Fundamental rights and humaneness in European private law: the case of health care

This is the final version. Available from Cambridge University Press via the DOI in this recor

Interactions at the silica-peptide interface: influence of the extent of functionalization on the conformational ensemble

In this contribution, the effect of silica particle size (28 and 210 nm) and surface chemistry (i.e. hydroxyl, methyl or amino groups) on peptide binding response is studied with a specific emphasis on the effect of extent of functionalization on binding. Exhaustive characterization of the silica surfaces was crucial for knowledge of the chemistry and topography of the solid surface under study; and thus, to understand their impact on adsorption and the conformational ensemble of the peptides. The extent of surface functionalization was shown to be particle-size dependent, a higher level of 3-aminopropyl functionality being obtained for smaller particles, while a higher degree of methyl group functionality was found on the larger particles. We demonstrated that peptide interactions at the aqueous interface were not only influenced by the surface chemistry but by the extent of functionalization where a 'switch' of peptide adsorption behavior was observed, while changes in the conformational ensemble revealed by circular dichroism were independent of the extent of functionalization. In addition to electrostatic interactions and hydrogen bonding driving interaction at the silica-peptide interface the data obtained suggested that stronger interactions such as hydrophobic and/or covalent interactions may moderate interaction. The insights gained from this peptide-mineral study give a more comprehensive view of mechanisms concerning mineral-peptide interactions which may allow for the design and synthesis of novel (nano)materials with properties tailored for specific applications

A platform for screening abiotic/biotic interactions using indicator displacement assays

This paper describes novel adaptations of optically sectioned planar format assays to screen compounds for their affinities to materials surfaces. The novel platform, which we name Optical sectioned Indicator Displacement Assays (O-IDA), makes use of displaceable dyes in a format adaptable to high-throughput multi-well plate technologies. We describe two approaches; in the first the dye exhibits fluorescence in both the surface-bound and unbound state. In the second, fluorescence is lost upon displacement of the dye from the surface. Half maximal inhibitory concentration (IC50), binding affinity (Ki), and binding free energy (ΔGads) values can be extracted from the raw data. Representative biomolecules were tested for interactions with silica in aqueous environment and ZnO (0001)-Zn and (10-10) facets in a non-aqueous environment. We provide the first experimental values for both the binding of small molecules to silica and the facet-dependent ZnO binding affinity of key amino acids associated with ZnO-specific oligopeptides. The specific data will be invaluable to those studying interactions at interfaces both experimentally and computationally. O-IDA provides a general framework for the high-throughput screening of molecules binding to materials surfaces, which has important applications in drug delivery, (bio-) catalysis, biosensing and biomaterials engineering

Impact of the Conformational Variability of Oligopeptides on the Computational Prediction of Their CD Spectra

Although successful in the structural determination of ordered biomolecules, the spectroscopic investigation of oligopeptides in solution is hindered by their complex and rapidly changing conformational ensemble. The measured circular dichroism (CD) spectrum of an oligopeptide is an ensemble average over all microstates, severely limiting its interpretation, in contrast to ordered biomolecules. Spectral deconvolution methods to estimate the secondary structure contributions in the ensemble are still mostly based on databases of larger ordered proteins. Here, we establish how the interpretation of CD spectra of oligopeptides can be enhanced by the ability to compute the same observable from a set of atomic coordinates. Focusing on two representative oligopeptides featuring a known propensity toward an α-helical and β-hairpin motif, respectively, we compare and cross-validate the structural information coming from deconvolution of the experimental CD spectra, sequence-based de novo structure prediction, and molecular dynamics simulations based on enhanced sampling methods. We find that small conformational variations can give rise to significant changes in the CD signals. While for the simpler conformational landscape of the α-helical peptide de novo structure prediction can already give reasonabl

Strong macroscale supercrystalline structures by 3D printing combined with self-assembly of ceramic functionalized nanoparticles

To translate the exceptional properties of colloidal nanoparticles (NPs) to macroscale geometries, assembly techniques must bridge a 106-fold range of length. Moreover, for successfully attaining a final mechanically robust nanocomposite macroscale material, some of the intrinsic NPs’ properties have to be maintained while minimizing the density of strength-limiting defects. However, the assembly of nanoscale building blocks into macroscopic dimensions, and their effective macroscale properties, are inherently affected by the precision of the conditions required for assembly and emergent flaws including point defects, dislocations, grain boundaries, and cracks. Herein, a direct-write self-assembly technique is used to construct free-standing, millimeter-scale columns comprising spherical iron oxide NPs (15 nm diameter) surface functionalized with oleic acid (OA), which self-assemble into face-centered cubic (FCC) supercrystals in minutes during the direct-writing process. The subsequent crosslinking of OA molecules results in nanocomposites with a maximum strength of 110 MPa and elastic modulus up to 58 GPa. These mechanical properties are interpreted according to the flaw size distribution and are as high as newly engineered platelet-based nanocomposites. The findings indicate a broad potential to create mechanically robust, multifunctional 3D structures by combining additive manufacturing with colloidal assembly.Financial support from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Projektnummer 192346071, SFB 986 -, the National Science Foundation CAREER Award (CMMI-1346638, to A.J.H.), and from the MIT-Skoltech Next Generation Program. A.T.L.T. was supported by a postgraduate fellowship from DSO National Laboratories, Singapore. XRM at the University of Bremen was funded within the CO 1043 12-1 (Call for Major Equipment, XRM)

Cyberspace, Blockchain, Governance:How Technology Implies Normative Power and Regulation

Technologies and their inherent design choices create normative structures that affect governance. This chapter aims to illustrate how blockchain technology in particular introduces new norms into a legal framework. We first analyze the different forms of governance by distinguishing between old and new governance. With a view to code that functions as legal norms, Blockchain technology is particularly suited to create governance structures and mechanisms. However, one needs to be aware of the norms that are implicitly introduced into the legal system by a specific blockchain technology. We look at the blockchain technology that underlies cryptocurrencies such as Bitcoin. This blockchain introduces a decentralized, transparent, cryptographically locked and thus immutable shared ledger. In summary, these design choices have normative powers over the user and over user interaction. If this is indeed the case, then regulators have to actively assess newly introduced digital ledger technology and other technologies for their effect on the normative and legal system.</p

Art. 70-71: Incorporation and making available of standard contract terms

Incorporation of standard terms is a much-debated issue in almost all legal systems. Any legal instrument on contract law therefore must provide an answer as to when terms are incorporated – but answers may vary considerably from one legal system to the next. In this chapter the provisions of the – now withdrawn – proposal for a Common European Sales Law pertaining to the incorporation of standard terms will be compared to the incorporation rules in German and Dutch law. The term ‘incorporation rules’ will be used in a rather broad sense and include rules pertaining to the acceptance of standard terms imposed on the other party, to rules pertaining to surprising and unclear terms, and to rules requiring the party imposing the terms to give the other party a reasonable opportunity to become aware of their content. The focus will therefore be on Article 70 of the CESL and its functional equivalents in German and Dutch law. It is hoped that the European legislator may benefit from this analysis when developing rules on incorporation of standard terms for upcoming legal instruments, such as an instrument for the Digital Single Market