Metallic glasses: Gaining plasticity for microsystems

Since the 1960s, metallic glasses (MGs) have attracted tremendous re-search interest in materials science and engineering, given their unique cornbination of mechanical properties. How-ever, the industrial applications of MGs have been hindered due to their lack of ductility in bulk form at room temperature. In contrast, it was observed that MGs could exhibit excellent plasticity at the small size scale. In this article, we summarize the related experimental findings having been reported so far together with the possible origins of such a size effect in MGs. The enhanced plasticity of MGs in small volumes, together with their high mechanical strengths and remarkable thermoplastic formability, strongly implies that MGs are the promising materials for fabricating the next generation of micro- and nano-devices.     

Square Foot Manufacturing: a new production concept for micro manufacturing

Today a large number of microstructures are already employed as separate components or as constituents of larger modules in a broad spectrum of production in medical technology, optics, biotechnology, mechatronics, fluidics, (micro)-forming and tool construction. Current research activities are directed towards the downscaling of manufacturing procedures or the formation of complex process chains for the manufacture of micro workpieces. The Square Foot Manufacturing concept represents one approach aimed at achieving significant technical, economic and ecological developments in the production of microstructures by means of machining techniques that can be applied to a spectrum of materials as broad as possible. This fabrication concept representing a refinement of existing desktop manufacturing concepts is currently being developed at the Institute of Production Engineering of Helmut-Schmidt-University/University of the Federal Armed Forces Hamburg. This paper is intended to provide an overview of the theoretical concept and the current state of its technical implementation.     

Influences of Ta, Nb, or Mo additions in Zr-based bulk metallic glasses on microstructure and thermal properties

The master-alloy ingots for casting bulk metallic glasses are routinely prepared by arc melting a mixture of pure elements. This paper addresses the difficulty in achieving complete and homogeneous melting of refractory component additions in Zr-based BMGs using the above procedure, and its influences on the microstructure and thermal behavior of alloys.     

Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing

The sodium-activated potassium channel Slack (K_Na1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I_KNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I_KNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I_KNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.     

Antioxidant vs. Prooxidant Properties of the Flavonoid,Kaempferol, in the Presence of Cu(II) Ions: A ROS-Scavenging Activity,Fenton Reaction and DNA Damage Study

Kaempferol is a flavonoid that occurs in tea and in many vegetables and fruits, including broccoli, cabbage, beans, grapes, apples, and strawberries. The efficacy of Kaempferol has been demonstrated in the treatment of breast, esophageal, cervical, ovarian, and liver cancers and leukemia, which very likely arises from its prooxidant properties and the activation of pro-apoptotic pathways. Indeed, this matter has already been the focus of a number of published studies and reviews. The aim of the present study was to elucidate the antioxidant vs. prooxidant properties of flavonoids in the presence of the redox-active metal, copper (II) ion, by means of the Fenton reaction. The specific motivation of this work is that, since an increased level of Cu(II) ions is known to be associated with many disease states such as neurological conditions (Alzheimer’s disease) and cancer, any interaction between these ions and flavonoids might affect the outcome of therapeutic uses of the latter. The structure of the Cu-kaempferol complex in DMSO was investigated by means of low temperature EPR spectroscopy, which confirmed the existence of at least two distinct coordination environments around the copper (II) ion. UV vis-spectra of kaempferol and its Cu(II) complex in DMSO revealed an interaction between the 5-OH (A ring) group and the 4-CO (C ring) group of kaempferol with Cu(II) ions. An ABTS assay confirmed that kaempferol acted as an effective radical scavenger, and that this effect was further enhanced in the form of the Cu(II)-kaempferol complex. Quantitative EPR spin trapping experiments, using DMPO as the spin trap, confirmed suppression of the formation of a mixture of hydroxyl, superoxide, and methyl radicals, in a Fenton reaction system, upon coordination of kaempferol to the redox-active Cu(II) ions, by 80% with respect to the free Cu(II) ions. A viscometric study revealed a better DNA-intercalating ability of the Cu-kaempferol complex than for free kaempferol, essential for conferring anticancer activity of these substances. The results of the viscometric measurements were compared with those from a DNA damage study of Cu-kaempferol complexes in a Fenton reaction system, using gel electrophoresis. At low concentrations of kaempferol (Cu–kaempferol ratios of 1:1 and 1:2), a very weak protective effect on DNA was noted, whereas when kaempferol was present in excess, a significant DNA-protective effect was found. This can be explained if the weakly intercalated kaempferol molecules present at the surface of DNA provide protection against attack by ROS that originate from the Fenton reaction involving intercalated Cu(II)-kaempferol complexes. Following the application of ROS scavengers, L-histidine, DMSO, and SOD, gel electrophoresis confirmed the formation of singlet oxygen, hydroxyl radicals, and superoxide radical anions, respectively. We propose that the prooxidant properties of Cu-kaempferol complexes may provide anticancer activity of these substances. When present in excess, kaempferol displays antioxidant properties under Cu-Fenton conditions. This suggests that kaempferol might prove a suitable candidate for the prevention or treatment of oxidative stress related medical conditions that involve a disturbed metabolism of redox metals such as copper, for example, Menkes disease, and neurological disorders, including Alzheimer’s disease. For the potential use of kaempferol in clinical practice, it will be necessary to optimize the dose size and critical age of the patient so that this flavonoid may be beneficial as a preventive drug against cancer and neurological disorders.     

One-step creation of hierarchical fractal structures

Relatively recently, we advanced a route to create, in a controlled fashion, combined horizontal and vertical stratified structures by simple and energy-efficient processing operations employing static mixing elements. While in state-of-the-art static mixing the focus is on layer multiplication, here the aim is to create hierarchical fractal structures. Therefore, the main question addressed in this article is how structures, rather than layers, can be multiplied. The key aspect is the addition of layers on the sides or in the midplane of the flow during the process; every addition step increases the hierarchy by one level. This article derives the general formalism for forming fractal structures with controlled hierarchy, and we develop the language required to design and construct the dies. The main part of the article addresses this main topic and is based on the splitting serpentine static mixer geometry that can be easily made on the parting surfaces of a mold on both the micro- and the macroscale. The second part of the article addresses the strategy to minimize the number of mirroring steps, eventually avoiding mirroring completely, and is based on the rotation-free multiflux static mixer geometry. With the design language derived, complex hierarchical fractal structures can be generated simply by changing the number and sequence of operators within extrusion dies or molds, providing a one-step solution to produce material structures for potential use in diverse applications ranging from advanced mechanical systems to photovoltaic devices, where controlled assembly of dissimilar materials, and the realization of huge interfaces and genuine cocontinuity throughout the cross section, is critical.     

Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

Biochemical Investigation of the Interaction of pICln,RioK1 and COPR5 with the PRMT5–MEP50 Complex

The PRMT5–MEP50 methyltransferase complex plays a key role in various cancers and is regulated by different protein–protein interactions. Several proteins have been reported to act as adaptor proteins that recruit substrate proteins to the active site of PRMT5 for the methylation of arginine residues. To define the interaction between these adaptor proteins and PRMT5, we employed peptide truncation and mutation studies and prepared truncated protein constructs. We report the characterisation of the interface between the TIM barrel of PRMT5 and the adaptor proteins pICln, RioK1 and COPR5, and identify the consensus amino acid sequence GQF[D/E]DA[E/D] involved in binding. Protein crystallography revealed that the RioK1 derived peptide interacts with a novel PPI site.