Harvardiana : March Song

https://digitalcommons.library.umaine.edu/mmb-vp/4967/thumbnail.jp

Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species

Highly pathogenic avian influenza A viruses (HPAIV) of the H5N1 subtype occasionally transmit from birds to humans and can cause severe systemic infections in both hosts. PB1-F2 is an alternative translation product of the viral PB1 segment that was initially characterized as a pro-apoptotic mitochondrial viral pathogenicity factor. A full-length PB1-F2 has been present in all human influenza pandemic virus isolates of the 20(th) century, but appears to be lost evolutionarily over time as the new virus establishes itself and circulates in the human host. In contrast, the open reading frame (ORF) for PB1-F2 is exceptionally well-conserved in avian influenza virus isolates. Here we perform a comparative study to show for the first time that PB1-F2 is a pathogenicity determinant for HPAIV (A/Viet Nam/1203/2004, VN1203 (H5N1)) in both mammals and birds. In a mammalian host, the rare N66S polymorphism in PB1-F2 that was previously described to be associated with high lethality of the 1918 influenza A virus showed increased replication and virulence of a recombinant VN1203 H5N1 virus, while deletion of the entire PB1-F2 ORF had negligible effects. Interestingly, the N66S substituted virus efficiently invades the CNS and replicates in the brain of Mx+/+ mice. In ducks deletion of PB1-F2 clearly resulted in delayed onset of clinical symptoms and systemic spreading of virus, while variations at position 66 played only a minor role in pathogenesis. These data implicate PB1-F2 as an important pathogenicity factor in ducks independent of sequence variations at position 66. Our data could explain why PB1-F2 is conserved in avian influenza virus isolates and only impacts pathogenicity in mammals when containing certain amino acid motifs such as the rare N66S polymorphism

Double marking revisited

In 2002, the Qualifications and Curriculum Authority (QCA) published the report of an independent panel of experts into maintaining standards at Advanced Level (A-Level). One of its recommendations was for: ‘limited experimental double marking of scripts in subjects such as English to determine whether the strategy would signi-ficantly reduce errors of measurement’ (p. 24). This recommendation provided the impetus for this paper which reviews the all but forgotten literature on double marking and considers its relevance now

Polarization dependence of four-wave mixing in a degenerate two-level system

Nearly degenerate four-wave mixing (NDFWM) within a closed degenerate two-level atomic transition is theoretically and experimentally examined. Using the model presented by A. Lezama et al [Phys. Rev. A 61, 013801 (2000)] the NDFWM spectra corresponding to different pump and probe polarization cases are calculated and discussed. The calculated spectra are compared to the observation of NDFWM within the $6S_{1/2}(F=4)\to 6P_{3/2}(F=5)$ transition of cesium in a phase conjugation experiment using magneto optically cooled atomsComment: 10 pages, 13 figures; submitted to Phys. Rev.

Near-zero anomalous dispersion Ge11.5As24Se64.5 glass nanowires for correlated photon pair generation: design and analysis

We show that highly nonlinear chalcogenide glass nanowire waveguides with near-zero anomalous dispersion should be capable of generating correlated photon-pairs by spontaneous four-wave mixing at frequencies detuned by over 17 THz from the pump where Raman noise is absent. In this region we predict a photon pair correlation of >100, a figure of merit >10 and brightness of ~8×108 pairs/s over a bandwidth of >15 THz in nanowires with group velocity dispersion of <5 ps∙km−1nm−1. We present designs for double-clad Ge11.5As24Se64.5 glass nanowires with realistic tolerance to fabrication errors that achieve near-zero anomalous dispersion at a 1420 nm pump wavelength. This structure has a fabrication tolerance of 80–170 nm in the waveguide width and utilizes a SiO2/Al2O3 layer deposited by atomic layer deposition to compensate the fabrication errors in the film thickness

Effective elements of cognitive behaviour therapy for psychosis: results of a novel type of subgroup analysis based on principal stratification

Background. Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology. Method. The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization. Results. Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective. Conclusions. Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment

Systematic effects and a new determination of the primordial abundance of 4He and dY/dZ from observations of blue compact galaxies

We use spectroscopic observations of a sample of 82 HII regions in 76 blue compact galaxies to determine the primordial helium abundance Yp and the slope dY/dZ from the Y-O/H linear regression. To improve the accuracy of the dY/dZ measurement, we have included new spectrophotometric observations of 33 HII regions which span a large metallicity range, with oxygen abundance 12+log(O/H) varying between 7.43 and 8.30 (Zsun/30<Z<Zsun/4). For a subsample of 7 HII regions, we derive the He mass fraction taking into account known systematic effects, including collisional and fluorescent enhancements of HeI emission lines, collisional excitation of hydrogen emission, underlying stellar HeI absorption and the difference between the temperatures Te(HeII) in the He^+ zone and Te(OIII) derived from the collisionally excited [OIII] lines. We find that the net result of all the systematic effects combined is small, changing the He mass fraction by less than 0.6%. By extrapolating the Y vs. O/H linear regression to O/H=0 for 7 HII regions of this subsample, we obtain Yp=0.2421+/-0.0021 and dY/dO=5.7+/-1.8, which corresponds to dY/dZ=3.7+/-1.2, assuming the oxygen mass fraction to be O=0.66Z. In the framework of the standard Big Bang nucleosynthesis theory, this Yp corresponds to Omega_b h^2 = 0.012^+0.003_-0.002, where h is the Hubble constant in units of 100 km/s/Mpc. This is smaller at the 2sigma level than the value obtained from recent deuterium abundance and microwave background radiation measurements. The linear regression slope dY/dO=4.3+/-0.7 (corresponding to dY/dZ=2.8+/-0.5) for the whole sample of 82 HII regions is similar to that derived for the subsample of 7 HII regions, although it has a considerably smaller uncertainty.Comment: 53 pages, 3 Postscript figures, accepted for publication in the Astrophysical Journa