Lentiviral vector design using alternative RNA export elements

<p>Abstract</p> <p>Background</p> <p>Lentiviral vectors have been designed with complex RNA export sequences in both the integrating and packaging plasmids in order to co-ordinate efficient vector production. Recent studies have attempted to replace the existing complex rev/RRE system with a more simplistic RNA export system from simple retroviruses to make these vectors in a rev-independent manner.</p> <p>Results</p> <p>Towards this end, lentiviral transfer plasmids were modified with various cis-acting DNA elements that co-ordinate RNA export during viral production to determine their ability to affect the efficiency of vector titer and transduction in different immortalized cell lines in vitro. It was found that multiple copies of the constitutive transport element (CTE) originating from different simian retroviruses, including simian retrovirus type 1 (SRV-1) and type-2 (SRV-2) and Mason-Pfizer (MPV) could be used to eliminate the requirement for the rev responsive element (RRE) in the transfer and packaging plasmids with titers >10⁶T.U./mL (n = 4–8 preparations). The addition of multiple copies of the murine intracisternal type A particle, the woodchuck post-regulatory element (WPRE), or single and dual copies of the simian CTE had minimal effect on viral titer. Immortalized cell lines from different species were found to be readily transduced by VSV-G pseudotyped lentiviral vectors containing the multiple copies of the CTE similar to the findings in HeLa cells, although the simian-derived CTE were found to have a lower infectivity into murine cell lines compared to the other species.</p> <p>Conclusion</p> <p>These studies demonstrated that the rev-responsive element (RRE) could be replaced with other constitutive transport elements to produce equivalent titers using lentivectors containing the RRE sequence <it>in vitro</it>, but that concatemerization of the CTE or the close proximity of RNA export sequences was needed to enhance vector production.</p

Higgs Boson Production at Hadron Colliders

I report on a calculation of the inclusive Higgs boson production cross section at hadron colliders at next-to-next-to-leading order in QCD. The result is computed as an expansion about the threshold region. By continuing the expansion to very high order, we map the result onto basis functions and obtain the result in closed analytic form.Comment: 3 pages, 2 figures, uses espcrc2.sty. Talk presented at XXXIst International Conference on High Energy Physics, Amsterdam, The Netherlands, 24-31 July, 200

Parton Distributions in the Valon Model

The parton distribution functions determined by CTEQ at low $Q^2$ are used as inputs to test the validity of the valon model. The valon distributions in a nucleon are first found to be nearly $Q$ independent. The parton distribution in a valon are shown to be consistent with being universal, independent of the valon type. The momentum fractions of the partons in the valon add up separately to one. These properties affirm the validity of the valon model. The various distributions are parameterized for convenient application of the model.Comment: 9 pages + 9 figures in ep

Grid-Enabled Non-Invasive Blood Glucose Measurement

Abstract. Earth and life sciences are at the forefront to successfully include computational simulations and modeling. Medical applications are often mentioned as the killer applications for the Grid. The complex methodology and models of Traditional Chinese Medicine offer different approaches to diagnose and treat a persons health condition than typical Western medicine. A possibility to make this often hidden knowledge ex-plicit and available to a broader audience will result in mutual synergies for Western and Chinese medicine as well as improved patient care. This paper proposes the design and implementation of a method to accurately estimate blood glucose values using a novel non-invasive method based on electro-transformation measures in human body meridians. The frame-work used for this scientific computing collaboration, namely the China-Austria Data Grid (CADGrid) framework, provides an Intelligence Base offering commonly used models and algorithms as Web/Grid-Services. The controlled execution of the Non-Invasive Blood Glucose Measure-ment Service and the management of scientific data that arise from model execution can be seen as the first application on top of the CADGrid

