Stabilization of Polar Nano Regions in Pb-free ferroelectrics

Formation of polar nano regions through solid-solution additions are known to enhance significantly the functional properties of ferroelectric materials. Despite considerable progress in characterizing the microscopic behavior of polar nano regions, understanding their real-space atomic structure and dynamics of formation remains a considerable challenge. Here, using the method of dynamic pair distribution function, we provide direct insights into the role of solid-solution additions towards the stabilization of polar nano regions in the Pb-free ferroelectric of Ba(Zr,Ti)O3. It is shown that for an optimum level of substitution of Ti by larger Zr ions, the dynamics of atomic displacements for ferroelectric polarization are slowed sufficiently, which leads to increased local correlation among dipoles below THz frequencies. The dynamic pair distribution function technique demonstrates unique capability to obtain insights into locally correlated atomic dynamics in disordered materials, including new Pb-free ferroelectrics, which is necessary to understand and control their functional properties

Intravenous delivery of adeno-associated virus 9-encoded IGF-1Ea propeptide improves post-infarct cardiac remodelling

The insulin-like growth factor Ea propeptide (IGF-1Ea) is a powerful enhancer of cardiac muscle growth and regeneration, also blocking age-related atrophy and beneficial in multiple skeletal muscle diseases. The therapeutic potential of IGF-1Ea compared with mature IGF-1 derives from its local action in the area of synthesis. We have developed an adeno-associated virus (AAV) vector for IGF-1Ea delivery to the heart to treat mice after myocardial infarction and examine the reparative effects of local IGF-1Ea production on left ventricular remodelling. A cardiotropic AAV9 vector carrying a cardiomyocyte-specific IGF-1Ea-luciferase bi-cistronic gene expression cassette (AAV9.IGF-1Ea) was administered intravenously to infarcted mice, 5 h after ischemia followed by reperfusion (I/R), as a model of myocardial infarction. Virally encoded IGF-1Ea in the heart improved global left ventricular function and remodelling, as measured by wall motion and thickness, 28 days after delivery, with higher viral titers yielding better improvement. The present study demonstrates that single intravenous AAV9-mediated IGF-1Ea Gene Therapy represents a tissue-targeted therapeutic approach to prevent the adverse remodelling after myocardial infarct

Aprofitem el moment de la 'postcoital'

Són moltes les informacions i opinions diverses que han sorgit últimament sobre l'anticoncep­ció postcoital. Els mitjans de comunicació no només han donat a conèixer aquest anticon­ceptiu d'emergència sinó que a més, han fet ressó del debat que suscita aquest producte en el nostre context social actual. Per això, per tractar tot el referent a la postcoital, s'ha de tenir present que aquest no és un tema nou d'ara, i que s'ha d'aprofitar aquest 'boom' informatiu i mediàtic per a reflexionar respec­te altres aspectes de la postcoital relacionats amb la sexualitat i l'adolescència. Aquest article d'opinió no vol donar més informació sobre la contracepció, sinó que vol fer públiques algunes reflexions al voltant de la contracepció d'emergència i remarcar el paper de la infermera com a educadora per a la salut sexual i reproductiva de la població

Presentación de las actividades que lleva a cabo el grupo ORIÓN de investigación del área de óptica de la Universidad de Extremadura

Per ser conseqüents amb la nostra línia de treball d'innovació en l’ensenyament de la física i amb la línia editorial d'aquesta revista, aquest article sobre els treballs d'innovació i investigació educativa del nostre grup Orión d’investigació, es presenta en forma de mapa conceptual. La millor manera de llegir-lo és, si es té instal·lat el CmapTools a l'ordinador, visitar el lloc Cmap Universitat d'Extremadura (Espanya) i entrar a la carpeta Investigaciones del Grupo Orión. Encara que d'una forma una mica més limitada (no es podran obrir els Post-its aclaridors que hi apareixen), també pot llegir-se anant a l'adreça web: <http://grupoorion.unex.es:8001> i entrant a la carpeta indicada. Per qualsevol d'aquests dos procediments s'arriba al mapa conceptual que apareix més endavant i que resumeix les activitats del nostre grup. En aquest mapa apareixen multitud de vincles que porten als resultats dels diferents treballs duts a terme.Para resultar consecuentes con nuestra línea de trabajo de Innovación en la Enseñanza de la Física y con la línea editorial de esta revista, este artículo sobre los trabajos de Innovación e Investigación Educativa de nuestro Grupo Orión de Investigación, se presenta en forma de Mapa Conceptual. La mejor forma de leerlo es, si se tiene instalado CmapTools en el ordenador, visitar el Sitio Cmap “Universidad de Extremadura (España)” y entrar en la carpeta “Investigaciones del Grupo Orión”. Aunque de una forma algo más limitada (no se podrán abrir los post-it aclaratorios que aparecen), también puede leerse yendo a la dirección Web: http://grupoorion.unex.es:8001 y entrando en la carpeta antes indicada. Por cualquiera de estos 2 procedimientos se llega al mapa conceptual que aparece más adelante y que resume las actividades de nuestro grupo. En dicho mapa aparecen multitud de vínculos que llevan a los resultados de los diferentes trabajos llevados a cabo

