480 research outputs found

    The â„“s\ell^s-boundedness of a family of integral operators on UMD Banach function spaces

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    We prove the â„“s\ell^s-boundedness of a family of integral operators with an operator-valued kernel on UMD Banach function spaces. This generalizes and simplifies earlier work by Gallarati, Veraar and the author, where the â„“s\ell^s-boundedness of this family of integral operators was shown on Lebesgue spaces. The proof is based on a characterization of â„“s\ell^s-boundedness as weighted boundedness by Rubio de Francia.Comment: 13 pages. Generalization of arXiv:1410.665

    Managing the Socially Marginalized: Attitudes Towards Welfare, Punishment and Race

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    Welfare and incarceration policies have converged to form a system of governance over socially marginalized groups, particularly racial minorities. In both of these policy areas, rehabilitative and social support objectives have been replaced with a more punitive and restrictive system. The authors examine the convergence in individual-level attitudes concerning welfare and criminal punishment, using national survey data. The authors\u27 analysis indicates a statistically significant relationship between punitive attitudes toward welfare and punishment. Furthermore, accounting for the respondents\u27 racial attitudes explains the bivariate relationship between welfare and punishment. Thus, racial attitudes seemingly link support for punitive approaches to opposition to welfare expenditures. The authors discuss the implications of this study for welfare and crime control policies by way of the conclusion

    Constructing Delaunay triangulations along space-filling curves

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    Incremental construction con BRIO using a space-filling curve order for insertion is a popular algorithm for constructing Delaunay triangulations. So far, it has only been analyzed for the case that a worst-case optimal point location data structure is used which is often avoided in implementations. In this paper, we analyze its running time for the more typical case that points are located by walking. We show that in the worst-case the algorithm needs quadratic time, but that this can only happen in degenerate cases. We show that the algorithm runs in O(n logn) time under realistic assumptions. Furthermore, we show that it runs in expected linear time for many random point distributions. This research was supported by the Deutsche Forschungsgemeinschaft within the European graduate program ’Combinatorics, Geometry, and Computation’ (No. GRK 588/2) and by the Netherlands’ Organisation for Scientific Research (NWO) under BRICKS/FOCUS grant number 642.065.503 and project no. 639.022.707

    Digital hyperplane fitting

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    International audienceThis paper addresses the hyperplane fitting problem of discrete points in any dimension (i.e. in Z d). For that purpose, we consider a digital model of hyperplane, namely digital hyperplane, and present a combinatorial approach to find the optimal solution of the fitting problem. This method consists in computing all possible digital hyperplanes from a set S of n points, then an exhaustive search enables us to find the optimal hyperplane that best fits S. The method has, however, a high complexity of O(n d), and thus can not be applied for big datasets. To overcome this limitation, we propose another method relying on the Delaunay triangulation of S. By not generating and verifying all possible digital hyperplanes but only those from the elements of the triangula-tion, this leads to a lower complexity of O(n d 2 +1). Experiments in 2D, 3D and 4D are shown to illustrate the efficiency of the proposed method

    Mapping the internal recognition surface of an octanuclear coordination cage using guest libraries

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    Size and shape criteria for guest binding inside the cavity of an octanuclear cubic coordination cage in water have been established using a new fluorescence displacement assay to quantify guest binding. For aliphatic cyclic ketones of increasing size (from C5 to C11), there is a linear relationship between ΔG for guest binding and the guest’s surface area: the change in ΔG for binding is 0.3 kJ mol–1 Å–2, corresponding to 5 kJ mol–1 for each additional CH2 group in the guest, in good agreement with expectations based on hydrophobic desolvation. The highest association constant is K = 1.2 × 106 M–1 for cycloundecanone, whose volume is approximately 50% of the cavity volume; for larger C12 and C13 cyclic ketones, the association constant progressively decreases as the guests become too large. For a series of C10 aliphatic ketones differing in shape but not size, ΔG for guest binding showed no correlation with surface area. These guests are close to the volume limit of the cavity (cf. Rebek’s 55% rule), so the association constant is sensitive to shape complementarity, with small changes in guest structure resulting in large changes in binding affinity. The most flexible members of this series (linear aliphatic ketones) did not bind, whereas the more preorganized cyclic ketones all have association constants of 104–105 M–1. A crystal structure of the cage·cycloundecanone complex shows that the guest carbonyl oxygen is directed into a binding pocket defined by a convergent set of CH groups, which act as weak hydrogen-bond donors, and also shows close contacts between the exterior surface of the disc-shaped guest and the interior surface of the pseudospherical cage cavity despite the slight mismatch in shape

