ALBERT

Description: A practical hyperdynamics method is proposed to accelerate systems with highly endothermic and exothermic reactions such as hydrocarbon pyrolysis and oxidation reactions. In this method, referred to as the “adaptive hyperdynamics (AHD) method,” the bias potential parameters are adaptively updated according to the change in potential energy. The approach is intensively examined for JP-10 (exo-tetrahydrodicyclopentadiene) pyrolysis simulations using the ReaxFF reactive force field. Valid boost parameter ranges are clarified as a result. It is shown that AHD can be used to model pyrolysis at temperatures as low as 1000 K while achieving a boost factor of around 10 5 .

Description: E -crotonic acid was isolated in cryogenic solid N 2 and xenon matrices, and subjected to Laser ultraviolet (UV) and near-infrared (NIR) irradiations. In the deposited matrices, the two low-energy cis C–O E -cc and E -ct conformers, which are the only forms significantly populated in the gas phase, were observed. UV irradiation (λ= 250 nm) of the compound in N 2 matrix allows for experimental detection, not just of the two low-energy cis C–O isomers of Z -crotonic acid previously observed in the experiments carried out in argon matrix [ Z -cc and Z -ct; R. Fausto, A. Kulbida, and O. Schrems, J. Chem. Soc., Faraday Trans.91, 3755–3770 (1995)] but also of the never observed before high-energy forms of both E - and Z -crotonic acids bearing the carboxylic acid group in the trans arrangement ( E -tc and Z -tc conformers). In turn, NIR irradiation experiments in the N 2 matrix allow to produce the high-energy E -tc trans C–O conformer in a selective way, from the initially deposited E -cc form. The vibrational signatures of all the 6 rotameric structures of the crotonic acids experimentally observed, including those of the new trans C–O forms, were determined and the individual spectra fully assigned, also with support of theoretically obtained data. On the other hand, as found before for the compound isolated in argon matrix, the experiments performed in xenon matrix failed to experimental detection of the trans C–O forms. This demonstrates that in noble gas matrices these forms are not stable long enough to allow for their observation by steady state spectroscopy techniques. In these matrices, the trans C–O forms convert spontaneously into their cis C–O counterparts, by tunnelling. Some mechanistic details of the studied processes were extracted and discussed.

Description: We describe a novel approach for the calculation of local electric dipole moments for periodic systems. Since the position operator is ill-defined in periodic systems, maximally localized Wannier functions based on the Berry-phase approach are usually employed for the evaluation of local contributions to the total electric dipole moment of the system. We propose an alternative approach: within a subsystem-density functional theory based embedding scheme, subset electric dipole moments are derived without any additional localization procedure, both for hybrid and non-hybrid exchange–correlation functionals. This opens the way to a computationally efficient evaluation of local electric dipole moments in (molecular) periodic systems as well as their rigorous splitting into atomic electric dipole moments. As examples, Infrared spectra of liquid ethylene carbonate and dimethyl carbonate are presented, which are commonly employed as solvents in Lithium ion batteries.

Description: Long-duration gamma-ray bursts (GRBs) are thought to come from the core collapse of Wolf–Rayet stars. Whereas their stellar masses M * have a rather narrow distribution, the population of GRBs is very diverse, with gamma-ray luminosities L spanning several orders of magnitude. This suggests the existence of a ‘hidden’ stellar variable whose burst-to-burst variation leads to a spread in L . Whatever this hidden variable is, its variation should not noticeably affect the shape of GRB light curves, which display a constant luminosity (in a time-average sense) followed by a sharp drop at the end of the burst seen with Swift /XRT. We argue that such a hidden variable is progenitor star's large-scale magnetic flux. Shortly after the core collapse, most of stellar magnetic flux accumulates near the black hole (BH) and remains there. The flux extracts BH rotational energy and powers jets of roughly a constant luminosity, L j . However, once BH mass accretion rate $\dot{M}$ falls below ~ L j / c 2 , the flux becomes dynamically important and diffuses outwards, with the jet luminosity set by the rapidly declining mass accretion rate, $L_{\rm j}\sim \dot{M}c^2$ . This provides a potential explanation for the sharp end of GRBs and the universal shape of their light curves. During the GRB, gas infall translates spatial variation of stellar magnetic flux into temporal variation of L j . We make use of the deviations from constancy in L j to perform stellar magnetic flux ‘tomography’. Using this method, we infer the presence of magnetized tori in the outer layers of progenitor stars for GRB 920513 and GRB 940210.

Description: We make use of a large set of fast simulations of an intensity mapping experiment with characteristics similar to those expected of the Square Kilometre Array in order to study the viability and limits of blind foreground subtraction techniques. In particular, we consider three different approaches: polynomial fitting, principal component analysis (PCA) and independent component analysis (ICA). We review the motivations and algorithms for the three methods, and show that they can all be described, using the same mathematical framework, as different approaches to the blind source separation problem. We study the efficiency of foreground subtraction both in the angular and radial (frequency) directions, as well as the dependence of this efficiency on different instrumental and modelling parameters. For well-behaved foregrounds and instrumental effects, we find that foreground subtraction can be successful to a reasonable level on most scales of interest. We also quantify the effect that the cleaning has on the recovered signal and power spectra. Interestingly, we find that the three methods yield quantitatively similar results, with PCA and ICA being almost equivalent.

Description: Observed galaxies with high stellar masses or in dense environments have low specific star formation rates, i.e. they are quenched. Based on cosmological hydrodynamic simulations that include a prescription where quenching occurs in regions dominated by hot (〉10 5.4  K) gas, we argue that this hot gas quenching in haloes 〉10 12 M drives both mass quenching (i.e. central quenching) and environment quenching (i.e. satellite quenching). These simulations reproduce a broad range of locally observed trends among quenching, halo mass, stellar mass, environment, and distance to halo centre. Mass quenching is independent of environment because ~10 12 –10 13 M ‘mass quenching haloes’ inhabit a large range of environments. On the other hand, environment quenching is independent of stellar mass because galaxies of all stellar masses may live in dense environments as satellites of groups and clusters. As in observations, the quenched fraction of satellites increases with halo mass and decreases with distance to the centre of the group or cluster. We investigate pre-processing in group haloes, ejected former satellites, and hot gas that extends beyond the virial radius. The agreement of our model with key observational trends suggests that hot gas in massive haloes plays a leading role in quenching low-redshift galaxies.

Description: We used Arecibo Observatory and the Green Bank Telescope to observe OH in 12 early-type galaxies with known reservoirs of dense gas. We present three new detections of OH in absorption in the 1667 MHz line. One objective of our survey was to find evidence of molecular outflows, but our sensitivity and the strength of the OH absorption were insufficient to detect outflows. The detected sources have infrared luminosities and dust temperatures among the lowest of any galaxy detected in OH absorption. The ratio L HCN / L CO , a measure of the dense gas fraction in galaxies, is a powerful selector of OH megamasers for galaxies with high infrared luminosity. In early-type galaxies, which have much lower infrared luminosities, L HCN / L CO is also a promising tool for discovering OH, but in absorption rather than in maser emission. In addition to dense molecular gas, a radio continuum source and a favourable line of sight to the observer are likely key factors in detecting OH absorbers.

Description: The initial mass function (IMF) of the Arches cluster, which was formed a few million years ago in the harsh environment of the Galactic Centre (GC), has long been a target of interest to those who study the GC and the theory of star formation. The distinct star-forming conditions in the GC might have caused the cluster to have a shallower slope or an elevated lower mass cutoff in its IMF. But its mass function (MF) has been revealed only down to 1–2 M (the lower limit of resolved stars), and the low-end MF of the Arches is still unknown. To estimate the unresolved part of the Arches MF, we have devised a novel photometric method that involves the histogram of pixel intensities in the observed image, which contains information on the unresolved, faint stars. By comparing the pixel intensity histograms (PIHs) of numerous artificial images constructed from model IMFs with the observed PIH, we find that the best-fitting model IMF for the Arches cluster has a cutoff mass less than or similar to 0.1 M and a shape very close to that of the Kroupa MF. Our findings imply that the IMF of the Arches cluster is similar to those found in the Galactic disc.

Description: The collision-less transfer of momentum and energy from explosive debris plasma to magnetized background plasma is a salient feature of various astrophysical and space environments. While much theoretical and computational work has investigated collision-less coupling mechanisms and relevant parameters, an experimental validation of the results demands the measurement of the complex, collective electric fields associated with debris-background plasma interaction. Emission spectroscopy offers a non-interfering diagnostic of electric fields via the Stark effect. A unique experiment at the University of California, Los Angeles, that combines the Large Plasma Device (LAPD) and the Phoenix laser facility has investigated the marginally super-Alfvénic, quasi-perpendicular expansion of a laser-produced carbon (C) debris plasma through a preformed, magnetized helium (He) background plasma via emission spectroscopy. Spectral profiles of the He II 468.6 nm line measured at the maximum extent of the diamagnetic cavity are observed to intensify, broaden, and develop equally spaced modulations in response to the explosive C debris, indicative of an energetic electron population and strong oscillatory electric fields. The profiles are analyzed via time-dependent Stark effect models corresponding to single-mode and multi-mode monochromatic (single frequency) electric fields, yielding temporally resolved magnitudes and frequencies. The proximity of the measured frequencies to the expected electron plasma frequency suggests the development of the electron beam-plasma instability, and a simple saturation model demonstrates that the measured magnitudes are feasible provided that a sufficiently fast electron population is generated during C debris–He background interaction. Potential sources of the fast electrons, which likely correspond to collision-less coupling mechanisms, are briefly considered.

Description: It is shown that co-linear injection of electrons or positrons into the wakefield of the self-modulating particle beam is possible and ensures high energy gain. The witness beam must co-propagate with the tail part of the driver, since the plasma wave phase velocity there can exceed the light velocity, which is necessary for efficient acceleration. If the witness beam is many wakefield periods long, then the trapped charge is limited by beam loading effects. The initial trapping is better for positrons, but at the acceleration stage a considerable fraction of positrons is lost from the wave. For efficient trapping of electrons, the plasma boundary must be sharp, with the density transition region shorter than several centimeters. Positrons are not susceptible to the initial plasma density gradient.

Description: The foundational theory for dusty plasmas is the dust charging theory that provides the dust potential and charge arising from the dust interaction with a plasma. The most widely used dust charging theory for negatively charged dust particles is the so-called orbital motion limited (OML) theory, which predicts the dust potential and heat collection accurately for a variety of applications, but was previously found to be incapable of evaluating the dust charge and plasma response in any situation. Here, we report a revised OML formulation that is able to predict the plasma response and hence the dust charge. Numerical solutions of the new OML model show that the widely used Whipple approximation of dust charge-potential relationship agrees with OML theory in the limit of small dust radius compared with plasma Debye length, but incurs large (order-unity) deviation from the OML prediction when the dust size becomes comparable with or larger than plasma Debye length. This latter case is expected for the important application of dust particles in a tokamak plasma.