SKOR1 mediates FER kinase-dependent invasive growth of breast cancer cells

High expression of the non-receptor tyrosine kinase FER is an independent prognostic factor that correlates with poor survival in breast cancer patients. To investigate whether the kinase activity of FER is essential for its oncogenic properties, we developed an ATP analogue-sensitive knock-in allele (FERASKI). Specific FER kinase inhibition in MDA-MB-231 cells reduces migration and invasion, as well as metastasis when xenografted into a mouse model of breast cancer. Using the FERASKI system, we identified Ski family transcriptional corepressor 1 (SKOR1) as a direct FER kinase substrate. SKOR1 loss phenocopies FER inhibition, leading to impaired proliferation, migration and invasion, and inhibition of breast cancer growth and metastasis formation in mice. We show that SKOR1 Y234, a candidate FER phosphorylation site, is essential for FER-dependent tumor progression. Finally, our work suggests that the SKOR1 Y234 residue promotes Smad2/3 signaling through SKOR1 binding to Smad3. Our study thus identifies SKOR1 as a mediator of FER-dependent progression of high-risk breast cancers. Cancer Signaling networks and Molecular Therapeutic

Spherically symmetric dissipative anisotropic fluids: A general study

The full set of equations governing the evolution of self--gravitating spherically symmetric dissipative fluids with anisotropic stresses is deployed and used to carry out a general study on the behaviour of such systems, in the context of general relativity. Emphasis is given to the link between the Weyl tensor, the shear tensor, the anisotropy of the pressure and the density inhomogeneity. In particular we provide the general, necessary and sufficient, condition for the vanishing of the spatial gradients of energy density, which in turn suggests a possible definition of a gravitational arrow of time. Some solutions are also exhibited to illustrate the discussion.Comment: 28 pages Latex. To appear in Phys.Rev.

Design and Test of a Forward Neutron Calorimeter for the ZEUS Experiment

A lead scintillator sandwich sampling calorimeter has been installed in the HERA tunnel 105.6 m from the central ZEUS detector in the proton beam direction. It is designed to measure the energy and scattering angle of neutrons produced in charge exchange ep collisions. Before installation the calorimeter was tested and calibrated in the H6 beam at CERN where 120 GeV electrons, muons, pions and protons were made incident on the calorimeter. In addition, the spectrum of fast neutrons from charge exchange proton-lucite collisions was measured. The design and construction of the calorimeter is described, and the results of the CERN test reported. Special attention is paid to the measurement of shower position, shower width, and the separation of electromagnetic showers from hadronic showers. The overall energy scale as determined from the energy spectrum of charge exchange neutrons is compared to that obtained from direct beam hadrons.Comment: 45 pages, 22 Encapsulated Postscript figures, submitted to Nuclear Instruments and Method

The Influence of the Degree of Heterogeneity on the Elastic Properties of Random Sphere Packings

The macroscopic mechanical properties of colloidal particle gels strongly depend on the local arrangement of the powder particles. Experiments have shown that more heterogeneous microstructures exhibit up to one order of magnitude higher elastic properties than their more homogeneous counterparts at equal volume fraction. In this paper, packings of spherical particles are used as model structures to computationally investigate the elastic properties of coagulated particle gels as a function of their degree of heterogeneity. The discrete element model comprises a linear elastic contact law, particle bonding and damping. The simulation parameters were calibrated using a homogeneous and a heterogeneous microstructure originating from earlier Brownian dynamics simulations. A systematic study of the elastic properties as a function of the degree of heterogeneity was performed using two sets of microstructures obtained from Brownian dynamics simulation and from the void expansion method. Both sets cover a broad and to a large extent overlapping range of degrees of heterogeneity. The simulations have shown that the elastic properties as a function of the degree of heterogeneity are independent of the structure generation algorithm and that the relation between the shear modulus and the degree of heterogeneity can be well described by a power law. This suggests the presence of a critical degree of heterogeneity and, therefore, a phase transition between a phase with finite and one with zero elastic properties.Comment: 8 pages, 6 figures; Granular Matter (published online: 11. February 2012

4pi Models of CMEs and ICMEs

Coronal mass ejections (CMEs), which dynamically connect the solar surface to the far reaches of interplanetary space, represent a major anifestation of solar activity. They are not only of principal interest but also play a pivotal role in the context of space weather predictions. The steady improvement of both numerical methods and computational resources during recent years has allowed for the creation of increasingly realistic models of interplanetary CMEs (ICMEs), which can now be compared to high-quality observational data from various space-bound missions. This review discusses existing models of CMEs, characterizing them by scientific aim and scope, CME initiation method, and physical effects included, thereby stressing the importance of fully 3-D ('4pi') spatial coverage.Comment: 14 pages plus references. Comments welcome. Accepted for publication in Solar Physics (SUN-360 topical issue