41 research outputs found
Uniform deterministic equivalent of additive functionals and non-parametric drift estimation for one-dimensional recurrent diffusions
Usually the problem of drift estimation for a diffusion process is considered
under the hypothesis of ergodicity. It is less often considered under the
hypothesis of null-recurrence, simply because there are fewer limit theorems
and existing ones do not apply to the whole null-recurrent class. The aim of
this paper is to provide some limit theorems for additive functionals and
martingales of a general (ergodic or null) recurrent diffusion which would
allow us to have a somewhat unified approach to the problem of non-parametric
kernel drift estimation in the one-dimensional recurrent case. As a particular
example we obtain the rate of convergence of the Nadaraya--Watson estimator in
the case of a locally H\"{o}lder-continuous drift.Comment: Published in at http://dx.doi.org/10.1214/07-AIHP141 the Annales de
l'Institut Henri Poincar\'e - Probabilit\'es et Statistiques
(http://www.imstat.org/aihp/) by the Institute of Mathematical Statistics
(http://www.imstat.org
Comment on ``Capacity of the Hopfield model''
In a recent paper ``The capacity of the Hopfield model, J. Feng and B.
Tirozzi claim to prove rigorous results on the storage capacity that are in
conflict with the predictions of the replica approach. We show that their
results are in error and that their approach, even when the worst mistakes are
corrected, is not giving any mathematically rigorous results.Comment: 4pp, Plain Te
Molecular Mechanism of Capacitative Calcium Entry Deficits in Familial Alzheimer’s Disease
Poster PresentationPresenilin (PS) is the catalytic subunit of the gamma-secretase which is responsible for the cleavage of
amyloid precursor protein to form beta amyloid (Aβ). Mutations in PS associated with familial
Alzheimer’s disease (FAD) increase the Aβ plaques formation in the brain and cause neurodegeneration.
Apart from this, FAD-linked PS mutations have been demonstrated to disrupt intracellular calcium (Ca2+)
regulation. Accumulating evidence suggests that Ca2+ disruption may play a proximal role in the AD
pathogenesis. Mutant PS exaggerated Ca2+ release from the endoplasmic reticulum (ER). It also attenuated
Ca2+ entry through the capacitative Ca2+ entry (CCE) pathway, yet, the mechanism is not fully understood.
Using a human neuroblast cell line SH-SY5Y and Ca2+ imaging technique, we observed CCE deficits in
FAD-linked PS1-M146L retroviral infected cell. The attenuation of CCE in PS1 mutant cells was not
mediated by the down-regulation of STIM1 and Orai1 expression, the known essential molecular players
in the CCE pathway. Instead, we identified a molecular interaction between PS and STIM1 proteins by
immunoprecipitation. On the other hand, immunofluorescence staining showed a significant reduction in
puncta formation after ER Ca2+ depleted by thapsigargin in cells infected with PS1-M146L as compared to
the wild type PS1 infected cells. Taken together, our results suggest a molecular mechanism for the CCE
deficits in FAD associated with PS1 mutations. The interaction of mutant PS1 with STIM1 exerts a
negative impact on its oligomerization and/or its interaction with Orai1. Our results may suggest molecular
targets for the development of therapeutic agents that help to treat the disease.published_or_final_versio
Improved Survival, Vascular Differentiation and Wound Healing Potential of Stem Cells Co-Cultured with Endothelial Cells
In this study, we developed a methodology to improve the survival, vascular differentiation and regenerative potential of umbilical cord blood (UCB)-derived hematopoietic stem cells (CD34+ cells), by co-culturing the stem cells in a 3D fibrin gel with CD34+-derived endothelial cells (ECs). ECs differentiated from CD34+ cells appear to have superior angiogenic properties to fully differentiated ECs, such as human umbilical vein endothelial cells (HUVECs). Our results indicate that the pro-survival effect of CD34+-derived ECs on CD34+ cells is mediated, at least in part, by bioactive factors released from ECs. This effect likely involves the secretion of novel cytokines, including interleukin-17 (IL-17) and interleukin-10 (IL-10), and the activation of the ERK 1/2 pathway in CD34+ cells. We also show that the endothelial differentiation of CD34+ cells in co-culture with CD34+-derived ECs is mediated by a combination of soluble and insoluble factors. The regenerative potential of this co-culture system was demonstrated in a chronic wound diabetic animal model. The co-transplantation of CD34+ cells with CD34+-derived ECs improved the wound healing relatively to controls, by decreasing the inflammatory reaction and increasing the neovascularization of the wound
