Estimating 750 years of temperature variations and uncertainties in the Pyrenees by tree-ring reconstructions and climate simulations.

Past temperature variations are usually inferred from proxy data or estimated using general circulation models. Comparisons between climate estimations derived from proxy records and from model simulations help to better understand mechanisms driving climate variations, and also offer the possibility to identify deficiencies in both approaches. This paper presents regional temperature reconstructions based on tree-ring maximum density series in the Pyrenees, and compares them with the output of global simulations for this region and with regional climate model simulations conducted for the target region. An ensemble of 24 reconstructions of May-to-September regional mean temperature was derived from 22 maximum density tree-ring site chronologies distributed over the larger Pyrenees area. Four different tree-ring series standardization procedures were applied, combining two detrending methods: 300-yr spline and the regional curve standardization (RCS). Additionally, different methodological variants for the regional chronology were generated by using three different aggregation methods. Calibration verification trials were performed in split periods and using two methods: regression and a simple variance matching. The resulting set of temperature reconstructions was compared with climate simulations performed with global (ECHO-G) and regional (MM5) climate models. The 24 variants of May-to-September temperature reconstructions reveal a generally coherent pattern of inter-annual to multi-centennial temperature variations in the Pyrenees region for the last 750 yr. However, some reconstructions display a marked positive trend for the entire length of the reconstruction, pointing out that the application of the RCS method to a suboptimal set of samples may lead to unreliable results. Climate model simulations agree with the tree-ring based reconstructions at multi-decadal time scales, suggesting solar variability and volcanism as the main factors controlling preindustrial mean temperature variations in the Pyrenees. Nevertheless, the comparison also highlights differences with the reconstructions, mainly in the amplitude of past temperature variations and in the 20th century trends. Neither proxy-based reconstructions nor model simulations are able to perfectly track the temperature variations of the instrumental record, suggesting that both approximations still need further improvements.

Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial.

INTRODUCTION: Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS: A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS: Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

Ventricularisation of the left atrium: a rare cause of left ventricular dysfunction in a patient with mitral valve prolapse

Case: A 11 yo girl with Marfan syndrome was referred to cardiac MR (CMR) to measure the size of her thoracic aorta. She had a typical phenotype with arachnodactyly, abnormally long arms, and was tall and slim (156 cm, 28 kg, body mass index 11,5 kg/m2). She complained of no symptoms. Cardiac auscultation revealed a prominent mid-systolic click and an end-systolic murmur at the apex. A recent echocardiogram showed a moderately dilated left ventricle with normal function and a mitral valve prolapse with moderate mitral valve regurgitation. CMR showed a dilatation of the aortic root (38 mm, Z-score 8.9) and a severe prolapse of the mitral valve with regurgitation. The ventricular cavity was moderately dilated (116 ml/m2) and its contraction was hyperdynamic (stroke volume (SV): 97 ml; LVEF 72%, with the LV volumes measured by modified Simpson method from the apex to the mitral annulus). In this patient however, the mitral prolapse was characterized by a severe backward movement of the valve toward the left atrium (LA) in systole and the dyskinetic movement of the atrioventricular plane caused a ventricularisation of a part of the LA in systole (Figure). This resulted in a significant reduction of LVEF: more than ¼ of the apparent SV was displaced backwards into the ventricularized LA volume, reducing the effective LVEF to 51% (effective SV 69ml). Moreover, by flow measurement, the SV across the ascending aorta was 30 ml (cardiac index 2.0 l/min/m2) allowing the calculation of a regurgitant fraction across the mitral valve of 56%, which was diagnostic for a severe mitral valve insufficiency. Conclusion: This case illustrates the phenomenon of a ventricularisation of the LA where the severe prolapse gives the illusion of a higher attachement of the mitral leaflets within the atrial wall. Besides the severe mitral regurgitation, this paradoxical backwards movement of the valve causes an intraventricular unloading during systole reducing the apparent LVEF of 72% to an effective LVEF of only 51%. In addition, forward flow fraction is only 22% after accounting for the regurgitant volume, as well. This combined involvement of the mitral valve could explain the discrepancy between a low output state and an apparently hyperdynamic LV contraction. Due to its ability to precisely measure flows and volumes, CMR is particularly suited to detect this phenomenon and to quantify its impact on the LV pump function.

The genetic basis of color-related local adaptation in a ring-like colonization around the Mediterranean.

