1,989 research outputs found
The light chain but not the heavy chain of botulinum A toxin inhibits exocytosis from permeabilized adrenal chromaffin cells
The heavy and light chains of botulinum A toxin were separated by anion exchange chromatography. Their intracellular actions were studied using bovine adrenal chromaffin cells permeabilized with streptolysin O. Purified light chain inhibited the Ca2+-stimulated [3H]noradrenaline release with a half-maximal effect at about 1.8 nM. The inhibition was incomplete. Heavy chain up to 28 nM was neither effective by itself nor did it enhance the inhibitory effect of light chain. It is concluded that the light chain of botulinum A toxin contains the functional domain responsible for the inhibition of exocytosis
Introduction of Macromolecules into Bovine Adrenal Medullary Chromaffin Cells and Rat Pheochromocytoma Cells (PC12) by Permeabilization with Streptolysin O: Inhibitory Effect of Tetanus Toxin on Catecholamine Secretion
Conditions are described for controlled plasma membrane permeabilization of rat pheochromocytoma cells (PC12) and cultured bovine adrenal chromaffin cells by Streptolysin O (SLO). The transmembrane pores created by SLO invoke rapid efflux of intracellular 86Rb+ and ATP, and also permit passive diffusion of proteins, including immunoglobulins, into the cells. SLO-permeabilized PC12 cells release [3H]dopamine in response to micromolar concentrations of free Ca2+. Permeabilized adrenal chromaffin cells present a similar exocytotic response to Ca2+ in the presence of Mg2+/ ATP. Permeabilized PC12 cells accumulate antibodies against synaptophysin and calmodulin, but neither antibody reduces the Ca2+-dependent secretory response. Reduced tetanus toxin, although ineffective when applied to intact chromaffin cells, inhibits Ca2+-induced exocytosis by both types of permeabilized cells studied. Omission of dithiothreitol, toxin inactivation by boiling, or preincubation with neutralizing antibodies abolishes the inhibitory effect. The data indicate that plasma membrane permeabilization by Streptolysin O is a useful tool to probe and define cellular components that are involved in the final steps of exocytosis
Tractable Pathfinding for the Stochastic On-Time Arrival Problem
We present a new and more efficient technique for computing the route that
maximizes the probability of on-time arrival in stochastic networks, also known
as the path-based stochastic on-time arrival (SOTA) problem. Our primary
contribution is a pathfinding algorithm that uses the solution to the
policy-based SOTA problem---which is of pseudo-polynomial-time complexity in
the time budget of the journey---as a search heuristic for the optimal path. In
particular, we show that this heuristic can be exceptionally efficient in
practice, effectively making it possible to solve the path-based SOTA problem
as quickly as the policy-based SOTA problem. Our secondary contribution is the
extension of policy-based preprocessing to path-based preprocessing for the
SOTA problem. In the process, we also introduce Arc-Potentials, a more
efficient generalization of Stochastic Arc-Flags that can be used for both
policy- and path-based SOTA. After developing the pathfinding and preprocessing
algorithms, we evaluate their performance on two different real-world networks.
To the best of our knowledge, these techniques provide the most efficient
computation strategy for the path-based SOTA problem for general probability
distributions, both with and without preprocessing.Comment: Submission accepted by the International Symposium on Experimental
Algorithms 2016 and published by Springer in the Lecture Notes in Computer
Science series on June 1, 2016. Includes typographical corrections and
modifications to pre-processing made after the initial submission to SODA'15
(July 7, 2014
Analysis of the doubly heavy baryons in the nuclear matter with the QCD sum rules
In this article, we study the doubly heavy baryon states ,
, and in the nuclear matter using the QCD
sum rules, and derive three coupled QCD sum rules for the masses, vector
self-energies and pole residues. The predictions for the mass-shifts in the
nuclear matter , , and
can be confronted with the
experimental data in the future.Comment: 10 pages, 4 figure
Against all odds: how the institutional context shapes diversity management in the Central and Eastern European Oil and Gas industry
Purpose:
Due to their multifarious backgrounds, multinational enterprises from emerging economies offer unique research opportunities to push the boundaries of our understanding knowledge of diversity management in transitional contexts. In that regard, Central and Eastern European multinationals present a blind spot in diversity management research.
Design/methodology/approach:
This article examines the extent to which context shapes the discourse on diversity management in the Oil and Gas industry across Central and Eastern Europe (CEE) through a qualitative approach based on content analyses of corporate communication data matched with data on national institutional contexts.
