Peptide Amphiphiles and their use in Supramolecular Chemistry

In this thesis the behavior and functionality of peptide amphiphiles at the surface of bilayer vesicles is examined. By controlling the behavior of the surface bound peptides, I was able to construct assemblies which could: 1) release their content (triggered by pH), 2) fuse in a targeted and controlled manner or 3) dock to cells and zebrafish embryosSoft Matter Chemistr

Rabbit serum esterase genotyping and relationship to serum cholesterol response and basal serum HDL cholesterol level

Previous studies have indicated that esterases might be involved in the serum cholesterol response in rabbits. The question addressed in this study is whether in rabbits esterase loci of Linkage Group VI (LG VI) are genetically linked withthe serum cholesterol response to dietary cholesterol or the basal serum HDL cholesterol level. For this purpose the Est-2 and Es-1 genotypes of rabbits in segregating populations derived from a cross between IIIVO/JU (hyporespender andhigh basal serum HDL cholesterol level) and AX/1U (hypettesponder and low basal serum HDL cholesterol level) rabbits were determined. The segregating populations were fed a cholesterol-rich diet for 35 days. Both the Est-2 and Es—1 alleles failed to cosegregate with the serum cholesterol response, whereas a highly significant cosegregation was found with the basal serum HDL cholesterol level. It is concluded that one or more genes of LG VI are regulating the basal serumHDL cholesterol level in rabbits

A sparse spin qubit array with integrated control electronics

Current implementations of quantum computers suffer from large numbers of control lines per qubit, becoming unmanageable with system scale up. Here, we discuss a sparse spin-qubit architecture featuring integrated control electronics significantly reducing the off-chip wire count. This quantum-classical hardware integration closes the feasibility gap towards a CMOS quantum computer.Comment: Paper accompanying an invited talk at the 2019 IEEE International Electron Devices Meeting (IEDM), December 7-11, 201

Junior doctors' experiences with interprofessional collaboration:Wandering the landscape

Context The transition from medical student to junior doctor is challenging. Junior doctors need to become part of the physician community of practice (CoP), while dealing with new responsibilities, tasks and expectations. At the same time, they need to learn how to navigate the frontiers and intersections with the other communities of practice that form the Landscape of Practice (LoP). This study aims to understand how junior doctors experience interprofessional collaboration (IPC) and what elements shape these experiences considering their transition to clinical practice. Methods In this multicentre qualitative study, 13 junior doctors individually drew two rich pictures of IPC experiences, one positive and one negative. A rich picture is a visual representation, a drawing of a particular situation intended to capture the complex and non-verbal elements of an experience. We used semi-structured interviews to deepen the understanding of junior doctors' depicted IPC experiences. We analysed both visual materials and interview transcripts iteratively, for which we adopted an inductive constructivist thematic analysis. Results While transitioning into a doctor, junior doctors become foremost members of the physician CoP and shape their professional identity based on perceived values in their physician community. Interprofessional learning occurs implicitly, without input from the interprofessional team. As a result, junior doctors struggle to bridge the gap between themselves and the interprofessional team, preventing IPC learning from developing into an integrative process. This professional isolation leaves junior doctors wandering the landscape of practice without understanding roles, attitudes and expectations of others. Conclusions Learning IPC needs to become a collective endeavour and an explicit learning goal, based on multisource feedback to take advantage of the expertise already present in the LoP. Furthermore, junior doctors need a safe environment to embrace and reflect on the emotions aroused by interprofessional interactions, under the guidance of experienced facilitators

Comparative genomics highlights symbiotic capacities and high metabolic flexibility of the marine genus Pseudovibrio

Pseudovibrio is a marine bacterial genus members of which are predominantly isolated from sessile marine animals, and particularly sponges. It has been hypothesised that Pseudovibrio spp. form mutualistic relationships with their hosts. Here, we studied Pseudovibrio phylogeny and genetic adaptations that may play a role in host colonization by comparative genomics of 31 Pseudovibrio strains, including 25 sponge isolates. All genomes were highly similar in terms of encoded core metabolic pathways, albeit with substantial differences in overall gene content. Based on gene composition, Pseudovibrio spp. clustered by geographic region, indicating geographic speciation. Furthermore, the fact that isolates from the Mediterranean Sea clustered by sponge species suggested host-specific adaptation or colonization. Genome analyses suggest that Pseudovibrio hongkongensis UST20140214-015BT is only distantly related to other Pseudovibrio spp., thereby challenging its status as typical Pseudovibrio member. All Pseudovibrio genomes were found to encode numerous proteins with SEL1 and tetratricopeptide repeats, which have been suggested to play a role in host colonization. For evasion of the host immune system, Pseudovibrio spp. may depend on type III, IV and VI secretion systems that can inject effector molecules into eukaryotic cells. Furthermore, Pseudovibrio genomes carry on average seven secondary metabolite biosynthesis clusters, reinforcing the role of Pseudovibrio spp. as potential producers of novel bioactive compounds. Tropodithietic acid, bacteriocin and terpene biosynthesis clusters were highly conserved within the genus, suggesting an essential role in survival e.g. through growth inhibition of bacterial competitors. Taken together, these results support the hypothesis that Pseudovibrio spp. have mutualistic relations with sponges

