Correlation between vortex structures and unsteady loads for flapping motion in hover

During the past decade, efforts were made to develop a new generation of unmanned aircrafts, qualified as Micro-Air Vehicles. The particularity of these systems resides in their maximum dimension limited to 15 cm, which, in terms of aerodynamics, corresponds to low Reynolds number flows (Re ≈ 10² to 10⁴). At low Reynolds number, the concept of flapping wings seems to be an interesting alternative to the conventional fixed and rotary wings. Despite the fact that this concept may lead to enhanced lift forces and efficiency ratios, it allows hovering coupled with a low-noise generation. Previous studies (Dickinson et al. in Science 284:1954–1960, 1999) revealed that the flow engendered by flapping wings is highly vortical and unsteady, inducing significant temporal variations of the loads experienced by the airfoil. In order to enhance the aerodynamic performance of such flapping wings, it is essential to give further insight into the loads generating mechanisms by correlating the spatial and temporal evolution of the vortical structures together with the time-dependent lift and drag. In this paper, Time Resolved Particle Image Velocimetry is used as a basis to evaluate both unsteady forces and vortical structures generated by an airfoil undergoing complex motion (i.e. asymmetric flapping flight), through the momentum equation approach and a multidimensional wavelet-like vortex parameterization method, respectively. The momentum equation approach relies on the integration of flow variables inside and around a control volume surrounding the airfoil (Noca et al. in J Fluids Struct 11:345–350, 1997; Unal et al. in J Fluids Struct 11:965–971, 1997). Besides the direct link performed between the flow behavior and the force mechanisms, the load characterization is here non-intrusive and specifically convenient for flapping flight studies thanks to its low Reynolds flows’ sensitivity and adaptability to moving bodies. Results are supported by a vortex parameterization which evaluates the circulation of the multiple vortices generated in such complex flows. The temporal evolution of the loads matches the flow behavior and hence reveals the preponderant inertial force component and that due to vortical structures.     

Photoswitchable Phase Separation and Oligonucleotide Trafficking in DNA Coacervate Microdroplets

Coacervate microdroplets produced by liquid–liquid phase separation have been used as synthetic protocells that mimic the dynamical organization of membrane‐free organelles in living systems. Achieving spatiotemporal control over droplet condensation and disassembly remains challenging. Herein, we describe the formation and photoswitchable behavior of light‐responsive coacervate droplets prepared from mixtures of double‐stranded DNA and an azobenzene cation. The droplets disassemble and reassemble under UV and blue light, respectively, due to azobenzene trans/cis photoisomerisation. Sequestration and release of captured oligonucleotides follow the dynamics of phase separation such that light‐activated transfer, mixing, hybridization, and trafficking of the oligonucleotides can be controlled in binary populations of the droplets. Our results open perspectives for the spatiotemporal control of DNA coacervates and provide a step towards the dynamic regulation of synthetic protocells.     

Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein

Histone methyltransferase DOT1L catalyzes mono-, di- and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect.     

Innovative method for determination of 19 polycyclic aromatic hydrocarbons in food and oil samples using gas chromatography coupled to tandem mass spectrometry based on an isotope dilution approach

An efficient and selective analytical method for the determination and the quantification of 19 polycyclic aromatic hydrocarbons (PAHs) in food and oil has been developed. This method includes the monitoring of 15 PAHs stated as a priority by the EU in their 2005/108 recommendation. The samples were extracted according to a selective extraction step using pressurized liquid extraction followed by a purification with polystyrene-divinylbenzene SPE. Identification and quantification were performed using GC-MS/MS, with an isotope dilution approach using (13)C-labelled PAHs. The novel combination of selective extraction followed by purification provides highly purified analytes combined to a fast and automated method. The advantages of GC-MS/MS as compared to other detection methods are tremendous in terms of sensitivity, selectivity and interpretation facilities. Limits of detection varied between 0.008 and 0.15 microg kg(-1), limits of quantification between 0.025 and 0.915 microg kg(-1) for PAHs in food. The calibration curves showed a good linearity for all PAHs (R(2)>0.99) and precision and recovery were fit for purpose. Trueness of the method was carried out using the US National Institute of Standards and Technology SRM 2977 reference material.     

A Combined Experimental and Theoretical Study of the Versatile Reactivity of an Oxocerium(IV) Complex: Concerted Versus Reductive Addition

A combined experimental and theoretical investigation on the cerium(IV) oxo complex [(L_OEt)₂Ce(=O)(H₂O)] ⋅ MeC(O)NH₂ ( 1 ; L_OEt⁻=[Co(η⁵-C₅H₅){P(O)(OEt)₂}₃]⁻) demonstrates that the intermediate spin-state nature of the ground state of the cerium complex is responsible for the versatility of its reactivity towards small molecules such as CO, CO₂, SO₂, and NO. CASSCF calculations together with magnetic susceptibility measurements indicate that the ground state of the cerium complex is of multiconfigurational character and comprised of 74 % of Ce^IV and 26 % of Ce^III. The latter is found to be responsible for its reductive addition behavior towards CO, SO₂, and NO. This is the first report to date on the influence of the multiconfigurational ground state on the reactivity of a metal–oxo complex.     

