Identification of 8-Hydroxyquinoline Derivatives That Decrease Cystathionine Beta Synthase (CBS) Activity

CBS encodes a pyridoxal 5′-phosphate-dependent enzyme that catalyses the condensation of homocysteine and serine to form cystathionine. Due to its implication in some cancers and in the cognitive pathophysiology of Down syndrome, the identification of pharmacological inhibitors of this enzyme is urgently required. However, thus far, attempts to identify such molecules have only led to the identification of compounds with low potency and limited selectivity. We consequently developed an original, yeast-based screening method that identified three FDA-approved drugs of the 8-hydroxyquinoline family: clioquinol, chloroxine and nitroxoline. These molecules reduce CBS enzymatic activity in different cellular models, proving that the molecular mechanisms involved in yeast phenotypic rescue are conserved in mammalian cells. A combination of genetic and chemical biology approaches also revealed the importance of copper and zinc intracellular levels in the regulation of CBS enzymatic activity—copper promoting CBS activity and zinc inhibiting its activity. Taken together, these results indicate that our effective screening approach identified three new potent CBS inhibitors and provides new findings for the regulation of CBS activity, which is crucial to develop new therapies for CBS-related human disorders.     

Improved temperature precision in rotational coherent anti-stokes raman spectroscopy with a modeless dye laser

Single-shot thermometry with dual-broadband rotational coherent anti-Stokes Raman spectroscopy that employs amplified spontaneous emission from a broadband modeless dye laser has been examined. Evaluation of single-shot spectra of air, N2, and O2 showed an improved temperature precision at room temperature compared with the precision obtained with a conventional dye laser. A comparison was also made between the use of single-mode and multimode Nd:YAG lasers as sources for narrowband radiation, and in all cases the single-mode Nd:YAG laser resulted in higher precision. The experimental results are compared with theoretical predictions.     

Comparison of methods for estimation of the intravoxel incoherent motion (IVIM) diffusion coefficient (<Emphasis Type="Italic">D</Emphasis>) and perfusion fraction (<Emphasis Type="Italic">f</Emphasis>)

Objective

Intravoxel incoherent motion (IVIM) shows great potential in many applications, e.g., tumor tissue characterization. To reduce image-quality demands, various IVIM analysis approaches restricted to the diffusion coefficient (D) and the perfusion fraction (f) are increasingly being employed. In this work, the impact of estimation approach for D and f is studied.

Materials and methods

Four approaches for estimating D and f were studied: segmented IVIM fitting, least-squares fitting of a simplified IVIM model (sIVIM), and Bayesian fitting of the sIVIM model using marginal posterior modes or posterior means. The estimation approaches were evaluated in terms of bias and variability as well as ability for differentiation between tumor and healthy liver tissue using simulated and in vivo data.

Results

All estimation approaches had similar variability and ability for differentiation and negligible bias, except for the Bayesian posterior mean of f, which was substantially biased. Combined use of D and f improved tumor-to-liver tissue differentiation compared with using D or f separately.

Discussion

The similar performance between estimation approaches renders the segmented one preferable due to lower numerical complexity and shorter computational time. Superior tissue differentiation when combining D and f suggests complementary biologically relevant information.

     

Self-diffusion of oil in lubricating greases by NMR

Self-diffusion of base oil in six model lubricating greases and in the base oils themselves was measured using pulsed-field gradient nucleic magnetic resonance (NMR) at 23, 40, 70, and 90°C. Three of the greases were based on naphthenic mineral oils, and three were based on synthetic polyalphaolefin oils. Soaps of 12-hydroxy stearic acid were used as thickener agents in all six greases. The purpose of the investigation using NMR was to see if structure varies with temperature, and if NMR is a viable method for structure determination. The ratio between the diffusion coefficient of the base oil in the grease and the neat base oil in itself was evaluated as a function of temperature. This ratio was taken as a direct indicator of the obstruction effect that the thickener has on the oil. The thickener showed a stronger obstruction effect on the base oil in the synthetic grease than in the mineral-based grease. This was related to the soap content, which, for these greases, is roughly twice as high in the synthetic greases as in the mineral ones. The obstruction effect was constant in the temperature range 40–90°C for mineral- as well as synthetic-based greases. NMR was judged to be a promising method for investigating how the gellant affects the diffusion coefficient of oil in a lubricating grease.     