Biotechnological Potential of Bacteria Isolated from the Sea Cucumber Holothuria leucospilota and Stichopus vastus from Lampung, Indonesia

In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung (Indonesia), and 127 bacterial strains were identified by partial 16S rRNA-gene sequencing analysis and compared with the NCBI database. In addition, the overall bacterial diversity from tissue samples of the sea cucumbers H. leucospilota and S. vastus was analyzed using the cultivation-independent Illumina MiSEQ analysis. Selected bacterial isolates were grown to high densities and the extracted biomass was tested against a selection of bacteria and fungi as well as the hepatitis C virus (HCV). Identification of putative bioactive bacterial-derived compounds were performed by analyzing the accurate mass of the precursor/parent ions (MS1) as well as product/daughter ions (MS2) using high resolution mass spectrometry (HRMS) analysis of all active fractions. With this attempt we were able to identify 23 putatively known and two previously unidentified precursor ions. Moreover, through 16S rRNA-gene sequencing we were able to identify putatively novel bacterial species from the phyla Actinobacteria, Proteobacteria and also Firmicutes. Our findings suggest that sea cucumbers like H. leucospilota and S. vastus are promising sources for the isolation of novel bacterial species that produce compounds with potentially high biotechnological potential

Switching the mode of drug release from a reaction-coupled low-molecular-weight gelator system by altering its reaction pathway

Low-molecular-weight hydrogels are attractive scaffolds for drug delivery applications because of their modular and facile preparation starting from inexpensive molecular components. The molecular design of the hydrogelator results in a commitment to a particular release strategy, where either noncovalent or covalent bonding of the drug molecule dictates its rate and mechanism. Herein, we demonstrate an alternative approach using a reaction-coupled gelator to tune drug release in a facile and user-defined manner by altering the reaction pathway of the low-molecular-weight gelator (LMWG) and drug components through an acylhydrazone-bond-forming reaction. We show that an off-the-shelf drug with a reactive handle, doxorubicin, can be covalently bound to the gelator through its ketone moiety when the addition of the aldehyde component is delayed from 0 to 24 h, or noncovalently bound with its addition at 0 h. We also examine the use of an L-histidine methyl ester catalyst to prepare the drugloaded hydrogels under physiological conditions. Fitting of the drug release profiles with the Korsmeyer-Peppas model corroborates a switch in the mode of release consistent with the reaction pathway taken: increased covalent ligation drives a transition from a Fickian to a semi-Fickian mode in the second stage of release with a decreased rate. Sustained release of doxorubicin from the reaction-coupled hydrogel is further confirmed in an MTT toxicity assay with MCF-7 breast cancer cells. We demonstrate the modularity and ease of the reaction-coupled approach to prepare drug-loaded self-assembled hydrogels in situ with tunable mechanics and drug release profiles that may find eventual applications in macroscale drug delivery.Supramolecular & Biomaterials Chemistr

Accidental allergic reactions to food in adolescents and adults: An overview of the factors involved and implications for prevention

Accidental allergic reactions to food are one of the major problems in adult patients diagnosed with food allergy. Such reactions occur frequently, are often severe and are associated with higher medical and non-medical costs. The aim of this Perspective is to provide insight into the different factors involved in the occurrence of accidental allergic reactions and to present an overview of practical implications for effective preventive measures. Several factors affect the occurrence of accidental reactions. These factors are related to the patient, health care, or food. The most important patient-related factors are age, social barriers to disclosing their allergy and non-adherence to the elimination diet. With regards to healthcare, the degree to which clinical practice is tailored to the individual patient is an important factor. The major food-related factor is the absence of adequate precautionary allergen labeling (PAL) guidelines. Since many factors are involved in accidental allergic reactions, different preventive strategies are needed. It is highly recommended that health care be tailored to the individual patient, with regard to education about the elimination diet, support on behavioral and psychosocial aspects, usage of shared decision-making and taking into account health literacy. In addition, it is crucial that steps are taken to improve policies and guidelines for PAL