The N-terminal region of the ubiquitin regulatory x (UBX) domain-containing Protein 1 (UBXD1) modulates interdomain communication within the valosin-containing Protein p97

Valosin-containing protein/p97 is an ATP-driven protein segregase that cooperates with distinct protein cofactors to control various aspects of cellular homeostasis. Mutations at the interface between the regulatory N-domain and the first of two ATPase domains (D1 and D2) deregulate the ATPase activity and cause a multisystem degenerative disorder, inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia/amyotrophic lateral sclerosis. Intriguingly, the mutations affect only a subset of p97-mediated pathways correlating with unbalanced cofactor interactions and most prominently compromised binding of the ubiquitin regulatory X domain-containing protein 1 (UBXD1) cofactor during endolysosomal sorting of caveolin-1. However, how the mutations impinge on the p97-cofactor interplay is unclear so far. In cell-based endosomal localization studies, we identified a critical role of the N-terminal region of UBXD1 (UBXD1-N). Biophysical studies using NMR and CD spectroscopy revealed that UBXD1-N can be classified as intrinsically disordered. NMR titration experiments confirmed a valosin-containing protein/p97 interaction motif and identified a second binding site at helices 1 and 2 of UBXD1-N as binding interfaces for p97. In reverse titration experiments, we identified two distant epitopes on the p97 N-domain that include disease-associated residues and an additional interaction between UBXD1-N and the D1D2 barrel of p97 that was confirmed by fluorescence anisotropy. Functionally, binding of UBXD1-N to p97 led to a reduction of ATPase activity and partial protection from proteolysis. These findings indicate that UBXD1-N intercalates into the p97-ND1 interface, thereby modulating interdomain communication of p97 domains and its activity with relevance for disease pathogenesis. We propose that the polyvalent binding mode characterized for UBXD1-N is a more general principle that defines a subset of p97 cofactors

Evaluation of electrochemical methods for determination of the seebeck coefficient of redox electrolytes

Recent advances in thermoelectrochemical cells, which are being developed for harvesting low grade waste heat, have shown the promise of cobalt bipyridyl salts as the active redox couple. The Seebeck coefficient, Se, of a redox couple determines the open circuit voltage achievable, for a given temperature gradient, across the thermoelectrochemical cell. Thus, the accurate determination of this thermodynamic parameter is key to the development and study of new redox electrolytes. Further, techniques for accurate determination of Se using only one half of the redox couple reduces the synthetic requirements. Here, we compare three different experimental techniques for measuring Se of a cobalt tris(bipyridyl) redox couple in ionic liquid electrolytes. The use of temperature dependent cyclic voltammetry (CV) in isothermal and non-isothermal cells was investigated in depth, and the Se values compared to those from thermo-electromotive force measurements. Within experimental error, the Se values derived from CV methods were found to be in accordance with those obtained from electromotive force (emf) measurements. The applicability of cyclic voltammetry techniques for determining Se when employing only one part of the redox couple was demonstrated

I et internationalt og komparativt perspektiv

Emnet for denne afhandling er dansk skatteretlig CFC-lovgivning. Denne form for lovgivning går kort fortalt ud på, at aktionæren i et selskab under særlige omstændigheder skal medregne en andel af selskabets indkomst til sin egen skattepligtige indkomst, selvom selskabet ikke har udloddet udbytte til aktionæren. I international sammenhæng er CFC en forkortelse for Controlled Foreign Corporation (eller Company), og som forkortelsen antyder, finder sådanne regler normalt kun anvendelse, hvis selskabet er kontrolleret af aktionæren og er hjemmehørende i udlandet. Med andre ord angår CFC-beskatning normalt indkomsten i udenlandske datterselskaber. Uden CFC-regler vil beskatningen af aktionæren normalt være udskudt til det tidspunkt, hvor det udenlandske datterselskab udlodder udbytte til aktionæren, eller hvor aktionæren afstår sin aktiepost i det udenlandske datterselskab. I andre tilfælde vil beskatning hos aktionæren slet ikke finde sted. Såfremt det land, hvori det udenlandske datterselskab er hjemmehørende, ikke beskatter datterselskabets indkomst eller kun beskatter indkomsten med en lav sats, er der således mulighed for at skatteudskydelse eller skatteundgåelse kan forekomme, hvis aktionæren indretter sig således, at indkomst oppebæres af det udenlandske datterselskab i stedet for hos aktionæren selv. Det grundlæggende formål med afhandlingen er – ved anvendelse at den retsdogmatiske metode – at analysere dansk CFC-lovgivning og praksis med henblik på at udlede gældende ret på området – de lege lata. I den forbindelse er det tillige hensigten at identificere uklarheder samt vurdere, om de danske CFCregler strider mod indgåede dobbeltbeskatningsoverenskomster eller EU-retten. Et yderligere formål med afhandlingen er at vurdere, hvorvidt dansk CFC-lovgivning kan anses for at imødekomme visse retspolitiske hensyn, og såfremt dette ikke er tilfældet at komme med alternative bud på, hvordan de danske CFC-regler med fordel kan udformes. Med andre ord har afhandlingen også haft til formål at komme med betragtninger de lege ferend

