The Fourier Singular Complement Method for the Poisson problem. Part II: axisymmetric domains

This paper is the second part of a threefold article, aimed at solving numerically the Poisson problem in three-dimensional prismatic or axisymmetric domains. In the first part of this series, the Fourier Singular Complement Method was introduced and analysed, in prismatic domains. In this second part, the FSCM is studied in axisymmetric domains with conical vertices, whereas, in the third part, implementation issues, numerical tests and comparisons with other methods are carried out. The method is based on a Fourier expansion in the direction parallel to the reentrant edges of the domain, and on an improved variant of the Singular Complement Method in the 2D section perpendicular to those edges. Neither refinements near the reentrant edges or vertices of the domain, nor cut-off functions are required in the computations to achieve an optimal convergence order in terms of the mesh size and the number of Fourier modes used

The Fourier Singular Complement Method for the Poisson problem. Part I: prismatic domains

This is the first part of a threefold article, aimed at solving numerically the Poisson problem in three-dimensional prismatic or axisymmetric domains. In this first part, the Fourier Singular Complement Method is introduced and analysed, in prismatic domains. In the second part, the FSCM is studied in axisymmetric domains with conical vertices, whereas, in the third part, implementation issues, numerical tests and comparisons with other methods are carried out. The method is based on a Fourier expansion in the direction parallel to the reentrant edges of the domain, and on an improved variant of the Singular Complement Method in the 2D section perpendicular to those edges. Neither refinements near the reentrant edges of the domain nor cut-off functions are required in the computations to achieve an optimal convergence order in terms of the mesh size and the number of Fourier modes used

Production of J/psi Mesons at HERA

Inelastic and diffractive production of J/psi mesons at HERA is reviewed. The data on inelastic photoproduction are described well within errors by the Colour Singlet Model in next-to-leading order. A search for colour octet processes predicted within the NRQCD/factorisation approach is conducted in many regions of phase space. No unambiguous evidence has been found to date. Diffractive elastic production of J/psi mesons has been measured in the limit of photoproduction up to the highest photon proton center of mass energies. The increase of the cross section is described by pQCD models. At larger Q^2, the W dependence is found to be similar to that observed in photoproduction. First analyses of data at high t yield a powerlike dependence on |t|. A LO BFKL calculation gives a good description of the data.Comment: 14 pages, 12 figures, contribution to Ringberg 200

Angiotensin II impairs endothelial function via tyrosine phosphorylation of the endothelial nitric oxide synthase

Proline-rich tyrosine kinase 2 (PYK2) can be activated by angiotensin II (Ang II) and reactive oxygen species. We report that in endothelial cells, Ang II enhances the tyrosine phosphorylation of endothelial NO synthase (eNOS) in an AT1-, H2O2-, and PYK2-dependent manner. Low concentrations (1–100 µmol/liter) of H2O2 stimulated the phosphorylation of eNOS Tyr657 without affecting that of Ser1177, and attenuated basal and agonist-induced NO production. In isolated mouse aortae, 30 µmol/liter H2O2 induced phosphorylation of eNOS on Tyr657 and impaired acetylcholine-induced relaxation. Endothelial overexpression of a dominant-negative PYK2 mutant protected against H2O2-induced endothelial dysfunction. Correspondingly, carotid arteries from eNOS−/− mice overexpressing the nonphosphorylatable eNOS Y657F mutant were also protected against H2O2. In vivo, 3 wk of treatment with Ang II considerably increased levels of Tyr657-phosphorylated eNOS in the aortae of wild-type but not Nox2y/− mice, and this was again associated with a clear impairment in endothelium-dependent vasodilatation in the wild-type but not in the Nox2y/− mice. Collectively, endothelial PYK2 activation by Ang II and H2O2 causes the phosphorylation of eNOS on Tyr657, attenuating NO production and endothelium-dependent vasodilatation. This mechanism may contribute to the endothelial dysfunction observed in cardiovascular diseases associated with increased activity of the renin–angiotensin system and elevated redox stress

Arginine methylation of the B cell antigen receptor promotes differentiation

Signals processed through the B cell antigen receptor (BCR) control both the proliferation and differentiation of B lymphocytes. How these different signaling modes are established at the BCR is poorly understood. We show that a conserved arginine in the tail sequence of the Igα subunit of the BCR is methylated by the protein arginine methyltransferase 1. This modification negatively regulates the calcium and PI-3 kinase pathways of the BCR while promoting signals leading to B cell differentiation. Thus, Igα arginine methylation can play an important role in specifying the outcome of BCR signaling

Covid-19 triage in the emergency department 2.0: how analytics and AI transform a human-made algorithm for the prediction of clinical pathways

The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department. The determination of the pathways is important not only for patient care, but also for capacity planning in hospitals. We examine the performance of a human-made triage algorithm for clinical pathways which is considered a guideline for emergency departments in Germany based on a large multicenter dataset with over 4,000 European Covid-19 patients from the LEOSS registry. We find an accuracy of 28 percent and approximately 15 percent sensitivity for the ward class. The results serve as a benchmark for our extensions including an additional category of palliative care as a new label, analytics, AI, XAI, and interactive techniques. We find significant potential of analytics and AI in Covid-19 triage regarding accuracy, sensitivity, and other performance metrics whilst our interactive human-AI algorithm shows superior performance with approximately 73 percent accuracy and up to 76 percent sensitivity. The results are independent of the data preparation process regarding the imputation of missing values or grouping of comorbidities. In addition, we find that the consideration of an additional label palliative care does not improve the results

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Peer reviewe