Bestimmung von Sauerstoff in Stahl

Ohne Zusammenfassung     

Combinatorial symbolic powers

Symbolic powers are studied in the combinatorial context of monomial ideals. When the ideals are generated by quadratic squarefree monomials, the generators of the symbolic powers are obstructions to vertex covering in the associated graph and its blowups. As a result, perfect graphs play an important role in the theory, dual to the role played by perfect graphs in the theory of secants of monomial ideals. We use Gröbner degenerations as a tool to reduce questions about symbolic powers of arbitrary ideals to the monomial case. Among the applications are a new, unified approach to the Gröbner bases of symbolic powers of determinantal and Pfaffian ideals.     

Reflection and refraction of attenuated waves in semi-infinite elastic solid media

In earthquakes it is known that waves of one type starting from the origin inside the earth produce waves of other types after impact at the free surface of the earth. A theoretical discussion is given here dealing with reflection and refraction of waves which have their amplitudes increasing with depth similar in nature to the initial diverging earthquake waves which after reflection produce the apparent surface waves in which the displacement decreases with depth. In one case it has been found that at a free surface a plane wave of SV type, travelling parallel to the surface, is capable of generating surface waves after internal reflection which under a certain state of attenuation are identical with the Rayleigh Waves.     

Developing conceptions of statistics by designing measures of distribution

Students often learn procedures for measuring, but rarely do they grapple with the foundational conceptual problem of generating and validating coordination between a measure and the phenomenon being measured. Coordinating measures with phenomenon involves developing an appreciation of the objects and relations in each as well as establishing their mutual correspondence. We supported students?? developing conceptions of statistics by positioning them to design measures of center and of variability for distributions that they had generated through repeated measure of a length. After students invented and explored the viability of their measures individually, they participated in a public (whole-class conversation) forum featuring justification and reflection about the viability of their designed measures. We illustrate how individual invention enticed students to attend to, and to make explicit, characteristics of distribution not initially noticed or known only tacitly. Conceptions of statistics and of relevant characteristics of distribution were further expanded as students justified and argued about the utility and prospective generalization of particular inventions. Teachers supported student learning by highlighting prospective relations between characteristics of measures and characteristics of distribution as they emerged during the course of activity in each setting.     

Numerical simulations of spalling tests in order to investigate material properties of UHPC

In order to evaluate the material composition of Ultra High Performance Concrete (UHPC), material properties such as dynamic tensile strength or fracture strength and also the fracture energy under impact loading are of significant importance. The use of a modified Hopkinson Bar enables the determination of the required data. On the basis of experimental investigations our contribution deals with the numerical finite element simulation of the Hopkinson Bar test. The propagation of stress waves is reproduced by means of a special time-integration scheme. We simulate the propagation of cracks by using adaptive cohesive elements including a corresponding separation law. The critical energy release rate (Griffith-energy) is calculated and compared to the values determined by experimental results. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Directed evolution of cyclic peptides for inhibition of autophagy

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Unfortunately, chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of the autophagosome maturation machinery—with mid-nanomolar affinities and disrupted protein–protein interactions (PPIs) between LC3 and its binding partners in vitro. The most promising LC3-binding SUPR peptide accessed the cytosol at low micromolar concentrations as measured by chloroalkane penetration assay (CAPA) and inhibited starvation-mediated GFP-LC3 puncta formation in a concentration-dependent manner. LC3-binding SUPR peptides re-sensitized platinum-resistant ovarian cancer cells to cisplatin treatment and triggered accumulation of the adapter protein p62 suggesting decreased autophagic flux through successful disruption of LC3 PPIs in cell culture. In mouse models of metastatic ovarian cancer, treatment with LC3-binding SUPR peptides and carboplatin resulted in almost complete inhibition of tumor growth after four weeks of treatment. These results indicate that SUPR peptide mRNA display can be used to develop cell-penetrating macrocyclic peptides that target and disrupt the autophagic machinery in vitro and in vivo.

SUPR peptide mRNA display was used to evolve a cell-permeable, macrocyclic peptide for autophagy inhibition.