Stanilov-Tsankov-Videv Theory

We survey some recent results concerning Stanilov-Tsankov-Videv theory, conformal Osserman geometry, and Walker geometry which relate algebraic properties of the curvature operator to the underlying geometry of the manifold.Comment: This is a contribution to the Proceedings of the 2007 Midwest Geometry Conference in honor of Thomas P. Branson, published in SIGMA (Symmetry, Integrability and Geometry: Methods and Applications) at http://www.emis.de/journals/SIGMA

Preferential attachment in the protein network evolution

The Saccharomyces cerevisiae protein-protein interaction map, as well as many natural and man-made networks, shares the scale-free topology. The preferential attachment model was suggested as a generic network evolution model that yields this universal topology. However, it is not clear that the model assumptions hold for the protein interaction network. Using a cross genome comparison we show that (a) the older a protein, the better connected it is, and (b) The number of interactions a protein gains during its evolution is proportional to its connectivity. Therefore, preferential attachment governs the protein network evolution. The evolutionary mechanism leading to such preference and some implications are discussed.Comment: Minor changes per referees requests; to appear in PR

Process optimization for semi-continuous virus production at high cell densities

Background. Unlike production of recombinant proteins, continuous production of viral vaccines at high cell densities (HCD) is still constrained by host cell lysis during virus propagation and limited virus recovery from culture broth. Nevertheless, advanced fed-batch [1] and perfusion strategies can be applied to achieve a high-yield virus production processes. In this study, the development of a high-yield semi-continuous process for the production and purification of the modified vaccinia Ankara virus isolate MVA-CR19 and influenza A/PR/8 in HCD cultivations of the suspension cell line AGE1.CR.pIX (ProBioGen AG, Berlin) is presented. Methods. Depending on the required scale, high cell concentrations (~ 50×106 cell mL-1) were achieved either through medium renewal by periodic centrifugation (semi-perfusion) in 50 mL cultivations or using an alternating tangential flow (ATF) perfusion system for 1 L bioreactors. Process development and optimization comprised three phases: 1) assessment of different fed-batch and medium exchange strategies for the propagation of MVA-CR19 or influenza A/PR/8 viruses in 50 mL cultivations; 2) scale-up and process optimization of the high-yield process strategy to a 1 L bioreactor with the ATF system, and 3) integration of a purification process step using magnetic sulfated cellulose particles (MSCP). For both viruses, conventional batch cultivation (no addition/medium exchange after infection) was compared with processes applying fed-batch, periodic medium exchange and the combination of both during virus propagation. Results. Perfusion and semi-perfusion at a feeding rate of 0.05 nL/cell×d was suitable to propagate AGE1.CR.pIX cells above 60×106 cells/mL with neither limitation nor overload of nutrients. For infections in 50 mL, the application of a combined strategy comprising an initial fed-batch phase followed by a periodic virus harvest phase resulted in the highest product yield with a more than 10-fold increase, compared to the conventional batch processes at 4 to 8×106 cell/mL [2]. Additionally, a 3-fold increase in both cell-specific yield (virus/cell) and volumetric productivity (virus/L×d) could be obtained. Although product harvesting was suboptimal when up-scaling to a 1 L bioreactor with ATF-system, comparable increases in virus yields and productivity with respect to the conventional batch process were observed. In all cases, cell-specific yields and volumetric productivities reached their peak values at the peak virus concentrations, indicating that the process should be stopped at that time point. Eventually, selection of the optimal pore size of the membrane of the ATF-system allowed semi-continuous harvesting of the produced viruses and its purification with MSCPs with a recovery of about 50%. Conclusion. Compared to conventional batch processes, the developed HCD process offers significantly higher productivities including the option to integrate a purification step in a semi-continuous mode. Overall, the results show that there is a great potential for semi-continuous HCD processes for the production of viral vaccines in larger scales, which could intensify the discussion towards the establishment of true continuous production process

Host genetic factors associated with hepatocellular carcinoma in patients with hepatitis C virus infection: a systematic review

Hepatitis C virus (HCV)-infected patients are at risk of developing hepatocellular carcinoma (HCC). Individuals at heightened riskcould be targeted by intensive follow-up surveillance. We have conducted a systematic review of the literature to identify host genetic predisposition to HCC in HCV-infected patients. A comprehensive search of Medline and Embase databases was performed and the strength of evidence of associations for each gene on development of HCC was evaluated. We identified 166 relevant studies, relating to 137 different genes, or combinations thereof. 17 genes were classified as having “good” evidence of an association, a significant association was observed for 37 genes but this finding had not yet been replicated, 56 genes had mixed or limited evidence of an association, and 27 genes showed no association. IFNL3/4, TNF-α and PNPLA3 genes had the most evidence of an association. There was, however, considerable heterogeneity in study design and data quality. In conclusion, we identified a number of genes with evidence of association with HCC, but also a need for more standardised approaches to address this clinically critical question. It is important to consider the underlying mechanism of these relationships and which are confounded by the presence of other HCC risk factors and response to therapy. We also identified many genes where the evidence of association is contradictory or requires replication, as well as a number where associations have been studied but no evidence found. These findings should help to direct future studies on host genetic predisposition to HCC in patients with HCV infection

