Some notes on the needs washed construction

This paper describes the geographic and social factors that correlate with the acceptability of the needs washed construction, based on the results of recent survey data. After briefly describing the survey methods, we discuss several ways to analyze the geographic distribution of the construction, focusing on the distribution of “hot” and “cold” spots across different versions of the construction. We find certain core areas where the construction is highly accepted, as well as core areas where the construction is highly rejected. Our survey looks at the effect of verb (need, want, like, and love), tense/modality (finite verb, modal would and would have), and population density (urban, suburban, rural). Moreover, we present maps that show how our results line up with previously proposed dialect regions of American English

NF-κB activation is a turn on for vaccinia virus phosphoprotein A49 to turn off NF-κB activation.

Vaccinia virus protein A49 inhibits NF-κB activation by molecular mimicry and has a motif near the N terminus that is conserved in IκBα, β-catenin, HIV Vpu, and some other proteins. This motif contains two serines, and for IκBα and β-catenin, phosphorylation of these serines enables recognition by the E3 ubiquitin ligase β-TrCP. Binding of IκBα and β-catenin by β-TrCP causes their ubiquitylation and thereafter proteasome-mediated degradation. In contrast, HIV Vpu and VACV A49 are not degraded. This paper shows that A49 is phosphorylated at serine 7 but not serine 12 and that this is necessary and sufficient for binding β-TrCP and antagonism of NF-κB. Phosphorylation of A49 S7 occurs when NF-κB signaling is activated by addition of IL-1β or overexpression of TRAF6 or IKKβ, the kinase needed for IκBα phosphorylation. Thus, A49 shows beautiful biological regulation, for it becomes an NF-κB antagonist upon activation of NF-κB signaling. The virulence of viruses expressing mutant A49 proteins or lacking A49 (vΔA49) was tested. vΔA49 was attenuated compared with WT, but viruses expressing A49 that cannot bind β-TrCP or bind β-TrCP constitutively had intermediate virulence. So A49 promotes virulence by inhibiting NF-κB activation and by another mechanism independent of S7 phosphorylation and NF-κB antagonism. Last, a virus lacking A49 was more immunogenic than the WT virus.Wellcome Trus

Leaky scanning translation generates a second A49 protein that contributes to vaccinia virus virulence.

Vaccinia virus (VACV) strain Western Reserve gene A49L encodes a small intracellular protein with a Bcl-2 fold that is expressed early during infection and has multiple functions. A49 co-precipitates with the E3 ubiquitin ligase β-TrCP and thereby prevents ubiquitylation and proteasomal degradation of IκBα, and consequently blocks activation of NF-κB. In a similar way, A49 stabilizes β-catenin, leading to activation of the wnt signalling pathway. However, a VACV strain expressing a mutant A49 that neither co-precipitates with β-TrCP nor inhibits NF-κB activation, is more virulent than a virus lacking A49, indicating that A49 has another function that also contributes to virulence. Here we demonstrate that gene A49L encodes a second, smaller polypeptide that is expressed via leaky scanning translation from methionine 20 and is unable to block NF-κB activation. Viruses engineered to express either only the large protein or only the small A49 protein both have lower virulence than wild-type virus and greater virulence than an A49L deletion mutant. This demonstrates that the small protein contributes to virulence by an unknown mechanism that is independent of NF-κB inhibition. Despite having a large genome with about 200 genes, this study illustrates how VACV makes efficient use of its coding potential and from gene A49L expresses a protein with multiple functions and multiple proteins with different functions

Probing Time-Dependent Molecular Dipoles on the Attosecond Time Scale

Photoinduced molecular processes start with the interaction of the instantaneous electric field of the incident light with the electronic degrees of freedom. This early attosecond electronic motion impacts the fate of the photoinduced reactions. We report the first observation of attosecond time scale electron dynamics in a series of small- and medium-sized neutral molecules (N2, CO2, and C2H4), monitoring time-dependent variations of the parent molecular ion yield in the ionization by an attosecond pulse, and thereby probing the time-dependent dipole induced by a moderately strong near- infrared laser field. This approach can be generalized to other molecular species and may be regarded as a first example of molecular attosecond Stark spectroscopy

Recent Developments in Few-Nucleon Systems

N-d elastic scattering is studied at different energies using one of the modern NN interactions, the Argonne v_{18} which explicitly includes the magnetic moment interaction between two nucleons. This interaction, which has been often neglected in the description of the few-nucleon continuum, produces sizable modifications in some elastic observables. Its effects, as well as those produced by the Coulomb potential, are analyzed as a function of energy. The magnetic moment interaction produces appreciable effects in $p-d$ scattering at low energies butthey are very small above 10 MeV. Above 65 MeV Coulomb effects can be observed only in specific observables as for example $T_{21}$.Comment: 9 pages, 5 figures, invited talk at the 17th International IUPAP Conference on Few-Body problems in Physics, June 5-10, 2003, Durham (USA