Polymeric particulates to improve oral bioavailability of peptide drugs

Oral administration remains the most convenient way of delivering drugs. Recent advances in biotechnology have produced highly potent new molecules such as peptides, proteins and nucleic acids. Due to their sensitivity to chemical and enzymatic hydrolysis as well as a poor cellular uptake, their oral bioavailability remains very low. Despite sophisticated new delivery systems, the development of a satisfactory oral formulation remains a challenge. Among the possible strategies to improve the absorption of drugs, micro- and nanoparticles represent an exciting approach to enhance the uptake and transport of orally administered molecules. Increasing attention has been paid to their potential use as carriers for peptide drugs for oral administration. This article reviews the most common manufacturing methods for polymeric particles and the physiology of particle absorption from the gastrointestinal (GI) tract. In a second part, the use of polymeric particulate systems to improve the oral absorption of insulin is discussed.     

Poisson integrals associated to Dunkl operators for dihedral groups

In this paper we study the boundary behavior of Poisson integrals associated to Dunkl differential-difference operators for dihedral groups and the boundary integral representations for functions on the unit disc of annihilated by the Laplace operator corresponding to these differential-difference operators.

     

Synthesis of Branched Polymers under Continuous‐Flow Microprocess: An Improvement of the Control of Macromolecular Architectures

Polymerization reactions can benefit from continuous‐flow microprocess in terms of kinetics control, reactants mixing or simply efficiency when high‐throughput screening experiments are carried out. In this work, we perform for the first time the synthesis of branched macromolecular architecture through a controlled/‘living' polymerization technique, in tubular microreactor. Just by tuning process parameters, such as flow rates of the reactants, we manage to generate a library of polymers with various macromolecular characteristics. Compared to conventional batch process, polymerization kinetics shows a faster initiation step and more interestingly an improved branching efficiency. Due to reduced diffusion pathway, a characteristic of microsystems, it is thus possible to reach branched polymers exhibiting a denser architecture, and potentially a higher functionality for later applications.     

Characterisation of ethoxylated fatty chains of anionic surfactants and determination of residual ethoxylated fatty alcohols

Bachus et al. [1] recently described a new derivatisation method using 2-furoyl chloride for the characterisation of mixtures of polyethoxylated alcohols and their corresponding sulfates. This paper deals with the control of the derivatisation steps; hydrolysis and extraction conditions were optimised. The method is extended to the characterisation of alkyl sulfosuccinates, alkyl sulfoacetates and alkyl phosphates and to the analysis of residual polyethoxylated alcohols in surfactants. Extraction of non-ionic compounds using solid-phase extraction cartridges was performed before derivatisation. Residual amounts of alcohol were determined in five commercial anionic surfactants. Moreover, direct derivatisation without preliminary SPE in the same anionic surfactants proved to be efficient for dry samples.     

Neuron participation in a synchrony-encoding assembly

Background

Caenorhabditis elegans actively crawls down thermal gradients until it reaches the temperature of its prior cultivation, exhibiting what is called cryophilic movement. Implicit in the worm's performance of cryophilic movement is the ability to detect thermal gradients, and implicit in regulating the performance of cryophilic movement is the ability to compare the current temperature of its surroundings with a stored memory of its cultivation temperature. Several lines of evidence link the AFD sensory neuron to thermotactic behavior, but its precise role is unclear. A current model contends that AFD is part of a thermophilic mechanism for biasing the worm's movement up gradients that counterbalances the cryophilic mechanism for biasing its movement down gradients.

Results

We used tightly-focused femtosecond laser pulses to dissect the AFD neuronal cell bodies and the AFD sensory dendrites in C. elegans to investigate their contribution to cryophilic movement. We establish that femtosecond laser ablation can exhibit submicrometer precision, severing individual sensory dendrites without causing collateral damage. We show that severing the dendrites of sensory neurons in young adult worms permanently abolishes their sensory contribution without functional regeneration. We show that the AFD neuron regulates a mechanism for generating cryophilic bias, but we find no evidence that AFD laser surgery reduces a putative ability to generate thermophilic bias. In addition, although disruption of the AIY interneuron causes worms to exhibit cryophilic bias at all temperatures, we find no evidence that laser killing the AIZ interneuron causes thermophilic bias at any temperature.

Conclusion

We conclude that laser surgical analysis of the neural circuit for thermotaxis does not support a model in which AFD opposes cryophilic bias by generating thermophilic bias. Our data supports a model in which the AFD neuron gates a mechanism for generating cryophilic bias.     

The Lie algebra of type G2 is rational over its quotient by the adjoint action

Let G be a split simple group of type $G_2$ over a field k, and let $\mathfrak{g}$ be its Lie algebra. Answering a question of J.-L. Colliot-Thélène, B. Kunyavski?, V.L. Popov, and Z. Reichstein, we show that the function field $k(\mathfrak{g})$ is generated by algebraically independent elements over the field of adjoint invariants $k{(\mathfrak{g})}^G$.     

Law of the iterated logarithm for the periodogram

We consider the almost sure asymptotic behavior of the periodogram of stationary and ergodic sequences. Under mild conditions we establish that the limsup of the periodogram properly normalized identifies almost surely the spectral density function associated with the stationary process. Results for a specified frequency are also given. Our results also lead to the law of the iterated logarithm for the real and imaginary parts of the discrete Fourier transform. The proofs rely on martingale approximations combined with results from harmonic analysis and techniques from ergodic theory. Several applications to linear processes and their functionals, iterated random functions, mixing structures and Markov chains are also presented.