The diffuse Nitsche method: Dirichlet constraints on phase-field boundaries

We explore diffuse formulations of Nitsche's method for consistently imposing Dirichlet boundary conditions on phase-field approximations of sharp domains. Leveraging the properties of the phase-field gradient, we derive the variational formulation of the diffuse Nitsche method by transferring all integrals associated with the Dirichlet boundary from a geometrically sharp surface format in the standard Nitsche method to a geometrically diffuse volumetric format. We also derive conditions for the stability of the discrete system and formulate a diffuse local eigenvalue problem, from which the stabilization parameter can be estimated automatically in each element. We advertise metastable phase-field solutions of the Allen-Cahn problem for transferring complex imaging data into diffuse geometric models. In particular, we discuss the use of mixed meshes, that is, an adaptively refined mesh for the phase-field in the diffuse boundary region and a uniform mesh for the representation of the physics-based solution fields. We illustrate accuracy and convergence properties of the diffuse Nitsche method and demonstrate its advantages over diffuse penalty-type methods. In the context of imaging based analysis, we show that the diffuse Nitsche method achieves the same accuracy as the standard Nitsche method with sharp surfaces, if the inherent length scales, i.e., the interface width of the phase-field, the voxel spacing and the mesh size, are properly related. We demonstrate the flexibility of the new method by analyzing stresses in a human vertebral body

Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor.

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model

Higher-order non-symmetric counterterms in pure Yang-Mills theory

We analyze the restoration of the Slavnov-Taylor (ST) identities for pure massless Yang-Mills theory in the Landau gauge within the BPHZL renormalization scheme with IR regulator. We obtain the most general form of the action-like part of the symmetric regularized action, obeying the relevant ST identities and all other relevant symmetries of the model, to all orders in the loop expansion. We also give a cohomological characterization of the fulfillment of BPHZL IR power-counting criterion, guaranteeing the existence of the limit where the IR regulator goes to zero. The technique analyzed in this paper is needed in the study of the restoration of the ST identities for those models, like the MSSM, where massless particles are present and no invariant regularization scheme is known to preserve the full set of ST identities of the theory.Comment: Final version published in the journa

Temporal ocular coherence tomography-measured changes in anterior chamber angle and diurnal intraocular pressure after laser iridoplasty: IMPACT study

Aims: To evaluate temporal change in anterior chamber angle anatomy following argon laser peripheral iridoplasty (ALPI) in eyes with occludable angles postlaser peripheral iridotomy (LPI) compared with control eyes. Additionally, the effect on diurnal intraocular pressure (DIOP) fluctuation (maximum-minimum IOP) was investigated. Methods: Twenty-two patients with bilateral primary angle closure/suspects with gonioscopically occludable anterior chamber angles following LPI were randomised to receive ALPI (n=11) or no further treatment (n=11). Angle opening distance (AOD), trabecular-iris angle, angle recess area and trabecular-iris space area were measured over eight sections with swept-source anterior segment optical coherence tomography and DIOP was measured pre-LPI and repeated at 3 months after ALPI (hourly measures). Results: All angle parameters increased following ALPI. This change was maintained for 3 months in seven of the eight sections (eg, inferotemporal AOD500 increased by 0.063 mm, p=0.004 at 1 day; 0.051 mm, p=0.029 at 1 week; 0.059 mm, p=0.006 at 6 weeks and 0.056 mm, p=0.011 at 3 months). The only exception was in the inferior sector (eg, AOD500 increased by 0.041 mm, p=0.025 at 1 day and by 0.029 mm, p=0.054 at 3 months). DIOP at 3 months was significantly reduced (5.04 mm Hg; ±1.61 mm Hg) compared with controls (6.61 mm Hg; ±1.63 mm Hg). Maximum IOP was significantly greater in the non-ALPI group (1.87 mm Hg, p=0.026). Conclusions: ALPI widened all angle sections in eyes that remained occludable post-LPI. Changes were maintained for 3 months. ALPI decreased DIOP fluctuation in the treated eyes by lowering the maximum IOP value

