Dissipative and generative fractional electric elements in modeling $${\varvec{RC}}$$ RC and $${\varvec{RL}}$$ RL circuits

Nonlinear Dynamics - Two types of constitutive equations consisting of instantaneous and power type hereditary contributions are proposed in order to model generalized capacitor (inductor). The...     

Design and Synthesis of High‐Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors

Gephyrin is the central scaffolding protein for inhibitory neurotransmitter receptors in the brain. Here we describe the development of dimeric peptides that inhibit the interaction between gephyrin and these receptors, a process which is fundamental to numerous synaptic functions and diseases of the brain. We first identified receptor‐derived minimal gephyrin‐binding peptides that displayed exclusive binding towards native gephyrin from brain lysates. We then designed and synthesized a series of dimeric ligands, which led to a remarkable 1220‐fold enhancement of the gephyrin affinity (K_D=6.8 nM ). In X‐ray crystal structures we visualized the simultaneous dimer‐to‐dimer binding in atomic detail, revealing compound‐specific binding modes. Thus, we defined the molecular basis of the affinity‐enhancing effect of multivalent gephyrin inhibitors and provide conceptually novel compounds with therapeutic potential, which will allow further elucidation of the gephyrin–receptor interplay.     

Targeted Photodynamic Therapy of Human Head and Neck Squamous Cell Carcinoma with Anti-epidermal Growth Factor Receptor Antibody Cetuximab and Photosensitizer IR700DX in the Mouse Skin-fold Window Chamber Model

Targeted photodynamic therapy (PDT) in head/neck cancer patients with a conjugate of the anti-epidermal growth factor receptor (EGFR) antibody, Cetuximab and a phthalocyanine photosensitizer IR700DX is under way, but the exact mechanisms of action are still not fully understood. In this study, the EGFR-overexpressing human head/neck OSC-19-luc2-cGFP tumor with transfected GFP gene was used in a skin-fold window chamber model in BALB/c nude mice. The uptake and localization of the conjugate in the tumor and its surrounding normal tissues were studied by an intravital confocal laser scanning microscopy with image analyses. The tumor was also irradiated with 690 nm laser light 24 h after conjugate administration. The vascular and tumor responses were examined by morphological evaluation and immunohistochemistry (IHC). The amount of conjugate in the tumor peaked at 24–48 h after injection. Image analyses of colocalization correlation parameters demonstrated a high fraction of the conjugate IR700DX colocalized in the GFP-expressing tumor cells. PDT-treated tumors showed extensive necrotic/apoptotic destruction with little vascular damage, while IHC showed no HIF-1α expression and decreased EGFR and Ki67 expression with activated caspase-3 overexpression, indicating a direct killing of tumor cells through both necrotic and apoptotic cell death.     

Simulation of 3D inclined/rotated UV lithography and its application to microneedles

A 3D model is set up to simulate the exposure process of inclined/rotated UV lithography for negative SU-8 resists. The formation of inclined resist pillars and microstructures with truncated cone shapes is simulated based on a 3D exposure model in combination with a post exposure bake model for chemically amplified resists and the Mack development model. As one of the interesting applications employing this promising lithography technique for MEMS fabrication, a solid microneedle for drug delivery is simulated.     

Polyurea microcapsules from isocyanatoethyl methacrylate copolymers

The synthesis of two types of isocyanate side chain containing copolymers, poly(methyl methacrylate‐co‐isocyanatoethyl methacrylate) (P(MMA‐co‐IEM)) and poly(benzyl methacrylate‐co‐isocyanatoethyl methacrylate) (P(BnMA‐co‐IEM)), which were synthesized by Cu(0)‐mediated radical polymerization, is reported. Polymerization proceeded to high conversion giving polymers of relatively narrow molar mass distributions. The incorporation of the bulky aromatic groups in the latter copolymer rendered it sufficiently stable toward hydrolysis and enabled the isolation of the product and its characterization by ¹H and ¹³C NMR, and FTIR spectroscopy and SEC. Both P(MMA‐co‐IEM) and P(BnMA‐co‐IEM) were functionalized with dibutylamine, octylamine, and (R)‐(+)‐α‐methylbenzyl‐amine, which further proved the successful incorporation of the isocyanate groups. Furthermore, P(BnMA‐co‐IEM) was used for the fabrication of liquid core microcapsules via oil‐in‐water interfacial polymerization with diethylenetriamine as crosslinker. The particles obtained were in the size range of 10–90 µm in diameter independent of the composition of copolymer. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2698–2705     

Aggressive dereplication using UHPLC–DAD–QTOF: screening extracts for up to 3000 fungal secondary metabolites

In natural-product drug discovery, finding new compounds is the main task, and thus fast dereplication of known compounds is essential. This is usually performed by manual liquid chromatography-ultraviolet (LC-UV) or visible light-mass spectroscopy (Vis-MS) interpretation of detected peaks, often assisted by automated identification of previously identified compounds. We used a 15 min high-performance liquid chromatography–diode array detection (UHPLC–DAD)–high-resolution MS method (electrospray ionization (ESI)⁺ or ESI^?), followed by 10–60 s of automated data analysis for up to 3000 relevant elemental compositions. By overlaying automatically generated extracted-ion chromatograms from detected compounds on the base peak chromatogram, all major potentially novel peaks could be visualized. Peaks corresponding to compounds available as reference standards, previously identified compounds, and major contaminants from solvents, media, filters etc. were labeled to differentiate these from compounds only identified by elemental composition. This enabled fast manual evaluation of both known peaks and potential novel-compound peaks, by manual verification of: the adduct pattern, UV–Vis, retention time compared with log D, co-identified biosynthetic related compounds, and elution order. System performance, including adduct patterns, in-source fragmentation, and ion-cooler bias, was investigated on reference standards, and the overall method was used on extracts of Aspergillus carbonarius and Penicillium melanoconidium, revealing new nitrogen-containing biomarkers for both species.