2,703 research outputs found
Topological Change in Mean Convex Mean Curvature Flow
Consider the mean curvature flow of an (n+1)-dimensional, compact, mean
convex region in Euclidean space (or, if n<7, in a Riemannian manifold). We
prove that elements of the m-th homotopy group of the complementary region can
die only if there is a shrinking S^k x R^(n-k) singularity for some k less than
or equal to m. We also prove that for each m from 1 to n, there is a nonempty
open set of compact, mean convex regions K in R^(n+1) with smooth boundary for
which the resulting mean curvature flow has a shrinking S^m x R^(n-m)
singularity.Comment: 19 pages. This version includes a new section proving that certain
kinds of mean curvature flow singularities persist under arbitrary small
perturbations of the initial surface. Newest update (Oct 2013) fixes some
bibliographic reference
Ionic conductivity on a wetting surface
Recent experiments measuring the electrical conductivity of DNA molecules
highlight the need for a theoretical model of ion transport along a charged
surface. Here we present a simple theory based on the idea of unbinding of ion
pairs. The strong humidity dependence of conductivity is explained by the
decrease in the electrostatic self-energy of a separated pair when a layer of
water (with high dielectric constant) is adsorbed to the surface. We compare
our prediction for conductivity to experiment, and discuss the limits of its
applicability.Comment: 5 pages, 3 figures; one section and two illustrations added; figures
updated and discussion added; typo fixe
mTORC2 signaling drives the development and progression of pancreatic cancer
mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer
Testbeam studies of pre-prototype silicon strip sensors for the LHCb UT upgrade project
The LHCb experiment is preparing for a major upgrade in 2018-2019. One of the
key components in the upgrade is a new silicon tracker situated upstream of the
analysis magnet of the experiment. The Upstream Tracker (UT) will consist of
four planes of silicon strip detectors, with each plane covering an area of
about 2 m. An important consideration of these detectors is their
performance after they have been exposed to a large radiation dose. In this
article we present test beam results of pre-prototype n-in-p and p-in-n sensors
that have been irradiated with fluences up to
cm.Comment: 25 pages, 20 figure
A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis.
The search for effective treatments for obesity and its comorbidities is of prime importance. We previously identified IKK-ε and TBK1 as promising therapeutic targets for the treatment of obesity and associated insulin resistance. Here we show that acute inhibition of IKK-ε and TBK1 with amlexanox treatment increases cAMP levels in subcutaneous adipose depots of obese mice, promoting the synthesis and secretion of the cytokine IL-6 from adipocytes and preadipocytes, but not from macrophages. IL-6, in turn, stimulates the phosphorylation of hepatic Stat3 to suppress expression of genes involved in gluconeogenesis, in the process improving glucose handling in obese mice. Preliminary data in a small cohort of obese patients show a similar association. These data support an important role for a subcutaneous adipose tissue-liver axis in mediating the acute metabolic benefits of amlexanox on glucose metabolism, and point to a new therapeutic pathway for type 2 diabetes
Weighted-density approximation for general nonuniform fluid mixtures
In order to construct a general density-functional theory for nonuniform
fluid mixtures, we propose an extension to multicomponent systems of the
weighted-density approximation (WDA) of Curtin and Ashcroft [Phys. Rev. A 32,
2909 (1985)]. This extension corrects a deficiency in a similar extension
proposed earlier by Denton and Ashcroft [Phys. Rev. A 42, 7312 (1990)], in that
that functional cannot be applied to the multi-component nonuniform fluid
systems with spatially varying composition, such as solid-fluid interfaces. As
a test of the accuracy of our new functional, we apply it to the calculation of
the freezing phase diagram of a binary hard-sphere fluid, and compare the
results to simulation and the Denton-Ashcroft extension.Comment: 4 pages, 4 figures, to appear in Phys. Rev. E as Brief Repor
EpsinR: an AP1/clathrin interacting protein involved in vesicle trafficking
EpsinR is a clathrin-coated vesicle (CCV) enriched 70-kD protein that binds to phosphatidylinositol-4-phosphate, clathrin, and the gamma appendage domain of the adaptor protein complex 1 (AP1). In cells, its distribution overlaps with the perinuclear pool of clathrin and AP1 adaptors. Overexpression disrupts the CCV-dependent trafficking of cathepsin D from the trans-Golgi network to lysosomes and the incorporation of mannose-6-phosphate receptors into CCVs. These biochemical and cell biological data point to a role for epsinR in AP1/clathrin budding events in the cell, just as epsin1 is involved in the budding of AP2 CCVs. Furthermore, we show that two gamma appendage domains can simultaneously bind to epsinR with affinities of 0.7 and 45 μM, respectively. Thus, potentially, two AP1 complexes can bind to one epsinR. This high affinity binding allowed us to identify a consensus binding motif of the form DFxDF, which we also find in γ-synergin and use to predict that an uncharacterized EF-hand–containing protein will be a new gamma binding partner
Inter-rater reliability of the Dysexecutive Questionnaire (DEX): comparative data from non-clinician respondents – all raters are not equal
Primary objective: The Dysexecutive Questionnaire (DEX) is used to obtain information about executive and emotional problems after neuropathology. The DEX is self-completed by the patient (DEX-S) and an independent rater such as a family member (DEX-I). This study examined the level of inter-rater agreement between either two or three non-clinician raters on the DEX-I in order to establish the reliability of DEX-I ratings.
Methods and procedures: Family members and/or carers of 60 people with mixed neuropathology completed the DEX-I. For each patient, DEX-I ratings were obtained from either two or three raters who knew the person well prior to brain injury.
Main outcomes and results: We obtained two independent-ratings for 60 patients and three independent-ratings for 36 patients. Intra-class correlations revealed that there was only a modest level of agreement for items, subscale and total DEX scores between raters for their particular family member. Several individual DEX items had low reliability and ratings for the emotion sub-scale had the lowest level of agreement.
Conclusions: Independent DEX ratings completed by two or more non-clinician raters show only moderate correlation. Suggestions are made for improving the reliability of DEX-I ratings.</p
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