Development of Magnesium Anode-Based Transient Primary Batteries

Biodegradable primary batteries, also known as transient batteries, are essential to realize autonomous biodegradable electronic devices with high performance and advanced functionality. In this work, magnesium, copper, iron, and zinc – metals that exist as trace elements in the human body – were tested as materials for biomedical transient electronic devices. Different full cell combinations of Mg and X (where X = Cu, Fe, and Zn and the anodized form of the metals) with phosphate buffered saline (PBS) as electrolyte were studied. To form the cathodes, metal foils were anodized galvanostatically at a current density of 2.0 mA cm⁻² for 30 mins. Electrochemical measurements were then conducted for each electrode combination to evaluate full cell battery performance. Results showed that the Mg−Cu_anodized chemistry has the highest power density at 0.99 mW/cm². Nominal operating voltages of 1.26 V for the first 0.50 h and 0.63 V for the next 3.7 h were observed for Mg−Cu_anodized which was discharged at a current density of 0.70 mA cm⁻². Among the materials tested, Mg−Cu_anodized exhibited the best discharge performance with an average specific capacity of 2.94 mAh cm⁻², which is comparable to previous reports on transient batteries.     

Late-Stage Modification of Aminoglycoside Antibiotics Overcomes Bacterial Resistance Mediated by APH(3’) Kinases

The continuous emergence of antimicrobial resistance is causing a threat to patients infected by multidrug-resistant pathogens. In particular, the clinical use of aminoglycoside antibiotics, broad-spectrum antibacterials of last resort, is limited due to rising bacterial resistance. One of the major resistance mechanisms in Gram-positive and Gram-negative bacteria is phosphorylation of these amino sugars at the 3’-position by O-phosphotransferases [APH(3’)s]. Structural alteration of these antibiotics at the 3’-position would be an obvious strategy to tackle this resistance mechanism. However, the access to such derivatives requires cumbersome multi-step synthesis, which is not appealing for pharma industry in this low-return-on-investment market. To overcome this obstacle and combat bacterial resistance mediated by APH(3’)s, we introduce a novel regioselective modification of aminoglycosides in the 3’-position via palladium-catalyzed oxidation. To underline the effectiveness of our method for structural modification of aminoglycosides, we have developed two novel antibiotic candidates overcoming APH(3’)s-mediated resistance employing only four synthetic steps.     

Runge–Kutta Lawson schemes for stochastic differential equations

In this paper, we present a framework to construct general stochastic Runge–Kutta Lawson schemes. We prove that the schemes inherit the consistency and convergence properties of the underlying Runge–Kutta scheme, and confirm this in some numerical experiments. We also investigate the stability properties of the methods and show for some examples, that the new schemes have improved stability properties compared to the underlying schemes.

     

Numerical correction of optical vortex using a wrapped phase map analysis algorithm

We demonstrate experimentally a technique for the numerical correction of an optical vortex with a unitary topological charge. A developed algorithm based on the axial behavior of a reconstructed wavefront is used in the detection of the optical vortex. Optimizations of the number of axial phase maps and the window size used in the algorithm yield the precise coordinates of the vortex eye. The obtained coordinates and vortex handedness are used in designing a proper filter, facilitating numerical correction of the vortex phase map. The developed algorithm can be applied to absolute phase and phase difference maps obtained through any reconstruction method.     

Variable angle NMR spectroscopy and its application to the measurement of residual chemical shift anisotropy

The successful measurement of anisotropic NMR parameters like residual dipolar couplings (RDCs), residual quadrupolar couplings (RQCs), or residual chemical shift anisotropy (RCSA) involves the partial alignment of solute molecules in an alignment medium. To avoid any influence of the change of environment from the isotropic to the anisotropic sample, the measurement of both datasets with a single sample is highly desirable. Here, we introduce the scaling of alignment for mechanically stretched polymer gels by varying the angle of the director of alignment relative to the static magnetic field, which we call variable angle NMR spectroscopy (VA-NMR). The technique is closely related to variable angle sample spinning NMR spectroscopy (VASS-NMR) of liquid crystalline samples, but due to the mechanical fixation of the director of alignment no sample spinning is necessary. Also, in contrast to VASS-NMR, VA-NMR works for the full range of sample inclinations between 0° and 90°. Isotropic spectra are obtained at the magic angle. As a demonstration of the approach we measure 13C-RCSA values for strychnine in a stretched PDMS/CDCl? gel and show their usefulness for assignment purposes. In this context special care has been taken with respect to the exact calibration of chemical shift data, for which three approaches have been derived and tested.     

