Bayesian estimation of incompletely observed diffusions

We present a general framework for Bayesian estimation of incompletely observed multivariate diffusion processes. Observations are assumed to be discrete in time, noisy and incomplete. We assume the drift and diffusion coefficient depend on an unknown parameter. A data-augmentation algorithm for drawing from the posterior distribution is presented which is based on simulating diffusion bridges conditional on a noisy incomplete observation at an intermediate time. The dynamics of such filtered bridges are derived and it is shown how these can be simulated using a generalised version of the guided proposals introduced in Schauer, Van der Meulen and Van Zanten (2017, Bernoulli 23(4A)).     

Enantioselective synthesis of ferrocenyl nucleoside analogues with apoptosis-inducing activity

[reaction: see text] As a contribution to bioorganometallic chemistry, an enantioselective synthesis of novel carbocyclic nucleoside analogues with a ferroceno-cyclopentene backbone was developed. Diastereoselective cuprate 1,4-addition or Mukaiyama-Michael addition to a planar-chiral enoate (ethyl (E)-2-[2-methoxycarbonyl-ferrocenyl]-acrylate) allowed for the introduction of different side chains (RCH(2)). Other important steps include a Dieckmann cyclization and the attachment of the nucleobase (NB) in an iron-assisted S(N)1 reaction. Some of the target compounds were shown to exhibit significant apoptosis-inducing activity (LD(50) = 10-20 microM) against tumor cells.     

Force-field dependence of the conformational properties of α,ω-dimethoxypolyethylene glycol

A molecular dynamics (MD) study of α,ω-dimethoxypolyethylene glycol has been carried out under various conditions with respect to solvent composition, ionic strength, chain length, force field and temperature. A previous MD study on a 15-mer of polyethyleneglycol (PEG) suggested a helical equilibrium structure that was stabilised by hydrogen bonding and bridging water molecules. Experiments show that PEG is highly soluble in water, and indicate that clustering is not favoured. In the present study using different force fields, the GROMOS force fields 45A3 and 53A6, a variation on the latter 53A6_OE, and a force field by Smith et al. produced different results. For the GROMOS force fields 45A3 and 53A6 no helical structure was found, but formation of more or less compact random coils in aqueous solution due to hydrophobic interactions was observed. For the other two force fields used, α,ω-dimethoxypolyethylene glycol stayed flexible and more or less elongated in aqueous solution, more in agreement with experimental observations and the previous MD study.     

Convergence of subdiagonal Padé approximations of C 0-semigroups

Let ${(r_{n})_{n \in \mathbb{N}}}$ be the sequence of subdiagonal Padé approximations of the exponential function. We prove that for ?A the generator of a uniformly bounded C ₀-semigroup T on a Banach space X, the sequence ${(r_{n}(-t A))_{n \in \mathbb{N}}}$ converges strongly to T(t) on D(A ^α ) for ${\alpha>\frac{1}{2}}$ . Local uniform convergence in t and explicit convergence rates in n are established. For specific classes of semigroups, such as bounded analytic or exponentially γ -stable ones, stronger estimates are proved. Finally, applications to the inversion of the vector-valued Laplace transform are given.     

The prescribed output pattern regulates the modular structure of flow networks

Modules are common functional and structural properties of many social, technical andbiological networks. Especially for biological systems it is important to understand howmodularity is related to function and how modularity evolves. It is known thattime-varying or spatially organized goals can lead to modularity in a simulated evolutionof signaling networks. Here, we study a minimal model of material flow in networks. Wediscuss the relation between the shared use of nodes, i.e., the cooperativity of modules,and the orthogonality of a prescribed output pattern. We study the persistence ofcooperativity through an evolution of robustness against local damages. We expect theresults to be valid for a large class of flow-based biological and technical networks.     

Helicoidal Patterning of Nanorods with Polymer Ligands

Chiral packing of ligands on the surface of nanoparticles (NPs) is of fundamental and practical importance, as it determines how NPs interact with each other and with the molecular world. Herein, for gold nanorods (NRs) capped with end‐grafted nonchiral polymer ligands, we show a new mechanism of chiral surface patterning. Under poor solvency conditions, a smooth polymer layer segregates into helicoidally organized surface‐pinned micelles (patches). The helicoidal morphology is dictated by the polymer grafting density and the ratio of the polymer ligand length to nanorod radius. Outside this specific parameter space, a range of polymer surface structures was observed, including random, shish‐kebab, and hybrid patches, as well as a smooth polymer layer. We characterize polymer surface morphology by theoretical and experimental state diagrams. The helicoidally organized polymer patches on the NR surface can be used as a template for the helicoidal organization of other NPs, masked synthesis on the NR surface, as well as the exploration of new NP self‐assembly modes.     

Application of affinity capillary electrophoresis for charge heterogeneity profiling of biopharmaceuticals

Charge heterogeneity profiling is important for the quality control (QC) of biopharmaceuticals. Because of the increasing complexity of these therapeutic entities [1], the development of alternative analytical techniques is needed. In this work, flow‐through partial‐filling affinity capillary electrophoresis (FTPFACE) has been established as a method for the analysis of a mixture of two similar monoclonal antibodies (mAbs). The addition of a specific ligand results in the complexation of one mAb in the co‐formulation, thus changing its migration time in the electric field. This allows the characterization of the charged variants of the non‐shifted mAb without interferences. Adsorption of proteins to the inner capillary wall has been circumvented by rinsing with guanidine hydrochloride before each injection. The presented FTPFACE approach requires only very small amounts of ligands and provides complete comparability with a standard CZE of a single mAb.