Allocation of the Right to Tax Income from Digital Intermediary Platforms – Challenges and Possibilities for Taxation in the Jurisdiction of the User

The authors analyse the current (lack of) possibilities for userjurisdictions to tax the value generated by the increased use of digital intermediary platforms. Focus is on analysing the possibilities for userjurisdictions to tax the remuneration received by a foreign enterprise owning a digital intermediary platform and on disucussing whether the users’ provision of personal data in exchange for access to the platform could be considered a barter transaction for tax purposes in the userjurisdiction. Among other things, it is concluded that user-jurisdictions, pursuant to current international tax treaties, will normally be precluded from taxing the income of foreign platform enterprises, as the platform enterprises are often able to deliver their digital services remotely. Against this background, a number of tax policy challenges and options of relevance for taxing platform enterprises are discussed, in particular the proposed directive on significant digital presence recently put forward by the European Commisssion. It is concluded that the proposal may prove to be an adequate step towards taxation in the userjurisdictions, even though the proposal needs further work in order to become sufficiently clear and targeted and the scope may be limited

Inducing High Ionic Conductivity in the Lithium Superionic Argyrodites Li_6+<i>x</i>P_1-<i>x</i>Ge_<i>x</i>S₅I for All-Solid-State Batteries

Solid-state batteries with inorganic solid electrolytes are currently being discussed as a more reliable and safer future alternative to the current lithium-ion battery technology. To compete with state-of-the-art lithium-ion batteries, solid electrolytes with higher ionic conductivities are needed, especially if thick electrode configurations are to be used. In the search for optimized ionic conductors, the lithium argyrodites have attracted a lot of interest. Here, we systematically explore the influence of aliovalent substitution in Li6+xP1–xGexS5I using a combination of X-ray and neutron diffraction, as well as impedance spectroscopy and nuclear magnetic resonance. With increasing Ge content, an anion site disorder is induced and the activation barrier for ionic motion drops significantly, leading to the fastest lithium argyrodite so far with 5.4 ± 0.8 mS cm–1 in a cold-pressed state and 18.4 ± 2.7 mS cm–1 upon sintering. These high ionic conductivities allow for successful implementation within a thick-electrode solid-state battery that shows negligible capacity fade over 150 cycles. The observed changes in the activation barrier and changing site disorder provide an additional approach toward designing better performing solid electrolytes

Permanent Establishment for Investors in Private Equity Funds—A Legal Analysis in Light of the Changes to the OECD Model (2017)

Abstract The article analyzes whether the investment in a private equity fund may create a permanent establishment (PE) for foreign investors. The analysis is divided into two main parts, as the question of creating a PE for the foreign investors is considered with respect to both the main PE rule and the agency PE rule. The amendments to the PE definition prescribed in the OECD/G20 BEPS report on Action 7, and incorporated into the 2017 version of the OECD Model with Commentary, are taken into consideration. It is concluded that the final outcome depends on the specific setup of the private equity fund at hand and that some degree of uncertainty may often remain. Moreover, the recent amendments to the PE definition do not appear to have reduced this uncertainty—rather the contrary.</jats:p