bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia
Authors:   Clozapine-Induced Agranulocytosis Consortium, Legge S E , Hamshere M L , Ripke S , Pardinas A F , Goldstein J I , Rees E , Richards A L , Leonenko G , Jorskog L F , Chambert K D , Collier D A , Genovese G , Giegling I , Holmans P , Jonasdottir A , Kirov G , McCarroll S A , MacCabe J H , Mantripragada K , Moran J L , Neale B M , Stefansson H , Rujescu D , Daly M J , Sullivan P F , Owen M J , O'Donovan M C , Walters J T R 
Published: July 2016

Abstract
The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10−8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect.
Germline MC1R status influences somatic mutation burden in melanoma
Authors: Robles-Espinoza Carla Daniela , Roberts Nicola D. , Chen Shuyang , Leacy Finbarr P. , Alexandrov Ludmil B. , Pornputtapong Natapol , Halaban Ruth , Krauthammer Michael , Cui Rutao , Timothy Bishop D. , Adams David J. 
Published: July 2016

AbstractThe major genetic determinants of cutaneous melanoma risk in the general population are disruptive variants (Ralleles) in the melanocortin 1 receptor (MC1R) gene. These alleles are also linked to red hair, freckling, and sun sensitivity, all of which are known melanoma phenotypic risk factors. Here we report that in melanomas and for somatic C>T mutations, a signature linked to sun exposure, the expected single-nucleotide variant count associated with the presence of anRallele is estimated to be 42% (95% CI, 15–76%) higher than that among persons without anRallele. This figure is comparable to the expected mutational burden associated with an additional 21 years of age. We also find significant and similar enrichment of non-C>T mutation classes supporting a role for additional mutagenic processes in melanoma development in individuals carryingRalleles.
Multiple scattering dynamics of fermions at an isolated p-wave resonance
Authors: Thomas R. , Roberts K. O. , Tiesinga E. , Wade A. C. J. , Blakie P. B. , Deb A. B. , Kjærgaard N. 
Published: July 2016

AbstractThe wavefunction for indistinguishable fermions is anti-symmetric under particle exchange, which directly leads to the Pauli exclusion principle, and hence underlies the structure of atoms and the properties of almost all materials. In the dynamics of collisions between two indistinguishable fermions, this requirement strictly prohibits scattering into 90° angles. Here we experimentally investigate the collisions of ultracold clouds fermionic 40K atoms by directly measuring scattering distributions. With increasing collision energy we identify the Wigner threshold for p-wave scattering with its tell-tale dumb-bell shape and no 90° yield. Above this threshold, effects of multiple scattering become manifest as deviations from the underlying binary p-wave shape, adding particles either isotropically or axially. A shape resonance for 40K facilitates the separate observation of these two processes. The isotropically enhanced multiple scattering mode is a generic p-wave threshold phenomenon, whereas the axially enhanced mode should occur in any colliding particle system with an elastic scattering resonance.
Automated circuit fabrication and direct characterization of carbon nanotube vibrations
Authors: Zeevi G. , Shlafman M. , Tabachnik T. , Rogachevsky Z. , Rechnitz S. , Goldshtein I. , Shlafman S. , Gordon N. , Alchanati G. , Itzhak M. , Moshe Y. , Hajaj E. M. , Nir H. , Milyutin Y. , Izraeli T. Y. , Razin A. , Shtempluck O. , Kotchtakov V. , Yaish Y. E. 
Published: July 2016

AbstractSince their discovery, carbon nanotubes have fascinated many researchers due to their unprecedented properties. However, a major drawback in utilizing carbon nanotubes for practical applications is the difficulty in positioning or growing them at specific locations. Here we present a simple, rapid, non-invasive and scalable technique that enables optical imaging of carbon nanotubes. The carbon nanotube scaffold serves as a seed for nucleation and growth of small size, optically visible nanocrystals. After imaging the molecules can be removed completely, leaving the surface intact, and thus the carbon nanotube electrical and mechanical properties are preserved. The successful and robust optical imaging allowed us to develop a dedicated image processing algorithm through which we are able to demonstrate a fully automated circuit design resulting in field effect transistors and inverters. Moreover, we demonstrate that this imaging method allows not only to locate carbon nanotubes but also, as in the case of suspended ones, to study their dynamic mechanical motion.
RUBIC identifies driver genes by detecting recurrent DNA copy number breaks
Authors: van Dyk Ewald , Hoogstraat Marlous , ten Hoeve Jelle , Reinders Marcel J. T. , Wessels Lodewyk F. A. 
Published: July 2016