Myosin VIIA, Important for Human Auditory Function, Is Necessary for Drosophila Auditory Organ Development
BACKGROUND: Myosin VIIA (MyoVIIA) is an unconventional myosin necessary for vertebrate audition [1]-[5]. Human auditory transduction occurs in sensory hair cells with a staircase-like arrangement of apical protrusions called stereocilia. In these hair cells, MyoVIIA maintains stereocilia organization [6]. Severe mutations in the Drosophila MyoVIIA orthologue, crinkled (ck), are semi-lethal [7] and lead to deafness by disrupting antennal auditory organ (Johnston's Organ, JO) organization [8]. ck/MyoVIIA mutations result in apical detachment of auditory transduction units (scolopidia) from the cuticle that transmits antennal vibrations as mechanical stimuli to JO. PRINCIPAL FINDINGS: Using flies expressing GFP-tagged NompA, a protein required for auditory organ organization in Drosophila, we examined the role of ck/MyoVIIA in JO development and maintenance through confocal microscopy and extracellular electrophysiology. Here we show that ck/MyoVIIA is necessary early in the developing antenna for initial apical attachment of the scolopidia to the articulating joint. ck/MyoVIIA is also necessary to maintain scolopidial attachment throughout adulthood. Moreover, in the adult JO, ck/MyoVIIA genetically interacts with the non-muscle myosin II (through its regulatory light chain protein and the myosin binding subunit of myosin II phosphatase). Such genetic interactions have not previously been observed in scolopidia. These factors are therefore candidates for modulating MyoVIIA activity in vertebrates. CONCLUSIONS: Our findings indicate that MyoVIIA plays evolutionarily conserved roles in auditory organ development and maintenance in invertebrates and vertebrates, enhancing our understanding of auditory organ development and function, as well as providing significant clues for future research
Phonon distributions of a single bath mode coupled to a quantum dot
The properties of an unconventional, single mode phonon bath coupled to a
quantum dot, are investigated within the rotating wave approximation. The
electron current through the dot induces an out of equilibrium bath, with a
phonon distribution qualitatively different from the thermal one. In selected
transport regimes, such a distribution is characterized by a peculiar selective
population of few phonon modes and can exhibit a sub-Poissonian behavior. It is
shown that such a sub-Poissonian behavior is favored by a double occupancy of
the dot. The crossover from a unequilibrated to a conventional thermal bath is
explored, and the limitations of the rotating wave approximation are discussed.Comment: 21 Pages, 7 figures, to appear in New Journal of Physics - Focus on
Quantum Dissipation in Unconventional Environment
Bone Marrow-Derived Progenitor Cells Augment Venous Remodeling in a Mouse Dorsal Skinfold Chamber Model
The delivery of bone marrow-derived cells (BMDCs) has been widely used to stimulate angiogenesis and arteriogenesis. We identified a progenitor-enriched subpopulation of BMDCs that is able to augment venular remodeling, a generally unexplored area in microvascular research. Two populations of BMDCs, whole bone marrow (WBM) and Lin−/Sca-1+ progenitor cells, were encapsulated in sodium alginate and delivered to a mouse dorsal skinfold chamber model. Upon observation that encapsulated Sca-1+ progenitor cells enhance venular remodeling, the cells and tissue were analyzed on structural and molecular levels. Venule walls were thickened and contained more nuclei after Sca-1+ progenitor cell delivery. In addition, progenitors expressed mRNA transcript levels of chemokine (C-X-C motif) ligand 2 (CXCL2) and interferon gamma (IFNγ) that are over 5-fold higher compared to WBM. Tissues that received progenitors expressed significantly higher protein levels of vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and platelet derived growth factor-BB (PDGF-BB) compared to tissues that received an alginate control construct. Nine days following cell delivery, tissue from progenitor recipients contained 39% more CD45+ leukocytes, suggesting that these cells may enhance venular remodeling through the modulation of the local immune environment. Results show that different BMDC populations elicit different microvascular responses. In this model, Sca-1+ progenitor cell-derived CXCL2 and IFNγ may mediate venule enlargement via modulation of the local inflammatory environment