Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide.

Sucroferric oxyhydroxide (VELPHORO(®)) is a polynuclear iron-based phosphate binder recently approved for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). As a number of the available phosphate binders do not provide the optimal combination of good efficacy, adequate tolerability and low pill burden, sucroferric oxyhydroxide constitutes a promising alternative. Among the attributes of an ideal phosphate binder is minimal absorption and, hence, low risk of systemic toxicity. Accordingly, the iron-releasing properties and absorption, distribution, metabolism and excretion (ADME) profile of sucroferric oxyhydroxide, as well as the possibility of iron accumulation and toxicity, were investigated in a series of preclinical studies. The effect of sucroferric oxyhydroxide on the progression of vascular calcification was also investigated. Sucroferric oxyhydroxide exhibited a high phosphate-binding capacity and low iron-releasing properties across the physiological pH range found in the gastrointestinal tract. In the ADME studies, uptake of (59)Fe-radiolabelled sucroferric oxyhydroxide was low in rats and dogs (<1% from a 50 mg Fe/kg bodyweight dose), with the majority of absorbed iron located in red blood cells. Long-term (up to 2 years) administration of sucroferric oxyhydroxide in rats and dogs was associated with modest increases in tissue iron levels and no iron toxicity. Moreoever, in uraemic rats, sucroferric oxyhydroxide was associated with reduced progression of vascular calcification compared with calcium carbonate. In conclusion, sucroferric oxyhydroxide offers a new option for the treatment of hyperphosphataemia, with a high phosphate-binding capacity, minimal iron release, and low potential for iron accumulation and toxicity

Dark matter annihilation and decay in dwarf spheroidal galaxies: The classical and ultrafaint dSphs

Dwarf spheroidal (dSph) galaxies are prime targets for present and future gamma-ray telescopes hunting for indirect signals of particle dark matter. The interpretation of the data requires careful assessment of their dark matter content in order to derive robust constraints on candidate relic particles. Here, we use an optimised spherical Jeans analysis to reconstruct the `astrophysical factor' for both annihilating and decaying dark matter in 21 known dSphs. Improvements with respect to previous works are: (i) the use of more flexible luminosity and anisotropy profiles to minimise biases, (ii) the use of weak priors tailored on extensive sets of contamination-free mock data to improve the confidence intervals, (iii) systematic cross-checks of binned and unbinned analyses on mock and real data, and (iv) the use of mock data including stellar contamination to test the impact on reconstructed signals. Our analysis provides updated values for the dark matter content of 8 `classical' and 13 `ultrafaint' dSphs, with the quoted uncertainties directly linked to the sample size; the more flexible parametrisation we use results in changes compared to previous calculations. This translates into our ranking of potentially-brightest and most robust targets---viz., Ursa Minor, Draco, Sculptor---, and of the more promising, but uncertain targets---viz., Ursa Major 2, Coma---for annihilating dark matter. Our analysis of Segue 1 is extremely sensitive to whether we include or exclude a few marginal member stars, making this target one of the most uncertain. Our analysis illustrates challenges that will need to be addressed when inferring the dark matter content of new `ultrafaint' satellites that are beginning to be discovered in southern sky surveys.Comment: 19 pages, 14 figures, submitted to MNRAS. Supplementary material available on reques

Report of the University of Missouri-Orissa University of Agriculture technology study team

Cover title.Includes bibliographical references (pages 34-36)

Search for axions in streaming dark matter

A new search strategy for the detection of the elusive dark matter (DM) axion is proposed. The idea is based on streaming DM axions, whose flux might get temporally enormously enhanced due to gravitational lensing. This can happen if the Sun or some planet (including the Moon) is found along the direction of a DM stream propagating towards the Earth location. The experimental requirements to the axion haloscope are a wide-band performance combined with a fast axion rest mass scanning mode, which are feasible. Once both conditions have been implemented in a haloscope, the axion search can continue parasitically almost as before. Interestingly, some new DM axion detectors are operating wide-band by default. In order not to miss the actually unpredictable timing of a potential short duration signal, a network of co-ordinated axion antennae is required, preferentially distributed world-wide. The reasoning presented here for the axions applies to some degree also to any other DM candidates like the WIMPs.Comment: 5 page

Investigation of preparative possibilities of iodinating systems on the basis of N-iodoacetamide

N-iodoacetamide in organic solvents with H2SО4 iodinates successfully alkylbenzenes, aromatic amines and phenol ether. Electrophilic iodine activity is controlled by medium acidity. Super electrophilic iodine formed at N-iodoacetamide dissolution in sulfuric acid reacts easily with electron-deficient arenes at 0...20 °C forming iodinated product

Actions of the braid group, and new algebraic proofs of results of Dehornoy and Larue

This article surveys many standard results about the braid group with emphasis on simplifying the usual algebraic proofs. We use van der Waerden's trick to illuminate the Artin-Magnus proof of the classic presentation of the algebraic mapping-class group of a punctured disc. We give a simple, new proof of the Dehornoy-Larue braid-group trichotomy, and, hence, recover the Dehornoy right-ordering of the braid group. We then turn to the Birman-Hilden theorem concerning braid-group actions on free products of cyclic groups, and the consequences derived by Perron-Vannier, and the connections with the Wada representations. We recall the very simple Crisp-Paris proof of the Birman-Hilden theorem that uses the Larue-Shpilrain technique. Studying ends of free groups permits a deeper understanding of the braid group; this gives us a generalization of the Birman-Hilden theorem. Studying Jordan curves in the punctured disc permits a still deeper understanding of the braid group; this gave Larue, in his PhD thesis, correspondingly deeper results, and, in an appendix, we recall the essence of Larue's thesis, giving simpler combinatorial proofs.Comment: 51`pages, 13 figure