This paper describes a fundamental challenge when using silicon oxide nanochannels for analytical systems, namely the occurrence of a strong proton release or proton uptake from the walls in any transient situation such as channel filling. Experimentally, when fluorescein solutions were introduced into silicon oxide nanochannels through capillary pressure, a distinct bisection of the fluorescence was observed, the zone of the fluid near the entrance fluoresced, while the zone near the meniscus, was dark. The ratio between the zones was found to be constant in time and to depend on ionic strength, pH, and the presence of a buffer and its characteristics. Theoretically, using the Gouy-Chapman-Stern model of the electrochemical double layer, we demonstrate that this phenomenon can be effectively modeled as a titration of the solution by protons released from silanol groups on the walls, as a function of the pH and ionic strength of the introduced solution. The results demonstrate the dominant influence of the surface on the fluid composition in nanofluidic experiments, in transient situations such as filling, and changes in solvent properties such as the pH or ionic strength. The implications of these fundamental properties of silicon oxide nanochannels are important for analytical strategies and in particular the analysis of complex biological samples.

Gels were produced using kappa-, iota-, or hybrid-carrageenan at a low (0.2-0.25%) and a high (0.7-1.0%) dosage in skim milk. The microstructure of carrageenan and protein was observed by confocal laser scanning microscopy using direct immunostaining. Additionally, rheology was used to characterize the gels. The low kappa- and iota-carrageenan dosages resulted in gels with a fine stranded carrageenan-protein microstructure and emulsion-like inclusions, while the high dosages resulted in strongly flocculated microstructures. Hybrid-carrageenan exhibited flocculation at both dosages. When using iota- and hybrid-carrageenan at a high dosage and kappa-carrageenan at both dosages, the gel characteristics were dominated by carrageenan-carrageenan interactions. On the other hand, the gel with a low dosage of iota-carrageenan in milk was barely fusible, indicating the presence of a true coupled network. We suggest that kappa-, iota-, and hybrid-carrageenan all interact with casein micelles but that the impact of this interaction on the total gel properties varied.

Research through design (RTD) is a frequently used concept in the daily practice of education and research in the field of landscape architecture. RTD as a concept usually refers to a research method in which spatial design plays the leading role. The underlying premise is that design is a form of research and involves a culture of thought. There is a dearth of literature addressing the act of design as a research process in the field of landscape architecture. This article contributes to the discourse by addressing how spatial design can be applied as a research strategy. We define design as a form of research and identify how design relates to other more conventional definitions of research methods. We elaborate on RTD as a concept and the types of knowledge that it generates. The article also addresses the design process and design methods in landscape architecture. Criteria for accepted, responsible research are translated into practical requirements that can guide RTD processes in academic and professional contexts. To continue developing landscape architecture as a design discipline, it is important that the theoretical, methodological, and technical foundations of spatial design are clarified and strengthened. KEYWORDS Research through design, research by design, spatial design, research methods, knowledge acquisition PEER REVIEW STATEMENT This submission was peer-reviewed by four reviewers selected by the Editorial Office. Their contributions are gratefully acknowledged and appreciated.

Background: Spinocerebellar ataxia type 3 is a rare neurodegenerative disease caused by a CAG repeat expansion in the ataxin-3 gene. Although no curative therapy is yet available, preclinical gene-silencing approaches to reduce polyglutamine (polyQ) toxicity demonstrate promising results. In view of upcoming clinical trials, quantitative and easily accessible molecular markers are of critical importance as pharmacodynamic and particularly as target engagement markers. Objective: We aimed at developing an ultrasensitive immunoassay to measure specifically polyQ-expanded ataxin-3 in plasma and cerebrospinal fluid (CSF).