Squalenoyl nanomedicines as potential therapeutics

Nucleoside analogues display significant anticancer or antiviral activity by interfering with DNA synthesis. However, there are some serious restrictions to their use, including their rapid metabolism and the induction of resistance. We have discovered that the linkage of nucleoside analogues to squalene leads to amphiphilic molecules that self-organize in water as nanoassemblies of 100-300 nm, irrespective of the nucleoside analogue used. The squalenoyl gemcitabine exhibited superior anticancer activity in vitro in human cancer cells and gemcitabine-resistant murine leukemia cells, and in vivo in experimental leukemia both after intravenous and oral administration. The squalenoylation of other antiretroviral nucleosides also led to more potent drugs when tested in primary cultures of HIV-infected lymphocytes. Thus, the squalenoylation is an original technology platform for generating more potent anticancer and antiviral nanomedicines.     

Strain-induced self organization of metal-insulator domains in single-crystalline VO2 nanobeams

We investigated the effect of substrate-induced strain on the metal-insulator transition (MIT) in single-crystalline VO(2) nanobeams. A simple nanobeam-substrate adhesion leads to uniaxial strain along the nanobeam length because of the nanobeam's unique morphology. The strain changes the relative stability of the metal (M) and insulator (I) phases and leads to spontaneous formation of periodic, alternating M-I domain patterns during the MIT. The spatial periodicity of the M-I domains can be modified by changing the nanobeam thickness and the Young's modulus of the substrate.     

Going beyond the reflectance limit of cholesteric liquid crystals

Cholesteric liquid-crystalline states of matter are abundant in nature: atherosclerosis, arthropod cuticles, condensed phases of DNA, plant cell walls, human compact bone osteon, and chiral biopolymers. The self-organized helical structure produces unique optical properties. Light is reflected when the wavelength matches the pitch (twice periodicity); cholesteric liquid crystals are not only coloured filters, but also reflectors and polarizers. But, in theory, the reflectance is limited to 50% of the ambient (unpolarized) light because circularly polarized light of the same handedness as the helix is reflected. Here we give details of a cholesteric medium for which the reflectance limit is exceeded. Photopolymerizable monomers are introduced into a cholesteric medium exhibiting a thermally induced helicity inversion, and the blend is then cured with ultraviolet light when the helix is right-handed. Because of memory effects attributable to the polymer network, the reflectance exceeds 50% when measured at the temperature assigned for a cholesteric helix with the same pitch but a left-handed sense before the reaction. As cholesteric materials are used as tunable bandpass filters, reflectors or polarizers and temperature or pressure sensors, novel opportunities to modulate the reflection over the whole light flux range, instead of only 50%, are offered.     

Perturbation analysis for continuous and discrete flow models: a study of the delivery time impact on the optimal buffer level

In this paper, a manufacturing system composed of a single-product machine, a buffer and a stochastic demand is considered. Two models are presented: continuous and discrete flow models including constant delivery times, machine failures and random demands. The objective is to determine the value of the optimal buffer level, for a hedging point policy which minimises the total average cost function. The cost function is the sum of inventory, transportation and lost sales costs. Infinitesimal perturbation analysis is used for optimisation of the failure-prone manufacturing system. The trajectories of buffer level are studied for the continuous and discrete cases and the infinitesimal perturbation analysis estimators are evaluated. These estimators are shown to be unbiased and then they are implemented in an optimisation algorithm which determines the optimal buffer level in the presence of constant delivery time. Numerical results are presented for continuous and discrete flow models and then compared in order to evaluate the application of the infinitesimal perturbation analysis on the discrete flow model.     

Variable energy positron beam study of Xe-implanted uranium oxide

Doppler broadening of annihilation gamma-line combined with a slow positron beam was used to measure the momentum density distribution of annihilating pair in a set of sintered UO₂ samples. The influence of surface polishing, of implantation with 800-keV ¹³⁶Xe²⁺ at fluences of 1 × 10¹⁵ and 1 × 10¹⁶ Xe cm^?2, and of annealing were studied by following the changes of the momentum distribution shape by means of S and W parameters. The program used for this purpose was VEPFIT. At the two fluences in the stoichiometric as-implanted UO₂, formation of Xe bubbles was not detected. The post-implantation annealing and over-stoichiometry in the as-implanted sample caused Xe precipitation and formation of Xe bubbles.     

Model reduction and control of multi-scale reaction-convection processes

This paper focuses on non-isothermal plug flow reactors with fast and slow reactions. These processes are modeled by first order hyperbolic partial differential equations with large and small parameters, which results in stiffness and multi-scale behavior. Through a combination of the method of characteristics and singular perturbation techniques, a model reduction method is developed for obtaining a non-stiff representation of the dominant dynamics of these systems. The application of the method and the advantages of using the reduced models for model-based control are illustrated through a case study.     

