Small Molecules Inspired by the Natural Product Withanolides as Potent Inhibitors of Wnt Signaling

Wnt signaling is a fundamental pathway that drives embryonic development and is essential for stem cell maintenance and tissue homeostasis. Dysregulation of Wnt signaling is linked to various diseases, and a constitutively active Wnt pathway drives tumorigenesis. Thus, disruption of the Wnt response is deemed a promising strategy for cancer drug discovery. However, only few clinical drug candidates that target Wnt signaling are available so far, and new small‐molecule modulators of Wnt‐related processes are in high demand. Here we describe the synthesis of small molecules inspired by withanolide natural products by using a pregnenolone‐derived β‐lactone as the key intermediate that was transformed into a δ‐lactone appended to the D‐ring of the steroidal scaffold. This natural‐product‐inspired compound library contained potent inhibitors of Wnt signaling that act upstream of the destruction complex to stabilize Axin in a tankyrase‐independent manner.     

Influence of bifunctionality of reactive dyes on the bending rigidity of viscose printed with polysaccharide thickeners

The bending rigidity and colour depth of viscose printed with a number of reactive dyes in the presence of alginate and guar gum thickeners has been investigated. Interactions between the fabric, the dyes and the thickener were evaluated to determine the bending rigidity of the printed substrate. The results show that mono- or bi-functional reactive dyes cause undesired stiff fabric handle depending on the structure (the type of the reactive system and the reactive group), the reactivity and the concentration of the reactive dye used. These interactions differ to a greater degree when guar gum thickeners are used.     

A comparative study on the effect of some antioxidants on the lipid and pigment oxidation in dry-fermented sausages

A comparative study on the effect of antioxidants on the lipid and pigment oxidation in Bulgarian dry‐fermented sausage type lukanka is described. A commercial mix of antioxidants, called ‘grindox 1021’ (GR), restricted the development of the peroxidation processes in dry‐fermented sausages (type lukanka) to a greater extent than either rosemary (RS), rutine (RT), sodium erythrobate (SE) or l ‐ascorbic acid, when applied at the same concentration. The latter compounds did not effectively stabilize lipids in sausages against oxidation; they only slowed down the lypolysis and did not greatly change the colour of the cross‐sectional surface. However, the sausage lipids were best stabilized when 1 g kg^?1 GR, RS or RT was added. The addition of 1 g kg^?1 RS and GR most efficiently suppressed the hydroperoxides – primary derivatives of lipid peroxidation, while the secondary derivatives in the final product were most reduced when 1 g kg^?1 GR and SE were added.     

Theoretical and experimental studies of Schottky diodes that use aligned arrays of single-walled carbon nanotubes

We present theoretical and experimental studies of Schottky diodes that use aligned arrays of single-walled carbon nanotubes. A simple physical model, taking into account the basic physics of current rectification, can adequately describe the single-tube and array devices. We show that for as-grown array diodes, the rectification ratio, defined by the maximum-to-minimum-current-ratio, is low due to the presence of metallic-single-walled nanotube (SWNT) shunts. These tubes can be eliminated in a single voltage sweep resulting in a high rectification array device. Further analysis also shows that the channel resistance, and not the intrinsic nanotube diode properties, limits the rectification in devices with channel length up to 10 μm.     

Instructing in generalized knowledge structures to develop flexible problem solving skills

In contrast to routine knowledge and skills, flexible problem solving is associated with the ability to apply one’s knowledge structures in relatively new situations. In the absence of specific knowledge-based guidance, such processes could be very cognitively demanding. This paper suggests that learning flexible problem solving skills could be enhanced by explicitly instructing learners in generalized forms of schematic knowledge structures that are applicable to a greater variety of problems. The paper presents results of an experimental study that has investigated this approach in learning the operation of a technical device, and discusses implications of these results for the design of computer-based instruction.     

High-performance electronics using dense, perfectly aligned arrays of single-walled carbon nanotubes

Single-walled carbon nanotubes (SWNTs) have many exceptional electronic properties. Realizing the full potential of SWNTs in realistic electronic systems requires a scalable approach to device and circuit integration. We report the use of dense, perfectly aligned arrays of long, perfectly linear SWNTs as an effective thin-film semiconductor suitable for integration into transistors and other classes of electronic devices. The large number of SWNTs enable excellent device-level performance characteristics and good device-to-device uniformity, even with SWNTs that are electronically heterogeneous. Measurements on p- and n-channel transistors that involve as many as approximately 2,100 SWNTs reveal device-level mobilities and scaled transconductances approaching approximately 1,000 cm(2) V(-1) s(-1) and approximately 3,000 S m(-1), respectively, and with current outputs of up to approximately 1 A in devices that use interdigitated electrodes. PMOS and CMOS logic gates and mechanically flexible transistors on plastic provide examples of devices that can be formed with this approach. Collectively, these results may represent a route to large-scale integrated nanotube electronics.     

Screening of Water Dipoles Inside Finite-Length Armchair Carbon Nanotubes

The electronic structure and dielectric screening of finite-length armchair carbon nanotubes are studied with both tight-binding and ab initio methods. Good agreement is found in the band gap oscillation patterns and dielectric constants, which validates the tight-binding method as a reliable and fast approach to describe the screening effect of carbon nanotubes. For an illustration, our method is applied to a system consisting of a short (6,6) nanotube filled with six water molecules. Substantial screening of the water dipoles through the nanotube is observed. This polarization effect should have an important influence on the permeation of water and other biomolecules inside carbon nanotubes.