Novel ‘Nano in Nano’ Composites for Sustained Drug Delivery: Biodegradable Nanoparticles Encapsulated into Nanofiber Non‐Wovens

Novel ‘nano in nano’ composites consisting of biodegradable polymer nanoparticles incorporated into polymer nanofibers may efficiently modulate drug delivery. This is shown here using a combination of model compound‐loaded biodegradable nanoparticles encapsulated in electrospun fibers. The dye coumarin 6 is used as model compound for a drug in order to simulate drug release from loaded poly(lactide‐co‐glycolide) nanoparticles. Dye release from the nanoparticles occurs immediately in aqueous solution. Dye‐loaded nanoparticles which are encapsulated by electrospun polymer nanofibers display a significantly retarded release.

     

Variation of the ultrafast fluorescence quenching in 2,6-sulfanyl-core-substituted naphthalenediimides by electron transfer

The ultrafast fluorescence quenching of 2,6-sulfanyl-core-substituted naphthalenediimides was investigated by transient spectroscopy. We find a strong dependence of the relaxation on the chemical structure of the substituent. Direct linking of an aryl rest to the sulfur atom leads to a strong red shift of the fluorescence in 1 ps and the disappearance of the emission in 5-7 ps depending on the polarity and viscosity of the solvent. This complex behavior is interpreted with the help of quantum chemical calculations. The calculations suggest that the initial relaxation corresponds to a planarization of the substituents and an associated partial electron transfer. This is followed by a twisting of the phenylsulfanyl substituents out of the molecular plane that allows a complete localization of the electron-donating orbital on the aryl group. Finally the back transfer happens in another 5-7 ps. For an additional methylene spacer group between the sulfur and the aryl, this sequence of relaxation steps is not possible and a simple exponential decay, slower by about 1 order of magnitude, is found.     

High-throughput isotherm determination and thermodynamic modeling of protein adsorption on mixed mode adsorbents

The thermodynamic modeling of protein adsorption on mixed-mode adsorbents functionalized with ligands carrying both hydrophobic and electrostatic groups was undertaken. The developed mixed mode isotherm was fitted with protein adsorption data obtained for five different proteins on four different mixed mode adsorbents by 96-well microtitre plate high throughput batch experiments on a robotic workstation. The developed mixed mode isotherm was capable of describing the adsorption isotherms of all five proteins (having widely different molecular masses and iso-electric points) on the four mixed mode adsorbents and over a wide range of salt concentrations and solution pH, and provided a unique set of physically meaningful parameters for each resin-protein-pH combination. The model could capture the typically observed minimum in mixed mode protein adsorption and predict the precise salt concentration at which this minimum occurs. The possibility of predicting the salt concentration at which minimum protein binding occurs presents new opportunities for designing better elution strategies in mixed mode protein chromatography. Salt-protein interactions were shown to have important consequences on mixed mode protein adsorption when they occur. Finally, the mixed mode isotherm also gave very good fit with literature data of BSA adsorption on a different mixed mode adsorbent not examined in this study. Hence, the mixed mode isotherm formalism presented in this study can be used with any mixed mode adsorbent having the hydrophobic and electrostatic functional groups. It also provides the basis for detailed modeling and optimization of mixed mode chromatographic separation of proteins.     

Magnetic Coupling in Enantiomerically Pure Trinuclear Helicate‐Type Complexes Formed by Hierarchical Self‐Assembly

Based on chiral, enantiomerically pure 7‐[(S)‐phenylethylurea]‐8‐hydroxyquinoline ( 1 ‐H), trinuclear helicate‐type complexes 2 – 5 are formed with divalent transition‐metal cations. X‐ray structural analyses reveal the connection of two monomeric complex units [M( 1 )₃]^? (M=Zn, Mn, Co, Ni) by a central metal ion to form a “dimer”. Due to the enantiopurity of the ligand, the complexes are obtained as pure enantiomers, resulting in pronounced circular dichroism (CD) spectra. Single‐ion effects and intra‐ and intermolecular coupling are observed with dominating ferromagnetic coupling in the case of the cobalt(II) and nickel(II) and dominating antiferromagnetic coupling in the case of the manganese(II) complex.     

