Adenovirus serotype 5 L4-22K and L4-33K proteins have distinct functions in regulating late gene expression

Adenoviruses express up to 20 distinct mRNAs from five major late transcription unit (MLTU) regions, L1 to L5, by differential splicing and polyadenylation of the primary transcript. MLTU expression is regulated at transcriptional and posttranscriptional levels. The L4-33K protein acts as a splicing factor to upregulate several MLTU splice acceptor sites as the late phase progresses. The L4 region also expresses a 22K protein whose sequence is related to the sequence of L4-33K. L4-22K is shown here also to have an important role in regulating the pattern of MLTU gene expression. An adenovirus genome containing a stop codon in the L4-22K open reading frame expressed low levels of both structural and nonstructural late proteins compared to the wild-type (wt) adenovirus genome; a decrease in intermediate proteins, IVa2 and IX, was also observed. However, early protein synthesis and replication were unaffected by the absence of L4-22K. Intermediate and late protein expression was restored to wt levels by L4-22K expressed in trans but not by L4-33K. Increased MLTU promoter activity, resulting from stabilization of the transcriptional activator IVa2 by L4-22K, made a small contribution to this restoration of late gene expression. However, the principal effect of L4-22K was on the processing of MLTU RNA into specific cytoplasmic mRNA. L4-22K selectively increased expression of penton mRNA and protein, whereas splicing to create penton mRNA is known not to be increased by L4-33K. These results indicate that L4-22K plays a key role in the early-late switch in MLTU expression, additional to and distinct from the role of L4-33K

Nonperturbative m_X cut effects in B -> Xs l+ l- observables

Recently, it was shown that in inclusive B -> Xs l+ l- decay, an angular decomposition provides three independent (q^2 dependent) observables. A strategy was formulated to extract all measurable Wilson coefficients in B -> Xs l+ l- from a few simple integrals of these observables in the low q^2 region. The experimental measurements in the low q^2 region require a cut on the hadronic invariant mass, which introduces a dependence on nonperturbative b quark distribution functions. The associated hadronic uncertainties could potentially limit the sensitivity of these decays to new physics. We compute the nonperturbative corrections to all three observables at leading and subleading order in the power expansion in \Lambda_QCD/m_b. We find that the subleading power corrections give sizeable corrections, of order -5% to -10% depending on the observable and the precise value of the hadronic mass cut. They cause a shift of order -0.05 GeV^2 to -0.1 GeV^2 in the zero of the forward-backward asymmetry.Comment: 11 pages, 4 figures, v2: corrected typos and Eq. (25), v3: journal versio

Color Intensity Projections: A simple way to display changes in astronomical images

To detect changes in repeated astronomical images of the same field of view (FOV), a common practice is to stroboscopically switch between the images. Using this method, objects that are changing in location or intensity between images are easier to see because they are constantly changing. A novel display method, called arrival time color intensity projections (CIPs), is presented that combines any number of grayscale images into a single color image on a pixel by pixel basis. Any values that are unchanged over the grayscale images look the same in the color image. However, pixels that change over the grayscale image have a color saturation that increases with the amount of change and a hue that corresponds to the timing of the changes. Thus objects moving in the grayscale images change from red to green to blue as they move across the color image. Consequently, moving objects are easier to detect and assess on the color image than on the grayscale images. A sequence of images of a comet plunging into the sun taken by the SOHO satellite (NASA/ESA) and Hubble Space Telescope images of a trans-Neptunian object (TNO) are used to demonstrate the method.Comment: 9 pages, 2 figures. Accepted for publication in Publications of the Astronomical Society of the Pacific. The quality of figure 1 been improved from the previous posted versio

Generation of cell lines to complement Adenovirus vectors using recombination-mediated cassette exchange

Background Adenovirus serotype 5 (Ad5) has many favourable characteristics for development as a gene therapy vector. However, the utility of current Ad5 vectors is limited by transient transgene expression, toxicity and immunogenicity. The most promising form of vector is the high capacity type, which is deleted for all viral genes. However, these vectors can only be produced to relatively low titres and with the aid of helper virus. Therefore a continuing challenge is the generation of more effective Ad5 vectors that can still be grown to high titres. Our approach is to generate complementing cell lines to support the growth of Ad5 vectors with novel late gene deficiencies. Results We have used LoxP/Cre recombination mediated cassette exchange (RMCE) to generate cell lines expressing Ad5 proteins encoded by the L4 region of the genome, the products of which play a pivotal role in the expression of Ad5 structural proteins. A panel of LoxP parent 293 cell lines was generated, each containing a GFP expression cassette under the control of a tetracycline-regulated promoter inserted at a random genome location; the cassette also contained a LoxP site between the promoter and GFP sequence. Clones displayed a variety of patterns of regulation, stability and level of GFP expression. Clone A1 was identified as a suitable parent for creation of inducible cell lines because of the tight inducibility and stability of its GFP expression. Using LoxP-targeted, Cre recombinase-mediated insertion of an L4 cassette to displace GFP from the regulated promoter in this parent clone, cell line A1-L4 was generated. This cell line expressed L4 100K, 22K and 33K proteins at levels sufficient to complement L4-33K mutant and L4-deleted viruses. Conclusions RMCE provides a method for rapid generation of Ad5 complementing cell lines from a pre-selected parental cell line, chosen for its desirable transgene expression characteristics. Parent cell lines can be selected for high or low gene expression, and for tight regulation, allowing viral protein expression to mirror that found during infection. Cell lines derived from a single parent will allow the growth of different vectors to be assessed without the complication of varying complementing protein expression

