Gadolinium chelates as NMR contrast agents

" Chelates of gadolinium with 1,4,7-triazacyclononane-N,N',N""-triacetate; 1,4,7,10-tetrazacyclododecane-N,N',N'""tetraacetate; and 1,5,9-triazacyclododecane-N,N',N""-triacetate are useful as NMR contrast agents. "Board of Regents, University of Texas Syste

Performance analysis of a parallel, multi-node pipeline for DNA sequencing

Post-sequencing DNA analysis typically consists of read mapping followed by variant calling and is very time-consuming, even on a multi-core machine. Recently, we proposed Halvade, a parallel, multi-node implementation of a DNA sequencing pipeline according to the GATK Best Practices recommendations. The MapReduce programming model is used to distribute the workload among different workers. In this paper, we study the impact of different hardware configurations on the performance of Halvade. Benchmarks indicate that especially the lack of good multithreading capabilities in the existing tools (BWA, SAMtools, Picard, GATK) cause suboptimal scaling behavior. We demonstrate that it is possible to circumvent this bottleneck by using multiprocessing on high-memory machines rather than using multithreading. Using a 15-node cluster with 360 CPU cores in total, this results in a runtime of 1 h 31 min. Compared to a single-threaded runtime of similar to 12 days, this corresponds to an overall parallel efficiency of 53%

Comparison of Crystal Field Dependent and Independent Methods to Analyse Lanthanide Induced NMR Shifts in Axially Symmetric Complexes. Part II: Systems with a C4 Symmetry Axis

Analysis of the LIS data for several series of Ln3+ complexes of C4 symmetry in terms of structural changes, crystal-field effects and/or variation of hyperfine constants along the lanthanide series was undertaken using a combination of the two-nuclei and three-nuclei techniques together with the classical onenucleus technique. Isostructurality of whole series of complexes, with changes of the Fi, and B02 parameters, was clearly defined for the complexes of L by the combination of the two first methods. Small changes, involving the three Fi, Gi and B02 parameters, are observed for the series of complexes of L-L4, using the three data plotting methods. Some of the plots according to the two- and three-nuclei methods are accidentally linear, without necessarily implying isostructurality of the complexes, as they involve parameters, which may be insensitive to any small structural changes occurring in these systems. These parameter variations could result from a magnification, by the present graphical analysis, of the breaks expected from the gradual structural changes along the series due to the lanthanide contraction. The α and β parameters of the three-nuclei method are not diagnostic of the type of structures the complexes have in solution, due to their very indirect dependence on the geometric factors

NMR conformational study of diamagnetic complexes of some triazatriacetate macrocycles

The conformational properties of the diamagnetic complexes formed by five triazatriacetic macrocyclic ligands with monovalent (alkaline) and divalent (alkaline-earth, Zn2+ and Cd2+) cations have been studied by proton nuclear magnetic resonance spectroscopy (1H NMR) in aqueous solution as a function of pH and temperature. These structurally related triazatriacetic ligands, 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA), 1,4,7-triazacyclodecane-N,N',N''-triacetic acid (DETA), 1,4,8-triazacycloundecane-N,N',N''-triacetic acid (UNTA), 1,5,9-triazacyclododecane-N,N',N''-triacetic acid (DOTRA), and 9,10-benzylidene-1,4,7-triazacyclotridecane-N,N',N''-triacetic acid, (BUNTA) have triazamacrocyclic rings with different sizes and flexibilities, bearing three pendant acetate arms. In the case of the alkaline-earth, Zn2+ and Cd2+ cations, only one complex form (1:1) has been detected for all the ligands studied. In most cases the metal ion is coordinated to all the ligand ring nitrogens and to all or some of the carboxylate groups of the pendant arms, except when a poor fit of the cations into the macrocyclic hole occurs, such as for the Ba2+ complexes of DETA, UNTA and DOTRA and the Ca2+ and Sr2+ complexes of BUNTA. The resonance patterns of the ring proton resonances, determined by the long lifetime of the metal-nitrogen bonds, indicate that the six-membered rings formed upon chelation are conformationally rigid and the five-membered rings are conformationally flexible. The multiplicity of the acetate proton resonances shows that the metal-oxygen bonds are long-lived or short lived depending whether the acetates are bound to nitrogens involved in two ring bridges of equal or unequal sizes.http://www.sciencedirect.com/science/article/B6TG5-3T829PD-1D/1/7651a74d4d83a8b051a5d0b9286244e

Glucose production, gluconeogenesis, and hepatic tricarboxylic acid cycle fluxes measured by nuclear magnetic resonance analysis of a single glucose derivative

A triple-tracer method was developed to provide absolute fluxes contributing to endogenous glucose production and hepatic tricarboxylic acid (TCA) cycle fluxes in 24-h-fasted rats by 2H and 13C nuclear magnetic resonance (NMR) analysis of a single glucose derivative. A primed, intravenous [3,4-13C2]glucose infusion was used to measure endogenous glucose production; intraperitoneal 2H2O (to enrich total body water) was used to quantify sources of glucose (TCA cycle, glycerol, and glycogen), and intraperitoneal [U-13C3] propionate was used to quantify hepatic anaplerosis, pyruvate cycling, and TCA cycle flux. Plasma glucose was converted to monoacetone glucose (MAG), and a single 2H and 13C NMR spectrum of MAG provided the following metabolic data (all in units of [mu]mol/kg/min; n=6): endogenous glucose production (40.4 ± 2.9), gluconeogenesis from glycerol (11.5 ± 3.5), gluconeogenesis from the TCA cycle (67.3 ± 5.6), glycogenolysis (1.0 ± 0.8), pyruvate cycling (154.4 ± 43.4), PEPCK flux (221.7 ± 47.6), and TCA cycle flux (49.1 ± 16.8). In a separate group of rats, glucose production was not different in the absence of 2H2O and [U-13C]propionate, demonstrating that these tracers do not alter the measurement of glucose turnover.http://www.sciencedirect.com/science/article/B6W9V-4BWYNW7-2/1/140b73c9df39bb7829a8519979c37a6