Size-exclusion chromatographic protein refolding: fundamentals, modeling and operation

Size-exclusion chromatography (SEC) has proven its capability to refold a variety of proteins using a range of gel filtration column materials, demonstrated in the growing body of experimental evidence. However, little effort has been allocated to the development of mechanistic models describing size-exclusion chromatographic refolding reactors (SECRR). Mechanistic models are important since they provide a link between process variables like denatured and reduced protein feed concentration (C_f,D&;R), flow rate, column length, etc., and performance indicators like refolding yield (Y_N), thereby opening the possibility for in silico design of SECRRs. A critical step, in the formulation of such models, is the selection of an adequate reaction mechanism, which provides the direct link between the separation and the refolding yield. Therefore, in this work we present a methodology using a SEC refolding reactor model, supported by a library of reaction mechanisms, to estimate a suitable reaction scheme using experimental SEC refolding data. SEC refolding data is used since it provides information about the mass distribution of monomers and aggregates after refolding, information not readily available from batch dilution refolding data alone. Additionally, this work presents (1) a systematic analysis of the reaction mechanisms considered using characteristic time analysis and Damköhler maps, revealing (a) the direct effect of a given reaction mechanism on the shape of the SEC refolding chromatogram (number of peaks and resolution) and (b) the effect that the competition between convection, refolding and aggregation is likely to have on the SEC refolding yield; (2) a comparison between the SECR reactor and the batch dilution refolding reactor based on mechanistic modeling, quantitatively showing the advantages of the former over the latter; and (3) the successful application of the modeling based strategy to study the SEC refolding data of an industrially relevant protein. In principle, the presented modeling strategy can be applied to any protein refolded using any gel filtration material, providing the proper mass balances and activity measurements are available.     

Inequalities for the Eigenvalues of Non-Selfadjoint Jacobi Operators

We prove Lieb-Thirring-type bounds on eigenvalues of non-selfadjoint Jacobi operators, which are nearly as strong as those proven previously for the case of selfadjoint operators by Hundertmark and Simon. We use a method based on determinants of operators and on complex function theory, extending and sharpening earlier work of Borichev, Golinskii and Kupin.     

Dissipative localized States with shieldlike phase structure

A novel type of parametrically excited dissipative solitons is unveiled. It differs from the well-known solitons with constant phase by an intrinsically dynamical evolving shell-type phase front. Analytical and numerical characterizations are proposed, displaying quite a good agreement. In one spatial dimension, the system shows three types of stationary solitons with shell-like structure whereas in two spatial dimensions it displays only one, characterized by a π-phase jump far from the soliton position.     

Optimal branching asymmetry of hydrodynamic pulsatile trees

Most of the studies on optimal transport are done for steady state regime conditions. Yet, there exists numerous examples in living systems where supply tree networks have to deliver products in a limited time due to the pulsatile character of the flow, as it is the case for mammalian respiration. We report here that introducing a systematic branching asymmetry allows the tree to reduce the average delivery time of the products. It simultaneously increases its robustness against the inevitable variability of sizes related to morphogenesis. We then apply this approach to the human tracheobronchial tree. We show that in this case all extremities are supplied with fresh air, provided that the asymmetry is smaller than a critical threshold which happens to match the asymmetry measured in the human lung. This could indicate that the structure is tuned at the maximum asymmetry level that allows the lung to feed all terminal units with fresh air.     

Measurability of semimartingale characteristics with respect to the probability law

Given a càdlàg process X$X$ on a filtered measurable space, we construct a version of its semimartingale characteristics which is measurable with respect to the underlying probability law. More precisely, let _Psem${\mathfrak{P}}_{sem}$ be the set of all probability measures P$P$ under which X$X$ is a semimartingale. We construct processes (B^P,C,ν^P)$(B^P,C,{\nu }^P)$ which are jointly measurable in time, space, and the probability law P$P$, and are versions of the semimartingale characteristics of X$X$ under P$P$ for each P∈_Psem$P\in {\mathfrak{P}}_{sem}$. This result gives a general and unifying answer to measurability questions that arise in the context of quasi-sure analysis and stochastic control under the weak formulation.     

Compact groups of positive operators on Banach lattices

In this paper, we study groups of positive operators on Banach lattices. If a certain factorization property holds for the elements of such a group, the group has a homomorphic image in the isometric positive operators which has the same invariant ideals as the original group. If the group is compact in the strong operator topology, it equals a group of isometric positive operators conjugated by a single central lattice automorphism, provided an additional technical assumption is satisfied, for which we have only examples. We obtain a characterization of positive representations of a group with compact image in the strong operator topology, and use this for normalized symmetric Banach sequence spaces to prove an ordered version of the decomposition theorem for unitary representations of compact groups. Applications concerning spaces of continuous functions are also considered.