(3+3)-Annulation of Carbonyl Ylides with Donor-Acceptor Cyclopropanes: Synergistic Dirhodium(II) and Lewis Acid Catalysis

The first (3+3)-annulation process of donor-acceptor cyclopropanes using synergistic catalysis is reported. The Rh2 (OAc)4 -catalyzed decomposition of diazo carbonyl compounds generated carbonyl ylides in situ. These 1,3-dipoles were converted with donor-acceptor cyclopropanes, activated by Lewis acid catalysis, to afford multiply substituted pyran scaffolds in high yield and diastereoselectivity. Extensive optimization studies enabled access to 9-oxabicyclo[3.3.1]nonan-2-one and 10-oxabicyclo[4.3.1]decen-2-ol cores, exploiting solvent effects on intermediate reactivity

Electrocatalytic Activation of Donor–Acceptor Cyclopropanes and Cyclobutanes: An Alternative C(sp 3 )−C(sp 3 ) Cleavage Mode

We describe the first electrochemical activation of D–A cyclopropanes and D–A cyclobutanes leading after C(sp3)−C(sp3) cleavage to the formation of highly reactive radical cations. This concept is utilized to formally insert molecular oxygen after direct or DDQ-assisted anodic oxidation of the strained carbocycles, delivering β- and γ-hydroxy ketones and 1,2-dioxanes electrocatalytically. Furthermore, insights into the mechanism of the oxidative process, obtained experimentally and by additional quantum-chemical calculations are presented. The synthetic potential of the reaction products is demonstrated by diverse derivatizations

Hyperforin and Myrtucommulone Derivatives Act as Natural Modulators of Wnt/β-Catenin Signaling in HCT116 Colon Cancer Cells

The therapeutic activities of natural plant extracts have been well known for centuries. Many of them, in addition to antiviral and antibiotic effects, turned out to have anti-tumor activities by targeting different signaling pathways. The canonical Wnt pathway represents a major tumorigenic pathway deregulated in numerous tumor entities, including colon cancer. Here, we investigated the acylphloroglucinols hyperforin (HF) from St. John’s wort ( Hypericum perforatum L.) and myrtucommulone A (MC A) from myrtle ( Myrtus communis ) and semi-synthetic derivatives thereof (HM 177, HM 297, HM298) for their effects on Wnt/β-catenin signaling. None of these substances revealed major cytotoxicity on STF293 embryonic kidney and HCT116 colon carcinoma cells at concentrations up to 10 μM. At this concentration, HF and HM 177 showed the strongest effect on cell proliferation, whereas MC A and HM 177 most prominently inhibited anchorage-independent growth of HCT116 cells. Western blot analyses of active β-catenin and β-catenin/TCF reporter gene assays in STF293 cells revealed inhibitory activities of HF, MC A and HM 177. In line with this, the expression of endogenous Wnt target genes, Axin and Sp5, in HCT116 cells was significantly reduced. Our data suggest that the acylphloroglucinols hyperforin, myrtucommulone A and its derivative HM 177 represent potential new therapeutic agents to inhibit Wnt/β-catenin signaling in colon cancer