Description: We report on the controlled removal of an amorphous Se capping layer from Bi 2 Te 3 and Bi 2 Se 3 topological insulators. We show that the Se coalesces into micron-sized islands before desorbing from the surface at a temperature of ∼150 °C. In situ Auger Electron Spectroscopy reveals that Se replaces a significant fraction of the Te near the top surface of the Bi 2 Te 3 . Rutherford Backscattering Spectrometry and Transmission Electron Microscopy show that after heating, Se has been incorporated in the Bi 2 Te 3 lattice down to ∼7 nm from its top surface while remaining iso-structural.

Description: A system of generating and receiving orbital angular momentum (OAM) radio beams, which are collectively formed by two circular array antennas (CAAs) and effectively optimized by two intensity controlled masks, is proposed and experimentally investigated. The scheme is effective in blocking of the unwanted OAM modes and enhancing the power of received radio signals, which results in the capacity gain of system and extended transmission distance of the OAM radio beams. The operation principle of the intensity controlled masks, which can be regarded as both collimator and filter, is feasible and simple to realize. Numerical simulations of intensity and phase distributions at each key cross-sectional plane of the radio beams demonstrate the collimated results. The experimental results match well with the theoretical analysis and the receive distance of the OAM radio beam at radio frequency (RF) 20 GHz is extended up to 200 times of the wavelength of the RF signals, the measured distance is 5 times of the original measured distance. The presented proof-of-concept experiment demonstrates the feasibility of the system.

Description: We demonstrate chemical doping of a topological insulator Bi 2 Se 3 using ion implantation. Ion beam-induced structural damage was characterized using grazing incidence X-ray diffraction and transmission electron microscopy. Ion damage was reversed using a simple thermal annealing step. Carrier-type conversion was achieved using ion implantation followed by an activation anneal in Bi 2 Se 3 thin films. These two sets of experiments establish the feasibility of ion implantation for chemical modification of Bi 2 Se 3 , a prototypical topological insulator. Ion implantation can, in principle, be used for any topological insulator. The direct implantation of dopants should allow better control over carrier concentrations for the purposes of achieving low bulk conductivity. Ion implantation also enables the fabrication of inhomogeneously doped structures, which in turn should make possible new types of device designs.

Description: Scanning near-field photoluminescence (PL) spectroscopy was applied to study spatial variations of emission spectra of Al x Ga 1−x N epilayers with 0.6 ≤ x ≤ 0.7 . PL spectra were found to be spatially uniform with peak wavelength standard deviations of only ∼2 meV and ratios between peak intensity standard deviations and average peak intensity values of 0.06. The observed absence of correlation between the PL peak wavelength and intensity shows that spatial distribution of nonradiative recombination centers is not related to band potential fluctuations. Our results demonstrate that the homogeneous broadening and the random cation distribution primarily determine PL linewidths for layers grown under optimized conditions.

Description: Using the ideal magnetohydrodynamic model, we calculate the temporal evolution of initial ripples on the boundaries of a planar plasma slab that is subjected to the magneto-Rayleigh-Taylor instability. The plasma slab consists of three regions. We assume that in each region the plasma density is constant with an arbitrary value and the magnetic field is also constant with an arbitrary magnitude and an arbitrary direction parallel to the interfaces. Thus, the instability may be driven by a combination of magnetic pressure and kinetic pressure. The general dispersion relation is derived, together with the feedthrough factor between the two interfaces. The temporal evolution is constructed from the superposition of the eigenmodes. Previously established results are recovered in the various limits. Numerical examples are given on the temporal evolution of ripples on the interfaces of the finite plasma slab.

Description: We demonstrate direct evidence that the strain variation induced by local lattice distortion exists in the surface layers of SnO 2 nanowires by coupled scanning transmission electron microscopy and digital image correlation techniques. First-principles calculations suggest that surface reduction and subsurface oxygen vacancies account for such vigorous wavelike strain. Our study revealed that the localized change of surface atomistic configuration was responsible for the observed reduction of elastic modulus and hardness of SnO 2 nanowires, as well as the superior sensing properties of SnO 2 nanowire network.

Description: Complementary logic based on tunnel field-effect transistors (TFETs) would drastically reduce power consumption thanks to the TFET's potential to obtain a sub-60 mV/dec subthreshold swing (SS). However, p-type TFETs typically do not meet the performance of n-TFETs for direct bandgap III-V configurations. The p-TFET SS stays well above 60 mV/dec, due to the low density of states in the conduction band. We therefore propose a source configuration in which a highly doped region is maintained only near the tunnel junction. In the remaining part of the source, the hot carriers in the exponential tail of the Fermi-Dirac distribution are blocked by reducing the doping degeneracy, either with a source section with a lower doping concentration or with a heterostructure. We apply this concept to n-p-i-p configurations consisting of In 0.53 Ga 0.47 As and an InP-InAs heterostructure. 15-band quantum mechanical simulations predict that the configurations with our source design can obtain sub-60 mV/dec SS, with an on-current comparable to the conventional source design.

Description: We design and experimentally realize an ultra-broad band metamaterial-based acoustic absorption material. Unlike traditional acoustic absorbers, the designed device features a simple configuration unrestricted by the material type and does not require extra sound-absorbing materials, suggesting the potential to have simultaneously structural-stiffness and environmental-friendliness. Analytical analyses are provided to explain such distinct characteristics, which are revealed to stem from the localization and dissipation of waves with different frequencies at particular spatial positions. This is also demonstrated both numerically and experimentally. Our results may offer possible designs for various applications such as noise reduction and making underwater anechoic materials.

Description: The absolute photoluminescence (PL) quantum yield (QY) of multilayers of Silicon nanocrystals (SiNCs) separated by SiO 2 barriers were thoroughly studied as function of the barrier thickness, excitation wavelength, and temperature. By mastering the plasma-enhanced chemical vapor deposition growth, we produce a series of samples with the same size-distribution of SiNCs but variable interlayer barrier distance. These samples enable us to clearly demonstrate that the increase of barrier thickness from ∼1 to larger than 2 nm induces doubling of the PL QY value, which corresponds to the change of number of close neighbors in the hcp structure. The temperature dependence of PL QY suggests that the PL QY changes are due to a thermally activated transport of excitation into non-radiative centers in dark NCs or in the matrix. We estimate that dark NCs represent about 68% of the ensemble of NCs. The PL QY excitation spectra show no significant changes upon changing the barrier thickness and no clear carrier multiplication effects. The dominant effect is the gradual decrease of the PL QY with increasing excitation photon energy.

Description: High-quality BN-Graphene-BN nanoribbon capacitors with double side-gates of graphene have been experimentally realized. The double side-gates can effectively modulate the electronic properties of graphene nanoribbon capacitors. By applying anti-symmetric side-gate voltages, we observed significant upward shifting and flattening of the V-shaped capacitance curve near the charge neutrality point. Symmetric side-gate voltages, however, only resulted in tilted upward shifting along the opposite direction of applied gate voltages. These modulation effects followed the behavior of graphene nanoribbons predicted theoretically for metallic side-gate modulation. The negative quantum capacitance phenomenon predicted by numerical simulations for graphene nanoribbons modulated by graphene side-gates was not observed, possibly due to the weakened interactions between the graphene nanoribbon and side-gate electrodes caused by the Ga + beam etching process.

Description: GaAs/Al-GaAs core-shell nanowires fabricated by molecular beam epitaxy contain quantum confining structures susceptible of producing narrow photoluminescence (PL) and single photons. The nanoscale chemical mapping of these structures is analyzed in 3D by atom probe tomography (APT). The study allows us to confirm that Al atoms tend to segregate within the AlGaAs shells towards the vertices of the hexagons defining the nanowire cross section. We also find strong alloy fluctuations remaining AlGaAs shell, leading occasionally to the formation of quantum dots (QDs). The PL emission energies predicted in the framework of a 3D effective mass model for a QD analyzed by APT and the PL spectra measured on other nanowires from the same growth batch are consistent within the experimental uncertainties.

Description: Rectilinear deposition of elongated DNA molecules was achieved by the forced dewetting of a DNA solution droplet over a nanograting. Uncoiling of double stranded DNA is made by the conjunction of both DNA terminal anchoring on a functionalized substrate and capillary force acting throughout the forced dewetting of a DNA solution droplet. The deposition over a nanograting allows the molecule to be uncoiled on the edges of the grooves and to maintain a rectilinear conformation. This DNA deposition technique uses transparent nanograting obtained by laser interference lithography and has been developed for the specific need in observation dsDNA molecules in extended conformation.

Description: Perfectly lattice-matched magnetic tunnel junctions (MTJs) consisting of a Heusler alloy B 2-Co 2 FeAl (CFA) electrode and a cation-disorder spinel (Mg-Al-O) barrier were fabricated by sputtering and plasma oxidation. We achieved a large tunnel magnetoresistance (TMR) ratio of 228% at room temperature (RT) (398% at 5 K) for the epitaxial CFA/MgAl-O/CoFe(001) MTJ, in which the effect of lattice defects on TMR ratios is excluded. With inserting a ultrathin (≤1.5 nm) CoFe layer between the CFA and Mg-Al-O, the TMR ratio further increased up to 280% at RT (453% at 5 K), which reflected the importance of controlling barrier-electrode interface states other than the lattice matching.

Description: A major goal of nanotechnology is to develop the capability to arrange matter at will by placing individual atoms at desired locations in a predetermined configuration to build a nanostructure with specific properties or function. The scanning tunneling microscope has demonstrated the ability to arrange the basic building blocks of matter, single atoms, in two-dimensional configurations. An array of various nanostructures has been assembled, which display the quantum mechanics of quantum confined geometries. The level of human interaction needed to physically locate the atom and bring it to the desired location limits this atom assembly technology. Here we report the use of autonomous atom assembly via path planning technology; this allows atomically perfect nanostructures to be assembled without the need for human intervention, resulting in precise constructions in shorter times. We demonstrate autonomous assembly by assembling various quantum confinement geometries using atoms and molecules and describe the benefits of this approach.

Description: We developed a silicon avalanche photodiode (Si-APD) linear-array detector for use in nuclear resonant scattering experiments using synchrotron X-rays. The Si-APD linear array consists of 64 pixels (pixel size: 100 × 200 μm 2 ) with a pixel pitch of 150 μm and depletion depth of 10 μm. An ultrafast frontend circuit allows the X-ray detector to obtain a high output rate of 〉10 7 cps per pixel. High-performance integrated circuits achieve multichannel scaling over 1024 continuous time bins with a 1 ns resolution for each pixel without dead time. The multichannel scaling method enabled us to record a time spectrum of the 14.4 keV nuclear radiation at each pixel with a time resolution of 1.4 ns (FWHM). This method was successfully applied to nuclear forward scattering and nuclear small-angle scattering on 57 Fe.

Description: We describe a nanosecond time-resolved fluorescence spectrometer that acquires fluorescence decay waveforms from each well of a 384-well microplate in 3 min with signal-to-noise exceeding 400 using direct waveform recording. The instrument combines high-energy pulsed laser sources (5–10 kHz repetition rate) with a photomultiplier and high-speed digitizer (1 GHz) to record a fluorescence decay waveform after each pulse. Waveforms acquired from rhodamine or 5-((2-aminoethyl)amino) naphthalene-1-sulfonic acid dyes in a 384-well plate gave lifetime measurements 5- to 25-fold more precise than the simultaneous intensity measurements. Lifetimes as short as 0.04 ns were acquired by interleaving with an effective sample rate of 5 GHz. Lifetime measurements resolved mixtures of single-exponential dyes with better than 1% accuracy. The fluorescence lifetime plate reader enables multiple-well fluorescence lifetime measurements with an acquisition time of 0.5 s per well, suitable for high-throughput fluorescence lifetime screening applications.