AbstractThe frequent recurrence of copy number aberrations across tumour samples is a reliable hallmark of certain cancer driver genes. However, state-of-the-art algorithms for detecting recurrent aberrations fail to detect several known drivers. In this study, we propose RUBIC, an approach that detects recurrent copy number breaks, rather than recurrently amplified or deleted regions. This change of perspective allows for a simplified approach as recursive peak splitting procedures and repeated re-estimation of the background model are avoided. Furthermore, we control the false discovery rate on the level of called regions, rather than at the probe level, as in competing algorithms. We benchmark RUBIC against GISTIC2 (a state-of-the-art approach) and RAIG (a recently proposed approach) on simulated copy number data and on three SNP6 and NGS copy number data sets from TCGA. We show that RUBIC calls more focal recurrent regions and identifies a much larger fraction of known cancer genes.
Leukaemia cell of origin identified by chromatin landscape of bulk tumour cells
Authors: George Joshy , Uyar Asli , Young Kira , Kuffler Lauren , Waldron-Francis Kaiden , Marquez Eladio , Ucar Duygu , Trowbridge Jennifer J. 
Published: July 2016

AbstractThe precise identity of a tumour’s cell of origin can influence disease prognosis and outcome. Methods to reliably define tumour cell of origin from primary, bulk tumour cell samples has been a challenge. Here we use a well-defined model of MLL-rearranged acute myeloid leukaemia (AML) to demonstrate that transforming haematopoietic stem cells (HSCs) and multipotent progenitors results in more aggressive AML than transforming committed progenitor cells. Transcriptome profiling reveals a gene expression signature broadly distinguishing stem cell-derived versus progenitor cell-derived AML, including genes involved in immune escape, extravasation and small GTPase signal transduction. However, whole-genome profiling of open chromatin reveals precise and robust biomarkers reflecting each cell of origin tested, from bulk AML tumour cell sampling. We find that bulk AML tumour cells exhibit distinct open chromatin loci that reflect the transformed cell of origin and suggest that open chromatin patterns may be leveraged as prognostic signatures in human AML.
Plastid-nucleus communication involves calcium-modulated MAPK signalling
Authors: Guo Hailong , Feng Peiqiang , Chi Wei , Sun Xuwu , Xu Xiumei , Li Yuan , Ren Dongtao , Lu Congming , David Rochaix Jean , Leister Dario , Zhang Lixin 
Published: July 2016

AbstractChloroplast retrograde signals play important roles in coordinating the plastid and nuclear gene expression and are critical for proper chloroplast biogenesis and for maintaining optimal chloroplast functions in response to environmental changes in plants. Until now, the signals and the mechanisms for retrograde signalling remain poorly understood. Here we identify factors that allow the nucleus to perceive stress conditions in the chloroplast and to respond accordingly by inducing or repressing specific nuclear genes encoding plastid proteins. We show that ABI4, which is known to repress the LHCB genes during retrograde signalling, is activated through phosphorylation by the MAP kinases MPK3/MPK6 and the activity of these kinases is regulated through 14-3-3ω-mediated Ca2+-dependent scaffolding depending on the chloroplast calcium sensor protein CAS. These findings uncover an additional mechanism in which chloroplast-modulated Ca2+ signalling controls the MAPK pathway for the activation of critical components of the retrograde signalling chain.
Chunking as the result of an efficiency computation trade-off
Authors: Ramkumar Pavan , Acuna Daniel E. , Berniker Max , Grafton Scott T. , Turner Robert S. , Kording Konrad P. 
Published: July 2016

