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The in situ study of temperature-dependent micro magnetic and twin structure in oriented single crystals of Ni-Mn-Ga heusler alloys is discussed. The magnetic domains in the martensite phase were uniformly spaced and the martensite twins could be reoriented in applied fields as low as 1300 Oe.

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]

The interactions between nonpolar surfaces and polarizable anions lie in a gray area between the hydrophobic and Hofmeister effects. To assess the affinity of these interactions, NMR and ITC were used to probe the thermodynamics of eight anions binding to four different hosts whose pockets each consist primarily of hydrocarbon. Two classes of host were examined: cavitands and cyclodextrins. For all hosts, anion affinity was found to follow the Hofmeister series, with associations ranging from 1.6-5.7 kcal mol-1. Despite the fact that cavitand hosts 1 and 2 possess intrinsic negative electrostatic fields, it was determined that these more enveloping hosts generally bound anions more strongly. The observation that the four hosts each possess specific anion affinities that cannot be readily explained by their structures, points to the importance of counter cations and the solvation of the "empty" hosts, free guests and host-guest complexes, in defining the affinity. [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]

We report comprehensive characterization of cytogenomic findings from a bone marrow sample with suspected acute promyelocytic leukemia (APL) based on morphology and immunophenotype. Fluorescence in situ hybridization (FISH) and chromosome banding analysis (CBA) were negative for canonical PML::RARA and variant RARA translocations. PCR was negative for increased PML::RARA transcripts. CBA analysis detected loss of 5q, 17p as well as double minutes (dmin). To further rule out other retinoic acid receptor (RAR) partners, such as RARB, RARG , and identify the dmin, we employed genome-wide structural variant analysis (gSVA) using optical genome mapping. Interestingly, gSVA unmasked the dmin to be of MYC origin with ∼44 copies; this abnormality has been reported in APL-like leukemia and explained the immunophenotype. gSVA also identified loss of TP53 , loss of chromosomes 1, 2, 8, 9 (includes CDKN2A), 10, and 11 along with gains of chromosomes 3, 6, 7, and 15 as separate clonal events. No additional RAR partner translocations were observed. gSVA also showed a complex translocation, adjacent to 3Mb euploid region of 17p, in a rearrangement with chromosome 5, fusing genes DMGDH-AKAP10. As part of the testing algorithm, heme exome-based panel analysis detected a Tier I deleterious variant in TP53 (p.S241C). A 4-month follow up bone marrow again analyzed by gSVA, post induction therapy, showed a reduction in MYC amplification (∼4 copies). This work helped explain the APL-like phenotype for this rare leukemia in an initially emergent situation, provided a marker for follow-up testing, and merits integrated genomic analysis of similar cases. [ABSTRACT FROM AUTHOR]

Background: About 1 in 7 of all hospitalized patients is readmitted within 30 days of discharge. The cost of readmissions is significant, with Medicare readmissions alone costing the health care system an estimated $28 billion a year., Objective: To identify the rates of and causes for readmission within 100 days of patients receiving a hematopoietic stem cell transplant., Methods: We performed a retrospective review of 235 consecutive transplant recipients (autologous, n = 144; allogeneic, n = 91) to determine rates and causes for readmission within 100 days of patients receiving a transplant. Medical records and hospital readmissions were reviewed for each patient., Results: 36 allogeneic patients accounted for 56 readmissions. 23 autologous patients accounted for 26 readmissions. Autologous transplant recipients were most commonly readmitted for the development of a fever (n = 15 patients) or cardiopulmonary issues (n = 4). The most prevalent reasons for readmission in the allogeneic recipients included a fever (n = 21) or the development or exacerbation of graft-versus-host disease (n = 5). The readmission length of stay was 6 days (median range, 1-91 days) for allogeneic patients and 4 days (median range, 1-22 days) for autologous patients. There was no difference in survival between the readmitted and the non-readmitted cohorts (𝑃 = .55 for allogeneic patients; 𝑃 = .24 for autologous patients). Although allogeneic graft recipients demonstrated a higher readmission rate (39.6%) compared with autologous recipients (16%), none of the variables examined, including age, gender, performance status, diagnosis, remission status at the time of transplant, comorbidities, type of preparative chemotherapy regimen or donor type, identified patients at increased risk for readmission., Limitations: Variations in clinical care, physician practices, and patient characteristics need to be considered when examining readmission rates. Most of the allogeneic patient population included unrelated donor recipients (65%) who received nonmyeloablative conditioning regimens (81% of allogeneic recipients). These features may not be characteristic of other centers., Conclusions: In these high-risk patients, readmissions following a transplant are common. Enhanced predischarge education by nurses and pharmacists, along with ongoing outpatient education and rigorous outpatient follow-up through phone calls or social media may decrease readmission rates., (©2015 Frontline Medical Communications.)