Concluding Chapter: Globalisation and Innovation Policy

The concluding chapter of the “Small Country Innovation Systems” book develops a comparative analysis that deals with only a very few of the many issues addressed empirically by the ten country case studies. The concluding chapter focuses to some extent on issues related to globalization, but devotes most of its attention to innovation policy. The chapter is intended as a contribution to the comparative analysis of NSIs, conceived in the spirit of ‘appreciative theorizing’.Globalization; Innovation Policy; comparative analysis

Design, synthesis, and evaluation of small molecules and associated bifunctional conjugates targeting the protein–RNA interaction of LIN28 and let-7

RNAs have evolved as prominent targets to tackle challenging topics in the field of chemical biology and medicinal chemistry. Concomitantly, RNA binding proteins (RBPs) are emerging as a new class of drug targets given the essential regulatory functions of RBPs in deciding cell fates. Despite the increasing understanding of the importance of RBPs, limited chemical tools are available to probe the biological functions of RBPs, which raises the need for the development of effective and selective tool compounds targeting RBPs. The LIN28–let-7 interaction is one of the most well-investigated protein–RNA interactions to date. Due to its association with a poor cancer prognosis, LIN28 is a potential new anticancer target. Among the current collection of reported LIN28 inhibitors, potent molecules with clear mechanisms of inhibition are lacking. Additionally, most reported LIN28 inhibitors were identified via high throughput screening of different formats against molecular libraries that were not tailored to target RBPs. Therefore, there is a need to diversify the discovery approaches for RBP-targeting molecules. In this context, small-molecule-based approaches were adopted to engage the challenging topic of targeting the miRNA-binding protein LIN28. Furthermore, we designed an intriguing bifunctional molecule in which an affinity-enhancing moiety was linked to a known LIN28 small-molecule inhibitor to build bifunctional molecules to improve efficacy. Inspired by a rationale, first established in targeting protein–protein interactions, hotspot amino acids were identified through an analysis of LIN28–let-7 crystal structure and a virtual alanine scan to design the corresponding affinity-enhancing moieties consisting of peptides. Conjugation between the designed peptides and the known LIN28 inhibitors led to enhanced binding affinity. In other approaches, we investigated compounds of three chemical scaffolds intending to study the structural features required for LIN28 inhibition, as well as identifying suitable small molecules to be used in the bifunctional molecule approach. After the initial investigation, chromeno[4,3-c]pyrazoles were used as the small molecule components to be conjugated to a peptide moiety through CuAAC chemistry. After screening for optimal linker length and the amino acid composition of the peptide, compound 111 was identified as a potent bifunctional molecule disrupting the LIN28–let-7 interaction. The resulting novel class of chromenopyrazole–peptide conjugates showed improved properties in comparison with peptide-based probes. Therefore, proving the design strategy of the study and underlining the advantageous properties of conjugated entities over nonconjugated inhibitor

The paradox of high R&D input and low innovation output: Sweden

This chapter takes its point of departure in the so-called Swedish paradox, according to which the Swedish NSI is plagued by low pay-off in relation to very high investments in R&D and innovation efforts. Using new data, we show that this paradox is still in operation, i.e. the productivity or efficiency of the Swedish NSI remains low. We also specify the paradox in several respects. By focussing upon nine activities in the NSI, we attempt to explain why and how the paradox operates. The paradox is also related to the moderate growth of labour productivity in Sweden. Further, we show that the paradox is linked to globalization: internationalization of production by Swedish firms has proceeded further than the internationalization of R&D. On the basis of this analysis, we identify strengths and weaknesses of the Swedish NSI – many of which are related to the Swedish paradox. We take account of the history of innovation policy in Sweden and – on the basis of the analysis as a whole -- we identify future policy initiatives that might help to mitigate the Swedish paradox.Innovation; innovation system; Swedish national system of innovation; Swedish paradox