Investigations Into Whole Water, Prototropic and Amide Proton Exchange in Lanthanide(III) DOTA-Tetraamide Chelates

Lanthanide(III) chelates of DOTA-tetraamide ligands have been an area of particular interest since the discovery that water exchange kinetics are dramatically affected by the switch from acetate to amide side-chain donors. More recently these chelates have attracted interest as potential PARACEST agents for use in MRI. In this paper we report the results of studies using chemical exchange saturation transfer (CEST) and some more recently reported chelates to re-examine the exchange processes in this class of chelate. We find that the conclusions of Parker and Aime are, for the most part, solid; water exchange is slow and a substantial amount of prototropic exchange occurs in aqueous solution. The extent of prototropic exchange increases as the pH increases above 8, leading to higher relaxivities at high pH. However, amide protons are found to contribute only a small amount to the relaxivity at high pH

Unexpected Changes in the Population of Coordination Isomers for the Lanthanide Ion Complexes of DOTMA–Tetraglycinate

[Abstract] Lanthanide complexes with DOTA–tetraglycinate (DOTA-(gly)4) heavily favor the square antiprismatic (SAP) coordination isomer in aqueous solution, a structural feature that has made them useful as water-based paraCEST agents. In an effort to create amide-based paraCEST agents with rapid water exchange rates, we prepared the analogous tetraglycinate complexes with DOTMA, a ligand known to favor the twisted square antiprismatic (TSAP) coordination structures. Unexpectedly, NMR investigations show that the LnDOTMA–(gly)4 complexes, like the LnDOTA–(gly)4 complexes, also favor the SAP isomers in solution. This observation led to density functional theory (DFT) calculations in order to identify the energy terms that favor the SAP structures in lanthanide complexes formed with macrocyclic DOTA– and DOTMA–tetraamide ligands. The DFT calculations revealed that, regardless the nature of the ligand, the TSAP isomers present more negative hydration energies than the SAP counterparts. The extent to which the TSAP isomer is stabilized varies, however, depending on the ligand structure, resulting in different isomeric populations in solution.Estados Unidos. National Institutes of Health; CA115531Estados Unidos. National Institutes of Health; EB015908Estados Unidos. National Institutes of Health; EB004582Estados Unidos. Robert A. Welch Foundation; AT-584Ministerio de Economía y Competitividad; CTQ2013-43243-PMinisterio de Economía y Competitividad; CTQ2015-71211-RED

Vision Care Utilization and Insurance Coverage Prior to and Following Medicaid Expansion in Ohio

Background: Increased access and utilization of vision care services has the potential to reduce preventable vision loss. The state of Ohio has been uniquely proactive when collecting vision-oriented data through population health surveys, including the Behavioral Risk Factor Surveillance System (BRFSS). These data can be used to better understand vision care utilization patterns and access to insurance. Methods: Responses to 3 items administered in the Ohio BRFSS that assess vision care utilization and insurance coverage were compared between 2 different administration periods, 2005-2011 and 2018-2019, using chi-square tests. Comparable data from 2 items assessing eye care utilization were available in 2005-2011 and 2019. Comparable data for insurance coverage were available in 2005-2011 and in 2018-2019. Responses were further stratified by population characteristics, including age, gender, household income, and education level. Results: The percentages of those reporting eye exams in the previous year were not significantly different between 2005-2011 and 2019 (chi-square, p = 0.06). In Ohio, the primary reason for not seeing a vision care provider in the past 12 months was “No reason to go” in 2005-2011 and in 2019. The second most common reason for not seeing a vision care provider in the past 12 months was “Cost/insurance,” which decreased between 2005-2011 and 2019 (chi-square, p <0.001). Insurance coverage for eye care increased between 2005-2011 and 2018-2019 (chi-square, p <0.001). Important differences were found within the demographic stratification. Conclusion: Population health surveillance data provide useful insight into vision care utilization and insurance coverage. Despite the increase in insurance coverage, eye care provider utilization remains relatively stable

The computational therapeutic: exploring Weizenbaum's ELIZA as a history of the present

This paper explores the history of ELIZA, a computer programme approximating a Rogerian therapist, developed by Jospeh Weizenbaum at MIT in the 1970s, as an early AI experiment. ELIZA’s reception provoked Weizenbaum to re-appraise the relationship between ‘computer power and human reason’ and to attack the ‘powerful delusional thinking’ about computers and their intelligence that he understood to be widespread in the general public and also amongst experts. The root issue for Weizenbaum was whether human thought could be ‘entirely computable’ (reducible to logical formalism). This also provoked him to re-consider the nature of machine intelligence and to question the instantiation of its logics in the social world, which would come to operate, he said, as a ‘slow acting poison’. Exploring Weizenbaum’s 20th Century apostasy, in the light of ELIZA, illustrates ways in which contemporary anxieties and debates over machine smartness connect to earlier formations. In particular, this article argues that it is in its designation as a computational therapist that ELIZA is most significant today. ELIZA points towards a form of human–machine relationship now pervasive, a precursor of the ‘machinic therapeutic’ condition we find ourselves in, and thus speaks very directly to questions concerning modulation, autonomy, and the new behaviorism that are currently arising