Modulation of Cellular Fate of Vinyl Triarylamines through Structural Fine Tuning: To Stay or Not To Stay in the Mitochondria?

Mitochondria are involved in many cellular pathways and dysfunctional mitochondria are linked to various diseases. Hence efforts have been made to design mitochondria-targeted fluorophores for monitoring the mitochondrial status. However, the factors that govern the mitochondria-targeted potential of dyes are not well-understood. In this context, we synthesized analogues of the TP-2Bzim probe belonging to the vinyltriphenylamine (TPA) class and already described for its capacity to bind nuclear DNA in fixed cells and mitochondria in live cells. These analogues ( TP-1Bzim, TPⁿ-2Bzim, TP¹⁺-2Bzim, TN-2Bzim ) differ in the cationic charge, the number of vinylbenzimidazolium branches and the nature of the triaryl core. Using microscopy, we demonstrated that the cationic derivatives accumulate in mitochondria but do not reach mtDNA. Under depolarisation of the mitochondrial membrane, TP-2Bzim and TP¹⁺-2Bzim translocate to the nucleus in direct correlation with their strong DNA affinity. This reversible phenomenon emphasizes that these probes can be used to monitor ΔΨ_m variations.     

Oxidative Metabolism of Ferrocene Analogues of Tamoxifen: Characterization and Antiproliferative Activities of the Metabolites

Ferrociphenols have been found to have high antiproliferative activity against estrogen‐independent breast cancer cells. The rat and human liver microsome‐mediated metabolism of three compounds of the ferrocifen ( FC ) family, 1,1‐bis(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC1 ), 1‐(4‐hydroxyphenyl)‐1‐(phenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC2 ), and 1‐[4‐(3‐dimethylaminopropoxy)phenyl]‐1‐(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC3 ), was studied. Three main metabolite classes were identified: quinone methides ( QM s) deriving from two‐electron oxidation of FC s, cyclic indene products ( CP s) deriving from acid‐catalyzed cyclization of QM s, and allylic alcohols ( AA s) deriving from hydroxylation of FC s. These metabolites are generated by cytochromes P450 (P450s), as shown by experiments with either N‐benzylimidazole as a P450 inhibitor or recombinant human P450s. Such P450‐dependent oxidation of the phenol function and hydroxylation of the allylic CH₂ group of FC s leads to the formation of QM and AA metabolites, respectively. Some of the new ferrociphenols obtained in this study were found to exhibit remarkable antiproliferative effects toward MDA‐MB‐231 hormone‐independent breast cancer cells.     

Lithium conducting solid electrolyte Li1.3Al0.3Ti1.7(PO4)3 obtained via solution chemistry

NaSICON-type lithium conductor Li_1.3Al_0.3Ti_1.7(PO₄)₃ (LATP) is synthesized with controlled grain size and composition using solution chemistry. After thermal treatment at 850 °C, sub-micronic crystallized powders with high purity are obtained. They are converted into ceramic through Spark Plasma Sintering at 850–1000 °C. By varying the processing parameters, pellet with conductivities up to 1.6 × 10^?4 S/cm with density of 97% of the theoretical density have been obtained. XRD, FEG-SEM, ac-impedance and Vickers indentation were used to characterize the products. The influence of sintering parameters on pellet composition, microstructure and conductivity is discussed in addition to the analysis of the mechanical behavior of the grains interfaces.     

Cognitive behavioral therapy for 4- to 7-year-old children with anxiety disorders: A randomized clinical trial.

Objective: To examine the efficacy of a developmentally appropriate parent–child cognitive behavioral therapy (CBT) protocol for anxiety disorders in children ages 4–7 years. Method: Design: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were randomized to a parent–child CBT intervention (n = 34) or a 6-month wait-list condition (n = 30). Children were assessed by interviewers blind to treatment assignment, using structured diagnostic interviews with parents, laboratory assessments of behavioral inhibition, and parent questionnaires. Analysis: Chi-square analyses of outcome rates and linear and ordinal regression of repeated measures, examining time by intervention interactions. Results: The response rate (much or very much improved on the Clinical Global Impression Scale for Anxiety) among 57 completers was 69% versus 32% (CBT vs. controls), p     

Simulation of the urban climate variations in connection with the transformations of the city of Nantes since the 17th century

The paper seeks to quantify the effect of urban politics on the microclimate of the city of Nantes (France), in particular those initiated by the sanitarians in the mid-19th century to find a remedy for the insalubrity that had been developing with urban densification since the late 17th century. Intensive historical research was first carried out in order to define and date the major transformations undergone by the city, its structure (densification, then widening of the streets, filling of water courses), the lifestyle habits (heating) or the building practices (appearance of stone and paving, higher buildings, insulation). This led to the definition of 5 characteristic states of the city, in 1680, 1756, 1835, 1880 and 1945.     