Description: Diagnostic for investigating and distinguishing different laser ion acceleration mechanisms has been developed and successfully tested. An ion separation wide angle spectrometer can simultaneously investigate three important aspects of the laser plasma interaction: (1) acquire angularly resolved energy spectra for two ion species, (2) obtain ion energy spectra for multiple species, separated according to their charge to mass ratio, along selected axes, and (3) collect laser radiation reflected from and transmitted through the target and propagating in the same direction as the ion beam. Thus, the presented diagnostic constitutes a highly adaptable tool for accurately studying novel acceleration mechanisms in terms of their angular energy distribution, conversion efficiency, and plasma density evolution.

Description: Motivation: Mapping of high-throughput sequencing data and other bulk sequence comparison applications have motivated a search for high-efficiency sequence alignment algorithms. The bit-parallel approach represents individual cells in an alignment scoring matrix as bits in computer words and emulates the calculation of scores by a series of logic operations composed of AND, OR, XOR, complement, shift and addition. Bit-parallelism has been successfully applied to the longest common subsequence (LCS) and edit-distance problems, producing fast algorithms in practice. Results: We have developed BitPAl, a bit-parallel algorithm for general, integer-scoring global alignment. Integer-scoring schemes assign integer weights for match, mismatch and insertion/deletion. The BitPAl method uses structural properties in the relationship between adjacent scores in the scoring matrix to construct classes of efficient algorithms, each designed for a particular set of weights. In timed tests, we show that BitPAl runs 7–25 times faster than a standard iterative algorithm. Availability and implementation: Source code is freely available for download at http://lobstah.bu.edu/BitPAl/BitPAl.html . BitPAl is implemented in C and runs on all major operating systems. Contact : jloving@bu.edu or yhernand@bu.edu or gbenson@bu.edu Supplementary information : Supplementary data are available at Bioinformatics online.

Description: : Next-generation sequencing (NGS) has a large potential in HIV diagnostics, and genotypic prediction models have been developed and successfully tested in the recent years. However, albeit being highly accurate, these computational models lack computational efficiency to reach their full potential. In this study, we demonstrate the use of graphics processing units (GPUs) in combination with a computational prediction model for HIV tropism. Our new model named gCUP, parallelized and optimized for GPU, is highly accurate and can classify 〉175 000 sequences per second on an NVIDIA GeForce GTX 460. The computational efficiency of our new model is the next step to enable NGS technologies to reach clinical significance in HIV diagnostics. Moreover, our approach is not limited to HIV tropism prediction, but can also be easily adapted to other settings, e.g. drug resistance prediction. Availability and implementation: The source code can be downloaded at http://www.heiderlab.de Contact: d.heider@wz-straubing.de

Description: : We present a new method to incrementally construct the FM-index for both short and long sequence reads, up to the size of a genome. It is the first algorithm that can build the index while implicitly sorting the sequences in the reverse (complement) lexicographical order without a separate sorting step. The implementation is among the fastest for indexing short reads and the only one that practically works for reads of averaged kilobases in length. Availability and implementation: https://github.com/lh3/ropebwt2 Contact: hengli@broadinstitute.org

Description: : AliView is an alignment viewer and editor designed to meet the requirements of next-generation sequencing era phylogenetic datasets. AliView handles alignments of unlimited size in the formats most commonly used, i.e. FASTA, Phylip, Nexus, Clustal and MSF. The intuitive graphical interface makes it easy to inspect, sort, delete, merge and realign sequences as part of the manual filtering process of large datasets. AliView also works as an easy-to-use alignment editor for small as well as large datasets. Availability and implementation: AliView is released as open-source software under the GNU General Public License, version 3.0 (GPLv3), and is available at GitHub ( www.github.com/AliView ). The program is cross-platform and extensively tested on Linux, Mac OS X and Windows systems. Downloads and help are available at http://ormbunkar.se/aliview Contact: anders.larsson@ebc.uu.se Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: The ability to accurately read the order of nucleotides in DNA and RNA is fundamental for modern biology. Errors in next-generation sequencing can lead to many artifacts, from erroneous genome assemblies to mistaken inferences about RNA editing. Uneven coverage in datasets also contributes to false corrections. Result: We introduce Trowel, a massively parallelized and highly efficient error correction module for Illumina read data. Trowel both corrects erroneous base calls and boosts base qualities based on the k -mer spectrum. With high-quality k -mers and relevant base information, Trowel achieves high accuracy for different short read sequencing applications.The latency in the data path has been significantly reduced because of efficient data access and data structures. In performance evaluations, Trowel was highly competitive with other tools regardless of coverage, genome size read length and fragment size. Availability and implementation: Trowel is written in C++ and is provided under the General Public License v3.0 (GPLv3). It is available at http://trowel-ec.sourceforge.net . Contact: euncheon.lim@tue.mpg.de or weigel@tue.mpg.de Supplementary information: Supplementary data are available at Bioinformatics online.

Description: : The application of protein–protein docking in large-scale interactome analysis is a major challenge in structural bioinformatics and requires huge computing resources. In this work, we present MEGADOCK 4.0, an FFT-based docking software that makes extensive use of recent heterogeneous supercomputers and shows powerful, scalable performance of 〉97% strong scaling. Availability and Implementation: MEGADOCK 4.0 is written in C++ with OpenMPI and NVIDIA CUDA 5.0 (or later) and is freely available to all academic and non-profit users at: http://www.bi.cs.titech.ac.jp/megadock . Contact: akiyama@cs.titech.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online

Description: Motivation: The identification of active transcriptional regulatory elements is crucial to understand regulatory networks driving cellular processes such as cell development and the onset of diseases. It has recently been shown that chromatin structure information, such as DNase I hypersensitivity (DHS) or histone modifications, significantly improves cell-specific predictions of transcription factor binding sites. However, no method has so far successfully combined both DHS and histone modification data to perform active binding site prediction. Results: We propose here a method based on hidden Markov models to integrate DHS and histone modifications occupancy for the detection of open chromatin regions and active binding sites. We have created a framework that includes treatment of genomic signals, model training and genome-wide application. In a comparative analysis, our method obtained a good trade-off between sensitivity versus specificity and superior area under the curve statistics than competing methods. Moreover, our technique does not require further training or sequence information to generate binding location predictions. Therefore, the method can be easily applied on new cell types and allow flexible downstream analysis such as de novo motif finding. Availability and implementation: Our framework is available as part of the Regulatory Genomics Toolbox. The software information and all benchmarking data are available at http://costalab.org/wp/dh-hmm . Contact: ivan.costa@rwth-aachen.de or eduardo.gusmao@rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: A proper target or marker is essential in any diagnosis (e.g. an infection or cancer). An ideal diagnostic target should be both conserved in and unique to the pathogen. Currently, these targets can only be identified manually, which is time-consuming and usually error-prone. Because of the increasingly frequent occurrences of emerging epidemics and multidrug-resistant ‘superbugs’, a rapid diagnostic target identification process is needed. Results: A new method that can identify uniquely conserved regions (UCRs) as candidate diagnostic targets for a selected group of organisms solely from their genomic sequences has been developed and successfully tested. Using a sequence-indexing algorithm to identify UCRs and a k -mer integer-mapping model for computational efficiency, this method has successfully identified UCRs within the bacteria domain for 15 test groups, including pathogenic, probiotic, commensal and extremophilic bacterial species or strains. Based on the identified UCRs, new diagnostic primer sets were designed, and their specificity and efficiency were tested by polymerase chain reaction amplifications from both pure isolates and samples containing mixed cultures. Availability and implementation: The UCRs identified for the 15 bacterial species are now freely available at http://ucr.synblex.com . The source code of the programs used in this study is accessible at http://ucr.synblex.com/bacterialIdSourceCode.d.zip Contact: yazhousun@synblex.com Supplementary Information: Supplementary data are available at Bioinformatics online.

Description: Motivation: A popular method for classification of protein domain movements apportions them into two main types: those with a ‘hinge’ mechanism and those with a ‘shear’ mechanism. The intuitive assignment of domain movements to these classes has limited the number of domain movements that can be classified in this way. Furthermore, whether intended or not, the term ‘shear’ is often interpreted to mean a relative translation of the domains. Results: Numbers of occurrences of four different types of residue contact changes between domains were optimally combined by logistic regression using the training set of domain movements intuitively classified as hinge and shear to produce a predictor for hinge and shear. This predictor was applied to give a 10-fold increase in the number of examples over the number previously available with a high degree of precision. It is shown that overall a relative translation of domains is rare, and that there is no difference between hinge and shear mechanisms in this respect. However, the shear set contains significantly more examples of domains having a relative twisting movement than the hinge set. The angle of rotation is also shown to be a good discriminator between the two mechanisms. Availability and implementation: Results are free to browse at http://www.cmp.uea.ac.uk/dyndom/interface/ . Contact: sjh@cmp.uea.ac.uk . Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Recent studies on human disease have revealed that aberrant interaction between proteins probably underlies a substantial number of human genetic diseases. This suggests a need to investigate disease inheritance mode using interaction, and based on which to refresh our conceptual understanding of a series of properties regarding inheritance mode of human disease. Results: We observed a strong correlation between the number of protein interactions and the likelihood of a gene causing any dominant diseases or multiple dominant diseases, whereas no correlation was observed between protein interaction and the likelihood of a gene causing recessive diseases. We found that dominant diseases are more likely to be associated with disruption of important interactions. These suggest inheritance mode should be understood using protein interaction. We therefore reviewed the previous studies and refined an interaction model of inheritance mode, and then confirmed that this model is largely reasonable using new evidences. With these findings, we found that the inheritance mode of human genetic diseases can be predicted using protein interaction. By integrating the systems biology perspectives with the classical disease genetics paradigm, our study provides some new insights into genotype–phenotype correlations. Contact: haodapeng@ems.hrbmu.edu.cn or biofomeng@hotmail.com Supplementary information: Supplementary data are available at Bioinformatics online.