Tilrettelegging for bruk av sansehager på vinterhalvåret for personer med demens

I Norge er det anlagt mange sansehager i tilknytning til institusjoner for personer med demens. Målet er å gi disse personene økt livsglede, ved å gi dem muligheten til å bruke sansene og oppleve mestring. Studier viser at personer med demens, med tilgang til en sansehage opplever mindre depresjon og aggresjon. I tillegg får de som gjør aktiviteter utendørs bedre nattesøvn, enn de som gjør samme aktivitetene innendørs. Det finnes en rekke veiledere for hva en sansehage skal og bør inneholde, men disse veilederne sier lite om hvordan man kan tilrettelegge for å bruke sansehagen gjennom vinterhalvåret. Gjennom casestudie, befaring og samtaler med ansatte, har vi kartlagt hvordan sansehager benyttes på vinterhalvåret per i dag. Oppgaven tar stilling til hva som fungerer godt, og hva som kan forbedres med fokus på tilgjengelighet og sanseopplevelser. Resultatet fra casestudien viser at mangel på tilrettelegging fører til at sansehagene blir lite brukt gjennom vinterhalvåret. Det er få endringer som skal til for å gjøre sansehagene tilgjengelige. Dagens løsninger på snøhåndtering fungerer ikke optimalt. Snøhåndtering er vesentlig for å kunne holde sansehagene åpne i vinterhalvåret. Casestudien viser også at det er lite fokus på å velge beplantning som kan stimulere til sanseopplevelser på vinterstid. Her kan små endringer bidra til økt sanseaktivering. Resultatet fra samtaler med ansatte viser at det er behov for aktiviteter å gjøre eller destinasjoner å gå til for at personer med demens skal ønske å gå ut på vinterhalvåret. Dette gjelder spesielt midtvinters. Det er i tillegg behov for at institusjonene stiller med varme klær som kan lånes ut. På bakgrunn av funnene i oppgaven foreslås noen anbefalinger for hvordan man bør tilrettelegge for tilgjengelighet og sanseopplevelser i sansehagene på vinterstid. Casene i oppgaven er fra Oslo og Sarpsborg, men store deler av anbefalingene vil være overførbare til resten av landet.In Norway, many sensory gardens have been established in connection with institutions for people with dementia. The goal is to give people with dementia increased joy of life by giving them the opportunity to use their senses and experience a feeling of mastery. Studies show that people with dementia who have access to a sensory garden experience less depression and aggression. People with dementia who do activities outside sleep better at night, than those who do the same activities inside. There are already several guidelines that explain what a sensory garden should contain. However, these guidelines say little about how to facilitate the sensory garden for winter use. This thesis maps how sensory gardens are used during the winter today. Through case study, site analysis and conversations with employees. The thesis takes a position on what works well and what could be improved when it comes to accessibility and sensory experiences. The results from the case study shows that lack of facilitation leads to sensory gardens being little used during wintertime. However, only a few changes needs to be done to make the gardens accessible. Today’s solution for snow handling is not working optimally. Snow handling is essential for the sensory garden to be accessible during winter. The case study also shows that little thought is given to sensory experiences during winter when it comes to choosing the plants. Small changes here can make a big difference. The results from conversations with employees show that there is a need for activities to do or destinations to reach, in order to make people with dementia want to go outside in the winter. Especially during midwinter. In addition, there is a need for warm clothes that people with dementia can borrow and use to stay warm outside during winter. Based on the findings in this thesis a recommendation on how to facilitate accessibility and sensory experiences in a sensory garden during winter is proposed. The cases in the thesis are from Oslo and Sarpsborg, but the main part of the guide will be transferable to the rest of Norway.B-L

Lithium Content of 160 Beverages and Its Impact on Lithium Status in Drosophila melanogaster

