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

Educational Priorities for Children with Cri-Du-Chat Syndrome

There are few data on the educational needs of children with cri-du-chat syndrome: a neurodevelopmental disorder that affects learning and development. We therefore designed an Internet survey to identify parents’ educational priorities in relation to children’s level of need/ability. The survey listed 54 skills/behaviors (e.g., toileting, expresses wants and needs, and tantrums) representing 10 adaptive behavior domains (e.g., self-care, communication, and problem behavior). Parents rated their child’s current level of ability/performance with respect to each skill/behavior and indicated the extent to which training/treatment was a priority. Fifty-four surveys were completed during the 3-month data collection period. Parents identified nine high priority skills/behaviors. Results supported the view that parent priorities are often based on the child’s deficits and emergent skills, rather than on child strengths. Implications for educational practice include the need for competence to develop high priority skills/behaviors and the value of assessing children’s deficits and emergent skills to inform the content of individualized education plans

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

Regelgebundene versus diskretionäre Wirtschaftspolitik: das Beispiel des Stabilitäts- und Wachstumspaktes

Der vorliegende Beitrag thematisiert den Stabilitäts- und Wachstumspakt unter Berücksichtigung von Zeitinkonsistenzproblemen. Die Verfasser gelangen zu dem Ergebnis, dass die bisherige Anwendungspraxis des Stabilitäts- und Wachstumspaktes nicht geeignet ist, die Zeitinkonsistenzprobleme zu reduzieren. Vom Stabilitäts- und Wachstumspakt wird nur dann eine disziplinierende Wirkung ausgehen, wenn dieser auch glaubwürdig umgesetzt wird. Daher betonen die Verfasser die Notwendigkeit einer stärkeren Regelbindung anstelle der in der bisherigen Anwendung bestehenden hohen diskretionären Ermessensspielräume.The following paper deals on the problems of time inconsistency in connection with the stability and growth pact. The authors conclude that the current practice of application of the stability and growth pact is not appropriate for reducing the problems of time inconsistency. The stability pact will yield disciplining effects only if it will be credible applied. Therefore, the authors emphasises a more rule and less discretion orientated application of the stability and growth pact

3

Since its start-up early 1996 KASCADE has collected more than 200 Mio. events with an energy threshold of approx. 10 eV. A unique feature of KASCADE is the simultaneous measurement of electrons, muons, and hadrons at high quality. The large body of data can consistently be described only, if an increasingly heavier composition is assumed above the knee. Quantitatively, subtle differences are identified between hadronic and electromagnetic measurements, with the former pointing to an overall heavier composition. The knee in the primary energy spectrum is observed at E k = 4-5 PeV with a change of the spectral index from fl &apos; 2:7 to 3.1. We critically discuss the preliminary results and point out possible future improvements, particularly in the modeling of EAS