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Sverige befinner sig i en tid av ständigt ökandekoldioxidutsläpp och byggbranschen specifiktstår för drygt en femtedel av dessa. En förändringmåste till för att råda bot på den rivningshungersom råder där det som rivs och deponeras interäknas in i den nya byggnadens miljöklassningvilket leder till att den verkliga miljöpåverkanförblir dold.Friska hus som endast stått färdiga i omkring50 år får lämna plats åt nya hus när staden växeroch kraven ökar men finns det en annan väg attgå? Kan delar av eller hela hus behållas och fånya liv men med annat syfte?Denna rapport undersöker möjligheten attkonvertera befintliga kontorsbyggnader till modernabostäder som följer dagens regelverk menockså är ett attraktivt boende för att på så sättkunna minska rivningsmassorna och därmedäven sänka koldioxidutsläppen.Rapporten fokuserar på objekt i Stockholmsområdetför att möjliggöra platsbesök men dekonverteringsförslag som tas fram ska vara applicerbarapå objekt i hela landet. En avgränsninggörs dock för flera faktorer såsom ekonomiskaaspekter, bärande konstruktionens skick ochspecifika tekniska lösningar. Med detta sagtönskar rapporten inspirera fastighetsägare attbevara och renovera befintliga byggnader ochpresenterar därför rimliga lösningar på de problemsom kan dyka upp.Förslag på möjlig planlösning, U-värden förytterväggar i befintligt skick och föreslagen förändringav detta skikt, håltagning i bjälklag föratt skapa utrymme för trapphus, hiss och schaktsamt en övergripande gestaltning av husets fasadoch omkringliggande omgivning, är delar avdet som presenteras i rapporten.

Interfacing electronics with neural tissue is crucial for understanding complex biological functions, but conventional bioelectronics consist of rigid electrodes fundamentally incompatible with living systems. The difference between static solid-state electronics and dynamic biological matter makes seamless integration of the two challenging. To address this incompatibility, we developed a method to dynamically create soft substrate-free conducting materials within the biological environment. We demonstrate in vivo electrode formation in zebrafish and leech models, using endogenous metabolites to trigger enzymatic polymerization of organic precursors within an injectable gel, thereby forming conducting polymer gels with long-range conductivity. This approach can be used to target specific biological substructures and is suitable for nerve stimulation, paving the way for fully integrated, in vivo-fabricated electronics within the nervous system., Funding Agencies|European Research Council [834677]; Swedish Research Council [2018-06197, RMX18-0083]; Swedish Foundation for Strategic Research [2021-05231]; Knut and Alice Wallenberg Foundation; Onnesjoe Foundation

Injectable bioelectronics could become an alternative or a complement to traditional drug treatments. To this end, a new self-doped p- type conducting PEDOT-S copolymer (A5) was synthesized. This copolymer formed highly water-dispersed nanoparticles and aggregated into a mixed ion-electron conducting hydrogel when injected into a tissue model. First, we synthetically repeated most of the published methods for PEDOT-S at the lab scale. Surprisingly, analysis using high-resolution matrix-assisted laser desorption ionization-mass spectroscopy showed that almost all the methods generated PEDOT-S derivatives with the same polymer lengths (i.e., oligomers, seven to eight monomers in average); thus, the polymer length cannot account for the differences in the conductivities reported earlier. The main difference, however, was that some methods generated an unintentional copolymer P(EDOT-S/EDOT-OH) that is more prone to aggregate and display higher conductivities in general than the PEDOT-S homopolymer. Based on this, we synthesized the PEDOT-S derivative A5, that displayed the highest film conductivity (33 S cm(-1)) among all PEDOT-S derivatives synthesized. Injecting A5 nanoparticles into the agarose gel cast with a physiological buffer generated a stable and highly conductive hydrogel (1-5 S cm(-1)), where no conductive structures were seen in agarose with the other PEDOT-S derivatives. Furthermore, the ion-treated A5 hydrogel remained stable and maintained initial conductivities for 7 months (the longest period tested) in pure water, and A5 mixed with Fe3O4 nanoparticles generated a magnetoconductive relay device in water. Thus, we have successfully synthesized a water-processable, syringe-injectable, and self-doped PEDOT-S polymer capable of forming a conductive hydrogel in tissue mimics, thereby paving a way for future applications within in vivo electronics., Funding Agencies|Swedish Research Council [2018-05258, 2018-06197]; Swedish Foundation for Strategic Research (e-NeuroPharmacology) [RMX18-0083]; European Research Council (ERC) project [e-NeuroPharma 834677]

The metabolism of drugs in the brain is difficult to study in most species because of enzymatic instability in vitro and interference from peripheral metabolism in vivo. A locust ex vivo model that combines brain barrier penetration, efflux, metabolism, and analysis of the unbound fraction in intact brains was evaluated using known drugs. Clozapine was analyzed, and its major metabolites, clozapine N-oxide (CNO) and N-desmethylclozapine (NDMC), were identified and quantified. The back-transformation of CNO into clozapine observed in humans was also observed in locusts. In addition, risperidone, citalopram, fluoxetine, and haloperidol were studied, and one preselected metabolite for each drug was analyzed, identified, and quantified. Metabolite identification studies of clozapine and midazolam showed that the locust brain was highly metabolically active, and 18 and 14 metabolites, respectively, were identified. The unbound drug fraction of clozapine, NDMC, carbamazepine, and risperidone was analyzed. In addition, coadministration of drugs with verapamil or fluvoxamine was performed to evaluate drug-drug interactions in all setups. All findings correlated well with the data in the literature for mammals except for the stated fact that CNO is a highly blood-brain barrier permeant compound. Overall, the experiments indicated that invertebrates might be useful for screening of blood-brain barrier permeation, efflux, metabolism, and analysis of the unbound fraction of drugs in the brain in early drug discovery.

The aim with the present study is to develop a blood-brain barrier (BBB) permeability model, which is applicable in the drug discovery phase. The BBB ensures proper neural function but it restricts many drugs from entering the brain and this complicates the development of new drugs against central nervous system diseases. Many in vitro models have been developed to predict BBB permeability but the permeability characteristics of the human BBB are notoriously complex and hard to predict. Consequently, one single suitable BBB permeability screening model, which is generally applicable in the early drug discovery phase, does not yet exist. A new refined ex vivo insect based BBB screening model that uses an intact, viable whole brain under controlled 'in vitro' like exposure conditions is presented. This model uses intact brains from dessert locusts, which are placed in a well containing the compound solubilized in an insect buffer. After a limited period of time the brain is removed and the compound concentration in the brain is measured by conventional LC-MS. The data presented here includes 25 known drugs and the data shows that the ex vivo insect model can be used to measure the brain uptake over the hemolymph barrier of drugs and that the brain uptake shows linear correlation with in situ perfusion data obtained in vertebrates. Moreover, this study shows that the insect ex vivo model is able to identify Pgp substrates and the model allows differentiation between low permeability compounds and compounds that are Pgp substrates.