AbstractHow to move efficiently is an optimal control problem, whose computational complexity grows exponentially with the horizon of the planned trajectory. Breaking a compound movement into a series of chunks, each planned over a shorter horizon can thus reduce the overall computational complexity and associated costs while limiting the achievable efficiency. This trade-off suggests a cost-effective learning strategy: to learn new movements we should start with many short chunks (to limit the cost of computation). As practice reduces the impediments to more complex computation, the chunking structure should evolve to allow progressively more efficient movements (to maximize efficiency). Here we show that monkeys learning a reaching sequence over an extended period of time adopt this strategy by performing movements that can be described as locally optimal trajectories. Chunking can thus be understood as a cost-effective strategy for producing and learning efficient movements.
Observation of interaction-induced modulations of a quantum Hall liquid’s area
Authors: Sivan I. , Choi H. K. , Park Jinhong , Rosenblatt A. , Gefen Yuval , Mahalu D. , Umansky V. 
Published: July 2016

AbstractStudies of electronic interferometers, based on edge-channel transport in the quantum Hall effect regime, have been stimulated by the search for evidence of abelian and non-abelian anyonic statistics of fractional charges. In particular, the electronic Fabry–Pérot interferometer has been found to be Coulomb dominated, thus masking coherent Aharonov–Bohm interference patterns: the flux trapped within the interferometer remains unchanged as the applied magnetic field is varied, barring unobservable modulations of the interference area. Here we report on conductance measurements indicative of the interferometer’s area ‘breathing’ with the variation of the magnetic field, associated with observable (a fraction of a flux quantum) variations of the trapped flux. This is the result of partial (controlled) screening of Coulomb interactions. Our results introduce a novel experimental tool for probing anyonic statistics.
The concordance between the volume hotspot and the grade hotspot: a 3-D reconstructive model using the pathology outputs from the PROMIS trial
Authors: El-Shater Bosaily A , Valerio M , Hu Y , Freeman A , Jameson C , Brown L , Kaplan R , Hindley R G , Barratt D , Emberton M , Ahmed H U 
Published: July 2016

Abstract

Objectives:
The rationale for directing targeted biopsy towards the centre of lesions has been questioned in light of prostate cancer grade heterogeneity. In this study, we assess the assumption that the maximum cancer Gleason grade (Gleason grade hotspot) lies within the maximum dimension (volume hotspot) of a prostate cancer lesion.

Methods:
3-D histopathological models were reconstructed using the outputs of the 5-mm transperineal mapping (TPM) biopsies used as the reference test in the pilot phase of Prostate Mri Imaging Study (PROMIS), a paired validating cohort study investigating the performance of multi-parametric magnetic resonance imaging (MRI) against transrectal ultrasound (TRUS) biopsies. The prostate was fully sampled with 5 mm intervals; each core was separately labelled, inked and orientated in space to register 3-D cancer lesions location. The data from the histopathology results were used to create a 3-D interpolated reconstruction of each lesion and identify the spatial coordinates of the largest dimension (volume hot spot) and highest Gleason grade (Gleason grade hotspot) and assess their concordance.

Results:
Ninety-four men, with median age 62 years (interquartile range, IQR= 58–68) and median PSA 6.5 ng ml−1 (4.6–8.8), had a median of 80 (I69–89) cores each with a median of 4.5 positive cores (0–12). In the primary analysis, the prevalence of homogeneous lesions was 148 (76%; 95% confidence interval (CI) ±6.0%). In all, 184 (94±3.2%) lesions showed concordant hotspots and 11/47 (23±12.1%) of heterogeneous lesions showed discordant hotspots. The median 3-D distance between discordant hotspots was 12.8 mm (9.9–15.5). These figures remained stable on secondary analyses using alternative reconstructive assumptions. Limitations include a certain degree of error within reconstructed models.

