Effect of Complete Revascularization on 10-Year Survival of Patients With Stable Multivessel Coronary Artery Disease MASS II Trial

Background-The importance of complete revascularization remains unclear and contradictory. This current investigation compares the effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease (CAD) who were randomly assigned to percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). Methods and Results-This is a post hoc analysis of the Second Medicine, Angioplasty, or Surgery Study (MASS II), which is a randomized trial comparing treatments in patients with stable multivessel CAD, and preserved systolic ventricular function. We analyzed patients who underwent surgery (CABG) or stent angioplasty (PCI). The survival free of overall mortality of patients who underwent complete (CR) or incomplete revascularization (IR) was compared. Of the 408 patients randomly assigned to mechanical revascularization, 390 patients (95.6%) underwent the assigned treatment; complete revascularization was achieved in 224 patients (57.4%), 63.8% of those in the CABG group and 36.2% in the PCI group (P = 0.001). The IR group had more prior myocardial infarction than the CR group (56.2% X 39.2%, P = 0.01). During a 10-year follow-up, the survival free of cardiovascular mortality was significantly different among patients in the 2 groups (CR, 90.6% versus IR, 84.4%; P = 0.04). This was mainly driven by an increased cardiovascular specific mortality in individuals with incomplete revascularization submitted to PCI (P = 0.05). Conclusions-Our study suggests that in 10-year follow-up, CR compared with IR was associated with reduced cardiovascular mortality, especially due to a higher increase in cardiovascular-specific mortality in individuals submitted to PCI.

SUFFICIENT CONDITIONS ON DIFFUSIVITY FOR THE EXISTENCE AND NONEXISTENCE OF STABLE EQUILIBRIA WITH NONLINEAR FLUX ON THE BOUNDARY

A reaction-diffusion equation with variable diffusivity and non-linear flux boundary condition is considered. The goal is to give sufficient conditions on the diffusivity function for nonexistence and also for existence of nonconstant stable stationary solutions. Applications are given for the main result of nonexistence.

Cwc24p Is a General Saccharomyces cerevisiae Splicing Factor Required for the Stable U2 snRNP Binding to Primary Transcripts

Splicing of primary transcripts is an essential process for the control of gene expression. Specific conserved sequences in premature transcripts are important to recruit the spliceosome machinery. The Saccharomyces cerevisiae catalytic spliceosome is composed of about 60 proteins and 5 snRNAs (U1, U2, U4/U6 and U5). Among these proteins, there are core components and regulatory factors, which might stabilize or facilitate splicing of specific substrates. Assembly of a catalytic complex depends on the dynamics of interactions between these proteins and RNAs. Cwc24p is an essential S. cerevisiae protein, originally identified as a component of the NTC complex, and later shown to affect splicing in vivo. In this work, we show that Cwc24p also affects splicing in vitro. We show that Cwc24p is important for the U2 snRNP binding to primary transcripts, co-migrates with spliceosomes, and that it interacts with Brr2p. Additionally, we show that Cwc24p is important for the stable binding of Prp19p to the spliceosome. We propose a model in which Cwc24p is required for stabilizing the U2 association with primary transcripts, and therefore, especially important for splicing of RNAs containing non- consensus branchpoint sequences.

Expression Analysis of Wound Healing Genes in Human Periapical Granulomas of Progressive and Stable Nature