Uncovering the genetic basis of phenotypic variation and the population history under which it established is key to understand the trajectories along which local adaptation evolves. Here, we investigated the genetic basis and evolutionary history of a clinal plumage color polymorphism in European barn owls (Tyto alba). Our results suggest that barn owls colonized the Western Palearctic in a ring-like manner around the Mediterranean and meet in secondary contact in Greece. Rufous coloration appears to be linked to a recently evolved nonsynonymous-derived variant of the melanocortin 1 receptor (MC1R) gene, which according to quantitative genetic analyses evolved under local adaptation during or following the colonization of Central Europe. Admixture patterns and linkage disequilibrium between the neutral genetic background and color found exclusively within the secondary contact zone suggest limited introgression at secondary contact. These results from a system reminiscent of ring species provide a striking example of how local adaptation can evolve from derived genetic variation.

Conforma: a program for determining ring conformations and puckering coordinates

A program (CONFORMA) was developed to calculate ring puckering coordinates using Cremer and Pople's (J. Am. Chem. Soc. 1975, 97, 1354) methodology, which quantifies the conformation of five or more atom rings. The program performs, also, a conformational analysis based on these results.

DFM(A)- aspects for a microwave waveguide ring resonator design

In this research manufacturability analysis is made for an E-plane waveguide ring resonator. About the electrical characteristics of the waveguide ring resonator is discussed. Possibilities to utilize concurrent engineering method both for designing and making manufacturability analysis for MW- and RF-components are discussed. For helping to establish the necessary guidelines for easy manufacturing and assembly of the waveguide ring resonator a specialised DFM(A)-questionnaire is generated. The questionnaire gives also new information for collaborative designing approach in MW-/RF- engineering. The advantages and disadvantages of the concurrent engineering design method are evaluated in the research.

Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

The natural occurrence, biological activities and synthetic approaches to natural eight-, nine-, and eleven-membered lactones is reviewed. These medium ring lactones are grouped according to ring size, and their syntheses are discussed. The structures of some natural products early identified as medium-ring lactones were revised after total synthesis.

Avaliação da evolução da área das valvas mitral e tricúspide fetal com ultrassonografia tridimensional

OBJETIVO: avaliar as áreas das válvulas atrioventriculares (tricúspide e mitral) de fetos normais por meio da ultrassonografia tridimensional (US3D) utilizando o método STIC (spatiotemporal image correlation). MÉTODOS: realizou-se estudo de corte transversal com 141 mulheres entre a 18ª e a 33ª semana de gestação. As medidas dos volumes cardíacos foram obtidas por um transdutor volumétrico transabdominal acoplado ao aparelho Voluson 730 Expert. Utilizou-se como referência o plano de quatro câmaras com a ROI (região de interesse) posicionada a partir dos ventrículos, sendo a área das valvas delimitada manualmente. Para conhecer a correlação das áreas valvulares com a idade gestacional, foram construídos diagramas de dispersão e calculou-se o coeficiente de correlação de Pearson (r). Foram calculadas médias, medianas, desvios padrão (DP), valores máximo e mínimo. Para se determinar intervalos de referência das áreas valvulares em função da idade gestacional, seguiu-se o modelo de regressão linear simples, utilizando o método de Altman, com nível de significância de p<0,05. Para o cálculo da reprodutibilidade intraobservador, utilizou-se o coeficiente de correlação intraclasse (CCI) e o gráfico de Bland-Altman. RESULTADOS: as áreas valvulares tricúspide e mitral se correlacionaram com a idade gestacional (r=0,80 para a tricúspide e r=0,79 para a mitral), sendo que a média aumentou da válvula tricúspide e mitral, respectivamente, de 0,22±0,10 cm² e de 0,23±0,10 cm² na 18º semana para 0,92±0,29 cm² e para 1,08±0,41 cm² na 33º semana de gestação. A reprodutibilidade intraobservador resultou em CCI=0,993 (IC95% 0,987; 0,996), com diferença média de 0,01 cm² (DP±0,2 cm² e IC95%±0,4 cm²). CONCLUSÃO: intervalos de referência para a área das valvares mitral e tricúspide entre a 18ªe a 33ª semana de gestação foram determinados pela US3D e se mostraram altamente reprodutíveis.