Perception of intrusive /r/ in English by native, cross-language and cross-dialect listeners

In sequences such as law and order, speakers of British English often insert /r/ between law and and. Acoustic analyses revealed such "intrusive" /r/ to be significantly shorter than canonical /r/. In a 2AFC experiment, native listeners heard British English sentences in which /r/ duration was manipulated across a word boundary [e.g., saw (r)ice], and orthographic and semantic factors were varied. These listeners responded categorically on the basis of acoustic evidence for /r/ alone, reporting ice after short /r/s, rice after long /r/s; orthographic and semantic factors had no effect. Dutch listeners proficient in English who heard the same materials relied less on durational cues than the native listeners, and were affected by both orthography and semantic bias. American English listeners produced intermediate responses to the same materials, being sensitive to duration (less so than native, more so than Dutch listeners), and to orthography (less so than the Dutch), but insensitive to the semantic manipulation. Listeners from language communities without common use of intrusive /r/ may thus interpret intrusive /r/ as canonical /r/, with a language difference increasing this propensity more than a dialect difference. Native listeners, however, efficiently distinguish intrusive from canonical /r/ by exploiting the relevant acoustic variation.     

Stable silencing of SNAP-25 in PC12 cells by RNA interference

Background  

SNAP-25 is a synaptic protein known to be involved in exocytosis of synaptic vesicles in neurons and of large dense-core vesicles in neuroendocrine cells. Its role in exocytosis has been studied in SNAP-25 knockout mice, in lysed synaptosomes lacking functional SNAP-25 and in cells after treatment with botulinum toxins A or E that specifically cleave SNAP-25. These studies have shown that SNAP-25 appears to be required for most but not all evoked secretion. In order to further study the role of SNAP-25 in catecholamine secretion from PC12 cells we have used the recently developed technique of RNA interference to generate PC12 cell lines with virtually undetectable levels of SNAP-25. RNA interference is the sequence-specific silencing or knockdown of gene expression triggered by the introduction of double-stranded RNA into a cell. RNA interference can be elicited in mammalian cells in a number of ways, one of which is by the expression of small hairpin RNAs from a transfected plasmid. Selection of stably transfected cell lines expressing a small hairpin RNA allows one-time characterization of the degree and specificity of gene silencing and affords a continuing source of well-characterized knockdown cells for experimentation.     

Self-Assembly Behavior and Application of Terphenyl-Cored Trimaltosides for Membrane-Protein Studies: Impact of Detergent Hydrophobic Group Geometry on Protein Stability

Amphipathic agents are widely used in various fields including biomedical sciences. Micelle-forming detergents are particularly useful for in vitro membrane-protein characterization. As many conventional detergents are limited in their ability to stabilize membrane proteins, it is necessary to develop novel detergents to facilitate membrane-protein research. In the current study, we developed novel trimaltoside detergents with an alkyl pendant-bearing terphenyl unit as a hydrophobic group, designated terphenyl-cored maltosides (TPMs). We found that the geometry of the detergent hydrophobic group substantially impacts detergent self-assembly behavior, as well as detergent efficacy for membrane-protein stabilization. TPM-Vs, with a bent terphenyl group, were superior to the linear counterparts (TPM-Ls) at stabilizing multiple membrane proteins. The favorable protein stabilization efficacy of these bent TPMs is likely associated with a binding mode with membrane proteins distinct from conventional detergents and facial amphiphiles. When compared to n-dodecyl-β-d -maltoside (DDM), most TPMs were superior or comparable to this gold standard detergent at stabilizing membrane proteins. Notably, TPM-L3 was particularly effective at stabilizing the human β₂ adrenergic receptor (β₂AR), a G-protein coupled receptor, and its complex with G_s protein. Thus, the current study not only provides novel detergent tools that are useful for membrane-protein study, but also suggests a critical role for detergent hydrophobic group geometry in governing detergent efficacy.