Synthesis and Biological Characterization of (3R,4R)‐4‐(2‐(Benzhydryloxy)ethyl)‐1‐((R)‐2‐hydroxy‐2‐phenylethyl)‐piperidin‐3‐ol and Its Stereoisomers for Activity toward Monoamine Transporters

A novel series of optically active molecules based on a 4‐(2‐(benzhydryloxy)ethyl)‐1‐((R)‐2‐hydroxy‐2‐phenylethyl)‐piperidin‐3‐ol template were developed. Depending on stereochemistry, the compounds exhibit various degrees of affinity for three dopamine, serotonin, and norepinephrine transporters. These molecules have the potential for treating several neurological disorders such as drug abuse, depression, and attention deficit hyperactivity disorder.

     

Gold-enhanced biomolecular surface imaging of cells and tissue by SIMS and MALDI mass spectrometry

Surface metallization by plasma coating enhances desorption/ionization of membrane components such as lipids and sterols in imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) of tissues and cells. High-resolution images of cholesterol and other membrane components were obtained for neuroblastoma cells and revealed subcellular details (resolving power 1.5 mum). Alternatively, in matrix-enhanced SIMS, 2,5-dihydroxybenzoic acid electrosprayed on neuroblastoma cells allowed intact molecular ion imaging of phosphatidylcholine and sphingomyelin at the cellular level. Gold deposition on top of matrix-coated rat brain tissue sections strongly enhanced image quality and signal intensity in stigmatic matrix-assisted laser desorption/ionization imaging mass spectrometry. High-quality total ion count images were acquired, and the neuropeptide vasopressin was localized in the rat brain tissue section at the hypothalamic area around the third ventricle. Although the mechanism of signal enhancement by gold deposition is under debate, the results we have obtained for cells and tissue sections illustrate the potential of this sample preparation technique for biomolecular surface imaging by mass spectrometry.     

Spray Drying of Lactobacillus plantarum WCFS1 Guided by Predictive Modeling

Shelf life of probiotic microorganisms can be retained by drying. Spray drying is an economically interesting alternative to freeze drying with that respect. However, the viability can decrease due to the drying process and testing it is laborious and expensive. This research shows that the viability of Lactobacillus plantarum WCFS1 during pilot scale drying can be predicted with kinetics gathered at a single droplet level. Using this approach, it could be demonstrated that the viability of L. plantarum WCFS1 during spray drying is mainly determined by the combination of temperature and moisture content during the first 0.5 seconds after atomization. The combination of a high moisture content and a high temperature appeared most detrimental to the residual viability. Moreover, it was found to be important to take into account the particle size distribution during atomization when predicting viability, since this has a large effect on the moisture content during this first 0.5 seconds. Finally, it was observed that shelf life during storage was mainly determined by the moisture content of the powder. A lower moisture content resulted in a higher viability. Above a moisture content of 6%, shelf life stability rapidly decreased in the applied maltodextrin (DE = 16) matrix.     

Identification of Phenylpyrazolone Dimers as a New Class of Anti-Trypanosoma cruzi Agents

Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC₅₀ value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC₅₀ value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells.     

A simple improvement of a tip loss model for actuator disc simulations

The loading of a wind turbine decreases towards the blade tip because of the velocities induced by the tip vortex. This tip loss effect has to be taken into account when performing actuator disc simulations, where the single blades of the turbine are not modeled. A widely used method applies a factor on the axial and tangential loading of the turbine. This factor decreases when approaching the blade tip. It has been shown that the factor should be different for the axial and tangential loading of the turbine to model the rotation of the resulting force vector at the airfoil sections caused by the induced velocity. The present article contains the derivation of a simple correction for the tangential load factor that takes this rotation into account. The correction does not need any additional curve fitting but just depends on the local airfoil characteristics and angle of attack. Actuator disc computations with the modified tip loss correction show improved agreement with results from actuator line, free wake lifting line, and blade element momentum simulations.     