Friction stir welded and deep drawn multi-material tailor welded blanks

The ever increasing demand for more resource-efficient and safer vehicles in today’s automotive industry makes lightweight construction techniques necessary. However, overcoming contradicting requirements arising from lightweight design and safety remains a challenging task. The extent to which lightweight measures can be applied in order to save fuel, heavily depends on the fact that rising safety requirements have to be met by increasing strength of parts. This contradicting demand for parts with high strength and low weight leads to the development of new production technologies. One example, regarding car body components, is the tailor welded blank (TWB) technology. In tailor welded blanks, materials and thicknesses are locally adapted to meet the needed strength and strain properties while keeping the weight as low as possible. While tailor welded blanks consisting of similar materials with different thicknesses are already used in vehicles, the use of TWBs with dissimilar materials, e.g. steel and aluminum, is still in development due to the problems in joining dissimilar materials. Especially when manufacturing parts made of TWBs through joining and subsequent deep drawing, the joint needs to have very good strength properties in order not to fail during forming. One way to overcome these joining difficulties is friction stir welding. In this paper, a methodology is presented to produce multi-material tailor welded blanks with varying thicknesses through friction stir welding (FSW) and deep drawing in a subsequent step. A newly developed FSW joint configuration is used to weld steel sheets in 1 mm thickness to 2 mm thick aluminum sheets. A welding parameter study is conducted to investigate the influence of the process parameters on the joint quality. Tensile and Nakajima tests show that the joint strength, obtained with optimal process parameters, exceeds the strength of the steel base material. Thus, failure occurs in the steel, whereas the joint remains intact. The friction stir welded blanks were furthermore deep drawn. Two different tool approaches were tested to compensate the different sheet thicknesses during the forming process. Using the more suitable approach, blanks were deep drawn with three different punch geometries to show the potential of friction stir welding for the manufacturing of multi-material tailor welded blanks

Bottom Effect in Atomic Force Microscopy Nanomechanics

In this work, the influence of the rigid substrate on the determination of the sample Young''s modulus, the so-called bottom-effect artifact, is demonstrated by an atomic force microscopy force-spectroscopy experiment. The nanomechanical properties of a one-component supported lipid membrane (SLM) exhibiting areas of two different thicknesses are studied: While a standard contact mechanics model (Sneddon) provides two different elastic moduli for these two morphologies, it is shown that Garcia''s bottom-effect artifact correction yields a unique value, as expected for an intrinsic material property. Remarkably, it is demonstrated that the ratio between the contact radius (and not only the indentation) and the sample thickness is the key parameter addressing the relevance of the bottom-effect artifact. The experimental results are validated by finite element method simulations providing a solid support to Garcia''s theory. The amphiphilic nature of the investigated material is representative of several kinds of lipids, suggesting that the results have far reaching implications for determining the correct Young''s modulus of SLMs. The generality of Garcia''s bottom-effect artifact correction allows its application to every kind of supported soft film

Kurzstudie über die Bibliotheksausstattung der Profillinie Maritime Systems an der Universität Rostock im Bereich der Geistes- und Sozialwissenschaften (unter Berücksichtigung der Museumslandschaft)

Im Juli 2009 wurde den Verfassern der Auftrag zu einer Kurzstudie über die Bibliotheksausstattung der Profillinie Maritime Systems an der Universität Rostock im Bereich der Geistes- und Sozialwissenschaften unter Berücksichtigung der Museumslandschaft erteilt. Sie wurde in den Monaten September und Oktober 2009 angefertigt und besteht aus vier Teilen: den beiden Schwerpunkten Bibliotheksausstattung und Museumslandschaft, Empfehlungen und einem Anhang

Expression and Characterization of Drosophila Signal Peptide Peptidase-Like (sppL), a Gene That Encodes an Intramembrane Protease

Intramembrane proteases of the Signal Peptide Peptidase (SPP) family play important roles in developmental, metabolic and signaling pathways. Although vertebrates have one SPP and four SPP-like (SPPL) genes, we found that insect genomes encode one Spp and one SppL. Characterization of the Drosophila sppL gene revealed that the predicted SppL protein is a highly conserved structural homolog of the vertebrate SPPL3 proteases, with a predicted nine-transmembrane topology, an active site containing aspartyl residues within a transmembrane region, and a carboxy-terminal PAL domain. SppL protein localized to both the Golgi and ER. Whereas spp is an essential gene that is required during early larval stages and whereas spp loss-of-function reduced the unfolded protein response (UPR), sppL loss of function had no apparent phenotype. This was unexpected given that genetic knockdown phenotypes in other organisms suggested significant roles for Spp-related proteases

Creative destruction in science

Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article

Bioinformatics and molecular modeling in glycobiology

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed