157 research outputs found
On admissibility criteria for weak solutions of the Euler equations
We consider solutions to the Cauchy problem for the incompressible Euler
equations satisfying several additional requirements, like the global and local
energy inequalities. Using some techniques introduced in an earlier paper we
show that, for some bounded compactly supported initial data, none of these
admissibility criteria singles out a unique weak solution.
As a byproduct we show bounded initial data for which admissible solutions to
the p-system of isentropic gas dynamics in Eulerian coordinates are not unique
in more than one space dimension.Comment: 33 pages, 1 figure; v2: 35 pages, corrected typos, clarified proof
Biocoating of seeds with plant growth-promoting rhizobacteria to improve plant establishment
Microbial Biotechnolog
Young Measures Generated by Ideal Incompressible Fluid Flows
In their seminal paper "Oscillations and concentrations in weak solutions of
the incompressible fluid equations", R. DiPerna and A. Majda introduced the
notion of measure-valued solution for the incompressible Euler equations in
order to capture complex phenomena present in limits of approximate solutions,
such as persistence of oscillation and development of concentrations.
Furthermore, they gave several explicit examples exhibiting such phenomena. In
this paper we show that any measure-valued solution can be generated by a
sequence of exact weak solutions. In particular this gives rise to a very
large, arguably too large, set of weak solutions of the incompressible Euler
equations.Comment: 35 pages. Final revised version. To appear in Arch. Ration. Mech.
Ana
The formation of vault-tubes: a dynamic interaction between vaults and vault PARP
Vaults are barrel-shaped cytoplasmic ribonucleoprotein particles that are
composed of a major vault protein (MVP), two minor vault proteins
[telomerase-associated protein 1 (TEP1), vault poly(ADP-ribose) polymerase
(VPARP)] and small untranslated RNA molecules. Not all expressed TEP1 and
VPARP in cells is bound to vaults. TEP1 is known to associate with the
telomerase complex, whereas VPARP is also present in the nuclear matrix
and in cytoplasmic clusters (VPARP-rods). We examined the subcellular
localization and the dynamics of the vault complex in a non-small cell
lung cancer cell line expressing MVP tagged with green fluorescent
protein. Using quantitative fluorescence recovery after photobleaching
(FRAP) it was shown that vaults move temperature independently by
diffusion. However, incubation at room temperature (21 degrees C) resulted
in the formation of distinct tube-like structures in the cytoplasm.
Raising the temperature could reverse this process. When the vault-tubes
were formed, there were fewer or no VPARP-rods present in the cytoplasm,
suggesting an incorporation of the VPARP into the vault-tubes. MVP
molecules have to interact with each other via their coiled-coil domain in
order to form vault-tubes. Furthermore, the stability of microtubules
influenced the efficiency of vault-tube formation at 21 degrees C. The
dynamics and structure of the tubes were examined using confocal
microscopy. Our data indicate a direct and dynamic relationship between
vaults and VPARP, providing further clues to unravel the function of
vaults
Disruption of the murine major vault protein (MVP/LRP) gene does not induce hypersensitivity to cytostatics
Vaults are ribonucleoprotein particles with a distinct structure and a
high degree of conservation between species. Although no function has been
assigned to the complex yet, there is some evidence for a role of vaults
in multidrug resistance. To confirm a direct relation between vaults and
multidrug resistance, and to investigate other possible functions of
vaults, we have generated a major vault protein (MVP/lung
resistance-related protein) knockout mouse model. The MVP(-/-) mice are
viable, healthy, and show no obvious abnormalities. We investigated the
sensitivity of MVP(-/-) embryonic stem cells and bone marrow cells derived
from the MVP-deficient mice to various cytostatic agents with different
mechanisms of action. Neither the MVP(-/-) embryonic stem cells nor the
MVP(-/-) bone marrow cells showed an increased sensitivity to any of the
drugs examined, as compared with wild-type cells. Furthermore, the
activities of the ABC-transporters P-glycoprotein, multidrug
resistance-associated protein and breast cancer resistance protein were
unaltered on MVP deletion in these cells. In addition, MVP wild-type and
deficient mice were treated with the anthracycline doxorubicin. Both
groups of mice responded similarly to the doxorubicin treatment. Our
results suggest that MVP/vaults are not directly involved in the
resistance to cytostatic agents
Overcoming bortezomib resistance in human B cells by anti-CD20/rituximab-mediated complement-dependent cytotoxicity and epoxyketone-based irreversible proteasome inhibitors
UNLABELLED: BACKGROUND: In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI) bortezomib (BTZ) treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or re-treatment, often with acquired resistance as a consequence. METHODS: Here we studied the molecular basis of acquired resistance to BTZ in JY human B lymphoblastic cells following prolonged exposure to this drug and examined possibilities to overcome resistance by next generation PIs and anti-CD20/rituximab-mediated complement-dependent cytotoxicity (CDC). RESULTS: Characterization of BTZ-resistant JY/BTZ cells compared to parental JY/WT cells revealed the following features: (a) 10-12 fold resistance to BTZ associated with the acquisition of a mutation in the PSMB5 gene (encoding the constitutive 5 proteasome subunit) introducing an amino acid substitution (Met45Ile) in the BTZ-binding pocket, (b) a significant 2-4 fold increase in the mRNA and protein levels of the constitutive 5 proteasome subunit along with unaltered immunoproteasome expression, (c) full sensitivity to the irreversible epoxyketone-based PIs carfilzomib and (to a lesser extent) the immunoproteasome inhibitor ONX 0914. Finally, in association with impaired ubiquitination and attenuated breakdown of CD20, JY/BTZ cells harbored a net 3-fold increase in CD20 cell surface expression, which was functionally implicated in conferring a significantly increased anti-CD20/rituximab-mediated CDC. CONCLUSIONS: These results demonstrate that acquired resistance to BTZ in B cells can be overcome by next generation PIs and by anti-CD20/rituximab-induced CDC, thereby paving the way for salvage therapy in BTZ-resistant disease
Proteasome inhibition and mechanism of resistance to a synthetic, library-based hexapeptide
Chemical Immunolog
Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5
Whole-exome sequencing of two brothers with drug-resistant, early-onset, focal epilepsy secondary to extensive type IIA focal cortical dysplasia identified a paternally inherited, nonsense variant of DEPDC5 (c.C1663T, p.Arg555*). This variant has previously been reported to cause familial focal epilepsy with variable foci in patients with normal brain imaging. Immunostaining of resected brain tissue from both brothers demonstrated mammalian target of rapamycin (mTOR) activation. This report shows the histopathological features of cortical dysplasia associated with a DEPDC5 mutation, confirms mTOR dysregulation in the malformed tissue and expands the spectrum of neurological manifestations of DEPDC5 mutations to include severe phenotypes with large areas of cortical malformation.Thomas Scerri, Jessica R. Riseley, Greta Gillies, Kate Pope, Rosemary Burgess, Simone A. Mandelstam ... et al
The clinical and molecular genetic approach to Duchenne and Becker muscular dystrophy: an updated protocol
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