RESUMEN
Zirconia has been used as an orthopaedic material since 1985 and is increasingly used in dental applications. One major concern with the use of zirconia is the significant loss in mechanical properties through hydrothermal degradation, with the uncontrolled transformation of tetragonal to monoclinic (tâm) zirconia. We report on the addition of alumina and lanthana as dopants to an yttria-stabilized tetragonal zirconia polycrystal ceramic as an effective strategy to significantly decelerate the hydrothermal degradation kinetics, without any loss of mechanical properties, in particular, fracture toughness. Hydrothermal degradation was studied on the exposed surface as well as in the sub-surface region using Raman microspectroscopy, atomic force microscopy and cross-sectional transmission electron microscopy, providing a comprehensive insight into the mechanism of propagation of the tâm transformation. The addition of dopants resulted in the reduction of monoclinic zirconia nucleation rate at the surface and a substantial deceleration of the overall transformation kinetics, in particular a greatly reduced propagation of the transformation into the bulk and decreased grain boundary microcracking. High-resolution transmission electron microscopy analysis showed that the co-dopant cations segregate to the grain boundaries where they play a key role in the stabilization of the zirconia tetragonal phase.
Asunto(s)
Óxido de Aluminio/química , Materiales Biocompatibles/química , Lantano/química , Óxidos/química , Agua/química , Circonio/química , Calor , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
Single-strand DNA (ssDNA)-binding proteins (SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand-exchange proteins, activating transcription and mediating protein-protein interactions. In eukaryotes, the major SSB, replication protein A (RPA), is a heterotrimer. Here we describe a second human SSB (hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell-cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S-phase cells and hSSB1 deficiency does not influence S-phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response.
Asunto(s)
Reparación del ADN , Proteínas de Unión al ADN/metabolismo , Inestabilidad Genómica , Proteínas de la Ataxia Telangiectasia Mutada , Ciclo Celular/efectos de los fármacos , Ciclo Celular/efectos de la radiación , Proteínas de Ciclo Celular/metabolismo , Reparación del ADN/efectos de la radiación , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/genética , Inestabilidad Genómica/efectos de la radiación , Células HeLa , Humanos , Proteínas Mitocondriales , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Transporte de Proteínas/efectos de la radiación , Radiación Ionizante , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Information processing pathways such as DNA replication are conserved in eukaryotes and archaea and are significantly different from those found in bacteria. Single-stranded DNA-binding (SSB) proteins (or replication protein A, RPA, in eukaryotes) play a central role in many of these pathways. However, whilst euryarchaea have a eukaryotic-type RPA homologue, crenarchaeal SSB proteins appear much more similar to the bacterial proteins, with a single OB fold for DNA binding and a flexible C-terminal tail that is implicated in protein-protein interactions. We have determined the crystal structure of the SSB protein from the crenarchaeote Sulfolobus solfataricus to 1.26 A. The structure shows a striking and unexpected similarity to the DNA-binding domains of human RPA, providing confirmation of the close relationship between archaea and eukaryotes. The high resolution of the structure, together with thermodynamic and mutational studies of DNA binding, allow us to propose a molecular basis for DNA binding and define the features required for eukaryotic and archaeal OB folds.
