5,473 research outputs found

    Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

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    We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

    Damping device for a stationary labyrinth seal

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    A stationary labyrinth seal system includes a seal housing having an annular cavity, a plurality of damping devices, and a retaining ring. The damping devices are positioned within the annular cavity and are maintained within the annular cavity by the retaining ring

    Sparse Deterministic Approximation of Bayesian Inverse Problems

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    We present a parametric deterministic formulation of Bayesian inverse problems with input parameter from infinite dimensional, separable Banach spaces. In this formulation, the forward problems are parametric, deterministic elliptic partial differential equations, and the inverse problem is to determine the unknown, parametric deterministic coefficients from noisy observations comprising linear functionals of the solution. We prove a generalized polynomial chaos representation of the posterior density with respect to the prior measure, given noisy observational data. We analyze the sparsity of the posterior density in terms of the summability of the input data's coefficient sequence. To this end, we estimate the fluctuations in the prior. We exhibit sufficient conditions on the prior model in order for approximations of the posterior density to converge at a given algebraic rate, in terms of the number NN of unknowns appearing in the parameteric representation of the prior measure. Similar sparsity and approximation results are also exhibited for the solution and covariance of the elliptic partial differential equation under the posterior. These results then form the basis for efficient uncertainty quantification, in the presence of data with noise

    Success of Ureteral Stents for Intrinsic Ureteral Obstruction

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    Purpose: Previous reports suggest a high success rate for retrograde ureteral stenting for intrinsic ureteral obstruction, but few preoperative predictors of success have been offered. We reviewed our experience to look for factors that suggest failure of stents for intrinsic ureteral obstruction. Materials and Methods: We retrospectively reviewed the outcome of retrograde ureteral stent placement for intrinsic ureteral obstruction without concurrent or intended definitive management of the obstruction. Results: Thirty-eight patients treated for intrinsic ureteral obstruction, representing 41 ureteral units (UUs), were monitored for an average of 25.5 months. The overall success rate was 88%. Of the successes, 13 UUs had definitive therapy to permanently remove the cause of obstruction, obstruction resolved in 12 UUs after stent placement, and 11 UUs were managed with indwelling stents. Therapy failed in five UUs, with a median time to failure of 1.9 months. Of the UUs in which failure occurred, three failures were caused by misdiagnosis; in the remaining two, the stent did not correct the obstruction. On univariate analysis, male sex (P = 0.006), increased creatinine level as a presenting symptom (P = 0.002), and more severe preoperative hydronephrosis (P = 0.042) were predictive of failure. Adverse events were low, with complications from stenting occurring on only four of 41 UUs. Conclusion: If initial stent placement was possible, intrinsic ureteral obstruction was managed successfully in 88% of patients. Given high success and minimal complications, retrograde placement of ureteral stents can be performed to treat patients with intrinsic ureteral obstruction. Treatment failure is more likely to occur in men and patients with severe hydronephrosis or an elevated creatinine level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63109/1/end.2007.0201.pd

    Vector meson dominance and the rho meson

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    We discuss the properties of vector mesons, in particular the rho^0, in the context of the Hidden Local Symmetry (HLS) model. This provides a unified framework to study several aspects of the low energy QCD sector. Firstly, we show that in the HLS model the physical photon is massless, without requiring off field diagonalization. We then demonstrate the equivalence of HLS and the two existing representations of vector meson dominance, VMD1 and VMD2, at both tree level and one loop order. Finally the S matrix pole position is shown to provide a model and process independent means of specifying the rho mass and width, in contrast to the real axis prescription currently used in the Particle Data Group tables.Comment: 18 pages, REVTE

    Mass-flowering crops dilute pollinator abundance in agricultural landscapes across Europe

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    Mass-flowering crops (MFCs) are increasingly cultivated and might influence pollinator communities in MFC fields and nearby semi-natural habitats (SNHs). Across six European regions and 2 years, we assessed how landscape-scale cover of MFCs affected pollinator densities in 408 MFC fields and adjacent SNHs. In MFC fields, densities of bumblebees, solitary bees, managed honeybees and hoverflies were negatively related to the cover of MFCs in the landscape. In SNHs, densities of bumblebees declined with increasing cover of MFCs but densities of honeybees increased. The densities of all pollinators were generally unrelated to the cover of SNHs in the landscape. Although MFC fields apparently attracted pollinators from SNHs, in landscapes with large areas of MFCs they became diluted. The resulting lower densities might negatively affect yields of pollinator-dependent crops and the reproductive success of wild plants. An expansion of MFCs needs to be accompanied by pollinator-supporting practices in agricultural landscapes
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