Optical Control of Antibody Activity by Using Photocleavable Bivalent Peptide–DNA Locks

Antibody-based molecular recognition plays a central role in today's life sciences, ranging from immunoassays to molecular imaging and antibody-based therapeutics. Control over antibody activity by using external triggers such as light could further increase the specificity of antibody-based targeting. Here we present bivalent peptide–DNA ligands containing photocleavable linkers as a noncovalent approach by which to allow photoactivation of antibody activity. Light-triggered cleavage of the 3-amino-3-(2-nitrophenyl)propionic acid peptide linker converted the high-affinity bivalent peptide–DNA lock into weakly binding monovalent ligands, effectively restoring antibody targeting of cell-surface receptors. In this work, a proof of principle was provided with an anti-hemagglutinin antibody, but the molecular design of the lock is generic and applicable to any monoclonal antibody for which an epitope or mimotope of sufficient affinity is available.     

Measurement of T1 and T2 relaxation times of the pancreas at 7 T using a multi-transmit system

Objective

To determine T₁ and T₂ relaxation times of healthy pancreas parenchyma at 7 T using a multi-transmit system.

Materials and methods

Twenty-six healthy subjects were scanned with a 7 T MR system using eight parallel transceiver antennas, each with two additional receive loops. A Look-Locker sequence was used to obtain images for T₁ determination, while T₂ was obtained from spin-echo images and magnetic resonance spectroscopy measurements with different echo times. T₁ and T₂ times were calculated using a mono-exponential fit of the average magnitude signal from a region of interest in the pancreas and were tested for correlation with age.

Results

The age range of the included subjects was 21–72 years. Average T₁ and T₂ relaxation times in healthy pancreas were 896 ± 149 ms, and 26.7 ± 5.3 ms, respectively. No correlation with age was found.

Conclusion

T₁ and T₂ relaxation times of the healthy pancreas were reported for 7 T, which can be used for image acquisition optimization. No significant correlations were found between age and T₁ or T₂ relaxation times of the pancreas. Considering their low standard deviation and no observable age dependence, these values may be used as a baseline to study potentially pancreatic tissue affected by disease.

     

A note on large-scale logistic prediction: using an approximate graphical model to deal with collinearity and missing data

Large-scale prediction problems are often plagued by correlated predictor variables and missing observations. We consider prediction settings in which logistic regression models are used and propose a novel approach to make accurate predictions even when predictor variables are highly correlated and only partly observed. Our approach comprises three steps: first, to overcome the collinearity issue, we propose to model the joint distribution of the outcome variable and the predictor variables using the Ising network model. Second, to render the application of Ising networks feasible, we use a latent variable representation to apply a low-rank approximation to the network’s connectivity matrix. Finally, we propose an approximation to the latent variable distribution that is used in the representation to handle missing observations. We demonstrate our approach with numerical illustrations.

     

A Facet‐Specific Quantum Dot Passivation Strategy for Colloid Management and Efficient Infrared Photovoltaics

Colloidal nanocrystals combine size‐ and facet‐dependent properties with solution processing. They offer thus a compelling suite of materials for technological applications. Their size‐ and facet‐tunable features are studied in synthesis; however, to exploit their features in optoelectronic devices, it will be essential to translate control over size and facets from the colloid all the way to the film. Larger‐diameter colloidal quantum dots (CQDs) offer the attractive possibility of harvesting infrared (IR) solar energy beyond absorption of silicon photovoltaics. These CQDs exhibit facets (nonpolar (100)) undisplayed in small‐diameter CQDs; and the materials chemistry of smaller nanocrystals fails consequently to translate to materials for the short‐wavelength IR regime. A new colloidal management strategy targeting the passivation of both (100) and (111) facets is demonstrated using distinct choices of cations and anions. The approach leads to narrow‐bandgap CQDs with impressive colloidal stability and photoluminescence quantum yield. Photophysical studies confirm a reduction both in Stokes shift (≈47 meV) and Urbach tail (≈29 meV). This approach provides a ≈50% increase in the power conversion efficiency of IR photovoltaics compared to controls, and a ≈70% external quantum efficiency at their excitonic peak.