Synthesis and Recognition Properties of Higher Order Tetrathiafulvalene (Ttf) Calix N Pyrroles (N=4-6)

Two new benzoTTF-annulated calix[n]pyrroles (n = 5 and 6) were synthesized via a one-step acid catalyzed condensation reaction and fully characterized via single crystallographic analyses. As compared to the known tetra-TTF annulated calix[4]pyrrole, which is also produced under the conditions of the condensation reaction, the expanded calix[n]pyrroles (n = 5 and 6) are characterized by a larger cavity size and a higher number of TTF units (albeit the same empirical formula). Analysis of the binding isotherms obtained from UV-Vis spectroscopic titrations carried out in CHCl3 in the presence of both anionic (Cl-, Br-, I-, CH3COO-, H2PO4-, and HSO4-) and neutral (1,3,5-trinitrobenzene (TNB) and 2,4,6-trinitrotoluene (TNT)) substrates revealed that as a general rule the calix[6]pyrrole derivative proved to be the most efficient molecular receptor for anions, while the calix[4]pyrrole congener proves most effective for the recognition of TNB and TNT. These findings are rationalized in terms of the number of electron rich TTF subunits and NH hydrogen bond donor groups within the series, as well as an ability to adopt conformations suitable for substrate recognition, and are supported by solid state structural analyses.National Science Foundation CHE 1057904, 0741973Robert A. Welch Foundation F-1018Danish Natural Science Research Council (FNU) 272-08-0047, 11-106744WCU (World Class University) program of Korea R32-2010-10217-0Villum FoundationChemistr

Magnetic Field scaling of Relaxation curves in Small Particle Systems

We study the effects of the magnetic field on the relaxation of the magnetization of small monodomain non-interacting particles with random orientations and distribution of anisotropy constants. Starting from a master equation, we build up an expression for the time dependence of the magnetization which takes into account thermal activation only over barriers separating energy minima, which, in our model, can be computed exactly from analytical expressions. Numerical calculations of the relaxation curves for different distribution widths, and under different magnetic fields H and temperatures T, have been performed. We show how a \svar scaling of the curves, at different T and for a given H, can be carried out after proper normalization of the data to the equilibrium magnetization. The resulting master curves are shown to be closely related to what we call effective energy barrier distributions, which, in our model, can be computed exactly from analytical expressions. The concept of effective distribution serves us as a basis for finding a scaling variable to scale relaxation curves at different H and a given T, thus showing that the field dependence of energy barriers can be also extracted from relaxation measurements.Comment: 12 pages, 9 figures, submitted to Phys. Rev.

Grain Boundaries in Graphene on SiC(0001ˉ\bar{1}) Substrate

Grain boundaries in epitaxial graphene on the SiC(000$\bar{1}$) substrate are studied using scanning tunneling microscopy and spectroscopy. All investigated small-angle grain boundaries show pronounced out-of-plane buckling induced by the strain fields of constituent dislocations. The ensemble of observations allows to determine the critical misorientation angle of buckling transition $\theta_c = 19 \pm~2^\circ$. Periodic structures are found among the flat large-angle grain boundaries. In particular, the observed $\theta = 33\pm2^\circ$ highly ordered grain boundary is assigned to the previously proposed lowest formation energy structural motif composed of a continuous chain of edge-sharing alternating pentagons and heptagons. This periodic grain boundary defect is predicted to exhibit strong valley filtering of charge carriers thus promising the practical realization of all-electric valleytronic devices

A ferroelectric memristor

Memristors are continuously tunable resistors that emulate synapses. Conceptualized in the 1970s, they traditionally operate by voltage-induced displacements of matter, but the mechanism remains controversial. Purely electronic memristors have recently emerged based on well-established physical phenomena with albeit modest resistance changes. Here we demonstrate that voltage-controlled domain configurations in ferroelectric tunnel barriers yield memristive behaviour with resistance variations exceeding two orders of magnitude and a 10 ns operation speed. Using models of ferroelectric-domain nucleation and growth we explain the quasi-continuous resistance variations and derive a simple analytical expression for the memristive effect. Our results suggest new opportunities for ferroelectrics as the hardware basis of future neuromorphic computational architectures

In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation

Overview of the 21CXRM Palaeozoic Project : a regional petroleum systems analysis of the offshore Carboniferous and Devonian of the UKCS

This report gives an overview of the 21CXRM Palaeozoic Project background, scope and products (Sections 1-3). It explains how the component reports and datasets of the project fit together. Overview technical information (e.g. key diagrams and charts applicable across the reports for each area) is reproduced in Sections 6 and 7 for reference, particularly as background for users of the specialist reports. A visual representation of the regional coverage and quantity of digital Palaeozoic Project products is given in Figure 1

Supernova / Acceleration Probe: A Satellite Experiment to Study the Nature of the Dark Energy

The Supernova / Acceleration Probe (SNAP) is a proposed space-based experiment designed to study the dark energy and alternative explanations of the acceleration of the Universe's expansion by performing a series of complementary systematics-controlled measurements. We describe a self-consistent reference mission design for building a Type Ia supernova Hubble diagram and for performing a wide-area weak gravitational lensing study. A 2-m wide-field telescope feeds a focal plane consisting of a 0.7 square-degree imager tiled with equal areas of optical CCDs and near infrared sensors, and a high-efficiency low-resolution integral field spectrograph. The SNAP mission will obtain high-signal-to-noise calibrated light-curves and spectra for several thousand supernovae at redshifts between z=0.1 and 1.7. A wide-field survey covering one thousand square degrees resolves ~100 galaxies per square arcminute. If we assume we live in a cosmological-constant-dominated Universe, the matter density, dark energy density, and flatness of space can all be measured with SNAP supernova and weak-lensing measurements to a systematics-limited accuracy of 1%. For a flat universe, the density-to-pressure ratio of dark energy can be similarly measured to 5% for the present value w0 and ~0.1 for the time variation w'. The large survey area, depth, spatial resolution, time-sampling, and nine-band optical to NIR photometry will support additional independent and/or complementary dark-energy measurement approaches as well as a broad range of auxiliary science programs. (Abridged)Comment: 40 pages, 18 figures, submitted to PASP, http://snap.lbl.go

Detection of MicroRNA processing intermediates through RNA ligation approaches

MicroRNAs (miRNA) are small RNAs of 20–22 nt that regulate diverse biological pathways through the modulation of gene expression. miRNAs recognize target RNAs by base complementarity and guide them to degradation or translational arrest. They are transcribed as longer precursors with extensive secondary structures. In plants, these precursors are processed by a complex harboring DICER-LIKE1 (DCL1), which cuts on the precursor stem region to release the mature miRNA together with the miRNA*. In both plants and animals, the miRNA precursors contain spatial clues that determine the position of the miRNA along their sequences. DCL1 is assisted by several proteins, such as the double-stranded RNA binding protein, HYPONASTIC LEAVES1 (HYL1), and the zinc finger protein SERRATE (SE). The precise biogenesis of miRNAs is of utter importance since it determines the exact nucleotide sequence of the mature small RNAs and therefore the identity of the target genes. miRNA processing itself can be regulated and therefore can determine the final small RNA levels and activity. Here, we describe methods to analyze miRNA processing intermediates in plants. These approaches can be used in wild-type or mutant plants, as well as in plants grown under different conditions, allowing a molecular characterization of the miRNA biogenesis from the RNA precursor perspective.Fil: Moro, Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Rojas, Arantxa Maria Larisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Palatnik, Javier Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario. Centro de Estudios Interdisciplinarios; Argentin

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C