Complexes of bifunctional DO3A-N-(α-amino)propinate ligands with Mg(II), Ca(II), Cu(II), Zn(II), and lanthanide(III) ions: thermodynamic stability, formation and dissociation kinetics, and solution dynamic NMR studies

The thermodynamic, kinetic, and structural properties of Ln3+ complexes with the bifunctional DO3A-ACE4− ligand and its amide derivative DO3A-BACE4− (modelling the case where DO3A-ACE4− ligand binds to vector molecules) have been studied in order to confirm the usefulness of the corresponding Gd3+ complexes as relaxation labels of targeted MRI contrast agents. The stability constants of the Mg2+ and Ca2+ complexes of DO3A-ACE4− and DO3A-BACE4− complexes are lower than for DOTA4− and DO3A3−, while the Zn2+ and Cu2+ complexes have similar and higher stability than for DOTA4− and DO3A3− complexes. The stability constants of the Ln(DO3A-BACE)− complexes increase from Ce3+ to Gd3+ but remain practically constant for the late Ln3+ ions (represented by Yb3+). The stability constants of the Ln(DO3A-ACE)4− and Ln(DO3A-BACE)4− complexes are several orders of magnitude lower than those of the corresponding DOTA4− and DO3A3− complexes. The formation rate of Eu(DO3A-ACE)− is one order of magnitude slower than for Eu(DOTA)−, due to the presence of the protonated amine group, which destabilizes the protonated intermediate complex. This protonated group causes the Ln(DO3A-ACE)− complexes to dissociate several orders of magnitude faster than Ln(DOTA)− and its absence in the Ln(DO3A-BACE)− complexes results in inertness similar to Ln(DOTA)− (as judged by the rate constants of acid assisted dissociation). The 1H NMR spectra of the diamagnetic Y(DO3A-ACE)− and Y(DO3A-BACE)− reflect the slow dynamics at low temperatures of the intramolecular isomerization process between the SA pair of enantiomers, R-Λ(λλλλ) and S-Δ(δδδδ). The conformation of the Cα-substituted pendant arm is different in the two complexes, where the bulky substituent is further away from the macrocyclic ring in Y(DO3A-BACE)− than the amino group in Y(DO3A-ACE)− to minimize steric hindrance. The temperature dependence of the spectra reflects slower ring motions than pendant arms rearrangements in both complexes. Although losing some thermodynamic stability relative to Gd(DOTA)−, Gd(DO3A-BACE)− is still quite inert, indicating the usefulness of the bifunctional DO3A-ACE4− in the design of GBCAs and Ln3+-based tags for protein structural NMR analysis.This research was funded by the Hungarian National Research, Development and Innovation Office (Projects NKFIH K-128201, K-134694, and FK-134551)

The Minimal Length of a Lagrangian Cobordism between Legendrians

To investigate the rigidity and flexibility of Lagrangian cobordisms between Legendrian submanifolds, we investigate the minimal length of such a cobordism, which is a $1$-dimensional measurement of the non-cylindrical portion of the cobordism. Our primary tool is a set of real-valued capacities for a Legendrian submanifold, which are derived from a filtered version of Legendrian Contact Homology. Relationships between capacities of Legendrians at the ends of a Lagrangian cobordism yield lower bounds on the length of the cobordism. We apply the capacities to Lagrangian cobordisms realizing vertical dilations (which may be arbitrarily short) and contractions (whose lengths are bounded below). We also study the interaction between length and the linking of multiple cobordisms as well as the lengths of cobordisms derived from non-trivial loops of Legendrian isotopies.Comment: 33 pages, 9 figures. v2: Minor corrections in response to referee comments. More general statement in Proposition 3.3 and some reorganization at the end of Section

Atherosclerosis of the descending aorta predicts cardiovascular events: a transesophageal echocardiography study

PURPOSE: Previous studies have shown that atherosclerosis of the descending aorta detected by transesophageal echocardiography (TEE) is a good marker of coexisting coronary artery disease. The aim of our study was to evaluate whether the presence of atherosclerosis on the descending aorta during TEE has any prognostic impact in predicting cardiovascular events. MATERIAL AND METHODS: The study group consisted of 238 consecutive in-hospital patients referred for TEE testing (135 males, 103 females, mean age 58 +/- 11 years) with a follow up of 24 months. The atherosclerotic lesions of the descending aorta were scored from 0 (no atherosclerosis) to 3 (plaque >5 mm and/or "complex" plaque with ulcerated or mobile parts). RESULTS: Atherosclerosis was observed in 102 patients, (grade 3 in 16, and grade 2 in 86 patients) whereas 136 patients only had an intimal thickening or normal intimal surface. There were 57 cardiovascular events in the follow-up period. The number of events was higher in the 102 patients with (n = 34) than in the 136 patients without atherosclerosis (n = 23, p < 0.01). The frequency of events was in close correlation with the severity of the atherosclerosis of the descending aorta. Fifty percent of the patients with grade 3 experienced cardiovascular events. Excluding patients with subsequent revascularization, the multivariate analysis only left ventricular function with EF < 40% (HR 3.0, CI 1.3–7.1) and TEE atherosclerotic plaque >=2 (HR 2.4, CI 1.0–5.5) predicted hard cardiovascular events. CONCLUSION: Atherosclerosis of the descending aorta observed during transesophageal echocardiography is a useful predictor of cardiovascular events

Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy

BACKGROUND: The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear. METHODS: From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years. RESULTS: A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test). CONCLUSIONS: In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number, NCT00023595.)