Introduction: Wound healing process involves the activation of extracellular matrix components, remodeling enzymes, cellular adhesion molecules, growth factors, cytokines and chemokines genes. However, the molecular patterns underlying the healing process periapical environment remain unclear. Here we hypothesized that endodontic infection might result in an imbalance in the expression of wound healing genes involved in the pathogenesis of periapical lesions. Furthermore, we suggest that differential expression of wound healing markers in active and latent granulomas could account for different clinical outcomes for such lesions. Methods: Study samples consisted of 93 periapical granulomas collected after endodontic surgeries and 24 healthy periodontal ligament tissues collected from premolars extracted for orthodontic purposes as control samples. Of these, 10 periapical granulomas and 5 healthy periapical tissues were used for expression analysis of 84 wound healing genes by using a pathway-specific real-time polymerase chain reaction array. The remaining 83 granulomas and all 24 control specimens were used to validate the obtained array data by real-time polymerase chain reaction. Observed variations in expression of wound healing genes were analyzed according to the classification of periapical granulomas as active/progressive versus inactive/stable (as determined by receptor activator for nuclear factor kappa B ligand/osteoprotegerin expression ratio). Results: We observed a marked increase of 5-fold or greater in SERPINE1, TIMP1, COL1A1, COL5A1, VTN, CTGF, FGF7, TGFB1, TNF, CXCL11, ITGA4, and ITGA5 genes in the periapical granulomas when compared with control samples. SERPINE1, TIMP1, COL1A1, TGFB1, and ITGA4 mRNA expression was significantly higher in inactive compared with active periapical granulomas (P < .001), whereas TNF and CXCL11 mRNA expression was higher in active lesions (P < .001). Conclusions: The identification of novel gene targets that curb the progression status of periapical lesions might contribute to a more accurate diagnosis and lead to treatment modalities more conducive to endodontic success. (J Endod 2012;38:185-190)

Colibacillosis in lambs is associated to type I heat-stable enterotoxin in a farm in Sao Paulo State, Brazil

Twenty seven (48.2%) culture supernatants of 56 Escherichia coli isolated from diarrheic lamb feces (7 to 10 days old) in Sao Paulo State, Brazil, presented positive results to suckling mice assay (fluid accumulation) but none caused cytopathic effects on Vero and CHO cells, indicating that these strains did not produced LT or VT toxins. PCR assays showed that these 27 E. coli strains harbored estA, that codifies for STa, but not for stx1, stx2 or cnf genes. The positive STa strains were checked for genes that codify for F41, F17 and K99 fimbriae, wich are considered colonization factors in ETEC. Only F17 was detect in two samples (7.4%). Twelve of 27 STa positive carried hlyA gene and presented hemolytic activity in blood Agar. Presence of rotavirus was not detected among the diarrheic feces. These data suggests that STa must be an important diarrheagenic factor to small ruminants in Sao Paulo State.

Sensitivity, specificity and predictive values of linear and nonlinear indices of heart rate variability in stable angina patients

Abstract Background Decreased heart rate variability (HRV) is related to higher morbidity and mortality. In this study we evaluated the linear and nonlinear indices of the HRV in stable angina patients submitted to coronary angiography. Methods We studied 77 unselected patients for elective coronary angiography, which were divided into two groups: coronary artery disease (CAD) and non-CAD groups. For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 40 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal], NN50 [total number of adjacent RR intervals with a difference of duration greater than 50ms] and RMSSD [root-mean square of differences]) and frequency domains ultra-low frequency (ULF) ≤ 0,003 Hz, very low frequency (VLF) 0,003 – 0,04 Hz, low frequency (LF) (0.04–0.15 Hz), and high frequency (HF) (0.15–0.40 Hz) as well as the ratio between LF and HF components (LF/HF). In relation to the nonlinear indices we evaluated SD1, SD2, SD1/SD2, approximate entropy (−ApEn), α1, α2, Lyapunov Exponent, Hurst Exponent, autocorrelation and dimension correlation. The definition of the cutoff point of the variables for predictive tests was obtained by the Receiver Operating Characteristic curve (ROC). The area under the ROC curve was calculated by the extended trapezoidal rule, assuming as relevant areas under the curve ≥ 0.650. Results Coronary arterial disease patients presented reduced values of SDNN, RMSSD, NN50, HF, SD1, SD2 and -ApEn. HF ≤ 66 ms2, RMSSD ≤ 23.9 ms, ApEn ≤−0.296 and NN50 ≤ 16 presented the best discriminatory power for the presence of significant coronary obstruction. Conclusion We suggest the use of Heart Rate Variability Analysis in linear and nonlinear domains, for prognostic purposes in patients with stable angina pectoris, in view of their overall impairment.