Asunto(s)
Proteínas Arqueales/química , Proteínas Arqueales/metabolismo , ADN de Cadena Simple/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Secuencia de Aminoácidos , Proteínas Arqueales/genética , Secuencia de Bases , Sitios de Unión , Cristalografía por Rayos X , ADN de Archaea/genética , ADN de Archaea/metabolismo , ADN de Cadena Simple/genética , Proteínas de Unión al ADN/genética , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Modelos Moleculares , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Pliegue de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteína de Replicación A , Homología de Secuencia de Aminoácido , Sulfolobus/genética , Sulfolobus/metabolismo , TermodinámicaAsunto(s)
Tiempo de Internación/economía , Trastornos Mentales/rehabilitación , Admisión del Paciente/economía , Servicio de Psiquiatría en Hospital/estadística & datos numéricos , Connecticut , Ahorro de Costo , Intervención en la Crisis (Psiquiatría) , Estudios de Seguimiento , Humanos , Programas Controlados de Atención en Salud/economía , Trastornos Mentales/economía , Grupo de Atención al Paciente/economía , Readmisión del Paciente/economía , Resultado del TratamientoRESUMEN
Right atrial cardioplegia has been advocated as a simple method of delivering retrograde cardioplegia. Passive distention of the right heart inherent with right atrial cardioplegia has been shown to impair right ventricular function in a canine model of global ischemia. This study was designed to compare right ventricular performance after right atrial cardioplegia administered intermittently (n = 5) and continuously (n = 5) with coronary sinus retrograde cardioplegia (n = 5) and aortic root cardioplegia (n = 8) in a canine model of acute right ventricular ischemia and reperfusion. Right ventricular performance was assessed using the load-independent relationship of end-systolic pressure versus dimension (myocardial fiber length). Right ventricular performance was well preserved after reperfusion in those dogs protected with intermittent right atrial cardioplegia (95% of control). Results with continuous right atrial cardioplegia (66% of control) and coronary sinus retrograde cardioplegia (40% of control) demonstrated diminished postreperfusion right ventricular performance. Right ventricular performance in the group protected with aortic root cardioplegia was significantly impaired after reperfusion when compared with all retrograde groups (34% of control, p less than 0.05). In this model, postreperfusion right ventricular performance was preserved in the right atrial cardioplegia groups despite passive ventricular distention. All methods of retrograde cardioplegia resulted in superior preservation of right ventricular performance when compared with standard aortic root cardioplegia.
Asunto(s)
Paro Cardíaco Inducido/métodos , Daño por Reperfusión Miocárdica/prevención & control , Reperfusión Miocárdica , Animales , Perros , Ecocardiografía , Atrios Cardíacos , Contracción Miocárdica , Volumen SistólicoRESUMEN
Although blood cardioplegia provides excellent protection, myocardial metabolic recovery is delayed. To evaluate the benefits of a terminal warm cardioplegic infusion after cold blood cardioplegia, we performed a prospective randomized trial in 20 patients undergoing elective coronary bypass grafting. Eleven patients received cold blood cardioplegia and nine patients received cold blood cardioplegia and warm blood cardioplegia before cross-clamp removal (hot shot). The hot shot provided oxygen and removed excess lactate from the arrested heart. After the hot shot lactate was extracted by the heart and tissue adenosine triphosphate and glycogen concentrations were preserved. Atrial pacing and volume loading 3 and 4 hours postoperatively decreased myocardial lactate extraction after cold blood cardioplegia but increased lactate extraction after the hot shot. Left atrial pressures were higher at similar end-diastolic volumes (by nuclear ventriculography), which suggested decreased diastolic compliance after cold blood cardioplegia. Terminal warm blood cardioplegia accelerated myocardial metabolic recovery, preserved high-energy phosphates, improved the metabolic response to postoperative hemodynamic stresses, and reduced left atrial pressures.
Asunto(s)
Puente de Arteria Coronaria , Paro Cardíaco Inducido/métodos , Miocardio/metabolismo , Adenosina Trifosfato/metabolismo , Adulto , Sangre , Ensayos Clínicos como Asunto , Frío , Glucógeno/metabolismo , Humanos , Lactatos/metabolismo , Persona de Mediana Edad , Oxígeno/metabolismo , Fosfocreatina/metabolismo , Estudios Prospectivos , Distribución Aleatoria , TemperaturaRESUMEN
The promise of technology for improving the quality of life has never been greater, and American science and technology has led the way toward fulfillment of that promise. Now this preeminence is threatened by forces that may affect technological progress throughout the world. It is up to those of us in science, industry, and government to strengthen the institutions that have made us the leaders and to restore our initiative.
RESUMEN
A technique is described for intermittent decompression of the left ventricle. This method provides all of the advantages of left ventricular venting while eliminating the hazards. The technique is most advantageous in coronary artery operations.