Occurrence of parasitism by Dioctophyma renale in ring-tailed coatis (Nasua nasua) of the Tiete Ecological Park, São Paulo, Brazil

Dioctophymosis is a worldwide renal parasitosis caused by the Dioctophyma renale nematode, which results in progressive destruction of renal tissue. Aquatics annelids are considered the main intermediate hosts and the literature refers as permanent hosts of dogs, wild mammals and even humans. During procedures for population control of coatis (Nasua nasua) in the Ecological Park of Tietê (PET), was noticed the presence of parasitosis by D. renale. From 68 animals, males and females, young and adults, submitted to exploratory laparotomy, 51 were positive for the presence of worms, 9 were found only in the right kidney. In 10 cases, in addition to right kidney parasitism, worms were also observed in the abdominal cavity. In 24 cases D. renale was found only in the abdominal cavity and in 8 animals the right kidney was reduced to a small rigid structure. The study showed that the preferred site for parasitism of the worm, considered erratic, was the abdominal cavity in 66.66% of the cases.

Clinical evaluation of enalapril maleate and furosemide usage in dogs with degenerative myxomatous mitral valve, CHF functional class Ib

Degenerative myxomatous mitral valve (DMMV) is a heart disease of high incidence in small animal clinical medicine, affecting mainly older dogs and small breeds. Thus, a scientific investigation was performed in order to evaluate the clinical use of the medicines furosemide and enalapril maleate in dogs with this disease in CHF functional class Ib before and after the treatment was established. For this purpose 16 dogs with the given valve disease were used, separated into two groups: the first received furosemide (n=8) and the second received enalapril maleate (n=8) throughout 56 days. The dogs were evaluated in four stages (T0, T14, T28 and T56 day) in relation to clinical signs, hematological, biochemical and serum assessment, which included serum angiotensin converting enzyme (ACE) and aldosterone, as well as radiography, electrocardiography, Doppler-echocardiography and blood pressure. The results regarding the clinical, hematological and serum chemistry evaluations revealed no significant changes in both groups, but significant reductions in the values of ACE and aldosterone in the group receiving enalapril maleate were verified. The radiographic examination revealed reductions of VHS values and variable Pms wave of the electrocardiogram in both groups, but no changes in blood pressure values were identified. The echocardiogram showed a significant decrease of the variables LVDd/s in the studied groups and the FS% in animals that received only enalapril. Therefore, analysis of results showed that monotherapy based on enalapril maleate showed better efficiency of symptoms control in patients with CHF functional class Ib.

Ring Dark Solitons in Toroidal Bose-Einstein Condensates

In this Thesis, we study various aspects of ring dark solitons (RDSs) in quasi-two-dimensional toroidally trapped Bose-Einstein condensates, focussing on atomic realisations thereof. Unlike the well-known planar dark solitons, exact analytic expressions for RDSs are not known. We address this problem by presenting exact localized soliton-like solutions to the radial Gross-Pitaevskii equation. To date, RDSs have not been experimentally observed in cold atomic gases, either. To this end, we propose two protocols for their creation in experiments. It is also currently well known that in dimensions higher than one, (ring) dark solitons are susceptible, in general, to an irreversible decay into vortex-antivortex pairs through the snake instability. We show that the snake instability is caused by an unbalanced quantum pressure across the soliton's notch, linking the instability to the Bogoliubov-de Gennes spectrum. In particular, if the angular symmetry is maintained (or the toroidal trapping is restrictive enough), we show that the RDS is stable (long-lived with a lifetime of order seconds) in two dimensions. Furthermore, when the decay does take place, we show that the snake instability can in fact be reversible, and predict a previously unknown revival phenomenon for the original (many-)RDS system: the soliton structure is recovered and all the point-phase singularities (i.e. vortices) disappear. Eventually, however, the decay leads to an example of quantum turbulence; a quantum example of the laminar-to-turbulent type of transition.

Indole ring oxidation by activated leukocytes prevents the production of hypochlorous acid