Synthesis and Physical-Chemical characterization of Metallic Nanoparticles

The stabilization of nanoparticles against their irreversible particle aggregation and oxidation reactions. is a requirement for further advancement in nanoparticle science and technology. For this reason the research aim on this topic focuses on the synthesis of various metal nanoparticles protected with monolayers containing different reactive head groups and functional tail groups. In this work cuprous bromide nanocrystals haave been synthetized with a diameter of about 20 nanometers according to a new sybthetic method adding dropwise ascorbic acid to a water solution of lithium bromide and cupric chloride under continuous stirring and nitrogen flux. Butane thiolate Cu protected nanoparticles have been synthetized according to three different syntesys methods. Their morphologies appear related to the physicochemical conditions during the synthesis and to the dispersing medium used to prepare the sample. Synthesis method II allows to obtain stable nanoparticles of 1-2 nm in size both isolated and forming clusters. Nanoparticle cluster formation was enhanced as water was used as dispersing medium probably due to the idrophobic nature of the butanethiolate layers coating the nanoparticle surface. Synthesis methods I and III lead to large unstable spherical nanoparticles with size ranging between 20 to 50 nm. These nanoparticles appeared in the TEM micrograph with the same morphology independently on the dispersing medium used in the sample preparation. The stability and dimensions of the copper nanoparticles appear inversely related. Using the same methods above described for the butanethiolate protected copper nanoparticles 4-methylbenzenethiol protected copper nanoparticles have been prepared. Diffractometric and spectroscopic data reveal that decomposition processes didn’t occur in both the 4-methylbenzenethiol copper protected nanoparticles precipitates from formic acid and from water in a period of time six month long. Se anticarcinogenic effects by multiple mechanisms have been extensively investigated and documented and Se is defined a genuine nutritional cancer-protecting element and a significant protective effect of Se against major forms of cancer. Furthermore phloroglucinol was found to possess cytoprotective effects against oxidative stress, thanks to reactive oxygen species (ROS) which are associated with cells and tissue damages and are the contributing factors for inflammation, aging, cancer, arteriosclerosis, hypertension and diabetes. The goal of our work has been to set up a new method to synthesize in mild conditions amorphous Se nanopaticles surface capped with phloroglucinol, which is used during synthesis as reducing agent to obtain stable Se nanoparticles in ethanol, performing the synergies offered by the specific anticarcinogenic properties of Se and the antioxiding ones of phloroalucinol. We have synthesized selenium nanoparticles protected by phenolic molecules chemically bonded to their surface. The phenol molecules coating the nanoparticles surfaces form low ordered arrays as can be seen from the wider shape of the absorptions in the FT-IR spectrum with respect to those appearing in that of crystalline phenol. On the other hand, metallic nanoparticles with unique optical properties, facile surface chemistry and appropriate size scale are generating much enthusiasm in nanomedicine. In fact Au nanoparticles has immense potential for both cancer diagnosis and therapy. Especially Au nanoparticles efficiently convert the strongly adsorbed light into localized heat, which can be exploited for the selective laser photothermal therapy of cancer. According to the about, metal nanoparticles-HA nanocrystals composites should have tremendous potential in novel methods for therapy of cancer. 11 mercaptoundecanoic surface protected Au4Ag1 nanoparticles adsorbed on nanometric apathyte crystals we have successfully prepared like an anticancer nanoparticles deliver system utilizing biomimetic hydroxyapatyte nanocrystals as deliver agents. Furthermore natural chrysotile, formed by densely packed bundles of multiwalled hollow nanotubes, is a mineral very suitable for nanowires preparation when their inner nanometer-sized cavity is filled with a proper material. Bundles of chrysotile nanotubes can then behave as host systems, where their large interchannel separation is actually expected to prevent the interaction between individual guest metallic nanoparticles and act as a confining barrier. Chrysotile nanotubes have been filled with molten metals such as Hg, Pb, Sn, semimetals, Bi, Te, Se, and with semiconductor materials such as InSb, CdSe, GaAs, and InP using both high-pressure techniques and metal-organic chemical vapor deposition. Under hydrothermal conditions chrysotile nanocrystals have been synthesized as a single phase and can be utilized as a very suitable for nanowires preparation filling their inner nanometer-sized cavity with metallic nanoparticles. In this research work we have synthesized and characterized Stoichiometric synthetic chrysotile nanotubes have been partially filled with bi and monometallic highly monodispersed nanoparticles with diameters ranging from 1,7 to 5,5 nm depending on the core composition (Au, Au4Ag1, Au1Ag4, Ag). In the case of 4 methylbenzenethiol protected silver nanoparticles, the filling was carried out by convection and capillarity effect at room temperature and pressure using a suitable organic solvent. We have obtained new interesting nanowires constituted of metallic nanoparticles filled in inorganic nanotubes with a inner cavity of 7 nm and an isolating wall with a thick ranging from 7 to 21 nm.