Restoration of supersymmetric Slavnov-Taylor and Ward identities in presence of soft and spontaneous symmetry breaking

Supersymmetric Slavnov-Taylor and Ward identities are investigated in presence of soft and spontaneous symmetry breaking. We consider an abelian model where soft supersymmetry breaking yields a mass splitting between electron and selectron and triggers spontaneous symmetry breaking, and we derive corresponding identities that relate the electron and selectron masses with the Yukawa coupling. We demonstrate that the identities are valid in dimensional reduction and invalid in dimensional regularization and compute the necessary symmetry-restoring counterterms.Comment: 35 pages, LaTeX, 9 postscript figure

The Apache Point Observatory Galactic Evolution Experiment (APOGEE) Spectrographs

We describe the design and performance of the near-infrared (1.51--1.70 micron), fiber-fed, multi-object (300 fibers), high resolution (R = lambda/delta lambda ~ 22,500) spectrograph built for the Apache Point Observatory Galactic Evolution Experiment (APOGEE). APOGEE is a survey of ~ 10^5 red giant stars that systematically sampled all Milky Way populations (bulge, disk, and halo) to study the Galaxy's chemical and kinematical history. It was part of the Sloan Digital Sky Survey III (SDSS-III) from 2011 -- 2014 using the 2.5 m Sloan Foundation Telescope at Apache Point Observatory, New Mexico. The APOGEE-2 survey is now using the spectrograph as part of SDSS-IV, as well as a second spectrograph, a close copy of the first, operating at the 2.5 m du Pont Telescope at Las Campanas Observatory in Chile. Although several fiber-fed, multi-object, high resolution spectrographs have been built for visual wavelength spectroscopy, the APOGEE spectrograph is one of the first such instruments built for observations in the near-infrared. The instrument's successful development was enabled by several key innovations, including a "gang connector" to allow simultaneous connections of 300 fibers; hermetically sealed feedthroughs to allow fibers to pass through the cryostat wall continuously; the first cryogenically deployed mosaic volume phase holographic grating; and a large refractive camera that includes mono-crystalline silicon and fused silica elements with diameters as large as ~ 400 mm. This paper contains a comprehensive description of all aspects of the instrument including the fiber system, optics and opto-mechanics, detector arrays, mechanics and cryogenics, instrument control, calibration system, optical performance and stability, lessons learned, and design changes for the second instrument.Comment: 81 pages, 67 figures, PASP, accepte

Disproportionate left atrial myopathy in heart failure with preserved ejection fraction among participants of the PROMIS-HFpEF study

Impaired left atrial (LA) function in heart failure with preserved ejection fraction (HFpEF) is associated with adverse outcomes. A subgroup of HFpEF may have LA myopathy out of proportion to left ventricular (LV) dysfunction; therefore, we sought to characterize HFpEF patients with disproportionate LA myopathy. In the prospective, multicenter, Prevalence of Microvascular Dysfunction in HFpEF study, we defined disproportionate LA myopathy based on degree of LA reservoir strain abnormality in relation to LV myopathy (LV global longitudinal strain [GLS]) by calculating the residuals from a linear regression of LA reservoir strain and LV GLS. We evaluated associations of disproportionate LA myopathy with hemodynamics and performed a plasma proteomic analysis to identify proteins associated with disproportionate LA myopathy; proteins were validated in an independent sample. Disproportionate LA myopathy correlated with better LV diastolic function but was associated with lower stroke volume reserve after passive leg raise independent of atrial fibrillation (AF). Additionally, disproportionate LA myopathy was associated with higher pulmonary artery systolic pressure, higher pulmonary vascular resistance, and lower coronary flow reserve. Of 248 proteins, we identified and validated 5 proteins (involved in cardiomyocyte stretch, extracellular matrix remodeling, and inflammation) that were associated with disproportionate LA myopathy independent of AF. In HFpEF, LA myopathy may exist out of proportion to LV myopathy. Disproportionate LA myopathy is a distinct HFpEF subtype associated with worse hemodynamics and a distinct proteomic signature, independent of AF

