Accumulation of silver nanoparticles by cultured primary brain astrocytes

Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4 h with identical amounts of silver as AgNO(3) already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4?°C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37?°C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways.     

Quantification of extreme thermal gradients during in situ transmission electron microscope heating experiments

Studies on materials affected by large thermal gradients and rapid thermal cycling are an area of increasing interest, driving the need for real time observations of microstructural evoultion under transient thermal conditions. However, current in situ transmission electron microscope (TEM) heating stages introduce uniform temperature distributions across the material during heating experiments. Here, a methodology is described to generate thermal gradients across a TEM specimen by modifying a commercially available MEMS-based heating stage. It was found that a specimen placed next to the metallic heater, over a window, cut by FIB milling, does not disrupt the overall thermal stability of the device. Infrared thermal imaging (IRTI) experiments were performed on unmodified and modified heating devices, to measure thermal gradients across the device. The mean temperature measured within the central viewing area of the unmodified device was 3–5% lower than the setpoint temperature. Using IRTI data, at setpoint temperatures ranging from 900 to 1,300°C, thermal gradients at the edge of the modified window were calculated to be in the range of 0.6 × 10⁶ to 7.0 × 10⁶°C/m. Additionally, the Ag nanocube sublimation approach was used, to measure the local temperature across a FIB-cut Si lamella at high spatial resolution inside the TEM, and demonstrate “proof of concept” of the modified MEMS device. The thermal gradient across the Si lamella, measured using the latter approach was found to be 6.3 × 10⁶°C/m, at a setpoint temperature of 1,000°C. Finally, the applicability of this approach and choice of experimental parameters are critically discussed.     

Assessing the impact of changes in landuse and management practices on the diffuse pollution and retention of nitrate in a riparian floodplain

In many European lowland rivers and riparian floodplains diffuse nutrient pollution is causing a major risk for the surface waters and groundwater to not achieve a good status as demanded by the European Water Framework Directive. In order to delimit the impact of diffuse nutrient pollution substantial and often controversial changes in landuse and management are under discussion. In this study we investigate the impact of two complex scenarios considering changes in landuse and land management practices on the nitrate loads of a typical lowland stream and the riparian groundwater in the North German Plains. Therefore the impacts of both scenarios on the nitrate dynamics, the attenuation efficiency and the nitrate exchange between groundwater and surface water were investigated for a 998.1 km(2) riparian floodplain of the Lower and Central Havel River and compared with the current conditions. Both scenarios target a substantial improvement of the ecological conditions and the water quality in the research area but promote different typical riparian landscape functions and consider a different grade of economical and legal feasibility of the proposed measures. Scenario 1 focuses on the optimisation of conservation measures for all natural resources of the riparian floodplain, scenario 2 considers measures in order to restore a good status of the water bodies mainly. The IWAN model was setup for the simulation of water balance and nitrate dynamics of the floodplain for a perennial simulation period of the current landuse and management conditions and of the scenario assumptions. The proposed landuse and management changes result in reduced rates of nitrate leaching from the root zone into the riparian groundwater (85% for scenario 1, 43% for scenario 2). The net contributions of nitrate from the floodplain can be reduced substantially for both scenarios. In case of scenario 2 a decrease by 70% can be obtained. For scenario 1 the nitrate exfiltration rates to the river drop even below the infiltration rates from the river, the riparian floodplain in that scenario represents a net sink for river derived nitrate. As the nitrate contributions from the investigated riparian floodplain represent only a small proportion of the total nitrate loads within the river (1% p.a.) the overall impact of the scenario measures on the nitrate loads at the river outlet remains small. However, during the ecologically most sensitive summer periods under current conditions nitrate contributions from the riparian groundwater of the Lower and Central Havel River (which covers only 5% of the area of the Havel catchment) represent more than 20% of the river loads. By the implementation of the investigated landuse changes within the research area the groundwater derived nitrate contributions could be halved to only 10% during summer baseflow conditions.     

Reference-free PRFS MR-thermometry using near-harmonic 2-D reconstruction of the background phase