Electrochemistry of carbon based engineered structures

The main aims of my PhD research work have been the investigation of the redox, photophysical and electronic properties of carbon nanotubes (CNT) and their possible uses as functional substrates for the (electro)catalytic production of oxygen and as molecular connectors for Quantum-dot Molecular Automata. While for CNT many and diverse applications in electronics, in sensors and biosensors field, as a structural reinforcing in composite materials have long been proposed, the study of their properties as individual species has been for long a challenging task. CNT are in fact virtually insoluble in any solvent and, for years, most of the studies has been carried out on bulk samples (bundles). In Chapter 2 an appropriate description of carbon nanotubes is reported, about their production methods and the functionalization strategies for their solubilization. In Chapter 3 an extensive voltammetric and vis-NIR spectroelectrochemical investigation of true solutions of unfunctionalized individual single wall CNT (SWNT) is reported that permitted to determine for the first time the standard electrochemical potentials of reduction and oxidation as a function of the tube diameter of a large number of semiconducting SWNTs. We also established the Fermi energy and the exciton binding energy for individual tubes in solution and, from the linear correlation found between the potentials and the optical transition energies, one to calculate the redox potentials of SWNTs that are insufficiently abundant or absent in the samples. In Chapter 4 we report on very efficient and stable nano-structured, oxygen-evolving anodes (OEA) that were obtained by the assembly of an oxygen evolving polyoxometalate cluster, (a totally inorganic ruthenium catalyst) with a conducting bed of multiwalled carbon nanotubes (MWCNT). Here, MWCNT were effectively used as carrier of the polyoxometallate for the electrocatalytic production of oxygen and turned out to greatly increase both the efficiency and stability of the device avoiding the release of the catalysts. Our bioinspired electrode addresses the major challenge of artificial photosynthesis, i.e. efficient water oxidation, taking us closer to when we might power the planet with carbon-free fuels. In Chapter 5 a study on surface-active chiral bis-ferrocenes conveniently designed in order to act as prototypical units for molecular computing devices is reported. Preliminary electrochemical studies in liquid environment demonstrated the capability of such molecules to enter three indistinguishable oxidation states. Side chains introduction allowed to organize them in the form of self-assembled monolayers (SAM) onto a surface and to study the molecular and redox properties on solid substrates. Electrochemical studies on SAMs of these molecules confirmed their attitude to undergo fast (Nernstian) electron transfer processes generating, in the positive potential region, either the full oxidized Fc+-Fc+ or the partly oxidized Fc+-Fc species. Finally, in Chapter 6 we report on a preliminary electrochemical study of graphene solutions prepared according to an original procedure recently described in the literature. Graphene is the newly-born of carbon nanomaterials and is certainly bound to be among the most promising materials for the next nanoelectronic generation.