Equation of State in a Strongly Interacting Relativistic System

We study the evolution of the equation of state of a strongly interacting quark system as a function of the diquark interaction strength. We show that for the system to avoid collapsing into a pressureless Boson gas at sufficiently strong diquark coupling strength, the diquark-diquark repulsion has to be self-consistently taken into account. In particular, we find that the tendency at zero temperature of the strongly interacting diquark gas to condense into the system ground state is compensated by the repulsion between diquarks if the diquark-diquark coupling constant is higher than a critical value $\lambda_C=7.65$. Considering such diquark-diquark repulsion, a positive pressure with no significant variation along the whole strongly interacting region is obtained. A consequence of the diquark-diquark repulsion is that the system maintains its BCS character in the whole strongly interacting region.Comment: 9 pages, 7 figs, To appear in Phys. Rev.

Universality and m_X cut effects in B -> Xs l+ l-

The most precise comparison between theory and experiment for the B -> Xs l+ l- rate is in the low q^2 region, but the hadronic uncertainties associated with an experimentally required cut on m_X potentially spoil the search for new physics in these decays. We show that a 10-30% reduction of d\Gamma(B -> Xs l+ l-) / dq^2 due to the m_X cut can be accurately computed using the B -> X_s gamma shape function. The effect is universal for all short distance contributions in the limit m_X^2 << m_B^2, and this universality is spoiled neither by realistic values of the m_X cut nor by alpha_s corrections. Both the differential decay rate and forward-backward asymmetry with an m_X cut are computed.Comment: 5 pages, journal versio

A Heuristic Framework for Next-Generation Models of Geostrophic Convective Turbulence

Many geophysical and astrophysical phenomena are driven by turbulent fluid dynamics, containing behaviors separated by tens of orders of magnitude in scale. While direct simulations have made large strides toward understanding geophysical systems, such models still inhabit modest ranges of the governing parameters that are difficult to extrapolate to planetary settings. The canonical problem of rotating Rayleigh-B\'enard convection provides an alternate approach - isolating the fundamental physics in a reduced setting. Theoretical studies and asymptotically-reduced simulations in rotating convection have unveiled a variety of flow behaviors likely relevant to natural systems, but still inaccessible to direct simulation. In lieu of this, several new large-scale rotating convection devices have been designed to characterize such behaviors. It is essential to predict how this potential influx of new data will mesh with existing results. Surprisingly, a coherent framework of predictions for extreme rotating convection has not yet been elucidated. In this study, we combine asymptotic predictions, laboratory and numerical results, and experimental constraints to build a heuristic framework for cross-comparison between a broad range of rotating convection studies. We categorize the diverse field of existing predictions in the context of asymptotic flow regimes. We then consider the physical constraints that determine the points of intersection between flow behavior predictions and experimental accessibility. Applying this framework to several upcoming devices demonstrates that laboratory studies may soon be able to characterize geophysically-relevant flow regimes. These new data may transform our understanding of geophysical and astrophysical turbulence, and the conceptual framework developed herein should provide the theoretical infrastructure needed for meaningful discussion of these results.Comment: 36 pages, 8 figures. CHANGES: in revision at Geophysical and Astrophysical Fluid Dynamic

Extracting short distance information from b-->s[script-l]+[script-l]- effectively

We point out that in inclusive B-->Xs[script-l]+[script-l]- decay an angular decomposition provides a third (q2 dependent) observable sensitive to a different combination of Wilson coefficients than the rate and the forward-backward asymmetry. Since a precise measurement of q2 dependence requires large data sets, it is important to consider the data integrated over regions of q2. We develop a strategy to extract all measurable Wilson coefficients in B-->Xs[script-l]+[script-l]- from a few simple integrated rates in the low q2 region. A similar decomposition in B-->K*[script-l]+[script-l]-, together with the B-->K*gamma rate, also provides a determination of the Wilson coefficients, without reliance on form factor models and without having to measure the zero of the forward-backward asymmetry