Hypochlorous acid (HOCl) released by activated leukocytes has been implicated in the tissue damage that characterizes chronic inflammatory diseases. In this investigation, 14 indole derivatives, including metabolites such as melatonin, tryptophan and indole-3-acetic acid, were screened for their ability to inhibit the generation of this endogenous oxidant by stimulated leukocytes. The release of HOCl was measured by the production of taurine-chloramine when the leukocytes (2 x 10(6) cells/mL) were incubated at 37ºC in 10 mM phosphate-buffered saline, pH 7.4, for 30 min with 5 mM taurine and stimulated with 100 nM phorbol-12-myristate acetate. Irrespective of the group substituted in the indole ring, all the compounds tested including indole, 2-methylindole, 3-methylindole, 2,3-dimethylindole, 2,5-dimethylindole, 2-phenylindole, 5-methoxyindole, 6-methoxyindole, 5-methoxy-2-methylindole, melatonin, tryptophan, indole-3-acetic acid, 5-methoxy-2-methyl-3-indole-acetic acid, and indomethacin (10 µM) inhibited the chlorinating activity of myeloperoxidase (MPO) in the 23-72% range. The compounds 3-methylindole and indole-3-acetic acid were chosen as representative of indole derivatives in a dose-response study using purified MPO. The IC50 obtained were 0.10 ± 0.03 and 5.0 ± 1.0 µM (N = 13), respectively. These compounds did not affect the peroxidation activity of MPO or the production of superoxide anion by stimulated leukocytes. By following the spectral change of MPO during the enzyme turnover, the inhibition of HOCl production can be explained on the basis of the accumulation of the redox form compound-II (MPO-II), which is an inactive chlorinating species. These results show that indole derivatives are effective and selective inhibitors of MPO-chlorinating activity.

In silico analysis identifies a C3HC4-RING finger domain of a putative E3 ubiquitin-protein ligase located at the C-terminus of a polyglutamine-containing protein

Almost identical polyglutamine-containing proteins with unknown structures have been found in human, mouse and rat genomes (GenBank AJ277365, AF525300, AY879229). We infer that an identical new gene (RING) finger domain of real interest is located in each C-terminal segment. A three-dimensional (3-D) model was generated by remote homology modeling and the functional implications are discussed. The model consists of 65 residues from terminal position 707 to 772 of the human protein with a total length of 796 residues. The 3-D model predicts a ubiquitin-protein ligase (E3) as a binding site for ubiquitin-conjugating enzyme (E2). Both enzymes are part of the ubiquitin pathway to label unwanted proteins for subsequent enzymatic degradation. The molecular contact specificities are suggested for both the substrate recognition and the residues at the possible E2-binding surface. The predicted structure, of a ubiquitin-protein ligase (E3, enzyme class number 6.3.2.19, CATH code 3.30.40.10.4) may contribute to explain the process of ubiquitination. The 3-D model supports the idea of a C3HC4-RING finger with a partially new pattern. The putative E2-binding site is formed by a shallow hydrophobic groove on the surface adjacent to the helix and one zinc finger (L722, C739, P740, P741, R744). Solvent-exposed hydrophobic amino acids lie around both zinc fingers (I717, L722, F738, or P765, L766, V767, V733, P734). The 3-D structure was deposited in the protein databank theoretical model repository (2B9G, RCSB Protein Data Bank, NJ).

Short-term follow-up of exercise training program and beta-blocker treatment on quality of life in dogs with naturally acquired chronic mitral valve disease

This study aimed to evaluate the effects of carvedilol treatment and a regimen of supervised aerobic exercise training on quality of life and other clinical, echocardiographic, and biochemical variables in a group of client-owned dogs with chronic mitral valve disease (CMVD). Ten healthy dogs (control) and 36 CMVD dogs were studied, with the latter group divided into 3 subgroups. In addition to conventional treatment (benazepril, 0.3-0.5 mg/kg once a day, and digoxin, 0.0055 mg/kg twice daily), 13 dogs received exercise training (subgroup I; 10.3±2.1 years), 10 dogs received carvedilol (0.3 mg/kg twice daily) and exercise training (subgroup II; 10.8±1.7 years), and 13 dogs received only carvedilol (subgroup III; 10.9±2.1 years). All drugs were administered orally. Clinical, laboratory, and Doppler echocardiographic variables were evaluated at baseline and after 3 and 6 months. Exercise training was conducted from months 3-6. The mean speed rate during training increased for both subgroups I and II (ANOVA, P>0.001), indicating improvement in physical conditioning at the end of the exercise period. Quality of life and functional class was improved for all subgroups at the end of the study. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level increased in subgroup I from baseline to 3 months, but remained stable after training introduction (from 3 to 6 months). For subgroups II and III, NT-proBNP levels remained stable during the entire study. No difference was observed for the other variables between the three evaluation periods. The combination of carvedilol or exercise training with conventional treatment in CMVD dogs led to improvements in quality of life and functional class. Therefore, light walking in CMVD dogs must be encouraged.