212 research outputs found
Elliptic obstacle problems with measure data : potentials and low order regularity
We consider obstacle problems with measure data related to elliptic equations of p-Laplace type, and investigate the connections between low order regularity properties of the solutions and non-linear potentials of the data. In particular, we give pointwise estimates for the solutions in terms of Wol potentials and address the questions of boundedness and continuity of the solution
Analysis of the genetic basis of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.
PFAPA syndrome is the most common autoinflammatory syndrome in children from Western countries. In spite of its strong familial clustering, its genetic basis and inheritance pattern are still unknown. We performed a comprehensive genetic study on 68 individuals from 14 families. Linkage analysis suggested a susceptibility locus on chromosome 8, but direct molecular sequencing did not support this initial statistical finding. Exome sequencing revealed the absence of any gene that was mutated in all patients. Exhaustive screening of genes involved in other autoinflammatory syndromes or encoding components of the human inflammasome showed no DNA variants that could be linked to PFAPA molecular pathology. Among these, the previously-reported missense mutation V198M in the NLRP3 gene was clearly shown not to co-segregate with PFAPA. Our results on this relatively large cohort indicate that PFAPA syndrome is unlikely to be a monogenic condition. Moreover, none of the several genes known to be involved in inflammation or in autoinflammatory disorders seem to be relevant, alone, to its etiology, suggesting that PFAPA results from oligogenic or complex inheritance of variants in multiple disease genes and/or non-genetic factors
Effect of dentin matrix components on the mineralization of human mesenchymal stromal cells
In teeth with an injured pulp, dentin matrix orchestrates hard tissue repair through the release of dentin extracellular matrix components (dEMCs). dEMCs regulate the differentiation of resident mesenchymal stromal cells (MSCs), thereby affecting mineral deposition. In this study, we show that low-concentration solubilized dEMCs in osteogenic cultures of human umbilical cord mesenchymal stromal cells (UC-MSCs) and dental pulp stromal cells (DPSCs) enhanced mineral deposition, while adipose stromal cells (ASCs) were barely affected. Interestingly, UC-MSCs displayed significantly greater hydroxyapatite formation compared with DPSCs. UC-MSCs and DPSCs showed a dose-dependent viability and proliferation, whereas proliferation of ASCs remained unaffected. Qualitative analysis of the dEMC-supplemented osteogenic cultures through scanning electron microscopy demonstrated differences in the architecture of the deposited mineralized structures. Large-sized mineral accretions on a poorly organized collagen network were the prominent feature of UC-MSC cultures, while mineral nodules interspersed throughout a collagen mesh were observed in the respective DPSC cultures. The ability of dEMCs to induce mineralization varies between different human MSC types in terms of total mineral formation and architecture. Mineral formation by UC-MSCs exposed to low-concentration dEMCs proved to be the most efficient and therefore could be considered a promising combination for mineralized tissue engineering. Impact Statement This research has been conducted with the aim to contribute to the development of treatment modalities for the reconstruction of lost/damaged mineralized tissues. Currently, determining the most appropriate stromal cell population and signaling cues stands at the core of developing effective treatments. We provide new insights into the effect of innate inductive cues found in human dentin matrix components, on the osteogenic differentiation of various human stromal cell types. The effects of dentin extracellular matrix components on umbilical cord mesenchymal stromal cells have not been investigated before. The findings of this study could underpin translational research based on the development of techniques for mineralized tissue engineering and will be of great interest for the readership of Tissue Engineering Part A
Osteoblast-Restricted Disruption of the Growth Hormone Receptor in Mice Results in Sexually Dimorphic Skeletal Phenotypes
Growth hormone (GH) exerts profound anabolic actions during postnatal skeletal development, in part, through stimulating the production of insulin-like growth factor-1 (IGF-1) in liver and skeletal tissues. To examine the requirement for the GH receptor (GHR) in osteoblast function in bone, we used Cre-LoxP methods to disrupt the GHR from osteoblasts, both in vitro and in vivo. Disruption of GHR from primary calvarial osteoblasts in vitro abolished GH-induced signaling, as assessed by JAK2/STAT5 phosphorylation, and abrogated GH-induced proliferative and anti-apoptotic actions. Osteoblasts lacking GHR exhibited reduced IGF-1-induced Erk and Akt phosphorylation and attenuated IGF-1-induced proliferation and anti-apoptotic action. In addition, differentiation was modestly impaired in osteoblasts lacking GHR, as demonstrated by reduced alkaline phosphatase staining and calcium deposition. In order to determine the requirement for the GHR in bone in vivo, we generated mice lacking the GHR specifically in osteoblasts (ΔGHR), which were born at the expected Mendelian frequency, had a normal life span and were of normal size. Three week-old, female ΔGHR mice had significantly reduced osteoblast numbers, consistent with the in vitro data. By six weeks of age however, female ΔGHR mice demonstrated a marked increase in osteoblasts, although mineralization was impaired; a phenotype similar to that observed previously in mice lacking IGF-1R specifically in osteoblasts. The most striking phenotype occurred in male mice however, where disruption of the GHR from osteoblasts resulted in a feminization of bone geometry in 16 week-old mice, as observed by μCT. These results demonstrate that the GHR is required for normal postnatal bone development in both sexes. GH appears to serve a primary function in modulating local IGF-1 action. However, the changes in bone geometry observed in male ΔGHR mice suggest that, in addition to facilitating IGF-1 action, GH may function to a greater extent than previously appreciated in establishing the sexual dimorphism of the skeleton
Chiral Surface States in the Bulk Quantum Hall Effect
In layered samples which exhibit a bulk quantum Hall effect (QHE), a
two-dimensional (2d) surface ``sheath" of gapless excitations is expected.