Echelle long-slit optical spectroscopy of evolved stars

We present echelle long-slit optical spectra of a sample of objects evolving off the AGB, most of them in the pre-planetary nebula (pPN) phase, obtained with the ESI and MIKE spectrographs at Keck-II and Magellan-I, respectively. The total wavelength range covered with ESI (MIKE) is ~3900 to 10900 A (~3600 to 7200A). In this paper, we focus our analysis mainly on the Halpha profiles. Prominent Halpha emission is detected in half of the objects, most of which show broad Halpha wings (up to ~4000 km/s). In the majority of the Halpha-emission sources, fast, post-AGB winds are revealed by P-Cygni profiles. In ~37% of the objects Halpha is observed in absorption. In almost all cases, the absorption profile is partially filled with emission, leading to complex, structured profiles that are interpreted as an indication of incipient post-AGB mass-loss. All sources in which Halpha is seen mainly in absorption have F-G type central stars, whereas sources with intense Halpha emission span a larger range of spectral types from O to G. Shocks may be an important excitation agent of the close stellar surroundings for objects with late type central stars. Sources with pure emission or P Cygni Halpha profiles have larger J-K color excess than objects with Halpha mainly in absorption, which suggests the presence of warm dust near the star in the former. The two classes of profile sources also segregate in the IRAS color-color diagram in a way that intense Halpha-emitters have dust grains with a larger range of temperatures. (abridged)Comment: 68 pages, 14 figures, accepted for publication in ApJS (abstract abridged

Turbulent dissipation in the ISM: the coexistence of forced and decaying regimes and implications for galaxy formation and evolution

We discuss the dissipation of turbulent kinetic energy Ek in the global ISM by means of 2-D, MHD, non-isothermal simulations in the presence of model radiative heating and cooling. We argue that dissipation in 2D is representative of that in three dimensions as long as it is dominated by shocks rather than by a turbulent cascade. Energy is injected at a few isolated sites in space, over relatively small scales, and over short time periods. This leads to the coexistence of forced and decaying regimes in the same flow. We find that the ISM-like flow dissipates its turbulent energy rapidly. In simulations with forcing, the input parameters are the radius l_f of the forcing region, the total kinetic energy e_k each source deposits into the flow, and the rate of formation of those regions, sfr_OB. The global dissipation time t_d depends mainly on l_f. In terms of measurable properties of the ISM, t_d >= Sigma_g u_rms^2/(e_k sfr_OB), where Sigma_g is the average gas surface density and u_rms is the rms velocity dispersion. For the solar neighborhood, t_d >= 1.5x10^7 yr. The global dissipation time is consistently smaller than the crossing time of the largest energy-containing scales. In decaying simulations, Ek decreases with time as t^-n, where n~0.8-0.9. This suggests a decay with distance d as Ek\propto d^{-2n/(2-n)} in the mixed forced+decaying case. If applicable to the vertical direction, our results support models of galaxy evolution in which stellar energy injection provides significant support for the gas disk thickness, but not models of galaxy formation in which this energy injection is supposed to reheat an intra-halo medium at distances of up to 10-20 times the optical galaxy size, as the dissipation occurs on distances comparable to the disk height.Comment: 23 pages, including figures. To appear in ApJ. Abstract abridge

Reconstruction of the Dark Energy equation of state

One of the main challenges of modern cosmology is to investigate the nature of dark energy in our Universe. The properties of such a component are normally summarised as a perfect fluid with a (potentially) time-dependent equation-of-state parameter $w(z)$. We investigate the evolution of this parameter with redshift by performing a Bayesian analysis of current cosmological observations. We model the temporal evolution as piecewise linear in redshift between `nodes', whose $w$-values and redshifts are allowed to vary. The optimal number of nodes is chosen by the Bayesian evidence. In this way, we can both determine the complexity supported by current data and locate any features present in $w(z)$. We compare this node-based reconstruction with some previously well-studied parameterisations: the Chevallier-Polarski-Linder (CPL), the Jassal-Bagla-Padmanabhan (JBP) and the Felice-Nesseris-Tsujikawa (FNT). By comparing the Bayesian evidence for all of these models we find an indication towards possible time-dependence in the dark energy equation-of-state. It is also worth noting that the CPL and JBP models are strongly disfavoured, whilst the FNT is just significantly disfavoured, when compared to a simple cosmological constant $w=-1$. We find that our node-based reconstruction model is slightly disfavoured with respect to the $\Lambda$CDM model.Comment: 17 pages, 5 figures, minor correction

First observation of a narrow charm-strange meson DsJ(2632) -> Ds eta and D0 K+

We report the first observation of a charm-strange meson DsJ(2632) at a mass of 2632.6+/-1.6 MeV/c^2 in data from SELEX, the charm hadro-production experiment E781 at Fermilab. This state is seen in two decay modes, Ds eta and D0 K+. In the Ds eta decay mode we observe an excess of 49.3 events with a significance of 7.2sigma at a mass of 2635.9+/-2.9 MeV/c^2. There is a corresponding peak of 14 events with a significance of 5.3sigma at 2631.5+/-1.9 MeV/c^2 in the decay mode D0 K+. The decay width of this state is <17 MeV/c^2 at 90% confidence level. The relative branching ratio Gamma(D0K+)/Gamma(Dseta) is 0.16+/-0.06. The mechanism which keeps this state narrow is unclear. Its decay pattern is also unusual, being dominated by the Ds eta decay mode.Comment: 5 pages, 3 included eps figures. v2 as accepted for publication by PR