Glycoconjugated Metallohelices have Improved Nuclear Delivery and Suppress Tumour Growth In Vivo

Monosaccharides are added to the hydrophilic face of a self‐assembled asymmetric Fe^II metallohelix, using CuAAC chemistry. The sixteen resulting architectures are water‐stable and optically pure, and exhibit improved antiproliferative selectivity against colon cancer cells (HCT116 p53^+/+) with respect to the non‐cancerous ARPE‐19 cell line. While the most selective compound is a glucose‐appended enantiomer, its cellular entry is not mainly glucose transporter‐mediated. Glucose conjugation nevertheless increases nuclear delivery ca 2.5‐fold, and a non‐destructive interaction with DNA is indicated. Addition of the glucose units affects the binding orientation of the metallohelix to naked DNA, but does not substantially alter the overall affinity. In a mouse model, the glucose conjugated compound was far better tolerated, and tumour growth delays for the parent compound (2.6 d) were improved to 4.3 d; performance as good as cisplatin but with the advantage of no weight loss in the subjects.     

Identification of geometric parameters influencing the flow-induced vibration of a two-layer self-oscillating computational vocal fold model

Simplified models have been used to simulate and study the flow-induced vibrations of the human vocal folds. While it is clear that the models' responses are sensitive to geometry, it is not clear how and to what extent specific geometric features influence model motion. In this study geometric features that played significant roles in governing the motion of a two-layer (body-cover), two-dimensional, finite element vocal fold model were identified. The model was defined using a flow solver based on the viscous, unsteady, Navier-Stokes equations and a solid solver that allowed for large strain and deformation. A screening-type design-of-experiments approach was used to identify the relative importance of 13 geometric parameters. Five output measures were analyzed to assess the magnitude of each geometric parameter's effect on the model's motion. The measures related to frequency, glottal width, flow rate, intraglottal angle, and intraglottal phase delay. The most significant geometric parameters were those associated with the cover--primarily the pre-phonatory intraglottal angle--as well as the body inferior angle. Some models exhibited evidence of improved model motion, including mucosal wave-like motion and alternating convergent-divergent glottal profiles, although further improvements are still needed to more closely mimic human vocal fold motion.     

Picosecond pulses from a cryogenically cooled, composite amplifier using Yb:YAG and Yb:GSAG

A cryogenic Yb amplifier using two laser materials, Gd3Sc2Al3O12 and Y3Al5O12 (YAG), has been used to obtain 70 W average power at 5 kHz pulse repetition frequency; the output was compressed to 1.6 ps, compared with an input compressible to 1.4 ps. The gain broadening obtained by combining two media enables shorter pulses than using Yb:YAG alone but retains the power-scaling advantages of cryogenic Yb:YAG.     

Selective spreading and jetting of electrically driven dielectric films

We study the electrically driven spreading of dielectric liquid films in wedge-shaped gaps across which a potential difference is applied. Our experiments are in a little-studied regime where, throughout the dynamics, the electrical relaxation time is long compared to the time for charge to be convected by the fluid motion. We observe that at a critical normal electric field the hump-shaped leading edge undergoes an instability in the form of a single Taylor cone and periodic jetting ensues, after which traveling waves occur along the trailing thin film. We propose a convection-dominated mechanism for charge transport to describe the observed dynamics and rationalize the viscosity dependence of the self-excited dynamics.     

A high-resolution NMR probe in which the coil and preamplifier are cooled with liquid helium. 1984

In a well designed NMR spectrometer, the noise originates predominantly from the resistance of the receiver coil. Significant improvements in sensitivity can be achieved by cooling the coil to cryogenic temperatures, provided that a preamplifier can be designed to match the coil’s performance. A probe is described in which the coil and preamplifier are cooled with liquid helium, but the sample is maintained at room temperature. Carbon-l3 spectra at 45 MHz demonstrate improved sensitivity over conventional probes at the same field.     

Every Large Point Set contains Many Collinear Points or an Empty Pentagon

We prove the following generalised empty pentagon theorem for every integer ℓ ≥ 2, every sufficiently large set of points in the plane contains ℓ collinear points or an empty pentagon. As an application, we settle the next open case of the “big line or big clique” conjecture of Kára, Pór, and Wood [Discrete Comput. Geom. 34(3):497–506, 2005].     

Sample path Large Deviations and optimal importance sampling for stochastic volatility models

Sample path Large Deviation Principles (LDP) of the Freidlin–Wentzell type are derived for a class of diffusions, which govern the price dynamics in common stochastic volatility models from Mathematical Finance. LDP are obtained by relaxing the non-degeneracy requirement on the diffusion matrix in the standard theory of Freidlin and Wentzell. As an application, a sample path LDP is proved for the price process in the Heston stochastic volatility model.     

Efficient 1645-nm Er:YAG laser

We report a resonantly fiber-laser-pumped Er:YAG laser operating at the eye-safe wavelength of 1645 nm, exhibiting 43% optical efficiency and 54% incident slope efficiency and emitting 7-W average power when repetitively Q switched at 10 kHz. To our knowledge, this is the best performance (conversion efficiency and average power) obtained from a bulk solid-state Q-switched erbium laser. At a 1.1-kHz pulse repetition frequency the laser produces 3.4-mJ pulses with a corresponding peak power of 162 kW. Frequency doubling to produce 822.5-nm, 4.7-kW pulses at 10 kHz was performed to demonstrate the laser's utility.