Stable isotope investigations of atmospheric nitrous oxide

ZusammenfassungDie Analyse von Isotopenverhältnissen ist von wachsender Bedeutung bei der Untersuchung von Quellen, Senken und chemischen Reaktionswegen atmosphärischer Spurengase. Distickstoffoxid (N2O) hat vier isotopisch einfach substituierte Spezies: 14N15N16O, 15N14N16O, 14N217O und 14N218O. In der vorliegenden Arbeit wurden massenspektrometrische Methoden entwickelt, die eine komplette Charakterisierung der Variationen im Vorkommen dieser Spezies ermöglichen. Es wird die bisher umfassendste Darstellung dieser Variationen in Troposphäre und Stratosphäre gegeben und mit Bezug auf eine Reihe von Laborexperimenten detailliert interpretiert.Die Laborexperimente machen einen großen Anteil dieser Doktorarbeit aus und konzentrieren sich auf die Isotopenfraktionierung in den stratosphärischen N2O-Senken, d. h. Photolyse und Reaktion mit elektronisch angeregten Sauerstoffatomen, O(1D). Diese Prozesse sind von dominantem Einfluß auf die Isotopenzusammensetzung von atmosphärischem N2O. Potentiell wichtige Parameter wie Temperatur- und Druckvariationen, aber auch Veränderungen der Wellenlänge im Fall der Photolyse wurden berücksichtigt. Photolyse bei stratosphärisch relevanten Wellenlängen > 190 nm zeigte immer Anreicherungen von 15N in beiden Stickstoffatomen des verbleibenden N2O wie auch in 17O und 18O. Die Anreicherungen waren am mittelständigen N-Atom signifikant höher als am endständigen N (mit mittleren Werten für 18O) und stiegen zu größeren Wellenlängen und niedrigeren Temperaturen hin an. Erstmalig wurden für 18O und 15N am endständigen N-Atom Isotopenabreicherungen bei 185 nm-Photolyse festgestellt. Im Gegensatz zur Photolyse waren die Isotopenanreicherungen bei der zweiten wichtigen N2O-Senke, Reaktion mit O(1D) vergleichsweise gering. Jedoch war das positionsabhängige Fraktionierungsmuster dem der Photolyse direkt entgegengesetzt und zeigte größere Anreicherungen am endständigen N-Atom. Demgemäß führen beiden Senkenprozesse zu charakteristischen Isotopensignaturen in stratosphärischem N2O. Weitere N2O-Photolyseexperimente zeigten, daß 15N216O in der Atmosphäre höchstwahrscheinlich mit der statistisch zu erwartenden Häufigkeit vorkommt.Kleine stratosphärische Proben erforderten die Anpassung der massenspektrometrischen Methoden an Permanentflußtechniken, die auch für Messungen an Firnluftproben von zwei antarktischen Stationen verwendet wurden. Das 'Firnluftarchiv' erlaubte es, den gegenwärtigen Trend und die präindustriellen Werte der troposphärischen N2O-Isotopensignatur zu bestimmen. Ein daraus konstruiertes globales N2O-Isotopenbudget ist im Einklang mit den besten Schätzungen der Gesamt-N2O-Emissionen aus Böden und Ozeanen.17O-Messungen bestätigten die Sauerstoffisotopenanomalie in atmosphärischem N2O, zeigten aber auch, daß N2O-Photolyse die Sauerstoffisotope gemäß einem massenabhängigen Fraktionierungsgesetz anreichert. Eine troposphärische Ursache für einen Teil des Exzeß-17O wurde vorgeschlagen, basierend auf der Reaktion von NH2 mit NO2, wodurch die Sauerstoffisotopenanomalie von O3 über NO2 an N2O übertragen wird.

