706 research outputs found
Governance of Offshore IT Outsourcing at Shell Global Functions IT-BAM Development and Application of a Governance Framework to Improve Outsourcing Relationships
The lack of effective IT governance is widely recognized as a key inhibitor to successful global IT outsourcing relationships. In this study we present the development and application of a governance framework to improve outsourcing relationships. The approach used to developing an IT governance framework includes a meta model and a customization process to fit the framework to the target organization. The IT governance framework consists of four different elements (1) organisational structures, (2) joint processes between in- and outsourcer, (3) responsibilities that link roles to processes and (4) a diverse set of control indicators to measure the success of the relationship. The IT governance framework is put in practice in Shell GFIT BAM, a part of Shell that concluded to have a lack of management control over at least one of their outsourcing relationships. In a workshop the governance framework was used to perform a gap analysis between the current and desired governance. Several gaps were identified in the way roles and responsibilities are assigned and joint processes are set-up. Moreover, this workshop also showed the usefulness and usability of the IT governance framework in structuring, providing input and managing stakeholders in the discussions around IT governance
Chaperone-mediated native folding of a β-scorpion toxin in the periplasm of E.coli
Background: Animal neurotoxin peptides are valuable probes for investigating ion channel structure/function relationships and represent lead compounds for novel therapeutics and insecticides. However, misfolding and aggregation are common outcomes when toxins containing multiple disulfides are expressed in bacteria.
Methods: The ß-scorpion peptide toxin Bj-xtrIT from Hottentotta judaica and four chaperone enzymes (DsbA, DsbC, SurA and FkpA) were co-secreted into the oxidizing environment of the E.coli periplasm. Expressed Bj-xtrIT was purified and analyzed by HPLC and FPLC chromatography. Its thermostability was assessed using synchrotron radiation circular dichroism spectroscopy and its crystal structure was determined.
Results: Western blot analysis showed that robust expression was only achieved when cells co-expressed the chaperones. The purified samples were homogenous and monodisperse and the protein was thermostable. The crystal structure of the recombinant toxin confirmed that it adopts the native disulfide connectivity and fold.
Conclusions: The chaperones enabled correct folding of the four-disulfide-bridged Bj-xtrIT toxin. There was no apparent sub-population of misfolded Bj-xtrIT, which attests to the effectiveness of this expression method.
General Significance: We report the first example of a disulfide-linked scorpion toxin natively folded during bacterial expression. This method eliminates downstream processing steps such as oxidative refolding or cleavage of a fusion-carrier and therefore enables efficient production of insecticidal Bj-xtrIT. Periplasmic chaperone activity may produce native folding of other extensively disulfide-reticulated proteins including animal neurotoxins. This work is therefore relevant to venomics and studies of a wide range of channels and receptors
Decay of flux vacua to nothing
We construct instanton solutions describing the decay of flux
compactifications of a gauge theory by generalizing the Kaluza-Klein
bubble of nothing. The surface of the bubble is described by a smooth
magnetically charged solitonic brane whose asymptotic flux is precisely that
responsible for stabilizing the 4d compactification. We describe several
instances of bubble geometries for the various vacua occurring in a
Einstein-Maxwell theory namely, AdS_4 x S^2, R^{1,3} x S^2, and dS_4 x S^2.
Unlike conventional solutions, the bubbles of nothing introduced here occur
where a {\em two}-sphere compactification manifold homogeneously degenerates.Comment: 31 pages, 15 figure
Nonlinear Lattice Waves in Random Potentials
Localization of waves by disorder is a fundamental physical problem
encompassing a diverse spectrum of theoretical, experimental and numerical
studies in the context of metal-insulator transition, quantum Hall effect,
light propagation in photonic crystals, and dynamics of ultra-cold atoms in
optical arrays. Large intensity light can induce nonlinear response, ultracold
atomic gases can be tuned into an interacting regime, which leads again to
nonlinear wave equations on a mean field level. The interplay between disorder
and nonlinearity, their localizing and delocalizing effects is currently an
intriguing and challenging issue in the field. We will discuss recent advances
in the dynamics of nonlinear lattice waves in random potentials. In the absence
of nonlinear terms in the wave equations, Anderson localization is leading to a
halt of wave packet spreading.
