A three-field phase-field model for mixed-mode fracture in rock based on experimental determination of the mode II fracture toughness

In this contribution, a novel framework for simulating mixed-mode failure in rock is presented. Based on a hybrid phase-field model for mixed-mode fracture, separate phase-field variables are introduced for tensile (mode I) and shear (mode II) fracture. The resulting three-field problem features separate length scale parameters for mode I and mode II cracks. In contrast to the classic two-field mixed-mode approaches it can thus account for different tensile and shear strength of rock. The two phase-field equations are implicitly coupled through the degradation of the material in the elastic equation, and the three fields are solved using a staggered iteration scheme. For its validation, the three-field model is calibrated for two types of rock, Solnhofen Limestone and Pfraundorfer Dolostone. To this end, double-edge notched Brazilian disk (DNBD) tests are performed to determine the mode II fracture toughness. The numerical results demonstrate that the proposed phase-field model is able to reproduce the different crack patterns observed in the DNBD tests. A final example of a uniaxial compression test on a rare drill core demonstrates, that the proposed model is able to capture complex, 3D mixed-mode crack patterns when calibrated with the correct mode I and mode II fracture toughness

Systems Immunology Analyses Following Porcine Respiratory and Reproductive Syndrome Virus Infection and Vaccination.

This study was initiated to better understand the nature of innate immune responses and the relatively weak and delayed immune response against porcine reproductive and respiratory syndrome virus (PRRSV). Following modified live virus (MLV) vaccination or infection with two PRRSV-2 strains, we analyzed the transcriptome of peripheral blood mononuclear cells collected before and at three and seven days after vaccination or infection. We used blood transcriptional modules (BTMs)-based gene set enrichment analyses. BTMs related to innate immune processes were upregulated by PRRSV-2 strains but downregulated by MLV. In contrast, BTMs related to adaptive immune responses, in particular T cells and cell cycle, were downregulated by PRRSV-2 but upregulated by MLV. In addition, we found differences between the PRRSV strains. Only the more virulent strain induced a strong platelet activation, dendritic cell activation, interferon type I and plasma cell responses. We also calculated the correlations of BTM with the neutralizing antibody and the T-cell responses. Early downregulation (day 0-3) of dendritic cell and B-cell BTM correlated to both CD4 and CD8 T-cell responses. Furthermore, a late (day 3-7) upregulation of interferon type I modules strongly correlated to helper and regulatory T-cell responses, while inflammatory BTM upregulation correlated more to CD8 T-cell responses. BTM related to T cells had positive correlations at three days but negative associations at seven days post-infection. Taken together, this work contributes to resolve the complexity of the innate and adaptive immune responses against PRRSV and indicates a fundamentally different immune response to the less immunogenic MLV compared to field strains which induced robust adaptive immune responses. The identified correlates of T-cell responses will facilitate a rational approach to improve the immunogenicity of MLV

Normofractionated and moderately hypofractionated proton therapy: Comparison of acute toxicity and early quality of life outcomes

Aim Data on the safety of moderately hypofractionated proton beam therapy (PBT) are limited. The aim of this study is to compare the acute toxicity and early quality of life (QoL) outcomes of normofractionated (nPBT) and hypofractionated PBT (hPBT). Results Overall, the highest toxicity grades of G0, G1, G2, and G3 were observed in 7 (5%), 40 (28.8%), 78 (56.1%), and 15 (10.8%) patients, respectively. According to organ and site, no statistically significant differences were detected in the majority of toxicity comparisons (66.7%). For A&P, hPBT showed a more favorable toxicity profile as compared to nPBT with a higher frequency of G0 and G1 and a lower frequency of G2 and G3 events (p = 0.04), more patients with improvement (95.7% vs 70%, p = 0.023), and full resolution of toxicities (87% vs 50%, p = 0.008). Skin toxicity was unanimously milder for hPBT compared to nPBT in A&P and ST locations (p = 0.018 and p = 0.025, respectively). No significant differences in QoL were observed in 97% of comparisons for QLQ-C30 scale except for loss of appetite in H&N patients (+33.3 for nPBT and 0 for hPBT, p = 0.02) and role functioning for A&P patients (0 for nPBT vs +16.7 hPBT, p = 0.003). For QLQ-HN35, 97.9% of comparisons did not reveal significant differences, with pain as the only scale varying between the groups (-8.33 vs -25, p = 0.016). Conclusion Hypofractionated proton therapy offers non-inferior early safety and QoL as compared to normofractionated irradiation and warrants further clinical investigation

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

Diet and Disease on the Plain: Diabetes Among the Omaha

Non-insulin dependent diabetes is a rising health concern among the Omaha Tribe. The problem has developed from negligible levels in the 1960s to a significant health threat today. As of 1992, 35% of the Omaha Tribe adult population residing on the reservation had been diagnosed with the condition. and the actual proportion of people with the condition is probably much higher. The age of onset of the disease is decreasing so that people as young as 10 years of age are diabetics. The increase in diabetes is at least partly due to changes in diet practices that include the emergence of new traditional foods and the consumption of prepared or convenience foods. Preliminary observations suggest that the modern diet that includes federally subsidized food programs may contribute to the problem

Förderung der personal-sozialen Kompetenzen mit Portfolioarbeit im Zyklus 1

Mit dem neuen Lehrplan 21 halten die überfachlichen Kompetenzen Einzug in den Volksschulunterricht. Offene Unterrichtsformen stellen eine geeignete Methode zu deren Förderung dar. Eine dieser Unterrichtsformen bildet die Arbeit mit dem Portfolio. Während dem selbstbestimmten Praktikum im Rahmen der Ausbildung an der Pädagogischen Hochschule Rorschach begegnete die Autorin zum ersten Mal dem Portfolio in der Praxis. Während dem Arbeitsprozess fiel ihr eine hohe Selbstständigkeit der Kindergartenkinder auf. Diese Eigen-schaft zählt zu den überfachlichen Kompetenzen. Das Zusammentreffen der genannten Aspekte führte zur übergeordneten Fragestellung im Rahmen der vorliegenden Literaturarbeit: Welche Formen der Portfolioarbeit eignen sich im Zyklus 1 zur Förderung von personalen und sozialen Kompetenzen nach dem Lehrplan Volksschule? Anhand der Grundlagen des Lehrplan Volksschule wurden die personalen und sozialen Kompetenzen zusammenfassend beleuchtet. In einem weiteren Teil dieser Arbeit ging man dem Verständnis der Portfolioarbeit nach. Darunter wurden verschiedene im Zyklus 1 anwendbare Portfolioformen vorgestellt, die abschliessend in Bezug auf die Förderung von personalen und sozialen Kompetenzen bewertet wurden. Das Ergebnis zeigt: Je höher die Partizipation der Schülerinnen und Schüler in dieser offenen Unterrichtsform, desto höher der Ertrag an gewonnenen überfachlichen Kompetenzen