Complexation of lanthanides, actinides and transition metal cations with a 6-(1,2,4-triazin-3-yl)-2,2’:6’,2’’-terpyridine ligand: implications for actinide(III) /lanthanide(III) partitioning

The quadridentate N-heterocyclic ligand 6-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-2,2’:6’,2’’-terpyridine (CyMe4-hemi-BTBP) has been synthesized and its interactions with Am(III), U(VI), Ln(III) and some transition metal cations have been evaluated by X-ray crystallographic analysis, Am(III)/Eu(III) solvent extraction experiments, UV absorption spectrophotometry, NMR studies and ESI-MS. Structures of the 1:1 complexes with Eu(III), Ce(III) and the linear uranyl (UO22+) ion were obtained by X-ray crystallographic analysis, and showed similar coordination behavior to related BTBP complexes. In methanol, the stability constants of the Ln(III) complexes are slightly lower than those of the analogous quadridentate bis-triazine BTBP ligands, while the stability constant for the Yb(III) complex is higher. 1H NMR titrations and ESI-MS with lanthanide nitrates showed that the ligand forms only 1:1 complexes with Eu(III), Ce(III) and Yb(III), while both 1:1 and 1:2 complexes were formed with La(III) and Y(III) in acetonitrile. A mixture of isomeric chiral 2:2 helical complexes was formed with Cu(I), with a slight preference (1.4:1) for a single directional isomer. In contrast, a 1:1 complex was observed with the larger Ag(I) ion. The ligand was unable to extract Am(III) or Eu(III) from nitric acid solutions into 1-octanol, except in the presence of a synergist at low acidity. The results show that the presence of two outer 1,2,4-triazine rings is required for the efficient extraction and separation of An(III) from Ln(III) by quadridentate N-donor ligand

The Attitudes of High School Guidance Counselors in Scioto County, Ohio, Toward Vocational-Technical Education

A thesis presented to the Business Education Graduate Committee at Morehead State University in partial fulfillment of the requirements for the Degree of Master of Business Education by Michael Lee Gampp November 25, 1974

Evolving Factor Analysis of Spectrophotometric Titrations: Forget About the Law of Mass Action?

Evolving Factor Analysis (EFA) is a new and powerful mathematical algorithm for the model-free analysis of any ordered set of multiwavelength data. Applied to spectrophotometric titrations, even strongly overlapping concentration profiles and the spectra of all absorbing species are correctly calculated without making use of the law of mass action and without even defining the stoichiometric composition of the species in question. The basic idea behind EFA is repetitive application of factor analysis to all subsets of 1, 2, ...N measurements and iterative refinement of the eigenvalues thus obtained into concentration profiles with concomitant least-squares estimation of the species spectra. EFA has been tested successfully with a dozen chemical systems as well as with model data for strongly overlapping concentration profiles

Characterization of a K+-induced conformational switch in a human telomeric DNA oligonucleotide using 2-aminopurine fluorescence

Human telomeric DNA consists of tandem repeats of the DNA sequence d(GGGTTA). Oligodeoxynucletotide telomere models such as d[A(GGGTTA)(3)GGG] (Tel22) fold in a cation-dependent manner into quadruplex structures consisting of stacked G-quartets linked by d(TTA) loops. NMR has shown that in Na(+) solutions Tel22 forms a ‘basket’ topology of four antiparallel strands; in contrast, Tel22 in K(+) solutions consists of a mixture of unknown topologies. Our previous studies on the mechanism of folding of Tel22 and similar telomere analogs utilized changes in UV absorption between 270 and 325 nm that report primarily on G-quartet formation and stacking showed that quadruplex formation occurs within milliseconds upon mixing with an appropriate cation. In the current study, we assessed the dynamics and equilibria of folding of specific loops by using Tel22 derivatives in which the dA residues were serially substituted with the fluorescent reporter base, 2-aminopurine (2-AP). Tel22 folding induced by Na(+) or K(+) assessed by changes in 2-AP fluorescence consists of at least three kinetic steps with time constants spanning a range of ms to several hundred seconds. Na(+)-dependent equilibrium titrations of Tel22 folding could be approximated as a cooperative two-state process. In contrast, K(+)-dependent folding curves were biphasic, revealing that different conformational ensembles are present in 1 mM and 30 mM K(+). This conclusion was confirmed by (1)H NMR. Molecular dynamics simulations revealed a K(+) binding pocket in Tel22 located near dA1 that is specific for the so-called hybrid-1 conformation in which strand 1 is in a parallel arrangement. The possible presence of this topologically specific binding site suggests that K(+) may play an allosteric role in regulating telomere conformation and function by modulating quadruplex tertiary structure