Nonlinearity couples localized eigenstates and, potentially, enables
spreading and destruction of Anderson localization due to nonintegrability,
chaos and decoherence. The spreading process is characterized by universal
subdiffusive laws due to nonlinear diffusion. We review extensive computational
studies for one- and two-dimensional systems with tunable nonlinearity power.
We also briefly discuss extensions to other cases where the linear wave
equation features localization: Aubry-Andre localization with quasiperiodic
potentials, Wannier-Stark localization with dc fields, and dynamical
localization in momentum space with kicked rotors.Comment: 45 pages, 19 figure
Equilibration processes in the Warm-Hot Intergalactic Medium
The Warm-Hot Intergalactic Medium (WHIM) is thought to contribute about 40-50
% to the baryonic budget at the present evolution stage of the universe. The
observed large scale structure is likely to be due to gravitational growth of
density fluctuations in the post-inflation era. The evolving cosmic web is
governed by non-linear gravitational growth of the initially weak density
fluctuations in the dark energy dominated cosmology. Non-linear structure
formation, accretion and merging processes, star forming and AGN activity
produce gas shocks in the WHIM. Shock waves are converting a fraction of the
gravitation power to thermal and non-thermal emission of baryonic/leptonic
matter. They provide the most likely way to power the luminous matter in the
WHIM. The plasma shocks in the WHIM are expected to be collisionless.
Collisionless shocks produce a highly non-equilibrium state with anisotropic
temperatures and a large differences in ion and electron temperatures. We
discuss the ion and electron heating by the collisionless shocks and then
review the plasma processes responsible for the Coulomb equilibration and
collisional ionisation equilibrium of oxygen ions in the WHIM. MHD-turbulence
produced by the strong collisionless shocks could provide a sizeable
non-thermal contribution to the observed Doppler parameter of the UV line
spectra of the WHIM.Comment: 13 pages, 4 figures, accepted for publication in Space Science
Reviews, special issue "Clusters of galaxies: beyond the thermal view",
Editor J.S. Kaastra, Chapter 8; work done by an international team at the
International Space Science Institute (ISSI), Bern, organised by J.S.
Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke
Magnetic Fields, Relativistic Particles, and Shock Waves in Cluster Outskirts
It is only now, with low-frequency radio telescopes, long exposures with
high-resolution X-ray satellites and gamma-ray telescopes, that we are
beginning to learn about the physics in the periphery of galaxy clusters. In
the coming years, Sunyaev-Zeldovich telescopes are going to deliver further
great insights into the plasma physics of these special regions in the
Universe. The last years have already shown tremendous progress with detections
of shocks, estimates of magnetic field strengths and constraints on the
particle acceleration efficiency. X-ray observations have revealed shock fronts
in cluster outskirts which have allowed inferences about the microphysical
structure of shocks fronts in such extreme environments. The best indications
for magnetic fields and relativistic particles in cluster outskirts come from
observations of so-called radio relics, which are megaparsec-sized regions of
radio emission from the edges of galaxy clusters. As these are difficult to
detect due to their low surface brightness, only few of these objects are
known. But they have provided unprecedented evidence for the acceleration of
relativistic particles at shock fronts and the existence of muG strength fields
as far out as the virial radius of clusters. In this review we summarise the
observational and theoretical state of our knowledge of magnetic fields,
relativistic particles and shocks in cluster outskirts.Comment: 34 pages, to be published in Space Science Review
Local and Global Casimir Energies: Divergences, Renormalization, and the Coupling to Gravity
From the beginning of the subject, calculations of quantum vacuum energies or
Casimir energies have been plagued with two types of divergences: The total
energy, which may be thought of as some sort of regularization of the
zero-point energy, , seems manifestly divergent. And
local energy densities, obtained from the vacuum expectation value of the
energy-momentum tensor, , typically diverge near
boundaries. The energy of interaction between distinct rigid bodies of whatever
type is finite, corresponding to observable forces and torques between the
bodies, which can be unambiguously calculated. The self-energy of a body is
less well-defined, and suffers divergences which may or may not be removable.
Some examples where a unique total self-stress may be evaluated include the
perfectly conducting spherical shell first considered by Boyer, a perfectly
conducting cylindrical shell, and dilute dielectric balls and cylinders. In
these cases the finite part is unique, yet there are divergent contributions
which may be subsumed in some sort of renormalization of physical parameters.