Quantum walks: a comprehensive review

Quantum walks, the quantum mechanical counterpart of classical random walks, is an advanced tool for building quantum algorithms that has been recently shown to constitute a universal model of quantum computation. Quantum walks is now a solid field of research of quantum computation full of exciting open problems for physicists, computer scientists, mathematicians and engineers. In this paper we review theoretical advances on the foundations of both discrete- and continuous-time quantum walks, together with the role that randomness plays in quantum walks, the connections between the mathematical models of coined discrete quantum walks and continuous quantum walks, the quantumness of quantum walks, a summary of papers published on discrete quantum walks and entanglement as well as a succinct review of experimental proposals and realizations of discrete-time quantum walks. Furthermore, we have reviewed several algorithms based on both discrete- and continuous-time quantum walks as well as a most important result: the computational universality of both continuous- and discrete- time quantum walks.Comment: Paper accepted for publication in Quantum Information Processing Journa

Automatic recognition of schwa variants in spontaneous Hungarian speech

This paper analyzes the nature of the process involved in optional vowel reduction in Hungarian, and the acoustic structure of schwa variants in spontaneous speech. The study focuses on the acoustic patterns of both the basic realizations of Hungarian vowels and their realizations as neutral vowels (schwas), as well as on the design, implementation, and evaluation of a set of algorithms for the recognition of both types of realizations from the speech waveform. The authors address the question whether schwas form a unified group of vowels or they show some dependence on the originally intended articulation of the vowel they stand for. The acoustic study uses a database consisting of over 4,000 utterances extracted from continuous speech, and recorded from 19 speakers. The authors propose methods for the recognition of neutral vowels depending on the various vowels they replace in spontaneous speech. Mel-Frequency Cepstral Coefficients are calculated and used for the training of Hidden Markov Models. The recognition system was trained on 2,500 utterances and then tested on 1,500 utterances. The results show that a neutral vowel can be detected in 72% of all occurrences. Stressed and unstressed syllables can be distinguished in 92% of all cases. Neutralized vowels do not form a unified group of phoneme realizations. The pronunciation of schwa heavily depends on the original articulation configuration of the intended vowel

The effects of acute and elective cardiac surgery on the anxiety traits of patients with Marfan syndrome

BACKGROUND: Marfan syndrome is a genetic disease, presenting with dysfunction of connective tissues leading to lesions in the cardiovascular and skeletal muscle system. Within these symptoms, the most typical is weakness of the connective tissue in the aorta, manifesting as aortic dilatation (aneurysm). This could, in turn, become annuloaortic ectasia, or life-threatening dissection. As a result, life-saving and preventative cardiac surgical interventions are frequent among Marfan syndrome patients. Aortic aneurysm could turn into annuloaortic ectasia or life-threatening dissection, thus life-saving and preventive cardiac surgical interventions are frequent among patients with Marfan syndrome. We hypothesized that patients with Marfan syndrome have different level of anxiety, depression and satisfaction with life compared to that of the non-clinical patient population. METHODS: Patients diagnosed with Marfan syndrome were divided into 3 groups: those scheduled for prophylactic surgery, those needing acute surgery, and those without need for surgery (n = 9, 19, 17, respectively). To examine the psychological features of the patients, Spielberger's anxiety (STAI) test, Beck's Depression questionnaire (BDI), the Berne Questionnaire of Subjective Well-being, and the Satisfaction with Life scale were applied. RESULTS: A significant difference was found in trait anxiety between healthy individuals and patients with Marfan syndrome after acute life-saving surgery (p 0.1). Finally, a significant, medium size effect was found between patient groups on the Joy in Living scale (F (2.39) = 3.51, p = 0.040, eta2 = 0.15). CONCLUSIONS: Involving psychiatric and mental-health care, in addition to existing surgical treatment interventions, is essential for more successful recovery of patients with Marfan syndrome

Coronary artery bypass surgery provokes alzheimer's disease-like changes in the cerebrospinal fluid

Several biomarkers are used in confirming the diagnosis of cognitive disorders. This study evaluates whether the level of these markers after heart surgery correlates with the development of cognitive dysfunction, which is a frequent complication of cardiac interventions. Concentrations of amyloid-β peptide, tau, and S100β in the cerebro-spinal fluid were assessed, as well as cognitive functions were evaluated before and after coronary artery bypass grafting, utilizing immuno-assays and psychometric tests, respectively. A drastic rise in the level of S100β was observed one week after the surgery, a mark of a severe generalized cerebral injury. The level of amyloid-β peptide significantly decreased, whereas the concentration of tau markedly increased six months postoperatively. Gradual cognitive decline was also present. These findings clearly demonstrate post-surgical cognitive impairment associated with changes in biomarkers similar to that seen in Alzheimer's disease, suggesting a unifying pathognomic factor between the two disorders. A holistic approach to coronary heart disease and Alzheimer's-type dementia is proposed. © 2010 IOS Press and the authors. All rights reserved

Evaluation of post-surgical cognitive function and protein fingerprints in the cerebro-spinal fluid utilizing surface-enhanced laser desorption/ionization time-of-flight mass-spectrometry (SELDI-TOF MS) after coronary artery bypass grafting: Review of proteomic analytic tools and introducing a new syndrome

Cognitive dysfunction following surgery is a common complication, which increases the incidence of other co-morbid conditions, hospital and health-care costs. The reported rate of the occurrence of post-operative cognitive decline varies with different studies, depending on population profile, type of surgery, definition of cognitive disorder and detection methods, design of study, etc. It remains unclear whether these psychiatric signs and symptoms are direct results of the effects of surgery or general anesthesia. Nonetheless they are more frequent after cardiac surgery and are likely to be multi-factorial, but the patho-mechanisms are not yet fully characterized. This communication provides a synopsis of proteomics tools and delineates novel SELDI-TOF results to evaluate biomarkers in this regard. Presented for the first time is a classification of the clinically relevant forms of post-operative cognitive decline with the advent of a novel subclass. © 2011 Bentham Science Publishers Ltd