How Prostate Cancer Growth Patterns Impact Detection and Interreader Agreement on Multiparametric MRI

RATIONALE AND OBJECTIVES Multiparametric MRI (mpMRI) substantially improves the detection of significant prostate carcinoma (PCa) compared to systematic biopsy. Nevertheless, mpMRI can overlook aggressive forms of PCa. Recent studies showed, that infiltrative growth (INF) has less restricted diffusion. This study aims to explore the impact of growth patterns on the detection of lesions. MATERIALS AND METHODS This retrospective study analyzed 52 patients who underwent radical prostatectomy, with preoperative mpMRI. For each patient, one dominant lesion was identified on one whole-mount prostatectomy section. Two pathologists (P1, P2) independently classified the growth pattern whether as expansive (EXP) being defined with at least three 5mm² regions of interest consisting entirely of carcinoma without benign glands or else as infiltrative (INF). Two radiologists (R1, R2) independently classified selected lesions according to PI-RADSv2.1. based on pathological localization. Apparent diffusion coefficient (ADC) values were measured in correlation with matched histopathology slides. Interreader-agreement was evaluated using weighted Cohen's Kappa. The relationship between PI-RADS scores and pathological diagnoses was analyzed using logistic regression. RESULTS Pathologic lesion characterization regarding growth patterns achieved almost perfect agreement (κ = 0.88), so did PI-RADS classification of mpMRI (κ = 0.90). PI-RADS scores correlated significantly with EXP growth patterns. Average ADC values were lower for EXP lesions (0.83×10$^{-3}$ mm$^{2}$/s, CI: 0.72-0.94×10$^{-3}$ mm$^{2}$/s) compared to INF lesions (0.97×10$^{-3}$ mm$^{2}$/s, CI: 0.86-1.07×10$^{-3}$ mm$^{2}$/s; p = 0.08). On T2 images, 8 of 28 (29%) INF lesions and 1 of 24 (4%) EXP lesions were not visible. CONCLUSION PCa missed on mpMRI more frequently demonstrate INF growth patterns. Lesions with EXP growth patterns show lower ADC values and have higher PI-RADS scores

Cardiac stereotactic body radiotherapy to treat malignant ventricular arrhythmias directly affects the cardiomyocyte electrophysiology.

BACKGROUND Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood. OBJECTIVES We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression. METHODS Following exposure to 20Gy of X-rays in a single fraction, neonatal rat ventricular cardiomyocytes (NRVCs) were analyzed 24 and 96h post-radiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration (APD) in both monolayers and single cells. Additionally, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and mRNA levels. RESULTS Following irradiation with 20Gy, NRVCs exhibited increased beat rate and conduction velocities 24 and 96h after treatment. mRNA and protein levels of ion channels were altered, with the most significant changes observed at the 96h-mark. Upregulation of Cacna1c (Cav1.2), Kcnd3 (Kv4.3), Kcnh2 (Kv11.1), Kcnq1 (Kv7.1), Kcnk2 (K2P2.1), Kcnj2 (Kir2.1), and Gja1 (Cx43) was noted, along with improved gap junctional coupling. Calcium handling was affected, with increased Ryr2 (RYR2) and Slc8a1 (NCX) expression and altered properties 96h post-treatment. Fibroblast and myofibroblast levels remained unchanged. CONCLUSIONS CSBRT modulates expression of various ion channels, calcium handling proteins, and gap-junction proteins. The described alterations in cellular electrophysiology may be the underlying cause of the immediate antiarrhythmic effects observed following cSBRT