Modelling the stable, nocturnal boundary layer: different approaches to turbulence closure problem

Il lavoro è dedicato all'analisi fisica e alla modellizzazione dello strato limite atmosferico in condizioni stabili. L'obiettivo principale è quello di migliorare i modelli di parametrizzazione della turbulenza attualmente utilizzati dai modelli meteorologici a grande scala. Questi modelli di parametrizzazione della turbolenza consistono nell' esprimere gli stress di Reynolds come funzioni dei campi medi (componenti orizzontali della velocità e temperatura potenziale) usando delle chiusure. La maggior parte delle chiusure sono state sviluppate per i casi quasi-neutrali, e la difficoltà è trattare l'effetto della stabilità in modo rigoroso. Studieremo in dettaglio due differenti modelli di chiusura della turbolenza per lo strato limite stabile basati su assunzioni diverse: uno schema TKE-l (Mellor-Yamada,1982), che è usato nel modello di previsione BOLAM (Bologna Limited Area Model), e uno schema sviluppato recentemente da Mauritsen et al. (2007). Le assunzioni delle chiusure dei due schemi sono analizzate con dati sperimentali provenienti dalla torre di Cabauw in Olanda e dal sito CIBA in Spagna. Questi schemi di parametrizzazione della turbolenza sono quindi inseriti all'interno di un modello colonnare dello strato limite atmosferico, per testare le loro predizioni senza influenze esterne. Il confronto tra i differenti schemi è effettuato su un caso ben documentato in letteratura, il "GABLS1". Per confermare la validità delle predizioni, un dataset tridimensionale è creato simulando lo stesso caso GABLS1 con una Large Eddy Simulation. ARPS (Advanced Regional Prediction System) è stato usato per questo scopo. La stratificazione stabile vincola il passo di griglia, poichè la LES deve essere ad una risoluzione abbastanza elevata affinchè le tipiche scale verticali di moto siano correttamente risolte. Il confronto di questo dataset tridimensionale con le predizioni degli schemi turbolenti permettono di proporre un insieme di nuove chiusure atte a migliorare il modello di turbolenza di BOLAM. Il lavoro è stato compiuto all' ISAC-CNR di Bologna e al LEGI di Grenoble.

Point defects in carbon nanostructures studied by in-situ electron microscopy

In the present work, the formation and migration of point defects induced by electron irradiation in carbon nanostructures, including carbon onions, nanotubes and graphene layers, were investigated by in-situ TEM. The mobility of carbon atoms normal to the layers in graphitic nanoparticles, the mobility of carbon interstitials inside SWCNTs, and the migration of foreign atoms in graphene layers or in layers of carbon nanotubes were studied. The diffusion of carbon atoms in carbon onions was investigated by annealing carbon onions and observing the relaxation of the compressed clusters in the temperature range of 1200 – 2000oC. An activation energy of 5.0±0.3 eV was obtained. This rather high activation energy for atom exchange between the layers not only prevents the exchange of carbon atoms between the layers at lower temperature but also explains the high morphological and mechanical stability of graphite nanostructures. The migration of carbon atoms in SWCNTs was investigated quantitatively by cutting SWCNT bundles repeatedly with a focused electron beam at different temperatures. A migration barrier of about 0.25 eV was obtained for the diffusion of carbon atoms inside SWCNTs. This is an experimental confirmation of the high mobility of interstitial atoms inside carbon nanotubes, which corroborates previously developed theoretical models of interstitial diffusivity. Individual Au and Pt atoms in one- or two-layered graphene planes and MWCNTs were monitored in real time at high temperatures by high-resolution TEM. The direct observation of the behavior of Au and Pt atoms in graphenic structures in a temperature range of 600 – 700°C allows us to determine the sites occupied by the metal atoms in the graphene layer and the diffusivities of the metal atoms. It was found that metal atoms were located in single or multiple carbon vacancies, not in off-plane positions, and diffused by site exchange with carbon atoms. Metal atoms showed a tendency to form clusters those were stable for a few seconds. An activation energy of around 2.5 eV was obtained for the in-plane migration of both Au and Pt atoms in graphene (two-dimensional diffusion). The rather high activation energy indicates covalent bonding between metal and carbon atoms. Metal atoms were also observed to diffuse along the open edge of graphene layers (one-dimensional diffusion) with a slightly lower activation energy of about 2.3 eV. It is also found that the diffusion of metal atoms in curved graphenic layers of MWCNTs is slightly faster than in planar graphene.