The in-plane electrodynamics of the superconductivity in Bi2Sr2CaCu2O8+d: energy scales and spectral weight distribution

The in-plane infrared and visible (3 meV-3 eV) reflectivity of Bi2Sr2CaCu2O8+d (Bi-2212) thin films is measured between 300 K and 10 K for different doping levels with unprecedented accuracy. The optical conductivity is derived through an accurate fitting procedure. We study the transfer of spectral weight from finite energy into the superfluid as the system becomes superconducting. In the over-doped regime, the superfluid develops at the expense of states lying below 60 meV, a conventional energy of the order of a few times the superconducting gap. In the underdoped regime, spectral weight is removed from up to 2 eV, far beyond any conventional scale. The intraband spectral weight change between the normal and superconducting state, if analyzed in terms of a change of kinetic energy is ~1 meV. Compared to the condensation energy, this figure addresses the issue of a kinetic energy driven mechanism.Comment: 13 pages with 9 figures include

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

Producción agroecológica de leche en el trópico de altura: sinergia entre restauración ecológica y sistemas silvopastoriles

Climate change and the inequality of the global trade of dairy products have seriously affected small milk producers who have adopted an artificial model based on industrial inputs and the extreme genetic specialization of livestock. Although the application of agroecological principles and the growing demand for natural foods indicate an escape route for these producers, agroecological milk production is not easy because the transition requires making difficult decisions that can affect short term productivity. This article summarizes the agroecological transition of a small dairy farm in the central Andes of Colombia.The starting point was the conventional model typical of many mountain dairies in Latin America, based on grass monocultures fertilized with urea and the supplementation of cows with feedstuffs made from imported cereals and soy cake. By adopting increasingly complex silvopastoral systems and phasing out farm chemical inputs this farm managed to reduce the production costs and increase the quality and price of its milk while improving food security and energy efficiency. Adding value to the organic milk is the final challenge that will improve the profitability of the farming system.El cambio climático y la inequidad que caracteriza al comercio global de los productos lácteos han golpeado duramente a los pequeños productores de leche que adoptaron un modelo artificial dependiente de insumos industriales y una exagerada especialización genética del ganado. Aunque la aplicación de los principios agroecológicos y la demanda creciente de alimentos naturales señalan una ruta de escape para estos productores, la producción agroecológica de leche no es fácil porque la etapa de transición exige tomar decisiones difíciles que pueden afectar la productividad en el corto plazo. Este artículo narra la transición agroecológica de una pequeña finca lechera en los Andes centrales de Colombia. El punto de partida fue el modelo convencional característico de muchas lecherías de montaña en América Latina, basado en monocultivos de gramíneas fertilizados con urea y la suplementación de las vacas con alimentos concentrados elaborados a partir de cereales y torta de soya importados. Mediante la adopción de sistemas silvopastoriles cada vez más complejos y la eliminación gradual de los insumos agroquímicos, la finca logró reducir el costo de producción de la leche, aumentar la calidad y el precio de la misma y mejorar la seguridad alimentaria y la eficiencia energética. El reto final será agregarle valor a la leche orgánica para aumentar la rentabilidad del sistema

La secuencia magmática Jurásico Superior-Cretácico Superior en la Cordillera Central, República Dominicana: sección cortical de un arco-isla intraoceánico.

The Late Jurassic-Late Cretaceous magmatic sequence exposed in the central-western sector of the Cordillera Central Dominican Republic, can be divided in five main lithostratigraphic units formed by plutonio, volcanic, volcanoclastic and sedimentary rocks. All rocks have suffered very heterogeneous ductile deformation and low-grade metamorphism with magmatic textures often preserved. From bottom to top, this magmatic sequence is made up of:: (1) Loma Caribe serpentinized peridotites, (2) the N-MORB volcano-plutonic assemblage of El Aguacate, of ophiolitic affinity, (3) the Duarte Complex oceanic plateau, (4) the arc-related volcanic and volcano-sedimentary sequence of the Tireo Formation, intruded by the Loma de Cabrera Batolith, and (5) the massive basaltic flows of Peña Blanca y Nalga de Maco. It is suggested that the magmatic sequence represents the crustal section of an intra-oceanic island arc, which was built onto a proto-caribbean oceanic crust and an overlying Lower Cretaceous oceanic plateau. The sequence is overlain by Upper Cretaceous basalts of the Caribbean oceanic plateau and limestones