Serum levels of caspase-cleaved cytokeratin-18 and mortality are associated in severe septic patients: Pilot study

Objective: Apoptosis is increased in sepsis. Cytokeratin 18 (CK-18), a protein of the intermediate filament group present in most epithelial and parenchymal cells, is cleaved by the action of caspases and released into the blood as caspase-cleaved CK (CCCK)-18 during apoptosis. Circulating levels of CCCK-18 have scarcely been explored in septic patients. In one study with 101 severe septic patients, the authors reported higher serum CCCK-18 levels in non-survivors than in survivors; however, the sample size was too small to demonstrate an association between serum CCCK-18 levels and early mortality and whether they could be used as a biomarker to predict outcomes in septic patients. Thus, these were the objectives of this study with a large series of patients. Methods: We performed a prospective, multicenter, observational study in six Spanish Intensive Care Units with 224 severe septic patients. Blood samples were collected at the time that severe sepsis was diagnosed to determine serum levels of CCCK-18, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-10. The end point was 30-day mortality. Results: Non-surviving patients (n = 80) showed higher serum CCCK-18 levels (P391 u/L were associated with 30-day survival (Odds ratio = 2.687; 95% confidence interval = 1.449-4.983; P = 0.002), controlling for SOFA score, serum lactic acid levels and age. Kaplan-Meier survival analysis showed that the risk of death in septic patients with serum CCCK-18 levels >391 u/L was higher than in patients with lower values (Hazard Ratio = 3.1; 95% CI = 1.96-4.84; P<0.001). Serum CCCK-18 levels were positively associated with serum levels of IL-6 and lactic acid, and with SOFA and APACHE scores. Conclusions: The major novel finding of our study, the largest cohort of septic patients providing data on circulating CCCK-18 levels, was that serum CCCK-18 levels are associated with mortality in severe septic patients

Multiple Folding Pathways of the SH3 domain

Experimental observations suggest that proteins follow different pathways under different environmental conditions. We perform molecular dynamics simulations of a model of the SH3 domain over a broad range of temperatures, and identify distinct pathways in the folding transition. We determine the kinetic partition temperature --the temperature for which the SH3 domain undergoes a rapid folding transition with minimal kinetic barriers-- and observe that below this temperature the model protein may undergo a folding transition via multiple folding pathways. The folding kinetics is characterized by slow and fast pathways and the presence of only one or two intermediates. Our findings suggest the hypothesis that the SH3 domain, a protein for which only two-state folding kinetics was observed in previous experiments, may exhibit intermediates states under extreme experimental conditions, such as very low temperatures. A very recent report (Viguera et al., Proc. Natl. Acad. Sci. USA, 100:5730--5735, 2003) of an intermediate in the folding transition of the Bergerac mutant of the alpha-spectrin SH3 domain protein supports this hypothesis.Comment: 16 pages, 4 figures To be published in the "Journal of Molecular Biology

Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio

Objective: Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and nonsurviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions. Methods: Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality. Results: We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p, 0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8. Conclusions: The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/ MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome

Elliptical Halbach magnet and gradient modules for low-field portable MRI

Objective. To develop methods to design the complete magnetic system for a truly portable MRI scanner for neurological and musculoskeletal (MSK) applications, optimized for field homogeneity, field of view (FoV) and gradient performance compared to existing low-weight configurations. Approach. We explore optimal elliptic-bore Halbach configurations based on discrete arrays of permanent magnets. In this way, we seek to improve the field homogeneity and remove constraints to the extent of the gradient coils typical of Halbach magnets. Specifically, we have optimized a tightly-packed distribution of magnetic Nd$_2$Fe$_14$B cubes with differential evolution algorithms, and a second array of shimming magnets with interior point and differential evolution methods. We have also designed and constructed an elliptical set of gradient coils that extend over the whole magnet length, maximizing the distance between the lobe centers. These are optimized with a target field method minimizing a cost function that considers also heat dissipation. Main result. We have employed the new toolbox to build the main magnet and gradient modules for a portable MRI scanner designed for point-of-care and residential use. The elliptical Halbach bore has semi-axes of 10 & 14 cm and the magnet generates a field of 87 mT homogeneous down to 5,700 ppm (parts per million) in a 20 cm diameter FoV, it weighs 216 kg and has a width of 65 cm and a height of 72 cm. Gradient efficiencies go up to around 0.8 mT/m/A, for a maximum of 12 mT/m with in 0.5 ms with 15 A & 15 V amplifier. The distance between lobes is 28 cm, significantly increased with respect to other Halbach-based scanners. Heat dissipation is around 25 W at maximum power, and gradient deviations from linearity are below 20% in a 20 cm sphere