Increased serum levels of MRP-8/14 in type 1 diabetes induce an increased expression of CD11b and an enhanced adhesion of circulating monocytes to fibronectin

The recruitment of monocytes from the bloodstream is crucial in the accumulation of macrophages and dendritic cells in type 1 diabetic pancreases. Adhesion via integrins to endothelium and extracellular matrix proteins, such as fibronectin (FN), and the production of myeloid-related protein (MRP)-8, -14, and -8/14 by recently transmigrated monocytes are thought to be instrumental in such recruitment. We determined the FN-adhesive capacity and integrin expression of monocytes of type 1 and type 2 diabetic patients and related them to the subjects' serum levels of MRP-8, -14 and -8/14. Monocytes of type 1 diabetic patients displayed an increased adhesion to fibronectin in comparison with type 2 patients and healthy control subjects but had a normal expression of the FN binding integrins CD29, CD49a, CD49d, and CD49e (although CD11b and CD18 expression was increased). MRP-8/14, which was increased in the sera of type 1 diabetic patients, induced healthy donor monocytes to adhere to FN and upregulate CD11b expression in a dosage-dependent manner. The observed MRP-induced increased adhesion of monocytes to FN and upregulation of CD11b most likely contributed to a facilitated accumulation of monocytes and monocyte-derived cells at the site of inflammation, in this case the pancreatic islets

Search for W' bosons decaying to an electron and a neutrino with the D0 detector

This Letter describes the search for a new heavy charged gauge boson W' decaying into an electron and a neutrino. The data were collected with the D0 detector at the Fermilab Tevatron proton-antiproton Collider at a center-of-mass energy of 1.96 TeV, and correspond to an integrated luminosity of about 1 inverse femtobarn. Lacking any significant excess in the data in comparison with known processes, an upper limit is set on the production cross section times branching fraction, and a W' boson with mass below 1.00 TeV can be excluded at the 95% C.L., assuming standard-model-like couplings to fermions. This result significantly improves upon previous limits, and is the most stringent to date.Comment: submitted to Phys. Rev. Let

Associations of depression and depressive symptoms with preeclampsia: results from a Peruvian case-control study

<p>Abstract</p> <p>Background</p> <p>Preeclampsia involves endothelial dysfunction, platelet dysfunction/activation and sympathetic over-activity similar to cardiovascular disorders (CVD). Depression, an independent risk factor for progression of CVD, was found to be associated with an increased risk of preeclampsia among Finnish women. We examined the relation between depression/depressive symptoms and preeclampsia risk among Peruvian women.</p> <p>Methods</p> <p>The study included 339 preeclamptic cases and 337 normotensive controls. Depression and depressive symptoms during pregnancy were assessed using the Patient Health Questionnaire (PHQ-9). Odds ratios (OR) and 95% confidence intervals (CI) were estimated from logistic regression models.</p> <p>Results</p> <p>The prevalence of moderate depression was 11.5% among cases and 5.3% among controls. The corresponding figures for moderate-severe depression were 3.5% for cases and 2.1% for controls. Compared with non-depressed women, those with moderate depression had a 2.3-fold increased risk of preeclampsia (95% CI: 1.2–4.4), while moderate-severe depression was associated with a 3.2-fold (95% CI: 1.1–9.6) increased risk of preeclampsia. Associations of each of the 9-items of the PHQ-9 depression screening module with preeclampsia risk were also observed.</p> <p>Conclusion</p> <p>Our findings are consistent with the only other published report on this topic. Collectively, available data support recent calls for expanded efforts to study and address depression among pregnant women.</p