41 and ≤2.19% in pol. HCW sequences revealed 12 discrete, low diversity lineages (each <0.27%) representing 12 distinct T/F viral genomes. 11 of 12 lineages showed no RT or protease drug resistance mutations. One minor lineage had 1 aa change indicative of IND resistance. Conclusion: Transmission of ≥12 viruses following a high-risk needlestick is consistent with multivariant HIV-1 transmission observed in injection drug users (Bar J Virol 2010). Delayed viremia and Ab seroconversion, low viral sequence diversification, and absence of drug resistance mutations suggest evolutionary stasis and low or absent viral replication during PEP therapy. Mechanisms of PEP failure thus include virus sequestration and post-treatment virus reactivation

Picosecond precessional magnetization reversal by magnetic field pulse shaping

Contains fulltext : 92612.pdf (publisher's version ) (Closed access

Activity of comets at large heliocentric distances pre-perihelion

We present observational data for two long-period and three dynamically new comets observed at heliocentric distances between 5.8 to 14.0 AU. All of the comets exhibited activity beyond the distance at which water ice sublimation can be significant. We have conducted experiments on gas-laden amorphous ice samples and show that considerable gas emission occurs when the ice is heated below the temperature of the amorphous-crystalline ice phase transition (T � 137 K). We propose that annealing of amorphous water ice is the driver of activity in comets as they first enter the inner Solar System. Experimental data show that large grains can be ejected at low velocity during annealing and that the rate of brightening of the comet should decrease as the heliocentric distance decreases. These results are consistent with both historical observations of distant comet activity and with the data presented here. If observations of the onset of activity in a dynamically new comet are ever made, the distance at which this occurs would be a sensitive indicator of the temperature at which the comet had formed or represents the maximum temperature that it has experienced. New surveys such as Pan STARRS, may be able to detect these comets while they are still inactive. © 2009 Elsevier Inc