Molecular dynamics simulations of dislocation interaction with voids in nickel

A high density of voids is expected to form in irradiated face centered cubic metals, which can have a negative impact on the ductility and cause an increasing strength. Molecular dynamics simulations of the interaction between gliding dissociated edge dislocations and voids in nickel have been performed to investigate the effect of the void size, the corresponding detachment mechanism, and dynamic effects of the dislocation on the obstacle strength. As expected, the void strength is observed to increase with increasing void size. The dislocation interaction and detachment process are determined by the applied shear stress, the repulsive interaction between partial dislocations and the image interaction between the partial dislocations and the void surface. For voids with a diameter smaller than 2 nm, the repulsive stress between the partials dominates, resulting in the detachment of the leading partial from the void while the trailing partial remains pinned. Consequently, the detachment process and obstacle strength are controlled by the trailing partial. For voids with a diameter larger than 2 nm, the attraction between the dissociated dislocations and the void dominates causing the detachment process and void strength to be influenced by both partials individually. This transition in detachment process at a void diameter of 2 nm is consistent with other research, and this transition is shown to be dependent on the void separation distance along the dislocation line and the dissociation distance between the partials, thus the stacking fault energy. Finally, by comparing the quasi-static and dynamic simulation results, an estimate for the static detachment stress is proposed in terms of the dynamic detachment stress and the dislocation velocity after detachment.     

Young’s modulus of ceramic particle reinforced aluminium: Measurement by the Impulse Excitation Technique and confrontation with analytical models

Young’s modulus of particulate metal matrix composites with volume fractions of reinforcement ranging from 40% to 60% is measured with the Impulse Excitation Technique. Results are compared with predictions of four common micromechanical mean-field models. Good agreement is obtained with the Torquato identical hard spheres (TIHS) and the generalized self-consistent (GSC) model.     

DESIGNING A RESILIENT WATERSCAPE USING A LIVING LAB AND CATALYZING POLYCENTRIC GOVERNANCE

The both polycentric governance and Living Labs concepts are based on decentralized participatory planning, co-design, and decisionmaking. While the concept of Living Lab is still emerging, the Isar-Plan (2000 ~ 2011) pioneered the approach for selecting, co-designing, and implementing nature-based solutions along the Isar River in Munich, Germany. Despite multiple governing authorities involved in the decisionmaking process of the Isar-Plan, the polycentric governance that led to the success of the project has to date not been analyzed. This paper presents the results of an ex-post-analysis of the Isar-Plan restoration planning process based on stakeholder interviews and a literature review. The contribution describes the evolution of Isar-Plan governance arrangements and discusses the Living Lab approaches to cooperative governance. The analysis demonstrates how polycentricity facilitated trust, learning, and the co-design of a resilient waterscape. The paper concludes that Living Labs can be a way of applying polycentric governance when autonomous and multi-scale decision-makers are collaboratively involved in the design of policy solutions, and vice-versa.     

Conceptual distinctiveness supports detailed visual long-term memory for real-world objects.

Humans have a massive capacity to store detailed information in visual long-term memory. The present studies explored the fidelity of these visual long-term memory representations and examined how conceptual and perceptual features of object categories support this capacity. Observers viewed 2,800 object images with a different number of exemplars presented from each category. At test, observers indicated which of 2 exemplars they had previously studied. Memory performance was high and remained quite high (82% accuracy) with 16 exemplars from a category in memory, demonstrating a large memory capacity for object exemplars. However, memory performance decreased as more exemplars were held in memory, implying systematic categorical interference. Object categories with conceptually distinctive exemplars showed less interference in memory as the number of exemplars increased. Interference in memory was not predicted by the perceptual distinctiveness of exemplars from an object category, though these perceptual measures predicted visual search rates for an object target among exemplars. These data provide evidence that observers' capacity to remember visual information in long-term memory depends more on conceptual structure than perceptual distinctiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of hydrothermal ripening on the photoluminescence properties of pure and doped cerium oxide nanoparticles

We synthesized and characterized a set of undoped and doped cerium oxide nanoparticles with the following chemical formula: Ce_1−xM_xO_2−(x/2) (M: Y or Gd and x = 0 or 0.15) by different coprecipitation protocols at room temperature. Room temperature photoluminescence spectra were similar whatever the protocols and doping. After hydrothermal ripening at neutral pH, a moderate but significant particle growth was observed for doped particles whereas undoped ones remained the same. Simultaneously, the photoluminescence band at 400 nm was significantly red-shifted and practically vanished for doped particles whereas it was only slightly weaker and shifted for pure ceria. All other bands in the same region were much less affected: the bands at 363 and 378 nm became more intense, the shoulder at 420 nm remained roughly unchanged. These phenomena were observed systematically whatever the coprecipitation protocol. As a consequence, the band at 400 nm can be specifically attributed to surface defects that disappear during growth under hydrothermal conditions.