Description: : Recently, several high profile studies collected cell viability data from panels of cancer cell lines treated with many drugs applied at different concentrations. Such drug sensitivity data for cancer cell lines provide suggestive treatments for different types and subtypes of cancer. Visualization of these datasets can reveal patterns that may not be obvious by examining the data without such efforts. Here we introduce Drug/Cell-line Browser (DCB), an online interactive HTML5 data visualization tool for interacting with three of the recently published datasets of cancer cell lines/drug-viability studies. DCB uses clustering and canvas visualization of the drugs and the cell lines, as well as a bar graph that summarizes drug effectiveness for the tissue of origin or the cancer subtypes for single or multiple drugs. DCB can help in understanding drug response patterns and prioritizing drug/cancer cell line interactions by tissue of origin or cancer subtype. Availability and implementation: DCB is an open source Web-based tool that is freely available at: http://www.maayanlab.net/LINCS/DCB Contact: avi.maayan@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: As an important subtype of structural variations, chromosomal translocation is associated with various diseases, especially cancers, by disrupting gene structures and functions. Traditional methods for identifying translocations are time consuming and have limited resolutions. Recently, a few studies have employed next-generation sequencing (NGS) technology for characterizing chromosomal translocations on human genome, obtaining high-throughput results with high resolutions. However, these studies are mainly focused on mechanism-specific or site-specific translocation mapping. In this study, we conducted a comprehensive genome-wide analysis on the characterization of human chromosomal material exchange with regard to the chromosome translocations. Using NGS data of 1,481 subjects from the 1000 Genomes Project, we identified 15,349,092 translocated DNA fragment pairs, ranging from 65 to 1,886 bp and with an average size of approximately 102 bp. On average, each individual genome carried about 10,364 pairs, covering approximately 0.069% of the genome. We identified 16 translocation hot regions, among which two regions did not contain repetitive fragments. Results of our study overlapped with a majority of previous results, containing approximately 79% of approximately 2,340 translocations characterized in three available translocation databases. In addition, our study identified five novel potential recurrent chromosomal material exchange regions with greater than 20% detection rates. Our results will be helpful for an accurate characterization of translocations in human genomes, and contribute as a resource for future studies of the roles of translocations in human disease etiology and mechanisms.

Description: Fractured rocks are known to exhibit seismic anisotropy and shear wave splitting (SWS). SWS is commonly used for fractured rock characterization and has been shown to be sensitive to fluid type. The presence of partial liquid/gas saturation is also known to affect the elastic properties of rocks. The combined effect of both fractures and partial liquid/gas saturation is still unknown. Using synthetic, silica-cemented sandstones with aligned penny-shaped voids, we conducted laboratory ultrasonic experiments to investigate the effect fractures aligned at an oblique angle to wave propagation would have on SWS under partial liquid/gas saturation conditions. The result for the fractured rock shows a saturation dependence which can be explained by combining a fractured rock model and a partial saturation model. At high to full water saturation values, SWS decreases as a result of the fluid bulk modulus effect on the quasi-shear wave. This bulk modulus effect is frequency dependent as a result of wave-induced fluid flow mechanisms, which would in turn lead to frequency dependent SWS. This result suggests the possible use of SWS for discriminating between full liquid saturation and partial liquid/gas saturation.

Description: The effect of network density and geometric distribution on kinematic non-linear source inversion is investigated by inverting synthetic ground motions from a buried strike-slip fault ( M w 6.5), that have been generated by dynamic spontaneous rupture modelling. For the inversion, we use a physics-based regularized Yoffe function as slip velocity function. We test three different cases of station network geometry: (i) single station, varying azimuth and epicentral distance; (ii) multistation circular configurations, that is stations at similar distances from the fault, and regularly spaced around the fault; (iii) irregular multistation configurations using different numbers of stations. Our results show: (1) single station tests suggest that it may be possible to obtain a relatively good source model even using a single station. The best source model using a single station is obtained with stations at which amplitude ratios between three components are not large. We infer that both azimuthal angle and source-to-station distance play an important role in the design of optimal seismic network for source inversion. (2) Multistation tests show that the quality of the inverted source systematically correlates neither with the number of stations, nor with waveform misfit. (3) Waveform misfit has a direct correlation with the number of stations, resulting in overfitting the observed data without any systematic improvement of the source. It suggests that the best source model is not necessarily derived from the model with minimum waveform misfit. (4) A seismic network with a small number of well-spaced stations around the fault may be sufficient to obtain acceptable source inversion.

Description: Fermat's interferometric principle is used to compute interior transmission traveltimes pq from exterior transmission traveltimes sp and sq . Here, the exterior traveltimes are computed for sources s on a boundary B that encloses a volume V of interior points p and q . Once the exterior traveltimes are computed, no further ray tracing is needed to calculate the interior times pq . Therefore this interferometric approach can be more efficient than explicitly computing interior traveltimes pq by ray tracing. Moreover, the memory requirement of the traveltimes is reduced by one dimension, because the boundary B is of one fewer dimension than the volume V . An application of this approach is demonstrated with interbed multiple (IM) elimination. Here, the IMs in the observed data are predicted from the migration image and are subsequently removed by adaptive subtraction. This prediction is enabled by the knowledge of interior transmission traveltimes pq computed according to Fermat's interferometric principle. We denote this principle as the ‘traveltime holographic principle’, by analogy with the holographic principle in cosmology where information in a volume is encoded on the region's boundary.

Description: Earthquake hypocentre locations are crucial in many domains of application (academic and industrial) as seismic event location maps are commonly used to delineate faults or fractures. The interpretation of these maps depends on location accuracy and on the reliability of the associated uncertainties. The largest contribution to location and uncertainty errors is due to the fact that the velocity model errors are usually not correctly taken into account. We propose a new Bayesian formulation that integrates properly the knowledge on the velocity model into the formulation of the probabilistic earthquake location. In this work, the velocity model uncertainties are first estimated with a Bayesian tomography of active shot data. We implement a sampling Monte Carlo type algorithm to generate velocity models distributed according to the posterior distribution. In a second step, we propagate the velocity model uncertainties to the seismic event location in a probabilistic framework. This enables to obtain more reliable hypocentre locations as well as their associated uncertainties accounting for picking and velocity model uncertainties. We illustrate the tomography results and the gain in accuracy of earthquake location for two synthetic examples and one real data case study in the context of induced microseismicity.

Description: Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.

Description: Mitochondrial DNA mutations at MT-ATP6 gene are relatively common in individuals suffering from striatal necrosis syndromes. These patients usually do not show apparent histochemical and/or biochemical signs of oxidative phosphorylation dysfunction. Because of this, MT-ATP6 is not typically analyzed in many other mitochondrial disorders that have not been previously associated to mutations in this gene. To correct this bias, we have performed a screening of the MT-ATP6 gene in a large collection of patients suspected of suffering different mitochondrial DNA (mtDNA) disorders. In three cases, biochemical, molecular-genetics and other analyses in patient tissues and cybrids were also carried out. We found three new pathologic mutations. Two of them in patients showing phenotypes that have not been commonly associated to mutations in the MT-ATP6 gene. These results remark the importance of sequencing the MT-ATP6 gene in patients with striatal necrosis syndromes, but also within other mitochondrial pathologies. This gene should be sequenced at least in all those patients suspected of suffering an mtDNA disorder disclosing normal results for histochemical and biochemical analyses of respiratory chain.

Description: Immunoglobulin-like domain containing receptor 1 ( ILDR1 ) is a poorly characterized gene that was first identified in lymphoma cells. Recently, ILDR1 has been found to be responsible for autosomal recessive hearing impairment DFNB42. Patients with ILDR1 mutations cause bilateral non-progressive moderate-to-profound sensorineural hearing impairment. However, the etiology and mechanism of ILDR1 -related hearing loss remains to be elucidated. In order to uncover the pathology of DFNB42 deafness, we used the morpholino injection technique to establish an ildr1b -morphant zebrafish model. Ildr1b -morphant zebrafish displayed defective hearing and imbalanced swimming, and developmental delays were seen in the semicircular canals of the inner ear. The gene expression profile and real-time PCR revealed down-regulation of atp1b2b (encoding Na + /K + transporting, beta 2b polypeptide) in ildr1b -morphant zebrafish. We found that injection of atp1b2b mRNA into ildr1b -knockdown zebrafish could rescue the phenotype of developmental delay of the semicircular canals. Moreover, ildr1b -morphant zebrafish had reduced numbers of lateral line neuromasts due to the disruption of lateral line primordium migration. In situ hybridization showed the involvement of attenuated FGF signaling and the chemokine receptor 4b ( cxcr4b ) and chemokine receptor 7b ( cxcr7b ) in posterior lateral line primordium of ildr1b -morphant zebrafish. We concluded that Ildr1b is crucial for the development of the inner ear and the lateral line system. This study provides the first evidence for the mechanism of Ildr1b on hearing in vivo and sheds light on the pathology of DFNB42.

Description: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by abnormal expansion of CAG repeats in the gene encoding huntingtin. Mutant huntingtin undergoes proteolytic processing and its N-terminal fragment containing polyglutamine repeat accumulates as inclusion not only in nucleus but also in cytoplasm and neuronal processes. Here, we demonstrate that removal of ubiquitin ligase Ube3a selectively from HD mice brain resulted in accelerated disease phenotype and shorter lifespan in comparison with HD mice. The deficiency of Ube3a in HD mice brain also caused significant increase in global aggregates load, and these aggregates were less ubiquitinated when compared with age-matched HD mice. These Ube3a -maternal deficient HD mice also showed drastic reduction of DARPP-32, a dopamine-regulated phoshphoprotein in their striatum. These results emphasize the crucial role of Ube3a in the progression of HD and its immense potential as therapeutic target.

Description: Parent-of-origin-specific expression at imprinted genes is regulated by allele-specific DNA methylation at imprinting control regions (ICRs). This mechanism of gene regulation, where one element controls allelic expression of multiple genes, is not fully understood. Furthermore, the mechanism of gene dysregulation through ICR epimutations, such as loss or gain of DNA methylation, remains a mystery. We have used genetic mouse models to dissect ICR-mediated genetic and epigenetic regulation of imprinted gene expression. The H19/insulin-like growth factor 2 (Igf2) ICR has a multifunctional role including insulation, activation and repression. Microdeletions at the human H19/IGF2 ICR (IC1) are proposed to be responsible for IC1 epimutations associated with imprinting disorders such as Beckwith–Wiedemann syndrome (BWS). Here, we have generated and characterized a mouse model that mimics BWS microdeletions to define the role of the deleted sequence in establishing and maintaining epigenetic marks and imprinted expression at the H19/IGF2 locus. These mice carry a 1.3 kb deletion at the H19/Igf2 ICR [2,3] removing two of four CCCTC-binding factor (CTCF) sites and the intervening sequence, ~75% of the ICR. Surprisingly, the 2,3 deletion does not perturb DNA methylation at the ICR; however, it does disrupt imprinted expression. While repressive functions of the ICR are compromised by the deletion regardless of tissue type, insulator function is only disrupted in tissues of mesodermal origin where a significant amount of CTCF is poly(ADP-ribosyl)ated. These findings suggest that insulator activity of the H19/Igf2 ICR varies by cell type and may depend on cell-specific enhancers as well as posttranslational modifications of the insulator protein CTCF.

Description: Cerebral cavernous malformation (CCM) is a disease of vascular malformations known to be caused by mutations in one of three genes: CCM1 , CCM2 or CCM3 . Despite several studies, the mechanism of CCM lesion onset remains unclear. Using a Ccm1 knockout mouse model, we studied the morphogenesis of early lesion formation in the retina in order to provide insight into potential mechanisms. We demonstrate that lesions develop in a stereotypic location and pattern, preceded by endothelial hypersprouting as confirmed in a zebrafish model of disease. The vascular defects seen with loss of Ccm1 suggest a defect in endothelial flow response. Taken together, these results suggest new mechanisms of early CCM disease pathogenesis and provide a framework for further study.