Generalization of entropy based divergence measures for symbolic sequence analysis

Entropy based measures have been frequently used in symbolic sequence analysis. A symmetrized and smoothed form of Kullback-Leibler divergence or relative entropy, the Jensen-Shannon divergence (JSD), is of particular interest because of its sharing properties with families of other divergence measures and its interpretability in different domains including statistical physics, information theory and mathematical statistics. The uniqueness and versatility of this measure arise because of a number of attributes including generalization to any number of probability distributions and association of weights to the distributions. Furthermore, its entropic formulation allows its generalization in different statistical frameworks, such as, non-extensive Tsallis statistics and higher order Markovian statistics. We revisit these generalizations and propose a new generalization of JSD in the integrated Tsallis and Markovian statistical framework. We show that this generalization can be interpreted in terms of mutual information. We also investigate the performance of different JSD generalizations in deconstructing chimeric DNA sequences assembled from bacterial genomes including that of E. coli, S. enterica typhi, Y. pestis and H. influenzae. Our results show that the JSD generalizations bring in more pronounced improvements when the sequences being compared are from phylogenetically proximal organisms, which are often difficult to distinguish because of their compositional similarity. While small but noticeable improvements were observed with the Tsallis statistical JSD generalization, relatively large improvements were observed with the Markovian generalization. In contrast, the proposed Tsallis-Markovian generalization yielded more pronounced improvements relative to the Tsallis and Markovian generalizations, specifically when the sequences being compared arose from phylogenetically proximal organisms.publishedVersionFil: Ré, Miguel Ángel. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Centro de Investigación en Informática para la Ingeniería. Departamento de Ciencias Básicas; Argentina.Fil: Ré, Miguel Ángel. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Azad, Rajeev K. University of North Texas. College of Science. Department of Biological Sciences; Estados Unidos de América.Fil: Azad, Rajeev K. University of North Texas. College of Science. Department of Mathematics; Estados Unidos de América.Ciencias de la Información y Bioinformática (desarrollo de hardware va en 2.2 "Ingeniería Eléctrica, Electrónica y de Información" y los aspectos sociales van en 5.8 "Comunicación y Medios"

Pooling/bootstrap-based GWAS (pbGWAS) identifies new loci modifying the age of onset in PSEN1 p.Glu280Ala Alzheimer\u27s disease

The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer\u27s disease (AD). Because of the challenges of obtaining such large cohorts, we describe here a novel sequential strategy that combines pooling of DNA and bootstrapping (pbGWAS) in order to significantly increase the statistical power and exponentially reduce expenses. We applied this method to a very homogeneous sample of patients belonging to a unique and clinically well-characterized multigenerational pedigree with one of the most severe forms of early onset AD, carrying the PSEN1 p.Glu280Ala mutation (often referred to as E280A mutation), which originated as a consequence of a founder effect. In this cohort, we identified novel loci genome-wide significantly associated as modifiers of the age of onset of AD (CD44, rs187116, P=1.29 _ 10?12; NPHP1, rs10173717, P=1.74 _ 10?12; CADPS2, rs3757536, P=1.54 _ 10?10; GREM2, rs12129547, P=1.69 _ 10?13, among others) as well as other loci known to be associated with AD. Regions identified by pbGWAS were confirmed by subsequent individual genotyping. The pbGWAS methodology and the genes it targeted could provide important insights in determining the genetic causes of AD and other complex conditions

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD

In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10−8) and 11q and 17p (P<1 × 10−6). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q–11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome