Targeting Bone Metastases with a Bispecific Anticancer and Antiangiogenic Polymer–Alendronate–Taxane Conjugate

A polymer therapeutic designed for combination anticancer and antiangiogenic therapy inhibited the proliferation of prostate carcinoma cells and the proliferation, migration, and tube‐formation of endothelial cells. The nanoconjugate was formed from an N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer, the bisphosphonate alendronate (for bone targeting), and the chemotherapy agent paclitaxel (PTX), which is cleaved by cathepsin B (see scheme).

     

Droplet microfluidics for high-throughput biological assays

Droplet microfluidics offers significant advantages for performing high-throughput screens and sensitive assays. Droplets allow sample volumes to be significantly reduced, leading to concomitant reductions in cost. Manipulation and measurement at kilohertz speeds enable up to 10(8) samples to be screened in one day. Compartmentalization in droplets increases assay sensitivity by increasing the effective concentration of rare species and decreasing the time required to reach detection thresholds. Droplet microfluidics combines these powerful features to enable currently inaccessible high-throughput screening applications, including single-cell and single-molecule assays.     

Electronic Filtering of Interferometric Homodyne Crosstalk in WDM Systems with Absolute Frequency Reference

Electronic high pass filtering of interferometric crosstalk noise is investigated theoretically and experimentally in systems with absolute frequency reference employing external modulation and DC balanced coding. 4 dB improvement in the tolerance to crosstalk is demonstrated.     

Diffusion kurtosis imaging of the human kidney: A feasibility study

Purpose

To assess the feasibility and to optimize imaging parameters of diffusion kurtosis imaging (DKI) in human kidneys.

Methods

The kidneys of ten healthy volunteers were examined on a clinical 3 T MR scanner. For DKI, respiratory triggered EPI sequences were acquired in the coronal plane (3 b-values: 0, 300, 600 s/mm², 30 diffusion directions). A goodness of fit analysis was performed and the influence of the signal-to-noise ratio (SNR) on the DKI results was evaluated. Region-of-interest (ROI) measurements were performed to determine apparent diffusion coefficient (ADC), fractional anisotropy (FA) and mean kurtosis (MK) of the cortex and the medulla of the kidneys. Intra-observer and inter-observer reproducibility using Bland-Altman plots as well as subjective image quality of DKI were examined and ADC, FA, and MK parameters were compared.

Results

The DKI model fitted better to the experimental data (r = 0.99) with p < 0.05 than the common mono-exponential ADC model (r = 0.96).Calculation of reliable kurtosis parameters in human kidneys requires a minimum SNR of 8.31 on b = 0 s/mm² images.Corticomedullary differentiation was possible on FA and MK maps. ADC, FA and MK revealed significant differences in medulla (ADC = 2.82 × 10^− 3 mm²/s ± 0.25, FA = 0.42 ± 0. 05, MK = 0.78 ± 0.07) and cortex (ADC = 3.60 × 10^− 3 mm²/s ± 0.28, FA = 0.18 ± 0.04, MK = 0.94 ± 0.07) with p < 0.001.

Conclusion

Our initial results indicate the feasibility of DKI in the human kidney presuming an adequate SNR. Future studies in patients with kidney diseases are required to determine the value of DKI for functional kidney imaging.     

Rapid Antibiotic Susceptibility Determination for <Emphasis Type="Italic">Yersinia pestis</Emphasis> Using Flow Cytometry Spectral Intensity Ratio (SIR) Fluorescence Analysis

Rapid antimicrobial susceptibility tests (ASTs) are essential tool for proper treatment of patients infected by Yersinia pestis (Y. pestis), the causative agent of plague, or for post-exposure prophylaxis of a population exposed to a naturally acquired or deliberately prepared resistant variant. The standard AST of Y. pestis is based on bacterial growth and requires 24–48 h of incubation in addition to the time required for prior isolation of a bacterial culture from the clinical or environmental sample, which may take an additional 24–48 h. In this study, we present a new and rapid AST method based on a fluorescence determination of the minimum inhibitory concentration (MIC). Our method includes the incubation of bacteria with an antibiotic, followed by staining of the bacteria with oxonol dye (SynaptoGreen C4/FM1–43), which enables the rapid detection of an antibiotic’s effect on bacterial viability. We show that stained, non-viable bacteria exhibit a spectral redshift and an increase in fluorescence intensity compared to intact control bacteria. Based on these criteria, we developed a rapid flow cytometer measurement procedure and a unique spectral intensity ratio (SIR) analysis that enables determination of antibiotic susceptibility for Y. pestis within 6 h instead of the 24 to 48 h required for the standard AST. This new rapid determination of antibiotic susceptibility could be crucial for reducing mortality and preventing the spread of disease.     

Absorption spectra and photolysis of methyl peroxide in liquid and frozen water

Methyl peroxide (CH(3)OOH) is commonly found in atmospheric waters and ices in significant concentrations. It is the simplest organic peroxide and an important precursor to hydroxyl radical. Many studies have examined the photochemical behavior of gaseous CH(3)OOH; however, the photochemistry of liquid and frozen water solutions is poorly understood. We present a series of experiments and theoretical calculations designed to elucidate the photochemical behavior of CH(3)OOH dissolved in liquid water and ice over a range of temperatures. The molar extinction coefficients of aqueous CH(3)OOH are different from the gas phase, and they do not change upon freezing. Between -12 and 43 °C, the quantum yield of CH(3)OOH photolysis is described by the following equation: Φ(T) = exp((-2175 ± 448)1/T) + 7.66 ± 1.56). We use on-the-fly ab initio molecular dynamics simulations to model structures and absorption spectra of a bare CH(3)OOH molecule and a CH(3)OOH molecule immersed inside 20 water molecules at 50, 200, and 220 K. The simulations predict large sensitivity in the absorption spectrum of CH(3)OOH to temperature, with the spectrum narrowing and shifting to the blue under cryogenic conditions because of constrained dihedral motion around the O-O bond. The shift in the absorption spectrum is not observed in the experiment when the CH(3)OOH solution is frozen suggesting that CH(3)OOH remains in a liquid layer between the ice grains. Using the extinction coefficients and photolysis quantum yields obtained in this work, we show that under conditions with low temperatures, in the presence of clouds with a high liquid-water content and large solar zenith angles, the loss of CH(3)OOH by aqueous photolysis is responsible for up to 20% of the total loss of CH(3)OOH due to photolysis. Gas phase photolysis of CH(3)OOH dominates under all other conditions.     

Classical trajectory simulations of photoionization dynamics of tryptophan: intramolecular energy flow, hydrogen-transfer processes and conformational transitions

One-photon and two-photon ionization dynamics of tryptophan is studied by classical trajectory simulations using the semiempirical parametric method number 3 (PM3) potential surface in "on the fly" calculations. The tryptophan conformer is assumed to be in the vibrational ground state prior to ionization. Initial conditions for the trajectories are weighted according to the Wigner distribution function computed for that state. Vertical ionization in the spirit of the classical Franck-Condon principle is assumed. For the two-photon ionization process the ionization is assumed to go resonantively through the first excited state. Most trajectories are computed, and the analysis is carried out for the first 10 ps. A range of interesting effects are observed. The main findings are as follows: (1) Multiple conformational transitions are observed in most of the trajectories within the ultrafast duration of 10 ps. (2) Hydrogen transfer from the carboxyl group to the amino group and back has been observed. A zwitterion is formed as a transient state. (3) Two new isomers are formed during the dynamics, which have apparently not been previously observed. (4) Fast energy flow between the ring modes and the amino acid backbone is observed for both one- and two-photon ionization. However, the effective vibrational temperatures only approach the same value after 90 ps. The conformation transition dynamics, the proton-transfer processes and the vibrational energy flow are discussed and analyzed.     

Plasticization of a polymer layer harnessed to a silicon microcantilever as a highly sensitive and selective means to detect nitroaromatic derivatives

A new approach to the chemo‐mechanical detection of trace amounts of nitroaromatics, even in the presence of high concentrations of background materials, is presented. The detection scheme is based on the plasticization of an aminopropyl silane layer that is harnessed to a silicon beam following its reaction with nitroaromatic systems. The reaction‐induced plasticization attenuates the temperature induced bending of the polymer‐beam sandwich, offering a simple and very sensitive tool for the detection of nitroaromatic systems. Using this approach, it was possible to detect a sample of 100 pg TNT even in the presence of a ～10⁹ fold excess of a background material such as acetonitrile. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2124–2130     

Microcantilevers as gas‐phase sensing platforms: Simplification and optimization of the production of polymer coated porous‐silicon‐over‐silicon microcantilevers

The asymmetric roughening of silicon microcantilevers using different vapor stain‐etching conditions is studied with the aim of optimizing face selective coating of microcantilevers by polymers through simple dipping. The effect of roughening is studied by following the time‐dependent guest‐induced bending of silicone microcantilevers coated with a poly‐4‐vinylpyridine sensing layer. A correlation between the surface roughness of the microcantilevers and their time‐dependent guest‐induced bending is gained from combining high resolution scanning electron microscopy studies of the surface of the microcantilevers as well as their cross‐sections with time‐dependent guest‐induced microcantilever bending. The purpose of the present work is to lay the foundations for a small and relatively simple gas‐phase sensing tool based on a microcantilever platform capable of offering wide range sensing capabilities. © 2013 Wiley Periodicals, 2014 , 52, 141–146