A photolabile protection strategy for terminal alkynes

AbstractWe present a strategy for photolabile protection of terminal alkynes. Several photo-caged alcohols were synthesized via mild copper(II)-catalyzed substitution between tertiary propargylic alcohols and 2-nitrobenzyl alcohol to build up robust, base stable o-nitrobenzyl (NB) photo-cleavable compounds. We compare the new photolabile protecting group with the commonly used alkyne protecting group, 2-methyl-3-butyn-2-ol and the results show that NB ethers are stable under the cleaving conditions for the cleavage of methylbutynol protected alkynes. Additionally, we present the synthesis of photo-cleavable NB derivatives containing thiol groups that can serve as agents for photoinduced surface functionalization reactions

Divalent metal transporter 1 (DMT1) in the brain:implications for a role in iron transport at the blood-brain barrier, and neuronal and glial pathology

Iron is required in a variety of essential processes in the body. In this review, we focus on iron transport in the brain and the role of the divalent metal transporter 1 (DMT1) vital for iron uptake in most cells. DMT1 locates to cellular membranes and endosomal membranes, where it is a key player in non-transferrin bound iron uptake and transferrin-bound iron uptake, respectively. Four isoforms of DMT1 exist, and their respective characteristics involve a complex cell-specific regulatory machinery all controlling iron transport across these membranes. This complexity reflects the fine balance required in iron homeostasis, as this metal is indispensable in many cell functions but highly toxic when appearing in excess. DMT1 expression in the brain is prominent in neurons. Of serious dispute is the expression of DMT1 in non-neuronal cells. Recent studies imply that DMT1 does exist in endosomes of brain capillary endothelial cells denoting the blood-brain barrier. This supports existing evidence that iron uptake at the BBB occurs by means of transferrin-receptor mediated endocytosis followed by detachment of iron from transferrin inside the acidic compartment of the endosome and DMT1-mediated pumping iron into the cytosol. The subsequent iron transport across the abluminal membrane into the brain likely occurs by ferroportin. The virtual absent expression of transferrin receptors and DMT1 in glial cells, i.e., astrocytes, microglia and oligodendrocytes, suggest that the steady state uptake of iron in glia is much lower than in neurons and/or other mechanisms for iron uptake in these cell types prevail

The macroscopic pancake bounce

We demonstrate that the so-called pancake bounce of millimetric water droplets on surfaces patterned with hydrophobic posts [Nat. Phys. 10, 515 (2014)] can be reproduced on larger scales. In our experiment, a bed of nails plays the role of the structured surface and a water balloon models the water droplet. The macroscopic version largely reproduces the features of the microscopic experiment, including the Weber number dependence and the reduced contact time for pancake bouncing. The scalability of the experiment confirms the mechanisms of pancake bouncing, and allows us to measure the force exerted on the surface during the bounce. The experiment is simple and inexpensive and is an example where front-line research is accessible to student projects.Comment: 7 pages, 8 figure

Glidninger: ’Usynlige’ forandringer inden for pædagogik og uddannelser

Udgangspunkt for bogens undersøgelser er en undren over, hvordan og hvorfor udefra initierede forandringer af relationer eller tankemønstre ikke registreres af berørte agenter, hvorfor aspekter af styring og ledelse ubemærket glider ind i tænkning og praksis.Vort fælles perspektiv i Forskningsenheden: ’Globalisering, governance og ledelse i uddannelsesinstitutioner’ er at undersøge relationerne mellem globale styringstendenser og deres veje gennem transnationale og nationale agenturer til lokale institutioner. Vi undersøger derfor ikke alene disse tendenser, men er i lige så høj grad interesserede i, hvordan styringen påvirker og bearbejdes på niveauerne og af forskningen: Hvordan institutionerne og aktørerne registrerer – eller måske netop ikke registrerer – påvirkningerne, dér, hvor de rammer praksis. Vi arbejder således på at finde og forklare sammenhænge mellem generelle styringstendenser og lokale oplevelser og reaktioner.Igennem introduktioner til teorier om governance, translationer, diskurser, meningsdannelse og praksis, og igennem brug af teorierne i case analyser indenfor folkeskolen, daginstitutioner, socialpædagogik, voksenuddannelse og universiteter undersøger vi, hvor langt teorierne bringer os, og hvordan de ofte må kombineres eller suppleres for at kunne klargøre vore indsigter.Undersøgelserne interesserer sig i alle casene både for de generelle styringstendenser og for aktørernes muligheder for demokratisk oplysning og deltagelse i stadig mere komplekse praksissammenhænge

Ethynylphosphonamidates for the Rapid and Cysteine-Selective Generation of Efficacious Antibody–Drug Conjugates

Requirements for novel bioconjugation reactions for the synthesis of antibody–drug conjugates (ADCs) are exceptionally high, since conjugation selectivity as well as the stability and hydrophobicity of linkers and payloads drastically influence the performance and safety profile of the final product. We report Cys-selective ethynylphosphonamidates as new reagents for the rapid generation of efficacious ADCs from native non-engineered monoclonal antibodies through a simple one-pot reduction and alkylation. Ethynylphosphonamidates can be easily substituted with hydrophilic residues, giving rise to electrophilic labeling reagents with tunable solubility properties. We demonstrate that ethynylphosphonamidate-linked ADCs have excellent properties for next-generation antibody therapeutics in terms of serum stability and in vivo antitumor activity.Peer Reviewe