Allosteric modulators of the hERG K+ channel Radioligand binding assays reveal allosteric characteristics of dofetilide analogs

Medicinal Chemistr

Heat-capacity measurements on small samples: The hybrid method

A newly developed method is presented for measuring heat capacities on small samples, particularly where thermal isolation is not sufficient for the use of the traditional semiadiabatic heat-pulse technique. This "hybrid technique" is a modification of this heat-pulse method in case the temperature drift of the sample after the heat pulse is not linear but exponential. Deliberate extrapolations of these exponential drift curves, dependent on the evaluated relaxation time, yield reliable results for the temperature steps. The method is faster than the traditional relaxation method, and by comparing with the values published by the National Bureau of Standards (NBS) on copper, the accuracy is shown to be of the order of 1%

Structure, magnetism, and magnetocaloric properties of MnFeP1−xSix compounds

MnFeP1-xSix compounds with x=0.10,0.20,0.24,0.28,...,0.80,1 were prepared by high-energy ball milling and solid-state reaction. The structural, magnetic, and magnetocaloric properties are investigated as a function of temperature and magnetic field. X-ray diffraction studies show that the samples in the range from x=0.28 to 0.64 adopt the hexagonal Fe2P-type structure with a small amount of second phase which increases with increasing Si content. The samples with lower Si content show the orthorhombic Co2P-type structure. Magnetic measurements show that the paramagnetic-ferromagnetic transition temperatures range from 214 to 377 K. Of much importance is the fact that these compounds do not contain any toxic components and exhibit excellent magnetocaloric properties

The superconducting ferromagnet UCoGe

The correlated metal UCoGe is a weak itinerant ferromagnet with a Curie temperature T_C = 3 K and a superconductor with a transition temperature T_s = 0.6 K. We review its basic thermal, magnetic - on the macro and microscopic scale - and transport properties, as well as the response to high pressure. The data unambiguously show that superconductivity and ferromagnetism coexist below T_s = 0.6 K and are carried by the same 5f electrons. We present evidence that UCoGe is a p-wave superconductor and argue that superconductivity is mediated by critical ferromagnetic spin fluctuations.Comment: 19 pages; review paper; accepted for publication in the Journal of Low Temperature Physics (Special issue: Quantum Phase Transitions 2010

Functional selectivity of adenosine receptor ligands

Adenosine receptors are plasma membrane proteins that transduce an extracellular signal into the interior of the cell. Basically every mammalian cell expresses at least one of the four adenosine receptor subtypes. Recent insight in signal transduction cascades teaches us that the current classification of receptor ligands into agonists, antagonists, and inverse agonists relies very much on the experimental setup that was used. Upon activation of the receptors by the ubiquitous endogenous ligand adenosine they engage classical G protein-mediated pathways, resulting in production of second messengers and activation of kinases. Besides this well-described G protein-mediated signaling pathway, adenosine receptors activate scaffold proteins such as β-arrestins. Using innovative and sensitive experimental tools, it has been possible to detect ligands that preferentially stimulate the β-arrestin pathway over the G protein-mediated signal transduction route, or vice versa. This phenomenon is referred to as functional selectivity or biased signaling and implies that an antagonist for one pathway may be a full agonist for the other signaling route. Functional selectivity makes it necessary to redefine the functional properties of currently used adenosine receptor ligands and opens possibilities for new and more selective ligands. This review focuses on the current knowledge of functionally selective adenosine receptor ligands and on G protein-independent signaling of adenosine receptors through scaffold proteins

Non-Fermi-liquid scaling in U(Cu,Al){sub 5} compounds

We report on the electronic properties of various UCu{sub x}Al{sub 5-x} compounds (2.9{le}x{le}3.5). These compounds crystallize in the hexagonal CaCu{sub 5} structure. For all compounds, we find that the low-temperature specific heat diverges logarithmitically, which may be taken as an indication of non-Fermi-liquid scaling in these materials. Also we find a large magnetic anisotropy in all compounds studied, and we show that the magnetic anisotropy should not be neglected in the analysis of other bulk properties. Though for some of UCu{sub x}Al{sub 5-x} polycrystals non-Fermi-liquid scaling is found also in the magnetic susceptibility, comparison with single-crystal results on UCu{sub 3}Al{sub 2} indicates that any temperature dependence may be due to averaging anisotropic response over all crystallographic directions