    In epithelial cancers, aberrant COL17A1 promoter methylation predicts its misexpression and increased invasion

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    Background: Metastasis is a leading cause of death among cancer patients. In the tumor microenvironment, altered levels of extracellular matrix proteins, such as collagens, can facilitate the first steps of cancer cell metastasis, including invasion into surrounding tissue and intravasation into the blood stream. However, the degree of misexpression of collagen genes in tumors remains understudied, even though this knowledge could greatly facilitate the development of cancer treatment options aimed at preventing metastasis. Methods: We systematically evaluate the expression of all 44 collagen genes in breast cancer and assess whether their misexpression provides clinical prognostic significance. We use immunohistochemistry on 150 ductal breast cancers and 361 cervical cancers and study DNA methylation in various epithelial cancers. Results: In breast cancer, various tests show that COL4A1 and COL4A2 overexpression and COL17A1 (BP180, BPAG2) underexpression provide independent prognostic strength (HR = 1.25, 95% CI = 1.17–1.34, p = 3.03 × 10; HR = 1.18, 95% CI = 1.11–1.25, p = 8.11 × 10; HR = 0.86, 95% CI = 0.81–0.92, p = 4.57 × 10; respectively). Immunohistochemistry on ductal breast cancers confirmed that the COL17A1 protein product, collagen XVII, is underexpressed. This strongly correlates with advanced stage, increased invasion, and postmenopausal status. In contrast, immunohistochemistry on cervical tumors showed that collagen XVII is overexpressed in cervical cancer and this is associated with increased local dissemination. Interestingly, consistent with the opposed direction of misexpression in these cancers, the COL17A1 promoter is hypermethylated in breast cancer and hypomethylated in cervical cancer. We also find that the COL17A1 promoter is hypomethylated in head and neck squamous cell carcinoma, lung squamous cell carcinoma, and lung adenocarcinoma, in all of which collagen XVII overexpression has previously been shown. Conclusions: Paradoxically, collagen XVII is underexpressed in breast cancer and overexpressed in cervical and other epithelial cancers. However, the COL17A1 promoter methylation status accurately predicts both the direction of misexpression and the increased invasive nature for five out of five epithelial cancers. This implies that aberrant epigenetic control is a key driver of COL17A1 gene misexpression and tumor cell invasion. These findings have significant clinical implications, suggesting that the COL17A1 promoter methylation status can be used to predict patient outcome. Moreover, epigenetic targeting of COL17A1 could represent a novel strategy to prevent metastasis in patients

    Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction

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    Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (≥ 50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated. Mechanistically, we showed that hyperglycemia and diabetes decreased PKM2 tetramer formation and activity by sulfenylation in mouse glomeruli and cultured podocytes. Pkm-knockdown immortalized mouse podocytes had higher levels of toxic glucose metabolites, mitochondrial dysfunction and apoptosis. Podocyte-specific Pkm2-knockout (KO) mice with diabetes developed worse albuminuria and glomerular pathology. Conversely, we found that pharmacological activation of PKM2 by a small-molecule PKM2 activator, TEPP-46, reversed hyperglycemia-induced elevation in toxic glucose metabolites and mitochondrial dysfunction, partially by increasing glycolytic flux and PGC-1α mRNA in cultured podocytes. In intervention studies using DBA2/J and Nos3 (eNos) KO mouse models of diabetes, TEPP-46 treatment reversed metabolic abnormalities, mitochondrial dysfunction and kidney pathology. Thus, PKM2 activation may protect against DN by increasing glucose metabolic flux, inhibiting the production of toxic glucose metabolites and inducing mitochondrial biogenesis to restore mitochondrial function

    Surgical activity in the COVID-19 era. Trend of slowdown from a multicentre observational study

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    COVID-19 outbreak represented an unprecedented event that led to a redefinition of health care systems worldwide. The impact of the emergency required a deviation of the care toward the assistance to COVID-19 patients, with reduction of resources for elective activities, including surgery. We aim to report the decrease of urological surgical activity during the first weeks from the beginning of the pandemic, aiming to highlight the prioritization we applied to select patients for surgery
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