Conclusions:
Guiding one biopsy needle to the maximum cancer diameter would lead to correct Gleason grade attribution in 94% of all lesions and 79% of heterogeneous ones if a true hit was obtained. Further correlation of histological lesions, their MRI appearance and the detectability of these hotspots on MRI will be undertaken once PROMIS results are released.
Fracture behaviors of ceramic tissue scaffolds for load bearing applications
Authors: Entezari Ali , Roohani-Esfahani Seyed-Iman , Zhang Zhongpu , Zreiqat Hala , Dunstan Colin R. , Li Qing 
Published: July 2016

AbstractHealing large bone defects, especially in weight-bearing locations, remains a challenge using available synthetic ceramic scaffolds. Manufactured as a scaffold using 3D printing technology, Sr-HT-Gahnite at high porosity (66%) had demonstrated significantly improved compressive strength (53 ± 9 MPa) and toughness. Nevertheless, the main concern of ceramic scaffolds in general remains to be their inherent brittleness and low fracture strength in load bearing applications. Therefore, it is crucial to establish a robust numerical framework for predicting fracture strengths of such scaffolds. Since crack initiation and propagation plays a critical role on the fracture strength of ceramic structures, we employed extended finite element method (XFEM) to predict fracture behaviors of Sr-HT-Gahnite scaffolds. The correlation between experimental and numerical results proved the superiority of XFEM for quantifying fracture strength of scaffolds over conventional FEM. In addition to computer aided design (CAD) based modeling analyses, XFEM was conducted on micro-computed tomography (μCT) based models for fabricated scaffolds, which took into account the geometric variations induced by the fabrication process. Fracture strengths and crack paths predicted by the μCT-based XFEM analyses correlated well with relevant experimental results. The study provided an effective means for the prediction of fracture strength of porous ceramic structures, thereby facilitating design optimization of scaffolds.
ZIF-8 Derived, Nitrogen-Doped Porous Electrodes of Carbon Polyhedron Particles for High-Performance Electrosorption of Salt Ions
Authors: Liu Nei-Ling , Dutta Saikat , Salunkhe Rahul R. , Ahamad Tansir , Alshehri Saad M. , Yamauchi Yusuke , Hou Chia-Hung , Wu Kevin C.-W. 
Published: July 2016

AbstractThree-dimensional (3-D) ZIF-8 derived carbon polyhedrons with high nitrogen (N) content, (denoted as NC-800) are synthesized for their application as high-performance electrodes in electrosorption of salt ions. The results showed a high specific capacitance of 160.8 F·g−1 in 1 M NaCl at a scan rate of 5 mV·s−1. Notably, integration of 3-D mesopores and micropores in NC-800 achieves an excellent capacitive deionization (CDI) performance. The electrosorption of salt ions at the electrical double layer is enhanced by N-doping at the edges of a hexagonal lattice of NC-800. As evidenced, when the initial NaCl solution concentration is 1 mM, the resultant NC-800 exhibits a remarkable CDI potential with a promising salt electrosorption capacity of 8.52 mg·g−1.
Electronic and magnetic properties of H-terminated graphene nanoribbons deposited on the topological insulator Sb2Te3
Authors: Zhang Wei , Hajiheidari Farideh , Li Yan , Mazzarello Riccardo 
Published: July 2016

AbstractMagnetism in zigzag graphene nanoribbons (GNRs) has received enormous attention recently, due to the one-dimensional nature of this phenomenon, as well as its potential applications in the field of spintronics. In this work, we present a density functional theory (DFT) investigation of H-passivated GNRs on the (111) surface of the topological insulator Sb2Te3. We show that the chemical interaction between the GNR and the substrate is weak. As a result, the GNR-surface distance is large, of the order of 3.4 Angstrom, doping effects are almost negligible, and the mean-field magnetic properties of the GNR are preserved. Nevertheless, the presence of the substrate affects significantly the magnitude of the exchange coupling constants between the edges. Although our DFT calculations do not properly describe quantum fluctuations that destabilize the edge magnetism in free-standing GNRs, they provide important information about the stabilizing mechanisms which originate from the substrate-induced spin orbit coupling and the decoherence effects due to the surface states of Sb2Te3. We argue that, owing to these mechanisms, Sb2Te3 may be a suitable substrate to investigate experimentally the transition from “quantum” to “classical” magnetism in GNRs.
A Comprehensive study of the Effects of Chain Morphology on the Transport Properties of Amorphous Polymer Films
Authors: Mendels Dan , Tessler Nir 
Published: July 2016

