Direct observation of the influence of the As-Fe-As angle on the Tc of superconducting SmFeAsO1−x_{1-x}Fx_{x}

The electrical resistivity, crystalline structure and electronic properties calculated from the experimentally measured atomic positions of the compound SmFeAsO$_{0.81}$F$_{0.19}$ have been studied up to pressures ~20GPa. The correlation between the pressure dependence of the superconducting transition temperature (Tc) and crystallographic parameters on the same sample shows clearly that a regular FeAs$_{4}$ tetrahedron maximizes Tc, through optimization of carrier transfer to the FeAs planes as indicated by the evolution of the electronic band structures.Comment: 15pages, 4 figure

Correlated pressure effects on structure and superconductivity in LaFeAsO0.9F0.1

We have studied the structural and superconductivity properties of the compound LaFeAsO0.9F0.1 under pressures up to 32GPa using synchrotron radiation and diamond anvil cells. We obtain an ambient pressure bulk modulus K_0 = 78(2)GPa, compressibility comparable to some cuprates. At high pressures, the sample is in the overdoped region, with a linear decrease with pressure variation of the superconducting transition temperature.Comment: 15 pages, 4 figures, 1 tabl

Selección, identificación y zonificación de café (Coffea arabica L.) por su adaptabilidad, rendimiento, calidad sensorial y resistencia a plagas y enfermedades

Con el objetivo de seleccionar, identificar y zonificar plantas madre de variedades de café (Coffea arabica L.) que presenten buena adaptabilidad, resistencia a plagas, enfermedades y alta calidad en taza en las provincias de Satipo, Chanchamayo y Oxapampa, se identificó 10 variedades de café en las parcelas de los productores cafetaleros entre 870 a 1638 msnm. La incidencia de la roya amarilla en el cultivo de café en los distritos de Pichanaqui y Río Negro fue 0% en Catuaí de fruto rojo con 5 años y en San Luis de Shuaro 18% en Bourbón de fruto amarillo con 14 años de la planta. Los agricultores obtienen en producción 11 qq/ha-1 en Bourbón de fruto rojo con 25 años de la planta, 27 qq/ha-1 a 54 qq/ha-1 en Catuaí de fruto rojo con 5 años de la planta. En rendimiento del análisis físico presentó el 73% en Bourbon de fruto amarillo, 78% H1 centroamericano y 76% en Catuaí de fruto rojo y amarillo, con respecto al análisis sensorial Catuaí de fruto rojo mostró 80,25 puntos en taza y Caturra de fruto rojo, Bourbón de fruto amarillo y Geisha con 85 puntos en taza

Characterization of heterogeneity and spatial distribution of phases in complex solid dispersions by thermal analysis by structural characterization and X-ray micro computed tomography

Purpose: This study investigated the effect of drug-excipient miscibility on the heterogeneity and spatial distribution of phase separation in pharmaceutical solid dispersions at a micron-scale using two novel and complementary characterization techniques, thermal analysis by structural characterization (TASC) and X-ray micro-computed tomography (XCT) in conjunction with conventional characterization methods. Method: Complex dispersions containing felodipine, TPGS, PEG and PEO were prepared using hot melt extrusion-injection moulding. The phase separation behavior of the samples was characterized using TASC and XCT in conjunction with conventional thermal, microscopic and spectroscopic techniques. The in vitro drug release study was performed to demonstrate the impact of phase separation on dissolution of the dispersions. Results: The conventional characterization results indicated the phase separating nature of the carrier materials in the patches and the presence of crystalline drug in the patches with the highest drug loading (30% w/w). TASC and XCT where used to provide insight into the spatial configuration of the separate phases. TASC enabled assessment of the increased heterogeneity of the dispersions with increasing the drug loading. XCT allowed the visualization of the accumulation of phase separated (crystalline) drug clusters at the interface of air pockets in the patches with highest drug loading which led to poor dissolution performance. Semi-quantitative assessment of the phase separated drug clusters in the patches were attempted using XCT. Conclusion: TASC and XμCT can provide unique information regarding the phase separation behavior of solid dispersions which can be closely associated with important product quality indicators such as heterogeneity and microstructure

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

Partial Order Optimum Likelihood (POOL): Maximum Likelihood Prediction of Protein Active Site Residues Using 3D Structure and Sequence Properties

A new monotonicity-constrained maximum likelihood approach, called Partial Order Optimum Likelihood (POOL), is presented and applied to the problem of functional site prediction in protein 3D structures, an important current challenge in genomics. The input consists of electrostatic and geometric properties derived from the 3D structure of the query protein alone. Sequence-based conservation information, where available, may also be incorporated. Electrostatics features from THEMATICS are combined with multidimensional isotonic regression to form maximum likelihood estimates of probabilities that specific residues belong to an active site. This allows likelihood ranking of all ionizable residues in a given protein based on THEMATICS features. The corresponding ROC curves and statistical significance tests demonstrate that this method outperforms prior THEMATICS-based methods, which in turn have been shown previously to outperform other 3D-structure-based methods for identifying active site residues. Then it is shown that the addition of one simple geometric property, the size rank of the cleft in which a given residue is contained, yields improved performance. Extension of the method to include predictions of non-ionizable residues is achieved through the introduction of environment variables. This extension results in even better performance than THEMATICS alone and constitutes to date the best functional site predictor based on 3D structure only, achieving nearly the same level of performance as methods that use both 3D structure and sequence alignment data. Finally, the method also easily incorporates such sequence alignment data, and when this information is included, the resulting method is shown to outperform the best current methods using any combination of sequence alignments and 3D structures. Included is an analysis demonstrating that when THEMATICS features, cleft size rank, and alignment-based conservation scores are used individually or in combination THEMATICS features represent the single most important component of such classifiers

\u3cem\u3eRPGRIP1\u3c/em\u3e and Cone-Rod Dystrophy in Dogs

Cone–rod dystrophies (crd) represent a group of progressive inherited blinding diseases characterized by primary dysfunction and loss of cone photoreceptors accompanying or preceding rod death. Recessive crd type 1 was described in dogs associated with an RPGRIP1 exon 2 mutation, but with lack of complete concordance between genotype and phenotype. This review highlights role of the RPGRIP1, a component of complex protein networks, and its function in the primary cilium, and discusses the potential mechanisms of genotype–phenotype discordance observed in dogs with the RPGRIP1 mutation

The Quijote CMB Experiment

We present the current status of the QUIJOTE (Q-U-I JOint TEnerife) CMB Experiment, a new instrument which will start operations early 2009 at Teide Observatory, with the aim of characterizing the polarization of the CMB and other processes of galactic and extragalactic emission in the frequency range 10-30 GHz and at large angular scales. QUIJOTE will be a valuable complement at low frequencies for the PLANCK mission, and will have the required sensitivity to detect a primordial gravitational-wave component if the tensor-to-scalar ratio is larger than r=0.05.Comment: 9 pages, 5 figures. To appear in "Highlights of Spanish Astrophysics V", Proceedings of the VIII Scientific Meeting of the Spanish Astronomical Society (SEA) held in Santander, 7-11 July, 2008. Edited by J. Gorgas, L. J. Goicoechea, J. I. Gonzalez-Serrano, J. M. Dieg