These excitations comprise a novel 2d chiral quantum liquid which should
dominate the low temperature transport along the field (z-axis). For the
integer QHE, we show that localization effects are completely absent in the
``sheath", giving a metallic z-axis conductivity. For fractional filling , the ``sheath" is a 2d non-Fermi liquid, with incoherent z-axis transport
and . Experimental implications for the Bechgaard salts
are discussed.Comment: 4 pages, RevTeX 3.0, with two encapsulated postscript figures, which
can be automatically included in-text if desired. The complete postscript
file is available on the WWW at http://www.itp.ucsb.edu/~balents/sheath.p
Edge electron states for quasi-one-dimensional organic conductors in the magnetic-field-induced spin-density-wave phases
We develop a microscopic picture of the electron states localized at the
edges perpendicular to the chains in the Bechgaard salts in the quantum Hall
regime. In a magnetic-field-induced spin-density-wave state (FISDW)
characterized by an integer N, there exist N branches of chiral gapless edge
excitations. Localization length is much longer and velocity much lower for
these states than for the edge states parallel to the chains. We calculate the
contribution of these states to the specific heat and propose a time-of-flight
experiment to probe the propagating edge modes directly.Comment: 4 pages, 2 figures. V.2: Minor changes to the final version published
in PR
The prescribed mean curvature equation in weakly regular domains
We show that the characterization of existence and uniqueness up to vertical
translations of solutions to the prescribed mean curvature equation, originally
proved by Giusti in the smooth case, holds true for domains satisfying very
mild regularity assumptions. Our results apply in particular to the
non-parametric solutions of the capillary problem for perfectly wetting fluids
in zero gravity. Among the essential tools used in the proofs, we mention a
\textit{generalized Gauss-Green theorem} based on the construction of the weak
normal trace of a vector field with bounded divergence, in the spirit of
classical results due to Anzellotti, and a \textit{weak Young's law} for
-minimizers of the perimeter.Comment: 23 pages, 1 figure --- The results on the weak normal trace of vector
fields have been now extended and moved in a self-contained paper available
at: arXiv:1708.0139
Pilot study comparing the childhood arthritis and rheumatology research alliance consensus treatment plans for induction therapy of juvenile proliferative lupus nephritis
BACKGROUND: To reduce treatment variability and facilitate comparative effectiveness studies, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) including one for juvenile proliferative lupus nephritis (LN). Induction immunosuppression CTPs outline treatment with either monthly intravenous (IV) cyclophosphamide (CYC) or mycophenolate mofetil (MMF) in conjunction with one of three corticosteroid (steroid) CTPs: primarily oral, primarily IV or mixed oral/IV. The acceptability and in-practice use of these CTPs are unknown. Therefore, the primary aims of the pilot study were to demonstrate feasibility of adhering to the LN CTPs and delineate barriers to implementation in clinical care in the US. Further, we aimed to explore the safety and effectiveness of the treatments for induction therapy.METHODS: Forty-one patients were enrolled from 10 CARRA sites. Patients had new-onset biopsy proven ISN/RPS class III or IV proliferative LN, were starting induction therapy with MMF or IV CYC and high-dose steroids and were followed for up to 24 months. Routine clinical data were collected at each visit. Provider reasons for CTP selection were assessed at baseline. Adherence to the CTPs was evaluated by provider survey and medication logs. Complete and partial renal responses were reported at 6 months.RESULTS: The majority of patients were female (83%) with a mean age of 14.7 years, SD 2.8. CYC was used more commonly than MMF for patients with ISN/RPS class IV LN (vs. class III), those who had hematuria, and those with adherence concerns. Overall adherence to the immunosuppression induction CTPs was acceptable with a majority of patients receiving the target MMF (86%) or CYC (63%) dose. However, adherence to the steroid CTPs was poor (37%) with large variability in dosing. Renal response endpoints were exploratory and did not show a significant difference between CYC and MMF.CONCLUSIONS: Overall, the immunosuppression CTPs were followed as intended in the majority of patients however, adherence to the steroid CTPs was poor indicating revision is necessary. In addition, our pilot study revealed several sources of treatment selection bias that will need to be addressed in for future comparative effectiveness research
Hot Spots and Transition from d-Wave to Another Pairing Symmetry in the Electron-Doped Cuprate Superconductors
We present a simple theoretical explanation for a transition from d-wave to
another superconducting pairing observed in the electron-doped cuprates. The
d_{x^2-y^2} pairing potential Delta, which has the maximal magnitude and
opposite signs at the hot spots on the Fermi surface, becomes suppressed with
the increase of electron doping, because the hot spots approach the Brillouin
zone diagonals, where Delta vanishes. Then, the d_{x^2-y^2} pairing is replaced
by either singlet s-wave or triplet p-wave pairing. We argue in favor of the
latter and discuss experiments to uncover it.Comment: 6 pages, 4 figures, RevTeX 4. V.2: Extra figure and many references
added. V.3: Minor update of references for the proof
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