Description: Genomic imprinting is the epigenetic process that results in monoallelic expression of genes depending on parental origin. These genes are known to be critical for placental development and fetal growth in mammals. Aberrant epigenetic profiles at imprinted loci, such as DNA methylation defects, are surprisingly rare in pregnancies with compromised fetal growth, while variations in transcriptional output from the expressed alleles of imprinted genes are more commonly reported in pregnancies complicated with intrauterine growth restriction (IUGR). To determine if PLAGL1 and HYMAI , two imprinted transcripts deregulated in Transient Neonatal Diabetes Mellitus, are involved in non-syndromic IUGR we compared the expression and DNA methylation levels in a large cohort of placental biopsies from IUGR and uneventful pregnancies. This revealed that despite appropriate maternal methylation at the shared PLAGL1 / HYMAI promoter, there was a loss of correlation between PLAGL1 and HYMAI expression in IUGR. This incongruity was due to higher HYMAI expression in IUGR gestations, coupled with PLAGL1 down-regulation in placentas from IUGR girls, but not boys. The PLAGL1 protein is a zinc-finger transcription factor that has been shown to be a master coordinator of a genetic growth network in mice. We observe PLAGL1 binding to the H19 / IGF2 shared enhancers in placentae, with significant correlations between PLAGL1 levels with H19 and IGF2 expression levels. In addition, PLAGL1 binding and expression also correlate with expression levels of metabolic regulator genes SLC2A4 , TCF4 and PPAR1 . Our results strongly suggest that fetal growth can be influenced by altered expression of the PLAGL1 gene network in human placenta.

Description: MicroRNAs (miRNAs) have emerged as a class of small, endogenous, regulatory RNAs that exhibit the ability to epigenetically modulate the translation of mRNAs into proteins. This feature enables them to control cell phenotypes and, consequently, modify cell function in a disease context. The role of inflammatory miRNAs in Alzheimer's disease (AD) and their ability to modulate glia responses are now beginning to be explored. In this study, we propose to disclose the functional role of miR-155, one of the most well studied immune-related miRNAs in AD-associated neuroinflammatory events, employing the 3xTg AD animal model. A strong upregulation of miR-155 levels was observed in the brain of 12-month-old 3xTg AD animals. This event occurred simultaneously with an increase of microglia and astrocyte activation, and before the appearance of extracellular Aβ aggregates, suggesting that less complex Aβ species, such as Aβ oligomers may contribute to early neuroinflammation. In addition, we investigated the contribution of miR-155 and the c-Jun transcription factor to the molecular mechanisms that underlie Aβ-mediated activation of glial cells. Our results suggest early miR-155 and c-Jun upregulation in the 3xTg AD mice, as well as in Aβ-activated microglia and astrocytes, thus contributing to the production of inflammatory mediators such as IL-6 and IFN-β. This effect is associated with a miR-155-dependent decrease of suppressor of cytokine signaling 1. Furthermore, since c-Jun silencing decreases the levels of miR-155 in Aβ-activated microglia and astrocytes, we propose that miR-155 targeting can constitute an interesting and promising approach to control neuroinflammation in AD.

Description: Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin ( HTT ) gene. Disease pathogenesis derives, at least in part, from the long polyglutamine tract encoded by mutant HTT . Therefore, considerable effort has been dedicated to the development of therapeutic strategies that significantly reduce the expression of the mutant HTT protein. Antisense oligonucleotides (ASOs) targeted to the CAG repeat region of HTT transcripts have been of particular interest due to their potential capacity to discriminate between normal and mutant HTT transcripts. Here, we focus on phosphorodiamidate morpholino oligomers (PMOs), ASOs that are especially stable, highly soluble and non-toxic. We designed three PMOs to selectively target expanded CAG repeat tracts (CTG22, CTG25 and CTG28), and two PMOs to selectively target sequences flanking the HTT CAG repeat (HTTex1a and HTTex1b). In HD patient–derived fibroblasts with expanded alleles containing 44, 77 or 109 CAG repeats, HTTex1a and HTTex1b were effective in suppressing the expression of mutant and non-mutant transcripts. CTGn PMOs also suppressed HTT expression, with the extent of suppression and the specificity for mutant transcripts dependent on the length of the targeted CAG repeat and on the CTG repeat length and concentration of the PMO. PMO CTG25 reduced HTT-induced cytotoxicity in vitro and suppressed mutant HTT expression in vivo in the N171-82Q transgenic mouse model. Finally, CTG28 reduced mutant HTT expression and improved the phenotype of Hdh Q7/Q150 knock-in HD mice. These data demonstrate the potential of PMOs as an approach to suppressing the expression of mutant HTT.

Description: Reduced expression of SMN protein causes spinal muscular atrophy (SMA), a neurodegenerative disorder leading to motor neuron dysfunction and loss. However, the molecular mechanisms by which SMN regulates neuronal dysfunction are not fully understood. Here, we report that reduced SMN protein level alters miRNA expression and distribution in neurons. In particular, miR-183 levels are increased in neurites of SMN-deficient neurons. We demonstrate that miR-183 regulates translation of mTor via direct binding to its 3' UTR. Interestingly, local axonal translation of mTor is reduced in SMN-deficient neurons, and this can be recovered by miR-183 inhibition. Finally, inhibition of miR-183 expression in the spinal cord of an SMA mouse model prolongs survival and improves motor function of Smn -mutant mice. Together, these observations suggest that axonal miRNAs and the mTOR pathway are previously unidentified molecular mechanisms contributing to SMA pathology.

Description: Microphthalmia-associated transcription factor ( MITF ) is a master regulator of pigmented cell survival and differentiation with direct transcriptional links to cell cycle, apoptosis and pigmentation. In mouse, Mitf is expressed early and uniformly in optic vesicle (OV) cells as they evaginate from the developing neural tube, and null Mitf mutations result in microphthalmia and pigmentation defects. However, homozygous mutations in MITF have not been identified in humans; therefore, little is known about its role in human retinogenesis. We used a human embryonic stem cell (hESC) model that recapitulates numerous aspects of retinal development, including OV specification and formation of retinal pigment epithelium (RPE) and neural retina progenitor cells (NRPCs), to investigate the earliest roles of MITF. During hESC differentiation toward a retinal lineage, a subset of MITF isoforms was expressed in a sequence and tissue distribution similar to that observed in mice. In addition, we found that promoters for the MITF-A , -D and -H isoforms were directly targeted by Visual Systems Homeobox 2 (VSX2), a transcription factor involved in patterning the OV toward a NRPC fate. We then manipulated MITF RNA and protein levels at early developmental stages and observed decreased expression of eye field transcription factors, reduced early OV cell proliferation and disrupted RPE maturation. This work provides a foundation for investigating MITF and other highly complex, multi-purposed transcription factors in a dynamic human developmental model system.

Description: The p.N478D missense mutation in human mitochondrial poly(A) polymerase (mtPAP) has previously been implicated in a form of spastic ataxia with optic atrophy. In this study, we have investigated fibroblast cell lines established from family members. The homozygous mutation resulted in the loss of polyadenylation of all mitochondrial transcripts assessed; however, oligoadenylation was retained. Interestingly, this had differential effects on transcript stability that were dependent on the particular species of transcript. These changes were accompanied by a severe loss of oxidative phosphorylation complexes I and IV, and perturbation of de novo mitochondrial protein synthesis. Decreases in transcript polyadenylation and in respiratory chain complexes were effectively rescued by overexpression of wild-type mtPAP. Both mutated and wild-type mtPAP localized to the mitochondrial RNA-processing granules thereby eliminating mislocalization as a cause of defective polyadenylation. In vitro polyadenylation assays revealed severely compromised activity by the mutated protein, which generated only short oligo(A) extensions on RNA substrates, irrespective of RNA secondary structure. The addition of LRPPRC/SLIRP, a mitochondrial RNA-binding complex, enhanced activity of the wild-type mtPAP resulting in increased overall tail length. The LRPPRC/SLIRP effect although present was less marked with mutated mtPAP, independent of RNA secondary structure. We conclude that (i) the polymerase activity of mtPAP can be modulated by the presence of LRPPRC/SLIRP, (ii) N478D mtPAP mutation decreases polymerase activity and (iii) the alteration in poly(A) length is sufficient to cause dysregulation of post-transcriptional expression and the pathogenic lack of respiratory chain complexes.

Description: During postnatal development, neuronal activity controls the remodeling of initially imprecise neuronal connections through the regulation of gene expression. MeCP2 binds to methylated DNA and modulates gene expression during neuronal development and MECP2 mutation causes the autistic disorder Rett syndrome. To investigate a role for MeCP2 in neuronal circuit refinement and to identify activity-dependent MeCP2 transcription regulations, we leveraged the precise organization and accessibility of olfactory sensory axons to manipulation of neuronal activity through odorant exposure in vivo . We demonstrate that olfactory sensory axons failed to develop complete convergence when Mecp2 is deficient in olfactory sensory neurons (OSNs) in an otherwise wild-type animal. Furthermore, we demonstrate that expression of selected adhesion genes was elevated in Mecp2 -deficient glomeruli, while acute odor stimulation in control mice resulted in significantly reduced MeCP2 binding to these gene loci, correlating with increased expression. Thus, MeCP2 is required for both circuitry refinement and activity-dependent transcriptional responses in OSNs.

Description: Simultaneous generation of neural cells and that of the nutrient-supplying vasculature during brain development is called neurovascular coupling. We report on a transgenic mouse with impaired transforming growth factor β (TGFβ)-signalling in forebrain-derived neural cells using a Foxg1-cre knock-in to drive the conditional knock-out of the Tgfbr2 . Although the expression of FOXG1 is assigned to neural progenitors and neurons of the telencephalon, Foxg1 cre/+ ; Tgfbr2 flox/flox (Tgfbr2-cKO) mutants displayed intracerebral haemorrhage. Blood vessels exhibited an atypical, clustered appearance were less in number and displayed reduced branching. Vascular endothelial growth factor (VEGF) A, insulin-like growth factor (IGF) 1, IGF2, TGFβ, inhibitor of DNA binding (ID) 1, thrombospondin (THBS) 2, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 1 were altered in either expression levels or tissue distribution. Accordingly, human umbilical vein endothelial cells (HUVEC) displayed branching defects after stimulation with conditioned medium (CM) that was derived from primary neural cultures of the ventral and dorsal telencephalon of Tgfbr2-cKO. Supplementing CM of Tgfbr2-cKO with VEGFA rescued these defects, but application of TGFβ aggravated them. HUVEC showed reduced migration towards CM of mutants compared with controls. Supplementing the CM with growth factors VEGFA, fibroblast growth factor (FGF) 2 and IGF1 partially restored HUVEC migration. In contrast, TGFβ supplementation further impaired migration of HUVEC. We observed differences along the dorso-ventral axis of the telencephalon with regard to the impact of these factors on the phenotype. Together these data establish a TGFBR2-dependent molecular crosstalk between neural and endothelial cells during brain vessel development. These findings will be useful to further elucidate neurovascular interaction in general and to understand pathologies of the blood vessel system such as intracerebral haemorrhages, hereditary haemorrhagic telangiectasia, Alzheimeŕs disease, cerebral amyloid angiopathy or tumour biology.