Findings:
The data suggests a lack of effective pro-diversity pressures across CEE except for cultural pressure in European Union member countries. However, CEE Oil and Gas companies report a broader scope of diversity management than studies of Western counterparts suggest. Companies with subsidiaries in Western countries show convergence towards etic diversity approaches, while local and regional companies are more divergent.
Originality/value:
This article defines the boundary conditions of diversity management in the Oil and Gas industry across nine CEE countries and how they impact the diversity discourse in the industry. This article also showcases the impact of foreign market presence in the West as a driver for diversity management reporting
Full-field measurements of strain localisation in sandstone by neutron tomography and 3D-volumetric Digital Image Correlation
AbstractRecent studies have demonstrated that the combination of x-ray tomography during triaxial tests (“in-situ” tests) and 3D- volumetric Digital Image Correlation (3D-DIC) can provide important insight into the mechanical behaviour and deformation processes of granular materials such as sand. The application of these tools to investigate the mechanisms of failure in rocks is also of obvious interest. However, the relevant applied confining pressures for triaxial testing on rocks are higher than those on sands and therefore stronger pressure containment vessels, i.e., made of thick metal walls, are required. This makes in-situ x-ray imaging of rock deformation during triaxial tests a challenge. One possible solution to overcome this problem is to use neutrons, which should better penetrate the metal-walls of the pressure vessels. In this perspective, this work assesses the capability of neutron tomography with 3D-DIC to measure deformation fields in rock samples. Results from pre- and post-deformation neutron tomography of a Bentheim sandstone sample deformed ex-situ at 40MPa show that clear images of the internal structure can be achieved and utilised for 3D-DIC analysis to reveal the details of the 3D strain field. From these results the character of the localised deformation in the study sample can thus be described. Furthermore, comparison with analyses based on equivalent x-ray tomography imaging of the same sample confirms the effectiveness of the method in relation to the more established x-ray based approach
Opioid receptor activation triggering downregulation of cAMP improves effectiveness of anti-cancer drugs in treatment of glioblastoma
Glioblastoma are the most frequent and malignant human brain tumors, having a very poor prognosis. The enhanced radio- and chemoresistance of glioblastoma and the glioblastoma stem cells might be the main reason why conventional therapies fail. The second messenger cyclic AMP (cAMP) controls cell proliferation, differentiation, and apoptosis. Downregulation of cAMP sensitizes tumor cells for anti-cancer treatment. Opioid receptor agonists triggering opioid receptors can activate inhibitory Gi proteins, which, in turn, block adenylyl cyclase activity reducing cAMP. In this study, we show that downregulation of cAMP by opioid receptor activation improves the effectiveness of anti-cancer drugs in treatment of glioblastoma. The µ-opioid receptor agonist D,L-methadone sensitizes glioblastoma as well as the untreatable glioblastoma stem cells for doxorubicin-induced apoptosis and activation of apoptosis pathways by reversing deficient caspase activation and deficient downregulation of XIAP and Bcl-xL, playing critical roles in glioblastomas' resistance. Blocking opioid receptors using the opioid receptor antagonist naloxone or increasing intracellular cAMP by 3-isobutyl-1-methylxanthine (IBMX) strongly reduced opioid receptor agonist-induced sensitization for doxorubicin. In addition, the opioid receptor agonist D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux, whereas doxorubicin increased opioid receptor expression in glioblastomas. Furthermore, opioid receptor activation using D,L-methadone inhibited tumor growth significantly in vivo. Our findings suggest that opioid receptor activation triggering downregulation of cAMP is a promising strategy to inhibit tumor growth and to improve the effectiveness of anti-cancer drugs in treatment of glioblastoma and in killing glioblastoma stem cells
Cell death sensitization of leukemia cells by opioid receptor activation
Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies
Direct and Inverse Variational Problems on Time Scales: A Survey
We deal with direct and inverse problems of the calculus of variations on
arbitrary time scales. Firstly, using the Euler-Lagrange equation and the
strengthened Legendre condition, we give a general form for a variational
functional to attain a local minimum at a given point of the vector space.
Furthermore, we provide a necessary condition for a dynamic
integro-differential equation to be an Euler-Lagrange equation (Helmholtz's
problem of the calculus of variations on time scales). New and interesting
results for the discrete and quantum settings are obtained as particular cases.
Finally, we consider very general problems of the calculus of variations given
by the composition of a certain scalar function with delta and nabla integrals
of a vector valued field.Comment: This is a preprint of a paper whose final and definite form will be
published in the Springer Volume 'Modeling, Dynamics, Optimization and
Bioeconomics II', Edited by A. A. Pinto and D. Zilberman (Eds.), Springer
Proceedings in Mathematics & Statistics. Submitted 03/Sept/2014; Accepted,
after a revision, 19/Jan/201
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