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Although computer-aided drug design has greatly improved over time, its application in the pharmaceutical industry is still limited by the accuracy of association constant (Ka) predictions. Towards improving this situation, the Statistical Assessment of the Modeling of Proteins and Ligands (SAMPL) is a series of community-wide blind challenges aimed to advance computational techniques as standard predictive tools in rational drug design (https://en.wikipedia.org/wiki/SAMPL%5fChallenge). As an empirical contribution to SAMPL6, we report here the Ka and thermodynamic parameters (∆G, ∆H, - T∆S) of eight guests binding to two hosts (OA and TEMOA) using ITC. Both hosts contain a unique, well-defined binding pocket capable of storing guests with up to ten non-hydrogen atoms, whilst the selection of amphiphilic guests contain a range of saturated and unsaturated substituents. The thermodynamic data from this study will allow the challenge participants of SAMPL6 to test the accuracy of their computational protocols for calculating host-guest affinities. [ABSTRACT FROM AUTHOR]

This study reports the first in situ observation of temperature-dependent micromagnetic and twin structure in oriented single crystals of Ni–Mn–Ga Heusler alloys. Micromagnetic measurements were made over a temperature interval of 50 to -35 °C covering both forward and reverse martensitic transformation. Magnetic domains in the martensite phase were found to be uniformly spaced (25–30 μm); the direction of the domain walls conforms to the changing direction of the magnetic easy axis as they traverse from one twin to another. The martensite twins could be reoriented in applied fields as low as 1300 Oe. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Deamination of nucleobases in DNA and RNA results in the formation of xanthine (X), hypoxanthine (I), oxanine, and uracil, all of which are miscoding and mutagenic in DNA and can interfere with RNA editing and function. Among many forms of nucleic acid damage, deamination arises from several unrelated mechanisms, including hydrolysis. nitrosative chemistry, and deaminase enzymes. Here we present a fourth mechanism contributing to th~ burden of nucleobase deamination: incorporation of hypoxanthine and xanthine into DNA and RNA caused by defects in purine nucleotide metabolism. Using Escherichia coil and Saccharomyces cerevisiae with defined mutations in purine metabolism in conjunction with analytical methods for quantifying deaminated nucleobases in DNA and RNA. we observed large increases (up to 600-fold) in hypoxanthine in both DNA and RNA in cells unable to convert IMP to XMP or AMP (IMP dehydrogenase, guaB; adenylosuccinate synthetase, purA. and ADE12), and unable to remove dITP/ITP and dXTP/XTP from the nucleotide pool (dITP/XTP pyrophosphohydrolase, rdgB and HAMI). Conversely, modest changes in xanthine levels were observed in RNA (but not DNA) from E. co/i lacking purA and rdgB and the enzyme converting XMP to GMP (GMP synthetase, guaA). These observations suggest that disturbances in purine metabolism caused by known genetic polymorphisms could increase the burden of mutagenic deaminated nucleobases in DNA and interfere with gene expression and RNA function, a situation possibly exacerbated by the nitrosative stress of concurrent inflammation. The results also suggest a mechanistic basis for the pathophysiology of human inborn errors of purine nucleotide metabolism. [ABSTRACT FROM AUTHOR]

Magnetic materials reduced to a single atom show unexpected magnetic properties that interact with the spin states of the transmitting electrons and modify the nature of the quantized conductance. This integration of quantized conductance and spin-dependent transport across a magnetic atom gives rise to a multichannel system across which the transmission of electron waves can be regulated by a domain wall acting as a ‘valve’ —a quantum spin-valve. Here we measure complete magnetoresistance loops across magnetic quantum point contacts as small as a single atom, using cobalt. ‘Discrete’ or quantum magnetoresistance loops are observed owing to the varying transmission probability from the available discrete conductance channels. A remarkable feature of these quantum contacts is the discovery of a rapid oscillatory decay in magnetoresistance with increasing contact size. The results provide an evolutionary trace of spin-dependent transport from a single atom to larger ensembles. [ABSTRACT FROM AUTHOR]

This article presents our recent results on magnetic shape memory alloys (SMAs) and reviews some of our relevant past work. By treating the martensite structure as an assembly of microscopic crystalline tiles (twins), the observed micromagnetic structure or 'magnetic mosaic' in these alloys can be explained in terms of a spatially varying axis of the magnetocrystalline anisotropy and magnetostatic interactions across the tiles. A systematic investigation of ferroelastic structural domains of increasing structural complexity leads to a novel concept of 'polymagnets'. Similar to the idea of hierarchical ferroelastic polydomains, polymagnets are hierarchical micromagnetic structures, and parallels the complexity of the underlying ferroelastic polydomains. Preliminary results on the dynamics of the transformation pathways reveal a strong correlation between the underlying microstructure and achievable strain. In addition, reversible shape memory effect has been observed in sputter-deposited Ni-Mn-Ga thin films, and Co-Ni films with controlled composition have been successfully made by electrodeposition. [ABSTRACT FROM AUTHOR]

A new method called magnetic transition spectrum (MTS) is described for studying magnetic phase transitions. The MTS method is an electronic method that monitors the dynamics of the micromagnetic structure as a function of temperature, stress, or any other perturbation that can cause a sudden variation in flux inside the magnetic material. It is based on the same principle upon which the well-known and established Barkhausen method is based, namely, Faraday’s law. However, instead of applying a magnetic field as in the Barkhausen method, temperature or stress is the external “force.” The efficacy of the MTS method is illustrated by studying magnetic transitions in magnetic shape memory alloys. The MTS method is simple to implement and is equally applicable for studying magnetic transitions in other systems, such as, for example, dynamics of exchange anisotropy, using the Co–CoO system, by cooling the sample across the Néel temperature. In general, it can be used to study magnetic phase transitions driven by any external influence that would cause an abrupt change in the micromagnetic state of the sample (for example, change in temperature, pressure, etc.). [ABSTRACT FROM AUTHOR]

Drug associated thrombotic microangiopathy (TMA) is a rare event causing thrombocytopenia, microangiopathic anemia, renal failure, and neurologic abnormalities. Here, we present a case of TMA that occurred during the first cycle of treatment with carfilzomib for relapsed multiple myeloma. J. Clin. Apheresis, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A complete understanding of the transcriptional regulation of developmental lineages requires that all relevant factors be identified. Here, we have taken a proteomic approach to identify novel proteins associated with GATA-1, a lineage-restricted zinc finger transcription factor required for terminal erythroid and megakaryocytic maturation. We identify the Krüppel-type zinc finger transcription factor ZBP-89 as being a component of multiprotein complexes involving GATA-1 and its essential cofactor Friend of GATA-1 (FOG-1). Using chromatin immunoprecipitation assays, we show that GATA-1 and ZBP-89 cooccupy cis-regulatory elements of certain erythroid and megakaryocyte-specific genes, including an enhancer of the GATA-1 gene itself. Loss-of-function studies in zebrafish and mice demonstrate an in vivo requirement for ZBP-89 in megakaryopoiesis and definitive erythropoiesis but not primitive erythropoiesis, phenocopying aspects of FOG-1- and GATA-1-deficient animals. These findings identify ZBP-89 as being a novel transcription factor involved in erythroid and megakaryocytic development and suggest that it serves a cooperative function with GATA-1 and/or FOG-1 in a developmental stage-specific manner. [ABSTRACT FROM AUTHOR]