Standoff determination of the particle size and concentration of small optical depth clouds based on double-scattering measurements: validation with calibrated target plates and limitations for daytime and nighttime measurements

Diffractive target plates are used to emulate aerosols of known size and concentration. These target plates are used to validate and determine the sensitivity of a multiple-field-of-view lidar signal inversion technique based on double-scattering measurement to retrieve the particle size and the concentration of small optical depth clouds. We estimate that nighttime and daytime quantification (size and concentration) is possible for optical depths as low as 0.005 and 0.016, respectively. The recovery technique limiting factors are the shot noise, the laser features, the optical lens quality, the background illumination level, the background aerosol fluctuations, and the noise introduced by the lidar detector, a gated intensified camera (camera G-ICCD).     

Effect of Oxime Ether Incorporation in Acyl Indole Derivatives on PPAR Subtype Selectivity

Compounds that simultaneously activate peroxisome proliferator‐activated receptor (PPAR) subtypes α and γ have the potential to effectively treat dyslipidemia and type 2 diabetes (T2D) in a single pharmaceutically active molecule. The frequently observed side effects of selective PPARγ agonists, such as edema and weight gain, were expected to be overcome by using additive PPARα activity, leading to dual PPARα/γ agonists with balanced activity for both subtypes. Herein we report the discovery, synthesis, and optimization of a new series of α‐ethoxyphenylpropionic acid bearing 5‐ or 6‐substituted indoles. The incorporation of oxime ethers on the carbonyl portion of the benzoyl group can bring the PPARα/γ potency ratio equal to or slightly greater than one, as is the case for compounds 20 c and 21 a . Compound 20 c shows high efficacy in an ob/ob mouse model of T2D and dyslipidemia, similar to that of rosiglitazone and tesaglitazar, but with a significant increase in body weight gain. In contrast, compound 21 a , less potent as a dual PPARα/γ activator than 20 c , showed an interesting pharmacological profile, as it elicits a decrease in body weight relative to reference compounds.     

Total lipid content, fatty acids and 4-desmethylsterols accumulation in developing fruit of Pistacia lentiscus L. growing wild in Tunisia

This research has determined oil, fatty acid and sterol contents of the Tunisian Pistacialentiscus (Lentisc) fruits during maturation. Low oil accumulation was observed during the first 35 days after the fruiting (DAF) date (from 1.83% to 2.57%). After that, two phases were distinguished (35th until the 60th and 105th to the 145th DAF), where the rate of oil accumulation increased significantly. At the last stage of maturation, the lentisc fruits had the highest percentage of lipid content, 42.54%. The changing profile of fatty acids during maturation had been marked mainly by an increase in oleic acid content (from 19.49% to 50.72%) paralleling a decrease in linoleic acid content (from 42.5% to 21.75%). At the 15th DAF, the alpha-linolenic acid was found with a maximum of 13.81%. At full maturity, the main fatty acids were oleic acid, followed by palmitic and linoleic acid. Other fatty acids were present in trace proportions, such as palmitoleic, stearic, linolenic, gadoleic and arachidic acid. In all stages of ripening only four sterols were identified and quantified. β-Sitosterol was the major 4-desmethylsterol in samples tested, followed by campesterol. Cholesterol and stigmasterol were detected in trace amounts. During the first stage of ripening, the amount of total sterols was about 5.19/100 g of oil. It decreased to 0.43/100 g in the last stage. Sitosterol and campesterol showed nearly the same profile during the ripening of P. lentiscus fruit which could be linked to the relation between these compounds during their biosynthesis.     

Bioefficacy of essential and vegetable oils of Zanthoxylum xanthoxyloides seeds against Acanthoscelides obtectus (Say) (Coleoptera: Bruchidae)

Experiments were conducted in the laboratory to evaluate the bioefficacy of essential and vegetable oils of Zanthoxylum xanthoxyloides (Rutaceae) against Acanthoscelides obtectus (Coleoptera: Bruchidae). The chemical composition of the essential oil and the fatty acid composition of the vegetable oil extracted from the seeds of Z. xanthoxyloides were determined. The insecticidal activities of these oils and the associated aromatized clay powder were evaluated against A. obtectus. Both oils were strongly repellent (100% repellency at 0.501 μl/cm2 essential oil and 3.144 μl/cm2 vegetable oil) and highly toxic (LC?? = 0.118 μl/cm2 for essential oil) to this beetle after contact on filter paper. The vapors of the essential oil were highly toxic to adult insects (LC?? = 0.044 μl/cm3), and the aromatized powder made from clay and essential oil was more toxic (LD?? = 0.137 μl/g) than the essential oil alone (LD?? = 0.193 μl/g) after 2 days of exposure on a common bean. Both oils greatly reduced the F? insect production and bean weight loss and did not adversely affect the bean seed viability. In general, the results obtained indicate that these plant oils can be used for control of A. obtectus in stored beans.