The divergences that occur in the local energy-momentum tensor near surfaces
are distinct from the divergences in the total energy, which are often
associated with energy located exactly on the surfaces. However, the local
energy-momentum tensor couples to gravity, so what is the significance of
infinite quantities here? For the classic situation of parallel plates there
are indications that the divergences in the local energy density are consistent
with divergences in Einstein's equations; correspondingly, it has been shown
that divergences in the total Casimir energy serve to precisely renormalize the
masses of the plates, in accordance with the equivalence principle.Comment: 53 pages, 1 figure, invited review paper to Lecture Notes in Physics
volume in Casimir physics edited by Diego Dalvit, Peter Milonni, David
Roberts, and Felipe da Ros
Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia
BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as a novel class of RNA due to its diverse mechanism in cancer development and progression. However, the role and expression pattern of lncRNAs in molecular subtypes of B cell acute lymphoblastic leukemia (BCP-ALL) have not yet been investigated. Here, we assess to what extent lncRNA expression and DNA methylation is driving the progression of relapsed BCP-ALL subtypes and we determine if the expression and DNA methylation profile of lncRNAs correlates with established BCP-ALL subtypes. METHODS: We performed RNA sequencing and DNA methylation (Illumina Infinium microarray) of 40 diagnosis and 42 relapse samples from 45 BCP-ALL patients in a German cohort and quantified lncRNA expression. Unsupervised clustering was applied to ascertain and confirm that the lncRNA-based classification of the BCP-ALL molecular subtypes is present in both our cohort and an independent validation cohort of 47 patients. A differential expression and differential methylation analysis was applied to determine the subtype-specific, relapse-specific, and differentially methylated lncRNAs. Potential functions of subtype-specific lncRNAs were determined by using co-expression-based analysis on nearby (cis) and distally (trans) located protein-coding genes. RESULTS: Using an integrative Bioinformatics analysis, we developed a comprehensive catalog of 1235 aberrantly dysregulated BCP-ALL subtype-specific and 942 relapse-specific lncRNAs and the methylation profile of three subtypes of BCP-ALL. The 1235 subtype-specific lncRNA signature represented a similar classification of the molecular subtypes of BCP-ALL in the independent validation cohort. We identified a strong correlation between the DUX4-specific lncRNAs and genes involved in the activation of TGF-β and Hippo signaling pathways. Similarly, Ph-like-specific lncRNAs were correlated with genes involved in the activation of PI3K-AKT, mTOR, and JAK-STAT signaling pathways. Interestingly, the relapse-specific lncRNAs correlated with the activation of metabolic and signaling pathways. Finally, we found 23 promoter methylated lncRNAs epigenetically facilitating their expression levels. CONCLUSION: Here, we describe a set of subtype-specific and relapse-specific lncRNAs from three major BCP-ALL subtypes and define their potential functions and epigenetic regulation. The subtype-specific lncRNAs are reproducible and can effectively stratify BCP-ALL subtypes. Our data uncover the diverse mechanism of action of lncRNAs in BCP-ALL subtypes defining which lncRNAs are involved in the pathogenesis of disease and are relevant for the stratification of BCP-ALL subtypes
The Physics of turbulent and dynamically unstable Herbig-Haro jets
The overall properties of the Herbig-Haro objects such as centerline
velocity, transversal profile of velocity, flow of mass and energy are
explained adopting two models for the turbulent jet. The complex shapes of the
Herbig-Haro objects, such as the arc in HH34 can be explained introducing the
combination of different kinematic effects such as velocity behavior along the
main direction of the jet and the velocity of the star in the interstellar
medium. The behavior of the intensity or brightness of the line of emission is
explored in three different cases : transversal 1D cut, longitudinal 1D cut and
2D map. An analytical explanation for the enhancement in intensity or
brightness such as usually modeled by the bow shock is given by a careful
analysis of the geometrical properties of the torus.Comment: 17 pages, 10 figures. Accepted for publication in Astrophysics &
Spac
Physics of Solar Prominences: II - Magnetic Structure and Dynamics
Observations and models of solar prominences are reviewed. We focus on
non-eruptive prominences, and describe recent progress in four areas of
prominence research: (1) magnetic structure deduced from observations and
models, (2) the dynamics of prominence plasmas (formation and flows), (3)
Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and
large-scale patterns of the filament channels in which prominences are located.
Finally, several outstanding issues in prominence research are discussed, along
with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape
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