From low-level programming to full-fledged industrial model-based development: the story of the Rubus Component Model

Developing distributed real-time systems is a complex task that has historically entailed specialized handcraft. In this paper, we propose a retrospective on the (r)evolutionary changes that led to the transition from low-level programming to industrial full-fledged model-based development embodied by the Rubus Component Model and its tool-ecosystem. We focus on the needs, challenges, and solutions of a 15-year-long evolution journey of a software development approach that has gone from low-level and manual programming to a highly automated environment offering modeling, analysis, and development of vehicular software systems with multi-criticality for deployment on single- and multi-core platforms.

     

Thermal and crystallization behavior of cotton—Polypropylene commingled composite systems

Techniques like thermogravimetric analysis, differential scanning calorimetry, and polarized optical microscopy were used to study the thermal and crystallization behavior of cotton‐polypropylene (PP) commingled composite system. Thermal analysis was used to understand the structure‐property relationship and also to quantify the amount of moisture and volatiles, which causes the deterioration of the composite performance. Thermal stability of the composite was found be intermediate between that of PP and cotton fibers. Presence of treated reinforcements had increased the crystallinity of PP. Also, fibers act as heterogeneous nucleants and favor the early crystallization of PP in the composites. The crystallization and onset crystallization temperature values were increased by the presence of cotton fibers. The theories of heterogeneous nucleation and crystal growth kinetics were used to explain the growth of transcrystalline layer (TCL) of PP on cotton fibers. The interfacial free energy difference for nucleation of PP on fiber was found to be smaller compared with that in the bulk PP. This favors the formation and growth of TCL. The thickness of TCL and radius of the spherulites increase with the increase in the crystallization temperature. Fiber surface roughness and thermal stresses facilitate the growth of transcrystallinity on cotton fiber. POLYM. COMPOS., 31:1487–1494, 2010. © 2009 Society of Plastics Engineers     

A software-based measurement system for testing and analysis of automotive brake squeal

A software-based measurement system using both analogue data acquisition and digital communication via a general-purpose interface bus (GPIB) board has been developed for analysis and evaluation of disc brake squeal. The system is built around a computer and based on commercial software. Brake pressure and torque, rotational speed, five different temperatures, and sound emission are logged once a second. If the sound is characterised as a squeal it is saved to file together with the other parameters. The measurement system is very flexible, allowing for different types of instruments and sensors to be used by adapting the software. Furthermore, the same software is used for evaluation of the collected data. Mechanically, the equipment consists of a complete front wheel suspension where the original brake disc and caliper are mounted in a steel tube chassis. The brake disc is driven by a DC electric motor, while a hydraulic system provides the brake pressure. Brake pressure and rotational speed can be controlled independently.     

Design of Hygroscopic Bioplastic Products Stable in Varying Humidities

Hygroscopic biopolymers like proteins and polysaccharides suffer from humidity-dependent mechanical properties. Because humidity can vary significantly over the year, or even within a day, these polymers will not generally have stable properties during their lifetimes. On wheat gluten, a model highly hygroscopic biopolymer material, it is observed that larger/thicker samples can be significantly more mechanically stable than thinner samples. It is shown here that this is due to slow water diffusion, which, in turn, is due to the rigid polymer structure caused by the double-bond character of the peptide bond, the many bulky peptide side groups, and the hydrogen bond network. More than a year is required to reach complete moisture saturation (≈10 wt.%) in a 1 cm thick plate of glycerol-plasticized wheat gluten, whereas this process takes only one day for a 0.5 mm thick plate. The overall moisture uptake is also retarded by swelling-induced mechanical effects. Hence, hygroscopic biopolymers are better suited for larger/thicker products, where the moisture-induced changes in mechanical properties are smeared out over time, to the extent that the product remains sufficiently tough over climate changes, for example, throughout the course of a year.