Lithium (Li) is an important micronutrient in human nutrition, although its exact molecular function as a potential essential trace element has not yet been fully elucidated. It has been previously shown that several mineral waters are rich and highly bioavailable sources of Li for human consumption. Nevertheless, little is known about the extent in which other beverages contribute to the dietary Li supply. To this end, the Li content of 160 different beverages comprising wine and beer, soft and energy drinks and tea and coffee infusions was analysed by inductively coupled plasma mass spectrometry (ICP-MS). Furthermore, a feeding study in Drosophila melanogaster was conducted to test whether Li derived from selected beverages changes Li status in flies. In comparison to the average Li concentration in mineral waters (108 µg/L; reference value), the Li concentration in wine (11.6 ± 1.97 µg/L) and beer (8.5 ± 0.77 µg/L), soft and energy drinks (10.2 ± 2.95 µg/L), tea (2.8 ± 0.65 µg/L) and coffee (0.1 ± 0.02 µg/L) infusions was considerably lower. Only Li-rich mineral water (~1600 µg/L) significantly increased Li concentrations in male and female flies. Unlike mineral water, most wine and beer, soft and energy drink and tea and coffee samples were rather Li-poor food items and thus may only contribute to a moderate extent to the dietary Li supply. A novelty of this study is that it relates analytical Li concentrations in beverages to Li whole body retention in Drosophila melanogaster

The effects of nickel on the structure and functioning of a freshwater plankton community under high dissolved organic carbon conditions : a microcosm experiment

A

How to evaluate the quality of toxicokinetic-Toxicodynamic models in the context of environmental risk assessment

Environmental risk assessment (ERA) of chemicals relies on the combination of exposure and effects assessment. Exposure concentrations are commonly estimated using mechanistic fate models, but the effects side is restricted to descriptive statistical treatment of toxicity data. Mechanistic effect models are gaining interest in a regulatory context, which has also sparked discussions on model quality and good modeling practice. Proposals for good modeling practice of effect models currently focus very much on population and community models, whereas effects models also exist at the individual level, falling into the category of toxicokinetic-toxicodynamic (TKTD) models. In contrast to the higher-level models, TKTD models are usually completely parameterized by fitting them to experimental data. In fact, one of their explicit aims is to replace descriptive methods for data analysis. Furthermore, the construction of these models does not fit into an orderly modeling cycle, given that most TKTD models have been under continuous development for decades and are being applied by many different research groups, for many different purposes. These aspects have considerable consequences for the application of frameworks for model evaluation. For example, classical sensitivity analysis becomes rather meaningless when all model parameters are fitted to a data set. We illustrate these issues with the General Unified Threshold model for Survival (GUTS), relate them to the quality issues for currently used models in ERA, and provide recommendations for the evaluation of TKTD models and their analyses. Integr Environ Assess Manag 2018;00:000-000. ©2018 SETAC

Weltraum-Mikrobiologie

Purpose Approaches in environmental risk assessment for pesticides are becoming more and more realistic. Thereby, risk assessment has to be protective in a way that no long-lasting (adverse) effects on populations will occur in the environment. Since this imperative includes species generally showing high population vulnerability due to their life history traits, prospective risk assessment should be based on realistic worst cases. Based on life history traits, the purpose of the current study was to verify whether a worst case combination of low potential for intrinsic recovery and low ability for recolonisation can be found in the field. Methods Combinations of traits related to dispersal ability and reproduction of macroinvertebrates were investigated using monitoring data from edge of field water bodies in Germany. The relative distribution of traits was analyzed across different agricultural regions and across sites of different potential for exposure to pesticides. Species were sorted in a tiered approach in order to gain a list of realistic worst case species. Results Life history traits were found equally distributed across different regions. Thereby, dispersal ability and voltinism were not randomly combined. Within the data analysed, low dispersal ability was found to be exclusive to semivoltine taxa. Owing to their appearance in reference sites, poor dispersal ability and a long time reproduction, three species were considered potentially worst case. Conclusions The trait approach was found to be suitable in comparing trait distributions within different regions and in compiling a list of critical taxa for consideration in environmental risk assessment