Description: Pneumoconiosis is the most serious occupational disease in China and its leading cause is occupational silica exposure. Pneumoconiosis takes several years to develop depending on the exposure level of silica. However, individual variation in the susceptibility to pneumoconiosis has been observed among the subjects with similar exposure. We conducted a genome-wide screening with 710 999 single nucleotide polymorphisms (SNPs) in a cohort of 400 coal workers (202 cases and 198 exposed controls) for pneumoconiosis susceptible loci. Seven promising variants were evaluated in an independent cohort of 568 coal workers (323 cases and 245 exposed controls), followed by a second replication on 463 iron ore workers (167 cases and 296 exposed controls). By pooling all of the genome-wide association studies and replication stages together, we found a genome-wide significant ( P 〈 5.0 x 10 –8 ) association for rs73329476 ( P = 1.74 x 10 –8 , OR = 2.17, 95% CI = 1.66–2.85) and two additional replicated associations for rs4320486 ( P 〈 0.05) and rs117626015 ( P 〈 0.05) with combined P -values of 4.29 x 10 –6 and 5.05 x 10 –6 , respectively. In addition, the risk allele T of rs73329476 was significantly associated with lower mRNA expression levels of carboxypeptidase M ( CPM ) in total cellular RNA from whole blood of 156 healthy individuals ( P = 0.0252). The identified pneumoconiosis susceptibility loci may provide new insights into the pathogenesis of pneumoconiosis, and may also have some clinical utility for risk prediction for pneumoconiosis and high-risk population screening for workers with occupational silica exposure.

Description: Hearing function is known to be heritable, but few significant and reproducible associations of genetic variants have been identified to date in the adult population. In this study, genome-wide association results of hearing function from the G-EAR consortium and TwinsUK were used for meta-analysis. Hearing ability in eight population samples of Northern and Southern European ancestry ( n = 4591) and the Silk Road ( n = 348) was measured using pure-tone audiometry and summarized using principal component (PC) analysis. Genome-wide association analyses for PC1–3 were conducted separately in each sample assuming an additive model adjusted for age, sex and relatedness of subjects. Meta-analysis was performed using 2.3 million single-nucleotide polymorphisms (SNPs) tested against each of the three PCs of hearing ability in 4939 individuals. A single SNP lying in intron 6 of the salt-inducible kinase 3 ( SIK3 ) gene was found to be associated with hearing PC2 ( P = 3.7 x 10 –8 ) and further supported by whole-genome sequence in a subset. To determine the relevance of this gene in the ear, expression of the Sik3 protein was studied in mouse cochlea of different ages. Sik3 was expressed in murine hair cells during early development and in cells of the spiral ganglion during early development and adulthood. Our results suggest a developmental role of Sik3 in hearing and may be required for the maintenance of adult auditory function.

Description: Genome instability, epigenetic remodelling and structural chromosomal rearrangements are hallmarks of cancer. However, the coordinated epigenetic effects of constitutional chromosomal rearrangements that disrupt genes associated with congenital neurodevelopmental diseases are poorly understood. To understand the genetic–epigenetic interplay at breakpoints of chromosomal translocations disrupting CG-rich loci, we quantified epigenetic modifications at DLGAP4 ( SAPAP4), a key post-synaptic density 95 (PSD95) associated gene, truncated by the chromosome translocation t(8;20)(p12;q11.23), co-segregating with cerebellar ataxia in a five-generation family. We report significant epigenetic remodelling of the DLGAP4 locus triggered by the t(8;20)(p12;q11.23) translocation and leading to dysregulation of DLGAP4 expression in affected carriers. Disruption of DLGAP4 results in monoallelic hypermethylation of the truncated DLGAP4 promoter CpG island. This induced hypermethylation is maintained in somatic cells of carriers across several generations in a t(8;20) dependent-manner however, is erased in the germ cells of the translocation carriers. Subsequently, chromatin remodelling of the locus-perturbed monoallelic expression of DLGAP4 mRNAs and non-coding RNAs in haploid cells having the translocation. Our results provide new mechanistic insight into the way a balanced chromosomal rearrangement associated with a neurodevelopmental disorder perturbs allele-specific epigenetic mechanisms at breakpoints leading to the deregulation of the truncated locus.

Description: We conducted blinded psychiatric assessments of 26 Amish subjects (52 ± 11 years) from four families with prevalent bipolar spectrum disorder, identified 10 potentially pathogenic alleles by exome sequencing, tested association of these alleles with clinical diagnoses in the larger Amish Study of Major Affective Disorder (ASMAD) cohort, and studied mutant potassium channels in neurons. Fourteen of 26 Amish had bipolar spectrum disorder. The only candidate allele shared among them was rs78247304, a non-synonymous variant of KCNH7 (c.1181G〉A, p.Arg394His). KCNH7 c.1181G〉A and nine other potentially pathogenic variants were subsequently tested within the ASMAD cohort, which consisted of 340 subjects grouped into controls subjects and affected subjects from overlapping clinical categories (bipolar 1 disorder, bipolar spectrum disorder and any major affective disorder). KCNH7 c.1181G〉A had the highest enrichment among individuals with bipolar spectrum disorder ( 2 = 7.3) and the strongest family-based association with bipolar 1 ( P = 0.021), bipolar spectrum ( P = 0.031) and any major affective disorder ( P = 0.016). In vitro, the p.Arg394His substitution allowed normal expression, trafficking, assembly and localization of HERG3/Kv11.3 channels, but altered the steady-state voltage dependence and kinetics of activation in neuronal cells. Although our genome-wide statistical results do not alone prove association, cumulative evidence from multiple independent sources (parallel genome-wide study cohorts, pharmacological studies of HERG-type potassium channels, electrophysiological data) implicates neuronal HERG3/Kv11.3 potassium channels in the pathophysiology of bipolar spectrum disorder. Such a finding, if corroborated by future studies, has implications for mental health services among the Amish, as well as development of drugs that specifically target HERG3/Kv11.3.

Description: Complex III (cytochrome bc 1 ) is a protein complex of the mitochondrial inner membrane that transfers electrons from ubiquinol to cytochrome c . Its assembly requires the coordinated expression of mitochondrial-encoded cytochrome b and nuclear-encoded subunits and assembly factors. Complex III deficiency is a severe multisystem disorder caused by mutations in subunit genes or assembly factors. Sequence-profile-based orthology predicts C11orf83 , hereafter named UQCC3 , to be the ortholog of the fungal complex III assembly factor CBP4 . We describe a homozygous c.59T〉A missense mutation in UQCC3 from a consanguineous patient diagnosed with isolated complex III deficiency, displaying lactic acidosis, hypoglycemia, hypotonia and delayed development without dysmorphic features. Patient fibroblasts have reduced complex III activity and lower levels of the holocomplex and its subunits than controls. They have no detectable UQCC3 protein and have lower levels of cytochrome b protein. Furthermore, in patient cells, cytochrome b is absent from a high-molecular-weight complex III. UQCC3 is reduced in cells depleted for the complex III assembly factors UQCC1 and UQCC2. Conversely, absence of UQCC3 in patient cells does not affect UQCC1 and UQCC2. This suggests that UQCC3 functions in the complex III assembly pathway downstream of UQCC1 and UQCC2 and is consistent with what is known about the function of Cbp4 and of the fungal orthologs of UQCC1 and UQCC2, Cbp3 and Cbp6. We conclude that UQCC3 functions in complex III assembly and that the c.59T〉A mutation has a causal role in complex III deficiency.

Description: Mutations in the photoreceptor-specific gene peripherin-2 ( PRPH-2 , also known as retinal degeneration slow/RDS) cause incurable retinal degeneration with a high degree of phenotypic variability. Patient phenotypes range from retinitis pigmentosa to various forms of macular and pattern dystrophy. Macular and pattern dystrophy in particular are associated with complex, poorly understood disease mechanisms, as severe vision loss is often associated both with defects in the photoreceptors, as well as the choroid and retinal pigment epithelium (RPE). Since there is currently no satisfactory model to study pattern dystrophy disease mechanisms, we generated a knockin mouse model expressing an RDS pattern dystrophy mutation, Y141C. Y141C mice exhibited clinical signs similar to those in patients including late-onset fundus abnormalities characteristic of RPE and choroidal defects and electroretinogram defects. Ultrastructural examination indicated that disc formation was initiated by the Y141C protein, but proper sizing and alignment of discs required wild-type RDS. The biochemical mechanism underlying these abnormalities was tied to defects in the normal process of RDS oligomerization which is required for proper RDS function. Y141C-RDS formed strikingly abnormal disulfide-linked complexes which were localized to the outer segment (OS) where they impaired the formation of proper OS structure. These data support a model of pattern dystrophy wherein a primary molecular defect occurring in all photoreceptors leads to secondary sequellae in adjacent tissues, an outcome which leads to macular vision loss. An understanding of the role of RDS in the interplay between these tissues significantly enhances our understanding of RDS-associated pathobiology and our ability to design rational treatment strategies.

Description: This paper analyses the use of impedance spectroscopy as a characterization tool applied to thermoelectric materials. The impedance function of the thermoelectric system under adiabatic conditions and Peltier mode operation is calculated by solving the heat equation in the frequency domain. The analysis, focused on the complex plane, provides the required equivalent circuit elements to interpret the impedance measurements. Using this approach, all the relevant thermoelectric parameters and thermal properties can be potentially extracted at a given temperature from the impedance spectra, i.e., the Seebeck coefficient, electrical resistivity, thermal conductivity, figure of merit (zT), specific heat, and thermal diffusivity. This can be done without the need of measuring temperature differences. To validate the models described, impedance measurements have been carried out in single thermoelectric elements and modules, showing an excellent agreement with the theory. The simple nature of the measurements in conjunction with the advantage of obtaining all the important thermoelectric parameters opens up the possibility of establishing impedance spectroscopy as a very useful characterization method for the thermoelectric field.

Description: Single-phase and oxygen doped Mn 2 N 0.86 thin films have been grown on MgO (111) by plasma-assisted molecular beam epitaxy. The films grow under tensile strain and, remarkably, they show ferromagnetic-like interactions at low temperature and ferromagnetic ordering agreed well with the Bloch-law T 3 / 2 at room-temperature. We further demonstrate the enlarged Mn 3s splitting (6.46 eV) and its possible relation to the observed ferromagnetism. Our study not only provide a strategy for further theoretical work on oxygen doped manganese nitrides, but also shed promising light on utilizing its room-temperature FM property to fabricate spintronic devices.

Description: An arsenic (As)-doped poly-silicon nanowire gate-all-around transistor fabricated using standard semiconductor methods was used to measure the Coulomb blockade effect by applying a tunable gate voltage. Two-level trapping states due to the random telegraph signal of fluctuating drain current were observed in the silicon transport channel. Under high magnetic fields, the superposition points of differential conductance revealed weak 2-electron singlet-triplet splitting states of the arsenic magnetic impurity. The weak spin-orbital coupling suggests that the electron-spin-polarization in the As-doped silicon nanowire and the two-level trapping state coexisted in the Coulomb blockade oscillations. These characteristics indicate that a few arsenic donors strongly affect the quantum behavior of the poly-silicon material.

