Lagrangian Floer superpotentials and crepant resolutions for toric orbifolds

We investigate the relationship between the Lagrangian Floer superpotentials for a toric orbifold and its toric crepant resolutions. More specifically, we study an open string version of the crepant resolution conjecture (CRC) which states that the Lagrangian Floer superpotential of a Gorenstein toric orbifold $\mathcal{X}$ and that of its toric crepant resolution $Y$ coincide after analytic continuation of quantum parameters and a change of variables. Relating this conjecture with the closed CRC, we find that the change of variable formula which appears in closed CRC can be explained by relations between open (orbifold) Gromov-Witten invariants. We also discover a geometric explanation (in terms of virtual counting of stable orbi-discs) for the specialization of quantum parameters to roots of unity which appears in Y. Ruan's original CRC ["The cohomology ring of crepant resolutions of orbifolds", Gromov-Witten theory of spin curves and orbifolds, 117-126, Contemp. Math., 403, Amer. Math. Soc., Providence, RI, 2006]. We prove the open CRC for the weighted projective spaces $\mathcal{X}=\mathbb{P}(1,\ldots,1,n)$ using an equality between open and closed orbifold Gromov-Witten invariants. Along the way, we also prove an open mirror theorem for these toric orbifolds.Comment: 48 pages, 1 figure; v2: references added and updated, final version, to appear in CM

Polar motion and UT1: Comparison of VLBI, lunar laser, satellite laser, satellite Doppler, and conventional astrometric determinations

Very long baseline interferometry observations made with a 3900 km baseline interferometer (Haystack Observatory in Massachusetts to Owens Valley Observation in California) were used to estimate changes in the X-component of the position of the Earth's pole and in UT1. These estimates are compared with corresponding ones from lunar laser ranging, satellite laser ranging, satellite Doppler, and stellar observations

Precision surveying using very long baseline interferometry

Radio interferometry measurements were used to measure the vector baselines between large microwave radio antennas. A 1.24 km baseline in Massachusetts between the 36 meter Haystack Observatory antenna and the 18 meter Westford antenna of Lincoln Laboratory was measured with 5 mm repeatability in 12 separate experiments. Preliminary results from measurements of the 3,928 km baseline between the Haystack antenna and the 40 meter antenna at the Owens Valley Radio Observatory in California are presented

Transplant glomerulopathy: the interaction of HLA antibodies and endothelium

Transplant glomerulopathy (TG) is a major cause of chronic graft dysfunction without effective therapy. Although the histological definition of TG is well characterized, the pathophysiological pathways leading to TG development are still poorly understood. Electron microscopy suggests an earlier appearance of TG and suggests that endothelial cell injury is the first sign of the disease. The pathogenic role of human leukocyte antigen (HLA) antibodies in endothelial cells has been described in acute vascular and humoral rejection. However the mechanisms and pathways of endothelial cell injury by HLA antibodies remain unclear. Despite the description of different causes of the morphological lesion of TG (hepatitis, thrombotic microangiopathy), the strong link between TG and chronic antibody mediated rejection suggests a major role for HLA antibodies in TG formation. In this review, we describe the effect of classes I or II HLA-antibodies in TG and especially the implication of donor specific antibodies (DSA). We update recent studies about endothelial cells and try to explain the different signals and intracellular pathways involved in the progression of TG.William Hanf, Claudine S. Bonder, and P. Toby H. Coate

Achieving minimal disease activity in psoriatic arthritis predicts meaningful improvements in patients’ health-related quality of life and productivity

Background Although psoriatic arthritis is complex and involves multiple domains, recent advances in treatments have made remission or near-remission of most symptoms a potentially achievable goal for many patients. We sought to evaluate whether achieving minimal disease activity (MDA) criteria represented meaningful improvement from the patient perspective. Methods Data were combined from two randomized, multinational, 24 week clinical studies of ixekizumab, a high-affinity monoclonal antibody selectively targeting interleukin-17A, in biological drug-naïve or experienced adults. MDA required 5 of 7 of: tender joint count ≤1; swollen joint count ≤1; Psoriasis Area and Severity Index total score ≤ 1 or body surface area ≤ 3%; patient’s assessment of pain visual analogue scale (VAS) ≤15; patient’s global assessment of disease activity VAS ≤20; Health Assessment Questionnaire Disability Index ≤0.5; and tender entheseal points ≤ 1. MDA responders and non-responders were compared for mean change from baseline on the 36-Item Short Form Health Survey (SF-36), European Quality of Life 5 Dimension 5 Level Health Questionnaire (EQ-5D-5 L); EQ-5D-5 L VAS; and Work Productivity and Activity Impairment–Specific Health Problem (WPAI-SHP) questionnaire. Results MDA responders had significantly greater improvements versus non-responders in each SF-36 domain and in the SF-36 physical summary score; improvements were also greater in the EQ-5D-5 L and EQ-5D-5 L VAS, and in 3 of the 4 WPAI-SHP domains. MDA responders were more likely to achieve minimal clinically important differences than non-responders. Conclusion These findings support MDA response as being strongly associated with achieving improved disease status based on measures of patient reported health-related quality of life and productivity. Trial registration SPIRIT-P1, NCT01695239, First Posted: September 27, 2012; and SPIRIT-P2, NCT02349295, First Posted: January 28, 2015

Independent Interactions of Phosphorylated β-Catenin with E-Cadherin at Cell-Cell Contacts and APC at Cell Protrusions

BACKGROUND: The APC tumour suppressor functions in several cellular processes including the regulation of β-catenin in Wnt signalling and in cell adhesion and migration. FINDINGS: In this study, we establish that in epithelial cells N-terminally phosphorylated β-catenin specifically localises to several subcellular sites including cell-cell contacts and the ends of cell protrusions. N-terminally phosphorylated β-catenin associates with E-cadherin at adherens junctions and with APC in cell protrusions. We isolated APC-rich protrusions from stimulated cells and detected β-catenin, GSK3β and CK1α, but not axin. The APC/phospho-β-catenin complex in cell protrusions appears to be distinct from the APC/axin/β-catenin destruction complex. GSK3β phosphorylates the APC-associated population of β-catenin, but not the cell junction population. β-catenin associated with APC is rapidly phosphorylated and dephosphorylated. HGF and wound-induced cell migration promote the localised accumulation of APC and phosphorylated β-catenin at the leading edge of migrating cells. APC siRNA and analysis of colon cancer cell lines show that functional APC is required for localised phospho-β-catenin accumulation in cell protrusions. CONCLUSIONS: We conclude that N-terminal phosphorylation of β-catenin does not necessarily lead to its degradation but instead marks distinct functions, such as cell migration and/or adhesion processes. Localised regulation of APC-phospho-β-catenin complexes may contribute to the tumour suppressor activity of APC