A Highly Potent and Cellularly Active β‐Peptidic Inhibitor of the p53/hDM2 Interaction

New and improved : The incorporation of a 6‐chlorotryptophan (6‐Cl‐Trp) into a β‐peptide (M)‐3₁₄ helix leads to a high‐affinity hDM2 inhibitor, as demonstrated by fluorescence fluctuation analysis at single molecule resolution. When conjugated to penetratin, the newly derived hDM2 binder specifically inhibits tumour cell growth in vitro.

     

Experimental investigation of an industrial scale black liquor gasifier. 1. The effect of reactor operation parameters on product gas composition

A novel technology to mitigate the climate changes and improve energy security is Pressurized Entrained flow High Temperature Black Liquor Gasification (PEHT-BLG) in combination with an efficient fuel synthesis using the resulting syngas. In order to optimise the technology for use in a pulp and paper mill based biorefinery, it is of great importance to understand how the operational parameters of the gasifier affect the product gas composition. The present paper is based on experiments where gas samples were withdrawn from the hot part of a 3 MW entrained flow pressurized black liquor gasifier of semi industrial scale using a high temperature gas sampling system. Specifically, the influence of process conditions on product gas composition (CO₂, CO, H₂, CH₄, H₂S, and COS) were examined by systematically varying the operational parameters: system pressure, oxygen to black liquor equivalence ratio, black liquor flow rate to pressure ratio and black liquor pre-heat temperature. Due to the harsh environment inside the gasification reactor, gas sampling is a challenging task. However, for the purpose of the current study, a specially designed high temperature gas sampling system was successfully developed and used. The results, obtained from two separate experimental campaigns, show that all of the investigated operational parameters have a significant influence on the product gas composition and present valuable information about to the process characteristics.     

Contributing to Understand the Crosstalk between Brain and Periphery in Methylmercury Intoxication: Neurotoxicity and Extracellular Vesicles

Human exposure to methylmercury (MeHg) is currently high in regions such as the Amazon. Understanding the molecular changes associated with MeHg-induced neurotoxicity and the crosstalk with the periphery is essential to support early diagnoses. This work aimed to evaluate cellular and molecular changes associated with behavioral alterations in MeHg acute exposure and the possible changes in extracellular vesicles (EVs) number and S100β content. Adults male Wistar rats were orally treated with 5 mg/kg for four days. Behavioral performance, molecular and histological changes in the cerebellum, and plasma EVs were assessed. MeHg-intoxicated animals performed significantly worse in behavioral tests. MeHg increased the number of GFAP+ cells and GFAP and S100β mRNA expression in the cerebellum but no change in NeuN+ or IBA-1+ cells number was detected. The number of exosomes isolated from plasma were decreased by the metal. S100B mRNA was detected in circulating plasma EVs cargo in MeHg exposure. Though preliminary, our results suggest astrocytic reactivity is displaying a protective role once there was no neuronal death. Interestingly, the reduction in exosomes number could be a new mechanism associated with MeHg-induced neurotoxicity and plasma EVs could represent a source of future biomarkers in MeHg intoxication.     

PdO/Pd system equilibrium phase diagram under a gas mixture of oxygen and nitrogen

The thermal equilibrium decomposition properties of the PdO-Pd system under oxygen partial pressures ranging from 0.1 to 1.0 atm in a total combined pressure of oxygen and nitrogen of 1.0 atm were investigated by means of thermal-gravimetric analyses. The phase diagram of Pd-PdO over the range of oxygen/nitrogen gas concentration was established. The decomposition temperature of PdO to Pd was found to increase with the partial pressure of oxygen.     

The distribution of lithium intercalated in V2O5 thin films studied by XPS and ToF-SIMS

The distribution of lithium in V₂O₅/V lower oxide duplex thin films prepared by thermal oxidation of V metal was analysed by XPS and ToF-SIMS after intercalation at 2.8 V versus Li/Li⁺ and de-intercalation at 3.8 V following cycling between 3.8 and 2.8 V in 1 M LiClO₄-PC. XPS analysis of the intercalated thin film evidenced a partial reduction (43 at.% V⁴⁺) of the V₂O₅ surface, the modification of its electronic structure and the presence of Li, consistent with the formation of the δ-Li_xV₂O₅ (0.9 ≤ x ≤ 1) phase. The Li in-depth distribution measured by ToF-SIMS shows a maximum in the outer layer of V₂O₅, but Li is also found at the oxide film/metal substrate interface indicating its diffusion across the inner layer of V lower oxides. The analyses performed after de-intercalation on the samples cycled 12, 120 and 300 times reveal the effect of aging on the trapping of lithium. A significant reduction (17-22 at.% V⁴⁺) of the V₂O₅ surface was measured after 300 cycles. The Li in-depth distribution shows a maximum at the interface between the outer layer of V₂O₅ and the inner layer of lower oxides. Aging favours the accumulation of lithium at this interface with a resulting enlarged distribution enriching the sub-surface of the outer layer of V₂O₅ and the inner layer of lower oxides after 300 cycles. Lithium is also found, but in smaller quantities, at the oxide film/metal substrate interface. Measurements performed in the non-electrochemically treated surface areas of the de-intercalated samples revealed the same type of modifications, evidencing the diffusion of lithium along the interfaces where it is trapped.     