Proton resonance frequency shift (PRFS) MR thermometry (MRT) is the generally preferred method for monitoring thermal ablation, typically implemented with gradient-echo (GRE) sequences. Standard PRFS MRT is based on the subtraction of a temporal reference phase map and is, therefore, intrinsically sensitive to tissue motion (including deformation) and to external perturbation of the magnetic field. Reference-free (or reference-less) PRFS MRT has been previously described by Rieke and was based on a 2-D polynomial fit performed on phase data from outside the heated region, to estimate the background phase inside the region of interest. While their approach was undeniably a fundamental progress in terms of robustness against tissue motion and magnetic perturbations, the underlying mathematical formalism requires a thick unheated border and may be subject to numerical instabilities with high order polynomials. A novel method of reference-free PRFS MRT is described here, using a physically consistent formalism, which exploits mathematical properties of the magnetic field in a homogeneous or near-homogeneous medium. The present implementation requires as input the MR GRE phase values along a thin, nearly-closed and unheated border. This is a 2-D restriction of a classic Dirichlet problem, working on a slice per slice basis. The method has been validated experimentally by comparison with the “ground truth” data, considered to be the standard PRFS method for static ex vivo tissue. “Zero measurement” of the gradient-echo phase baseline was performed in healthy volunteer liver with rapid acquisition (300 ms/image). In vivo data acquired in sheep liver during MR-guided high intensity focused ultrasound (MRgHIFU) sonication were post-processed as proof of applicability in a therapeutic scenario. Bland and Altman mean absolute difference between the novel method and the “ground truth” thermometry in ex vivo static tissue ranged between 0.069 °C and 0.968 °C, compared to the inherent “white” noise SD of 0.23 °C. The accuracy and precision of the novel method in volunteer liver were found to be on average 0.13 °C and respectively 0.65 °C while the inherent “white” noise SD was on average 0.51 °C. The method was successfully applied to large ROIs, up to 6.2 cm inner diameter, and the computing time per slice was systematically less than 100 ms using C++. The current limitations of reference-free PRFS thermometry originate mainly from the need to provide a nearly-closed border, where the MR phase is artifact-free and the tissue is unheated, plus the potential need to reposition that border during breathing to track the motion of the anatomic zone being monitored.A reference-free PRFS thermometry method based on the theoretical framework of harmonic functions is described and evaluated here. The computing time is compatible with online monitoring during local thermotherapy. The current reference-free MRT approach expands the workflow flexibility, eliminates the need for respiratory triggers, enables higher temporal resolution, and is insensitive to unique-event motion of tissue.     

The Facile Synthesis and Energetic Properties of an Energetic Furoxan Lacking Traditional “Explosophore” Moieties: (E,E)‐3,4‐bis(oximomethyl)furoxan (DPX1)

Energetic furoxan (E,E)‐3,4‐bis(oximomethyl)furoxan (DPX1) was synthesized in 75 % yield, using a literature procedure, from a precursor readily available in one step from nitromethane. DPX1 was characterized for the first time as an energetic material in terms of calculated performance (V_det = 8245 m s⁻¹; p_C‐J = 29.0 GPa) and measured sensitivity (impact: 10 J; friction: 192 N; T_dec: 168 °C). DPX1 exhibits a sensitivity less than that of RDX, and a performance significantly higher than 2,4,6‐trinitrotoluene (TNT).     

Cinnamon and health

Cinnamon has been used as a spice and as traditional herbal medicine for centuries. The available in vitro and animal in vivo evidence suggests that cinnamon has anti-inflammatory, antimicrobial, antioxidant, antitumor, cardiovascular, cholesterol-lowering, and immunomodulatory effects. In vitro studies have demonstrated that cinnamon may act as an insulin mimetic, to potentiate insulin activity or to stimulate cellular glucose metabolism. Furthermore, animal studies have demonstrated strong hypoglycemic properties. However, there are only very few well-controlled clinical studies, a fact that limits the conclusions that can be made about the potential health benefits of cinnamon for free-living humans. The use of cinnamon as an adjunct to the treatment of type 2 diabetes mellitus is the most promising area, but further research is needed before definitive recommendations can be made.     

Rapid,Label-Free Screening of Diverse Biotransformations by Flow-Injection Mass Spectrometry

Mass spectrometry-based high-throughput screening methods combine the advantages of photometric or fluorometric assays and analytical chromatography, as they are reasonably fast (throughput ≥1 sample/min) and broadly applicable, with no need for labelled substrates or products. However, the established MS-based screening approaches require specialised and expensive hardware, which limits their broad use throughout the research community. We show that a more common instrumental platform, a single-quadrupole HPLC-MS, can be used to rapidly analyse diverse biotransformations by flow-injection mass spectrometry (FIA-MS), that is, by automated infusion of samples to the ESI-MS detector without prior chromatographic separation. Common organic buffers can be employed as internal standard for quantification, and the method provides readily validated activity and selectivity information with an analytical run time of one minute per sample. We report four application examples that cover a broad range of analyte structures and concentrations (0.1–50 mM before dilution) and diverse biocatalyst preparations (crude cell lysates and whole microbial cells). Our results establish FIA-MS as a versatile and reliable alternative to more traditional methods for screening enzymatic reactions.     

Reduction of 3‐Substituted 1‐Arylcyclobutanols

A useful and specific method for the the title reaction ( 1 → 2 ) involves treatment with NaBH₄ in CF₃COOH whereas other procedures from the literature yield hard‐toseparate mixtures. 1‐Arylcyclohexanols 3 give mainly cyclohexenes with borohydride/trifluoroacetic acid. Their reduction to compounds 4 ,however, is possible with MeSO₃H/NaBH₄.