Effects of crack tip geometry on dislocation emission and cleavage: A possible path to enhanced ductility

We present a systematic study of the effect of crack blunting on subsequent crack propagation and dislocation emission. We show that the stress intensity factor required to propagate the crack is increased as the crack is blunted by up to thirteen atomic layers, but only by a relatively modest amount for a crack with a sharp 60$^\circ$ corner. The effect of the blunting is far less than would be expected from a smoothly blunted crack; the sharp corners preserve the stress concentration, reducing the effect of the blunting. However, for some material parameters blunting changes the preferred deformation mode from brittle cleavage to dislocation emission. In such materials, the absorption of preexisting dislocations by the crack tip can cause the crack tip to be locally arrested, causing a significant increase in the microscopic toughness of the crack tip. Continuum plasticity models have shown that even a moderate increase in the microscopic toughness can lead to an increase in the macroscopic fracture toughness of the material by several orders of magnitude. We thus propose an atomic-scale mechanism at the crack tip, that ultimately may lead to a high fracture toughness in some materials where a sharp crack would seem to be able to propagate in a brittle manner. Results for blunt cracks loaded in mode II are also presented.Comment: 12 pages, REVTeX using epsfig.sty. 13 PostScript figures. Final version to appear in Phys. Rev. B. Main changes: Discussion slightly shortened, one figure remove

Wirtschaftsbauten in der antiken Stadt

Über die Wirtschaft der Antike sind wir gut informiert. Für den Waren- und Geldverkehr standen in den Städten eigene Gebäude zur Verfügung, die im römischen Reich von Speicherbauten in bedeutenden Wirtschaftszentren und Hafenorten bis zu Bank- und Börsengebäuden an den zentralen Plätzen der Städte reichten. Diese Bauten wurden von Archäologen und Bauhistorikern vielfach untersucht, wobei Bauweise und Gestaltung im Vordergrund standen. Wirtschaftshistoriker befassten sich intensiv mit Handels- und Geldgeschäften, ohne Zusammenhänge mit Baulichkeiten in den Blick zu nehmen. Interdisziplinäre Zusammenarbeit eröffnet neue Perspektiven. Mit dem Wissen über wirtschaftliche Vorgänge lassen sich Bauten besser verstehen, und Bauwerke können ökonomische Vorgänge sichtbar machen. Das wurde beim erstmaligen Gedankenaustausch zwischen den verschiedenen Forschungsdisziplinen rasch deutlich. Der vorliegende Tagungsband enthält Beiträge über Handelsformen und Handelsbeziehungen, er stellt Speichergebäude und Kaufmannshäuser vor und beleuchtet mit dem Magdalensberg bei Kärnten ein bedeutendes Zentrum der Erzgewinnung und der Metallverarbeitung. Einen besonderen Platz nimmt die römische Basilika als großartiges Bank- und Börsengebäude ein, dessen Entwicklung um 200 v. Chr. quasi schlagartig am Forum Romanum begann und die neue Vormacht Rom als Zentrum der antiken Wirtschaft und zentrale Instanz des Wirtschafts- und Steuerrechts mit neuen Maßstäben auch städtebaulich prägte. Die beiden letzten Beiträge befassen sich mit der weiteren Entwicklung des Begriffes Basilika und seinen Nachwirkungen im Kirchenbau und in der Architekturtheorie bis heute

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Energy Equity Investment Opportunities

Trends, once in place, often are carried to extremes. Certainly this occurred on the upside just a few years ago. Oil prices may well drop below equilibrium levels during this cycle, thereby sowing the seeds of the next shortage and, presumably, the opportunity for potential investment gains. </jats:p