Description: Enhancing the visibility of images taken in the hazy weather is important in many applications. Among many dehazing methods, those based on polarimetric imaging techniques have several advantages, such as ease of keeping detailed information, low cost, and high efficiency. In this paper, we propose a novel and robust dehazing algorithm based on polarimetric imaging. By introducing the orientation-angle information from the Stokes matrix, all the parameters used in dehazing performance can be effectively, precisely and automatically estimated, and no additional human-computer interaction is needed. Besides, this method can also be used in handling hazy images without sky region. Experimental results show that such a method can greatly enhance the visibility of hazy images.

Description: The field-orientation dependent magnetoelectric coupling is experimentally studied for a rectangular Terfenol-D/PZT/Terfenol-D laminated structure. The considered magnetic field, namely the dc-bias magnetic field or the ac-excitation magnetic field, is allowed to be spatially re-orientated between two orthogonal geometric dimensions of the composite. In the study, the direction of the excitation can be fixed in the longitudinal (Scheme-I) or thickness (Scheme-II) directions, while considering the bias orientation. Alternatively, the bias field can be restricted to the longitudinal (Scheme-III) or thickness (Scheme-IV) directions, while the excitation orientation is considered. The variation in magnetoelectric coefficient as a function of the bias magnitude is studied with special attention paid to the field-orientation dependency. For the testing schemes of I and II, the direction of the dc-bias field can be re-oriented by forming an angle with the fixed direction of the ac-excitation field. As the angle changes from 0° to 90°, the magnetoelectric coupling evolves from L-T mode to S-T surface shear for Scheme-I, and from T-T mode to S-T thickness shear for Scheme-II. The bias-field-orientation dependence demonstrates a complex pattern due to the varying overall state of anisotropy in Terfenol-D. In Scheme-I with low bias magnitude, the orientation dependence can be represented by the measured effective longitudinal piezomagnetic coefficient. In addition, the optimal bias field for maximum magnetoelectric coefficient is observed to linearly increase with the bias orientation angle. Alternatively, the orientation dependence in Schemes III and IV is more predictable due to the barely changed overall state of anisotropy. In this case, Scheme-III shows that the magnetoelectric coefficient decreases monotonically with the orientation angle and Scheme-IV indicates that the maximum coefficient is attained at around 60°. The dependence of the magnetoelectric coupling on the excitation-filed orientation can be understood via analysis of the resultant magnetostriction in Terfenol-D with assumed effective magnetization, which may depart from the bias field due to the strong demagnetization effect. The analysis is supported by the computed field-orientation dependence of the magnetostriction in Terfenol-D.

Description: The results of electronic structure calculations for a variety of palladium hydrides are presented. The calculations are based on density functional theory and used different local and semilocal approximations. The thermodynamic stability of all structures as well as the electronic and chemical bonding properties are addressed. For the monohydride, taking into account the zero-point energy is important to identify the octahedral Pd-H arrangement with its larger voids and, hence, softer hydrogen vibrational modes as favorable over the tetrahedral arrangement as found in the zincblende and wurtzite structures. Stabilization of the rocksalt structure is due to strong bonding of the 4 d and 1 s orbitals, which form a characteristic split-off band separated from the main d -band group. Increased filling of the formerly pure d states of the metal causes strong reduction of the density of states at the Fermi energy, which undermines possible long-range ferromagnetic order otherwise favored by strong magnetovolume effects. For the dihydride, octahedral Pd-H arrangement as realized, e.g., in the pyrite structure turns out to be unstable against tetrahedral arrangement as found in the fluorite structure. Yet, from both heat of formation and chemical bonding considerations, the dihydride turns out to be less favorable than the monohydride. Finally, the vacancy ordered defect phase Pd 3 H 4 follows the general trend of favoring the octahedral arrangement of the rocksalt structure for Pd:H ratios less or equal to one.

Description: The strategy of suppressing grain growth by dispersing nanoscale particles that pin the grain boundaries is demonstrated in a nanocrystalline thermoelectric compound. Yttria nanoparticles that were incorporated by mechanical alloying enabled nanocrystalline (i.e., d 

Description: This work shows the application of metal ion-implantation to realize an efficient second-generation TiO 2 photocatalyst. High fluence Fe + ions were implanted into thin TiO 2 films and subsequently annealed up to 550 °C. The ion-implantation process modified the TiO 2 pure film, locally lowering its band-gap energy from 3.2 eV to 1.6–1.9 eV, making the material sensitive to visible light. The measured optical band-gap of 1.6–1.9 eV was associated with the presence of effective energy levels in the energy band structure of the titanium dioxide, due to implantation-induced defects. An accurate structural characterization was performed by Rutherford backscattering spectrometry, transmission electron microscopy, Raman spectroscopy, X-ray diffraction, and UV/VIS spectroscopy. The synthesized materials revealed a remarkable photocatalytic efficiency in the degradation of organic compounds in water under visible light irradiation, without the help of any thermal treatments. The photocatalytic activity has been correlated with the amount of defects induced by the ion-implantation process, clarifying the operative physical mechanism. These results can be fruitfully applied for environmental applications of TiO 2 .

Description: Monolayers of tin (stannanane) functionalized with halogens have been shown to be topological insulators. Using density functional theory (DFT), we study the electronic properties and room-temperature transport of nanoribbons of iodine-functionalized stannanane showing that the overlap integral between the wavefunctions associated to edge-states at opposite ends of the ribbons decreases with increasing width of the ribbons. Obtaining the phonon spectra and the deformation potentials also from DFT, we calculate the conductivity of the ribbons using the Kubo-Greenwood formalism and show that their mobility is limited by inter-edge phonon backscattering. We show that wide stannanane ribbons have a mobility exceeding 10 6 cm 2 /Vs. Contrary to ordinary semiconductors, two-dimensional topological insulators exhibit a high conductivity at low charge density, decreasing with increasing carrier density. Furthermore, the conductivity of iodine-functionalized stannanane ribbons can be modulated over a range of three orders of magnitude, thus rendering this material extremely interesting for classical computing applications.

Description: Work function, photoemission yield, and Auger electron spectra were measured on (001) p-type GaAs during negative electron affinity (NEA) surface preparation, surface degradation, and heating processes. The emission current sensitively depends on work function change and its dependence allows us to determine that the shape of the vacuum barrier was close to double triangular. Regarding the NEA surface degradation during photoemission, we discuss the importance of residual gas components the oxygen and hydrogen. We also found that gentle annealing (≤100 °C) of aged photocathodes results in a lower work function and may offer a patch to reverse the performance degradation.

Description: Trivalent dysprosium-doped Lu 3 Ga 5 O 12 nano-garnets have been prepared by sol-gel method and characterized by X-ray powder diffraction, high-resolution transmission electron microscopy, dynamic light scattering, and laser excited spectroscopy. Under a cw 457 nm laser excitation, the white luminescence properties of Lu 3 Ga 5 O 12 nano-garnets have been studied as a function of the optically active Dy 3+ ion concentration and at low temperature. Decay curves for the 4 F 9/2 level of Dy 3+ ion exhibit non-exponential nature for all the Dy 3+ concentrations, which have been well-fitted to a generalized energy transfer model for a quadrupole-quadrupole interaction between Dy 3+ ions without diffusion. From these data, a simple rate-equations model can be applied to predict that intense white luminescence could be obtained from 1.8 mol% Dy 3+ ions-doped nano-garnets, which is in good agreement with experimental results. Chromaticity color coordinates and correlated color temperatures have been determined as a function of temperature and are found to be within the white light region for all Dy 3+ concentrations. These results indicate that 2.0 mol% Dy 3+ ions doped nano-garnet could be useful for white light emitting device applications.

Description: In this paper, 80GeO 2 -8Ga 2 O 3 -10BaO-2Nb 2 O 5 -6PbO (in mol%) glass samples with different Tm 2 O 3 concentrations (0, 0.5, 0.75, 1, 1.25, and 1.5 mol. %) were prepared by traditional melt-quenching method. According to the measurement of thermal properties of the host glass, the glass transition temperature is 596.7 °C and no crystallization peak is observed. Judd–Ofelt parameters Ω t (t = 2, 4, 6) and fluorescent lifetimes were obtained by Judd-Ofelt theory. The similar values of Judd–Ofelt parameters and the full-width at half-maximums of ∼1800 nm indicate the local environment of Tm 3+ changes little with increment of Tm 2 O 3 concentrations. Maximum stimulated emission cross-section of ∼1800 nm is 6.22 × 10 −21 cm 2 as calculated by Fuchtbauer–Ladenburg formula. Energy migration among Tm 3+ ions was analyzed by the extended overlap integral method. The non-radiative transition rates between mainly energy levels of Tm 3+ were calculated. Non-radiative transition rate of 3 F 4 energy level caused by OH was analyzed by rate equation and deduced by fitting the fluorescence decay curve.

Description: The concept of chemical bonding can ultimately be seen as a rationalization of the recurring structural patterns observed in molecules and solids. Chemical intuition is nothing but the ability to recognize and predict such patterns, and how they transform into one another. Here, we discuss how to use a computer to identify atomic patterns automatically, so as to provide an algorithmic definition of a bond based solely on structural information. We concentrate in particular on hydrogen bonding – a central concept to our understanding of the physical chemistry of water, biological systems, and many technologically important materials. Since the hydrogen bond is a somewhat fuzzy entity that covers a broad range of energies and distances, many different criteria have been proposed and used over the years, based either on sophisticate electronic structure calculations followed by an energy decomposition analysis, or on somewhat arbitrary choices of a range of structural parameters that is deemed to correspond to a hydrogen-bonded configuration. We introduce here a definition that is univocal, unbiased, and adaptive, based on our machine-learning analysis of an atomistic simulation. The strategy we propose could be easily adapted to similar scenarios, where one has to recognize or classify structural patterns in a material or chemical compound.

Description: We investigate the performance of Stieltjes Imaging applied to Lanczos pseudo-spectra generated at the coupled cluster singles and doubles, coupled cluster singles and approximate iterative doubles and coupled cluster singles levels of theory in modeling the photodetachment cross sections of the closed shell anions H − , Li − , Na − , F − , Cl − , and OH − . The accurate description of double excitations is found to play a much more important role than in the case of photoionization of neutral species.

Description: For conical intersections of two states ( I,J = I + 1) the vectors defining the branching or g-h plane, the energy difference gradient vector g I,J , and the interstate coupling vector h I,J , can be made orthogonal by a one parameter rotation of the degenerate electronic eigenstates. The representation obtained from this rotation is used to construct the parameters that describe the vicinity of the conical intersection seam, the conical parameters, s I,J x ( R ), s I,J y ( R ), g I,J ( R ), and h I,J ( R ). As a result of the orthogonalization these parameters can be made continuous functions of R , the internuclear coordinates. In this work we generalize this notion to construct continuous parametrizations of conical intersection seams of three or more states. The generalization derives from a recently introduced procedure for using non-degenerate electronic states to construct coupled diabatic states that represent adiabatic states coupled by conical intersections. The procedure is illustrated using the seam of conical intersections of three states in parazolyl as an example.