Dynamic contrast with reversibly photoswitchable fluorescent labels for imaging living cells

Interrogating living cells requires sensitive imaging of a large number of components in real time. The state-of-the-art of multiplexed imaging is usually limited to a few components. This review reports on the promise and the challenges of dynamic contrast to overcome this limitation.

Interrogating living cells requires sensitive imaging of a large number of components in real time.     

Hydrogen Peroxide-Responsive Triggers Based on Borinic Acids: Molecular Insights into the Control of Oxidative Rearrangement

Arylborinic acids represent new, efficient, and underexplored hydrogen peroxide-responsive triggers. In contrast to boronic acids, two concomitant oxidative rearrangements are involved in the complete oxidation of these species, which might represent a major limitation for an efficient effector (drug or fluorophore) release. Herein, a comprehensive study of H₂O₂-mediated unsymmetrical arylborinic acid oxidation to investigate the factors that could selectively guide their oxidative rearrangement is described. The o-CF₃ substituent was found to be an excellent directing group allowing a complete regioselectivity on borinic acid models. This result was successfully applied to synthesizing new borinic acid-based fluorogenic probes, which exclusively release the fluorescent moiety upon H₂O₂ treatment. These compounds maintained their superior kinetic properties compared to boronic acids, thus further enhancing the potential of arylborinic acids as valuable new H₂O₂-sensitive triggers.     

Importance of the C12 Carbon Chain in the Biological Activity of Rhamnolipids Conferring Protection in Wheat against Zymoseptoria tritici

The hemibiotrophic fungus Zymoseptoria tritici, responsible for Septoria tritici blotch, is currently the most devastating foliar disease on wheat crops worldwide. Here, we explored, for the first time, the ability of rhamnolipids (RLs) to control this pathogen, using a total of 19 RLs, including a natural RL mixture produced by Pseudomonas aeruginosa and 18 bioinspired RLs synthesized using green chemistry, as well as two related compounds (lauric acid and dodecanol). These compounds were assessed for in vitro antifungal effect, in planta defence elicitation (peroxidase and catalase enzyme activities), and protection efficacy on the wheat-Z. tritici pathosystem. Interestingly, a structure-activity relationship analysis revealed that synthetic RLs with a 12 carbon fatty acid tail were the most effective for all examined biological activities. This highlights the importance of the C12 chain in the bioactivity of RLs, likely by acting on the plasma membranes of both wheat and Z. tritici cells. The efficacy of the most active compound Rh-Est-C12 was 20-fold lower in planta than in vitro; an optimization of the formulation is thus required to increase its effectiveness. No Z. tritici strain-dependent activity was scored for Rh-Est-C12 that exhibited similar antifungal activity levels towards strains differing in their resistance patterns to demethylation inhibitor fungicides, including multi-drug resistance strains. This study reports new insights into the use of bio-inspired RLs to control Z. tritici.     

Salinomycin Derivatives Kill Breast Cancer Stem Cells by Lysosomal Iron Targeting

Salinomycin ( 1 ) exhibits a large spectrum of biological activities including the capacity to selectively eradicate cancer stem cells (CSC), making it and its derivatives promising candidates for the development of drug leads against CSC. It has been previously shown that salinomycin and its C20-propargylamine derivative (Ironomycin ( 2 )) accumulate in lysosomes and sequester iron in this organelle. Herein, a library of salinomycin derivatives is reported, including products of C20-amination, C1-esterification, C9-oxidation, and C28-dehydration. The biological activity of these compounds is evaluated against transformed human mammary epithelial HMLER CD24^low/CD44^high cells, a well-established model of breast CSC, and HMLER CD24^high/CD44^low cells deprived of CSC properties. Unlike other structural alterations, derivative 4 , which displays a cyclopropylamine at position C20, showed a strikingly low IC₅₀ value of 23 nm against HMLER CD24^low/CD44^high cells. This study provides highly selective molecules to target the CSC niche, a potential interesting advance for drug development to prevent cancer resistance.     

Free-energy calculations of the host–guest association in grafted supramolecular assemblies

Herein, we investigate the impact of grafting macrocyclic hosts with hydrophobic cavities onto a gold surface on the association with a guest molecule of particular importance to applications for molecular machines. We establish that the increase of the grafted alkyl chain length and number of anchor points strengthens the binding of the guest with the β-cyclodextrin host. This is the opposite effect with the p-sulfonatocalix[4]arene host for which the grafting considerably reduces the strength of the host–guest association. The structural and thermodynamic characterizations, carried out with free energy simulations, are combined to rationalize the differences in the association process in both heterogeneous and homogeneous conditions.