575 research outputs found
Regulation of nucleocytoplasmic trafficking by cell adhesion receptors and the cytoskeleton
It has become widely accepted that adhesion receptors can either directly activate, or significantly modulate, many of the signaling cascades initiated by circulating growth factors. An interesting recent development is the realization that adhesion receptors and their cytoskeletal partners can regulate the trafficking of signaling proteins between the cytoplasm and nucleus. Cell adhesion molecule control of nucleocytoplasmic trafficking allows adhesion to influence many cell decisions, and highlights the diversity of nuclear import and export mechanisms
Regulation of nucleocytoplasmic trafficking by cell adhesion receptors and the cytoskeleton
It has become widely accepted that adhesion receptors can either directly activate, or significantly modulate, many of the signaling cascades initiated by circulating growth factors. An interesting recent development is the realization that adhesion receptors and their cytoskeletal partners can regulate the trafficking of signaling proteins between the cytoplasm and nucleus. Cell adhesion molecule control of nucleocytoplasmic trafficking allows adhesion to influence many cell decisions, and highlights the diversity of nuclear import and export mechanisms
The role of vascular endothelial growth factor (VEGF) in repair and recovery from acute respiratory distress syndrome (ARDS)
Acute Respiratory Distress Syndrome (ARDS) is the most extreme form of acute
lung injury and continues to have a significant morbidity and mortality.
Unfortunately, the mechanisms involved in the recovery and repair of the lung
following ARDS remain poorly understood. An understanding of these is pivotal to
improving outcome from acute lung injury. Several observational studies have
suggested a potential relationship between Vascular Endothelial Growth Factor
(VEGF) in the lung and the development/outcome of ARDS. In this thesis, three potential mechanisms underlying these observations have been explored:
1. What is the anatomical distribution of VEGF receptor and isoform expression in
normal and ARDS lung? How does this change at early and later time points
following acute lung injury?
2. Are human type 2 alveolar epithelial (ATII) cells a source of and target for
VEGF? How does exposure to a pro-inflammatory milieu modify their
expression of VEGF isoforms and receptors?
3. Is there a relationship between a functional VEGF polymorphism and
susceptibility to developing and severity of ARDS?
I have demonstrated VEGF receptor expression on both sides of the alveolarcapillary
membrane with upregulation in later ARDS. All three principal isoforms
(VEGF121, VEGF165 and VEGF189) are expressed in normal human lung with uniform
downregulation of all three in early ARDS, which normalises with increasing time
following injury. I have not found any evidence of VEGF isoform switching.
I have also demonstrated human ATII cells are both a significant cellular source of
and a target for VEGF (via VEGF receptor expression) confirming autocrine VEGF
activity in the lung. VEGF is an ATII cell survival factor. ATII cells differentially
respond to pro-inflammatory stimuli by increasing VEGF isoform but not receptor
expression, which may serve as a regulatory control mechanism.
Finally, I have demonstrated the VEGF 936 T allele increases susceptibility to and
the severity of lung injury. The T allele is associated with an increase in plasma
VEGF level in ARDS patients but intra-alveolar levels are unaffected
Regulation of nucleocytoplasmic trafficking by cell adhesion receptors and the cytoskeleton: Figure 1.
It has become widely accepted that adhesion receptors can either directly activate, or significantly modulate, many of the signaling cascades initiated by circulating growth factors. An interesting recent development is the realization that adhesion receptors and their cytoskeletal partners can regulate the trafficking of signaling proteins between the cytoplasm and nucleus. Cell adhesion molecule control of nucleocytoplasmic trafficking allows adhesion to influence many cell decisions, and highlights the diversity of nuclear import and export mechanisms
An explicit height bound for the classical modular polynomial
For a prime m, let Phi_m be the classical modular polynomial, and let
h(Phi_m) denote its logarithmic height. By specializing a theorem of Cohen, we
prove that h(Phi_m) <= 6 m log m + 16 m + 14 sqrt m log m. As a corollary, we
find that h(Phi_m) <= 6 m log m + 18 m also holds. A table of h(Phi_m) values
is provided for m <= 3607.Comment: Minor correction to the constants in Theorem 1 and Corollary 9. To
appear in the Ramanujan Journal. 17 pages
The Dynamic Structure of Thrombin in Solution
AbstractThe backbone dynamics of human α-thrombin inhibited at the active site serine were analyzed using R1, R2, and heteronuclear NOE experiments, variable temperature TROSY 2D [1H-15N] correlation spectra, and Rex measurements. The N-terminus of the heavy chain, which is formed upon zymogen activation and inserts into the protein core, is highly ordered, as is much of the double beta-barrel core. Some of the surface loops, by contrast, remain very dynamic with order parameters as low as 0.5 indicating significant motions on the ps-ns timescale. Regions of the protein that were thought to be dynamic in the zymogen and to become rigid upon activation, in particular the γ-loop, the 180s loop, and the Na+ binding site have order parameters below 0.8. Significant Rex was observed in most of the γ-loop, in regions proximal to the light chain, and in the β-sheet core. Accelerated molecular dynamics simulations yielded a molecular ensemble consistent with measured residual dipolar couplings that revealed dynamic motions up to milliseconds. Several regions, including the light chain and two proximal loops, did not appear highly dynamic on the ps-ns timescale, but had significant motions on slower timescales
Closed forms and multi-moment maps
We extend the notion of multi-moment map to geometries defined by closed
forms of arbitrary degree. We give fundamental existence and uniqueness results
and discuss a number of essential examples, including geometries related to
special holonomy. For forms of degree four, multi-moment maps are guaranteed to
exist and are unique when the symmetry group is (3,4)-trivial, meaning that the
group is connected and the third and fourth Lie algebra Betti numbers vanish.
We give a structural description of some classes of (3,4)-trivial algebras and
provide a number of examples.Comment: 36 page
Photoelectrons in the Enceladus plume
The plume of Enceladus is a remarkable plasma environment containing several charged particle species. These include cold magnetospheric electrons, negative and positive water clusters, charged nanograins, and “magnetospheric photoelectrons” produced from ionization of neutrals throughout the magnetosphere near Enceladus. Here we discuss observations of a population newly identified by the Cassini Plasma Spectrometer (CAPS) electron spectrometer instrument—photoelectrons produced in the plume ionosphere itself. These were found during the E19 encounter, in the energetic particle shadow where penetrating particles are absent. Throughout E19, CAPS was oriented away from the ram direction where the clusters and nanograins are observed during other encounters. Plume photoelectrons are also clearly observed during the E9 encounter and are also seen at all other Enceladus encounters where electron spectra are available. This new population, warmer than the ambient plasma population, is distinct from, but adds to, the magnetospheric photoelectrons. Here we discuss the observations and examine the implications, including the ionization source these electrons provide
Adiabatic elimination in quantum stochastic models
We consider a physical system with a coupling to bosonic reservoirs via a
quantum stochastic differential equation. We study the limit of this model as
the coupling strength tends to infinity. We show that in this limit the
solution to the quantum stochastic differential equation converges strongly to
the solution of a limit quantum stochastic differential equation. In the
limiting dynamics the excited states are removed and the ground states couple
directly to the reservoirs.Comment: 17 pages, no figures, corrected mistake
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