Description: Properties of metallic materials are intrinsically determined by their electron behavior. However, relevant theoretical treatment involving quantum mechanics is complicated and difficult to be applied in materials design. Electron work function (EWF) has been demonstrated to be a simple but fundamental parameter which well correlates properties of materials with their electron behavior and could thus be used to predict material properties from the aspect of electron activities in a relatively easy manner. In this article, we propose a method to extract the electron work functions of binary solid solutions or alloys from their phase diagrams and use this simple approach to predict their mechanical strength and surface properties, such as adhesion. Two alloys, Fe-Ni and Cu-Zn, are used as samples for the study. EWFs extracted from phase diagrams show same trends as experimentally observed ones, based on which hardness and surface adhesive force of the alloys are predicted. This new methodology provides an alternative approach to predict material properties based on the work function, which is extractable from the phase diagram. This work may also help maximize the power of phase diagram for materials design and development.

Description: State averaged complete active space self-consistent field (SA-CASSCF) is a workhorse for determining the excited-state electronic structure of molecules, particularly for states with multireference character; however, the method suffers from known issues that have prevented its wider adoption. One issue is the presence of discontinuities in potential energy surfaces when a state that is not included in the state averaging crosses with one that is. In this communication I introduce a new dynamical weight with spline (DWS) scheme that mimics SA-CASSCF while removing energy discontinuities due to unweighted state crossings. In addition, analytical gradients for DWS-CASSCF (and other dynamically weighted schemes) are derived for the first time, enabling energy-conserving excited-state ab initio molecular dynamics in instances where SA-CASSCF fails.

Description: Modern materials processing applications and technologies often occur far from equilibrium. To this end, the processing of complex materials such as polymer melts and nanocomposites generally occurs under strong deformations and flows, conditions under which equilibrium thermodynamics does not apply. As a result, the ability to determine the nonequilibrium thermodynamic properties of polymeric materials from measurable quantities such as heat and work is a major challenge in the field. Here, we use work relations to show that nonequilibrium thermodynamic quantities such as free energy and entropy can be determined for dilute polymer solutions in flow. In this way, we determine the thermodynamic properties of DNA molecules in strong flows using a combination of simulations, kinetic theory, and single molecule experiments. We show that it is possible to calculate polymer relaxation timescales purely from polymer stretching dynamics in flow. We further observe a thermodynamic equivalence between nonequilibrium and equilibrium steady-states for polymeric systems. In this way, our results provide an improved understanding of the energetics of flowing polymer solutions.

Description: Over the course of the past few decades, there has been an exponential growth in environmental courts and tribunals (ECTs). At present, over 350 of these specialized fora for resolving environmental disputes exist, spanning across every region throughout the world. Some of the ECTs have been more successful but others have been less successful. This article identifies 12 characteristics that experience suggests are required for an environmental court or tribunal to operate successfully in practice, drawing upon examples from multiple jurisdictions. In identifying best practices, both substantive and procedural, from existing ECTs, this article will assist two groups: first, stakeholders who are in the process of planning or creating environmental courts or tribunals in their jurisdictions and, secondly, stakeholders and countries that are looking to improve the functioning and performance of their own ECTs.

Description: Cohesive interactions between filamentous molecules have broad implications for a range of biological and synthetic materials. While long-standing theoretical approaches have addressed the problem of inter-filament forces from the limit of infinitely rigid rods, the ability of flexible filaments to deform intra-filament shape in response to changes in inter-filament geometry has a profound affect on the nature of cohesive interactions. In this paper, we study two theoretical models of inter-filament cohesion in the opposite limit, in which filaments are sufficiently flexible to maintain cohesive contact along their contours, and address, in particular, the role played by helical-interfilament geometry in defining interactions. Specifically, we study models of featureless, tubular filaments interacting via: (1) pair-wise Lennard-Jones (LJ) interactions between surface elements and (2) depletion-induced filament binding stabilized by electrostatic surface repulsion. Analysis of these models reveals a universal preference for cohesive filament interactions for non-zero helical skew, and further, that in the asymptotic limit of vanishing interaction range relative to filament diameter, the skew-dependence of cohesion approaches a geometrically defined limit described purely by the close-packing geometry of twisted tubular filaments. We further analyze non-universal features of the skew-dependence of cohesion at small-twist for both potentials, and argue that in the LJ model the pair-wise surface attraction generically destabilizes parallel filaments, while in the second model, pair-wise electrostatic repulsion in combination with non-pairwise additivity of depletion leads to a meta-stable parallel state.

Description: Legal education plays an important but under-acknowledged role in anthropogenic environmental change because it shapes and qualifies people to become lawyers, judges and policy makers. Their work can prohibit and legitimate particular environmental practices. The conceptual framework of law, its taxonomy, as taught to students of law, often perpetuates an unsustainable relationship to the environment where it separates questions of entitlement to land and natural resources from questions of responsibility for them. The implication of perpetuating this separation in law curricula is that generations of legal practitioners will remain unlikely to develop a coherent system of environmental law that aligns rights with responsibilities. Environmental education scholar David Orr argues that ‘all education is environmental education’. But legal education often excludes environmental considerations even where these are materially relevant. Given the role of legal education in shaping future law, this article contends that rethinking its categories opens the possibility to create sustainable land use practice laws and policy.

Description: The effect of strong intermolecular hydrogen bonding on torsional degrees of freedom is investigated by far-infrared absorption spectroscopy for different methanol dimer isotopologues isolated in supersonic jet expansions or embedded in inert neon matrices at low temperatures. For the vacuum-isolated and Ne-embedded methanol dimer, the hydrogen bond OH librational mode of the donor subunit is finally observed at ∼560 cm −1 , blue-shifted by more than 300 cm −1 relative to the OH torsional fundamental of the free methanol monomer. The OH torsional mode of the acceptor embedded in neon is observed at ∼286 cm −1 . The experimental findings are held against harmonic predictions from local coupled-cluster methods with single and double excitations and a perturbative treatment of triple excitations [LCCSD(T)] and anharmonic. VPT2 corrections at canonical MP2 and density functional theory (DFT) levels in order to quantify the contribution of vibrational anharmonicity for this important class of intermolecular hydrogen bond vibrational motion.

Description: Extensive numerical solutions of the hypernetted-chain (HNC) and Rogers-Young (RY) integral equations are presented for the pair structure of a system of two coupled replicae (1 and 2) of a “soft-sphere” fluid of atoms interacting via an inverse-12 pair potential. In the limit of vanishing inter-replica coupling ɛ 12 , both integral equations predict the existence of three branches of solutions: (1) A high temperature liquid branch ( L ), which extends to a supercooled regime upon cooling when the two replicae are kept at ɛ 12 = 0 throughout; upon separating the configurational and vibrational contributions to the free energy and entropy of the L branch, the Kauzmann temperature is located where the configurational entropy vanishes. (2) Starting with an initial finite coupling ɛ 12 , two “glass” branches G 1 and G 2 are found below some critical temperature, which are characterized by a strong remnant spatial inter-replica correlation upon taking the limit ɛ 12 → 0. Branch G 2 is characterized by an increasing overlap order parameter upon cooling, and may hence be identified with the hypothetical “ideal glass” phase. Branch G 1 exhibits the opposite trend of increasing order parameter upon heating; its free energy lies consistently below that of the L branch and above that of the G 2 branch. The free energies of the L and G 2 branches are found to intersect at an alleged “random first-order transition” (RFOT) characterized by weak discontinuities of the volume and entropy. The Kauzmann and RFOT temperatures predicted by RY differ significantly from their HNC counterparts.

Description: We present a continuum solvent model (CSM) with a smooth cavity for the application in grid-based electronic structure methods. The cavity is identified with the inherently smooth distribution function of a binary mixture at infinite dilution. We obtain a cavity model based on atomic van der Waals radii and one free parameter controlling the overall size. This single parameter is sufficient to adequately reproduce experimental partial molar volumes. The CSM based on this cavity is of similar accuracy in the prediction of aqueous solvation Gibbs energies of small neutral molecules and ions as other CSMs with a smooth cavity. We apply the model to systems in non-aqueous solution, i.e., spiropyran/merocyanin energetics, a proton transfer reaction in dimethyl sulfoxide, and the electrostatic screening of charged gold clusters in an ionic liquid.

Description: This article utilises the concept of interdisciplinarity as a background against which to reflect on the nature of environmental law scholarship. The article argues that, while interdisciplinary scholarship has some tangible benefits in terms of expanding the perimeters of a discipline, the effects of interdisciplinary work are often exaggerated. In fact, interdisciplinary scholarship may have the unintended consequence of entrenching academic disciplines even further. In light of this, it is argued that environmental law scholarship is best perceived and defined as a deliberative practice which takes place within, and speaks to, a specific community of scholars—an interpretive community. In order to secure a vibrant discipline, the article argues that the community ought to maintain a flexible, open-ended and broadly defined approach to environmental law scholarship.

Description: European Union (EU) legal studies generally picture the Member States’ local and regional authorities as implementers of national and supranational norms rather than independent regulators. Yet, sub-national authorities (SNAs) have become active regulators in the context of climate change mitigation and adaptation, a role not foreseen by EU primary law, which this article understands to constitute the surface of EU law. This article examines regulatory activity of SNAs from the perspective of EU law. It illustrates that sub-national, national, supranational and international actors are engaged in a process of mutual learning and experimentation and that, below its surface, EU law recognises that SNAs are not mere implementers of norms but also independent regulators.

Description: This article presents a fresh analysis of the implications of the 2006 judgment of the Court of Justice of the European Union (CJEU) in Case C-244/05 Bund Naturschutz in Bayern , which clarified the standard of legal protection afforded to sites eligible for adoption as Sites of Community Importance (SCIs) under the EU’s Habitats Directive. The article argues that, as a result of this line of case law, it will be unlawful ( at least in certain cases, and perhaps in all) to apply the Article 6(4) Habitats Directive derogation in respect of eligible sites which have not yet been adopted by the European Commission as SCIs. The Commission appears to have been aware of this potential implication, and acted swiftly to minimise the potentially disruptive impact of the judgment on plans and projects within the EU. The article also considers the relevance of the CJEU’s Sweetman judgment ( C-258/11 ) to the Bund Naturschutz in Bayern line of jurisprudence.

Description: What does the specialised nature of an environment court entitle it to do? The recent decision of the New Zealand Supreme Court in Environmental Defence Society Incorporated v Marlborough District Council (‘the King Salmon case’)[2014] NZSC 38 helps to answer this question. For the past 20 years, the New Zealand Environment Court has decided applications within a framework of the broadly defined statutory purpose of sustainable resource management. The King Salmon case narrows this wide discretion. This article analyses the implications of the decision, suggesting that it helps to delineate between functions of specialist environment courts that may be considered appropriate (adjudicative and legislative fact finding) and decision-making that strays too far into the policy-sphere.

Description: This article compares the protection from unnecessary suffering afforded to wild animals with that afforded to domesticated animals and animals under human control. It considers various forms of species-specific biodiversity- and conservation-based protection for wild animals, under legislation such as the Wildlife and Countryside Act 1981 and the Conservation of Habitats and Species Regulations 2010, as well as the general protection from intentionally inflicted unnecessary suffering afforded to wild mammals under the Wild Mammals (Protection) Act 1996. The article then compares the standard of protection afforded to wild animals with that afforded to non-wild animals under section 4 of the Animal Welfare Act 2006, which criminalises unnecessary suffering unreasonably caused to non-wild animals.