AbstractOrganic semiconductors constitute one of the main components underlying present-day paradigm shifting optoelectronic applications. Among them, polymer based semiconductors are deemed particularly favorable due to their natural compatibility with low-cost device fabrication techniques. In light of recent advances in the syntheses of these classes of materials, yielding systems exhibiting charge mobilities comparable with those found in organic crystals, a comprehensive study of their charge transport properties is presented. Among a plethora of effects arising from these systems morphological and non morphological attributes, it is shown that a favorable presence of several of these attributes, including that of rapid on-chain carrier propagation and the presence of elongated conjugation segments, can lead to an enhancement of the system’s mobility by more than 5 orders of magnitude with respect to ‘standard’ amorphous organic semiconductors. New insight for the formulation of new engineering strategies for next generation polymer based semiconductors is thus gathered.
Overcoming the matched-sample bottleneck: an orthogonal approach to integrate omic data
Authors: Nguyen Tin , Diaz Diana , Tagett Rebecca , Draghici Sorin 
Published: July 2016

AbstractMicroRNAs (miRNAs) are small non-coding RNA molecules whose primary function is to regulate the expression of gene products via hybridization to mRNA transcripts, resulting in suppression of translation or mRNA degradation. Although miRNAs have been implicated in complex diseases, including cancer, their impact on distinct biological pathways and phenotypes is largely unknown. Current integration approaches require sample-matched miRNA/mRNA datasets, resulting in limited applicability in practice. Since these approaches cannot integrate heterogeneous information available across independent experiments, they neither account for bias inherent in individual studies, nor do they benefit from increased sample size. Here we present a novel framework able to integrate miRNA and mRNA data (vertical data integration) available in independent studies (horizontal meta-analysis) allowing for a comprehensive analysis of the given phenotypes. To demonstrate the utility of our method, we conducted a meta-analysis of pancreatic and colorectal cancer, using 1,471 samples from 15 mRNA and 14 miRNA expression datasets. Our two-dimensional data integration approach greatly increases the power of statistical analysis and correctly identifies pathways known to be implicated in the phenotypes. The proposed framework is sufficiently general to integrate other types of data obtained from high-throughput assays.
A consolidated analysis of the physiologic and molecular responses induced under acid stress in the legume-symbiont model-soil bacterium Sinorhizobium meliloti
Authors: Draghi W. O. , Del Papa M. F. , Hellweg C. , Watt S. A. , Watt T. F. , Barsch A. , Lozano M. J. , Lagares A. , Salas M. E. , López J. L. , Albicoro F. J. , Nilsson J. F. , Torres Tejerizo G. A. , Luna M. F. , Pistorio M. , Boiardi J. L. , Pühler A. , Weidner S. , Niehaus K. , Lagares A. 
Published: July 2016

AbstractAbiotic stresses in general and extracellular acidity in particular disturb and limit nitrogen-fixing symbioses between rhizobia and their host legumes. Except for valuable molecular-biological studies on different rhizobia, no consolidated models have been formulated to describe the central physiologic changes that occur in acid-stressed bacteria. We present here an integrated analysis entailing the main cultural, metabolic, and molecular responses of the model bacterium Sinorhizobium meliloti growing under controlled acid stress in a chemostat. A stepwise extracellular acidification of the culture medium had indicated that S. meliloti stopped growing at ca. pH 6.0–6.1. Under such stress the rhizobia increased the O2 consumption per cell by more than 5-fold. This phenotype, together with an increase in the transcripts for several membrane cytochromes, entails a higher aerobic-respiration rate in the acid-stressed rhizobia. Multivariate analysis of global metabolome data served to unequivocally correlate specific-metabolite profiles with the extracellular pH, showing that at low pH the pentose-phosphate pathway exhibited increases in several transcripts, enzymes, and metabolites. Further analyses should be focused on the time course of the observed changes, its associated intracellular signaling, and on the comparison with the changes that operate during the sub lethal acid-adaptive response (ATR) in rhizobia.