The reaction of NiO/NiAl2O4 particles with alternating methane and oxygen

The reduction and oxidation behaviour of oxygen carrier particles of NiO and NiAl₂O₄ has been investigated in a fluidized bed reactor as well as a thermogravimetric analyzer (TGA). The particles showed high reactivity and gas yield to CO₂ with methane in the temperature interval 750–950°C. In the fluidized bed the yield to CO₂ was between 90 and 99% using bed masses corresponding to 16–57 kg/MW_fuel. Complementary experiments in a TGA at 750 and 950°C showed a clear reaction of the NiAl₂O₄ with CH₄ at the higher temperature. There was methane released from the reactor at high degrees of solid oxidation, which is likely associated with the lack of Ni‐sites on the particles which can reform the methane. There was some carbon formation during the reduction, although the amount was minor when the gas yield to carbon dioxide and degree of oxidation of the solid was high. A simple reactor model using kinetic data from a previous study predicted the gas yield during the reduction in the fluidized bed experiments with reasonable accuracy. The oxygen carrier system investigated in this work shows high promise for use in a real CLC system, provided that the particle manufacturing process can be scaled up with reasonable cost.     

Volatilization and Transport Mechanisms During Cr Oxidation at 300 °C Studied In Situ by ToF-SIMS

The oxidation of chromium at 300 °C was investigated in situ by ToF-SIMS for three different oxygen pressures (\(P_{{{\text{O}}_{2} }} = 2.0 \times 10^{ - 7}\), 6.0 × 10^?7 and 2.0 × 10^?6 mbar). Sequential exposure to the ¹⁸O isotopic tracer was performed to reveal the governing transport mechanism in the oxide film. The evolution of the oxide thickness was monitored. Volatilization of Cr₂O₃ was evidenced. A model was used to describe the kinetics resulting from the measurements. Both the parabolic and volatilization constants showed a dependence on oxygen partial pressure like \(P_{{{\text{O}}_{2} }}^{ - 1/n}\), with n = 1.9 ± 0.1, indicating a defect structure mainly consisting of oxygen vacancies. The re-oxidation in ¹⁸O₂ shows a growth of the oxide layer at the metal/oxide interface, demonstrating an oxidation process governed by anionic transport via oxygen vacancies. The diffusion coefficient of oxygen in the oxide was determined by fitting the ToF-SIMS depth profiles. It is 2.0 × 10^?18 cm² s^?1.     

Selective Pharmacophore Models of Dopamine D1 and D2 Full Agonists Based on Extended Pharmacophore Features

This study is focused on the identification of structural features that determine the selectivity of dopamine receptor agonists toward D₁ and D₂ receptors. Selective pharmacophore models were developed for both receptors. The models were built by using projected pharmacophoric features that represent the main agonist interaction sites in the receptor (the Ser residues in TM5 and the Asp in TM3), a directional aromatic feature in the ligand, a feature with large positional tolerance representing the positively charged nitrogen in the ligand, and sets of excluded volumes reflecting the shapes of the receptors. The sets of D₁ and D₂ ligands used for modeling were carefully selected from published sources and consist of structurally diverse, conformationally rigid full agonists as active ligands together with structurally related inactives. The robustness of the models in discriminating actives from inactives was tested against four ensembles of conformations generated by using different established methods and different force fields. The reasons for the selectivity can be attributed to both geometrical differences in the arrangement of the features, e.g., different tilt angels of the π system, as well as shape differences covered by the different sets of excluded volumes. This work provides useful information for the design of new D₁ and D₂ agonists and also for comparative homology modeling of D₁ and D₂ receptors. The approach is general and could therefore be applied to other ligand–protein interactions for which no experimental protein structure is available.     

Using discrete optimization for designing dental shade guides

A key criterion in the design of dental shade guides used for matching tooth color is that the shade tabs cover the natural tooth color space as completely as possible with a manageable number of tabs. Earlier studies have designed hypothetical shade guides from a given population of tooth colors described in the CIELAB system using the goal of minimizing the mean coverage error. In this study, we investigate this topic using the goal of maximizing coverage, meaning that as many measured colors as possible were within a given color difference from the nearest shade tab of the guide. We use techniques of linear discrete optimization to determine the positions of the shade tabs and consider both color difference formulas, CIELAB and CIEDE2000, in an exemplary tooth color population. We obtain coverage error and coverage figures for hypothetical shade guides of various numbers of tabs designed with the goal of either minimizing coverage error or maximizing coverage. Results show that discrete optimization and the goal of maximizing coverage could be used to improve shade guide development. The described technique could be used not only for dental shade guides development, but also for any purpose requiring coverage of as many colors as possible while keeping the number of reference colors manageable. © 2009 Wiley Periodicals, Inc. Col Res Appl, 2010     

A cubic ordered, mesoporous carbide-derived carbon for gas and energy storage applications

A hierarchical and highly porous carbide-derived carbon (CDC) was obtained by nanocasting of pre-ceramic precursors into cubic ordered silica (KIT-6) and subsequent chlorination. Resulting CDC replica materials show high methane and n-butane uptake and excellent performance as electrode materials in supercapacitors.