bluuebunny/crossref_metadata_2025 huggingface dataset:
Autonomy and Happiness in Rousseau's Justification of the State
Authors: Hasan Rafeeq
Published: July 2016

Recent interpretations of Rousseau suggest that autonomy is the master concept by which to understand his justification of the state. The Rousseauian state is legitimate insofar as it enables individuals to obey only their own wills and thus to be free. Autonomy-based interpretations cannot adequately account for Rousseau's remarks on the role of the state in securing a collective form of happiness through political community. These interpretations incorrectly construe collective happiness as pertaining only to how civic-minded citizens might be psychologically motivated to obey the state's dictates, rather than to what makes the state legitimate. By contrast, I offer a new interpretation according to which the Rousseauian state is justified because it enables a mutually constitutive relationship between the autonomy of individuals and the happiness that stems from participation in political community.
Thoughts on Leo Strauss's Interpretation of Aristotle's Natural Right Teaching
Authors: Cruz Sousa André Luiz
Published: July 2016

The essay discusses the interpretation of Aristotle's natural right teaching by Leo Strauss. This interpretation ought to be seen as the result of an investigation into the history of philosophy and of an attempt to philosophically address political problems. By virtue of this twofold origin, the Straussian commentary is unorthodox: it deviates from traditional Aristotelianism (Aquinas and Averroes) and it seems alien to the text of the Nicomachean Ethics. Strauss's criticism of medieval variants results from their incapacity—shared by contemporary political thought—to address a perplexing issue: political exception. He sees in Aristotle's political teaching a way to escape from this failure: the unification, in natural right, of the requirements of statesmanship and ethics. The discovery of this way allowed Strauss to produce an interpretation of natural right that articulates important points pertaining to Aristotelian political science.
Multiple streams in member state implementation: politics, problem construction and policy paths in Swiss asylum policy
Authors: Sager Fritz , Thomann Eva
Published: July 2016

This article applies the multiple streams approach to a multilevel implementation setting to analyse why Swiss member states enabled the labour market integration of asylum seekers between 2000 and 2003. It argues for integrating the social construction of target groups into the problem stream, and complementing the policy stream with inherited policy paths. A fuzzy-set qualitative comparative analysis reveals that institutionalised policy paths trump politics in explaining the enabling of labour market integration of asylum seekers. Conversely, a weak political left combined with negative problem constructions aces out policy paths in explaining restrictions of labour market integration. The results illustrate how social constructions influence problem framing. Historical institutionalism theory helps us understand how inherited policy logics feed back with actors’ problem perceptions. Because of the parallels in their multilevel systems, political contexts and problem pressures, this historical case offers salient lessons for the refugee crisis in the European Union today.
Obsessive compulsive and related disorders: comparing DSM-5 and ICD-11
Authors: Marras Anna , Fineberg Naomi , Pallanti Stefano
Published: July 2016

Obsessive-compulsive disorder (OCD) has been recognized as mainly characterized by compulsivity rather than anxiety and, therefore, was removed from the anxiety disorders chapter and given its own in both the American Psychiatric Association (APA)Diagnostic and Statistical Manual of Mental Disorders(DSM-5) and the Beta Draft Version of the 11th revision of the World Health Organization (WHO)International Classification of Diseases(ICD-11). This revised clustering is based on increasing evidence of common affected neurocircuits between disorders, differently from previous classification systems based on interrater agreement. In this article, we focus on the classification of obsessive-compulsive and related disorders (OCRDs), examining the differences in approach adopted by these 2 nosological systems, with particular attention to the proposed changes in the forthcoming ICD-11. At this stage, notable differences in the ICD classification are emerging from the previous revision, apparently converging toward a reformulation of OCRDs that is closer to the DSM-5.
The European Union Joint Procurement Agreement for cross-border health threats: what is the potential for this new mechanism of health system collaboration?
Authors: Azzopardi-Muscat Natasha , Schroder-Bäck Peter , Brand Helmut
Published: July 2016

The Joint Procurement Agreement (JPA) is an innovative instrument for multi-country procurement of medical countermeasures against cross-border health threats. This paper aims to assess its potential performance. A literature review was conducted to identify key features of successful joint procurement programmes. Documentary analysis and a key informants’ interview were carried out to analyse the European Union (EU) JPA. Ownership, equity, transparency, stable central financing, standardisation, flexibility and gradual development were identified as important prerequisites for successful establishment of multi-country joint procurement programmes in the literature while security of supply, favourable prices, reduction of operational costs and administrative burden and creation of professional expert networks were identified as desirable outcomes. The EU JPA appears to fulfil the criteria of ownership, transparency, equity, flexibility and gradual development. Standardisation is only partly fulfilled and central EU level financing is not provided. Security of supply is an important outcome for all EU Member States (MS). Price savings, reduction in administrative burden and creation of professional networks may be particularly attractive for the smaller MS. The JPA has the potential to increase health system collaboration and efficiency at EU level provided that the incentives for sustained commitment of larger MS are sufficiently attractive.
In-Group Versus Out-Group Source Memory
Authors: Greenstein Michael , Franklin Nancy , Klug Jessica
Published: July 2016

Abstract. A common finding in the source monitoring literature is that greater similarity impairs source discriminability. Experiments traditionally manipulate similarity overtly by describing or showing sources with explicitly differentiable features. However, people may also infer source characteristics themselves, which should also affect discriminability. Two studies examined inferred source characteristics by capitalizing on the out-group homogeneity effect, whereby in-group members are conceptualized as more diverse than out-group members. Participants learned about two sources who were described only as members of an in-group or an out-group and whose actions did not have higher a priori association with either group. Source memory was superior when participants believed the sources to be in-group members. This demonstrates that people spontaneously include inferred features with source representations and can capitalize on these features during source monitoring. Interestingly, information suggesting membership in one’s in-group improved performance even for sources who had previously been considered out-group members (Experiment 2).
Is the Emotional Dog Blind to Its Choices?
Authors: Vranka Marek A. , Bahník Štěpán
Published: July 2016

Abstract. Previous choice blindness studies showed that people sometimes fail to notice when their choice is changed. Subsequently, they are willing to provide reasons for the manipulated choice which is the opposite of the one they made just seconds ago. In the present study, participants first made binary judgments about the wrongness of described behaviors and then were shown an opposite answer during a second reading of some of the descriptions. Half of the participants saw the answer during the second presentation of the description and the other half saw it only after the presentation. Based on Haidt’s Social intuitionist model, we hypothesized that participants in the latter group would be less likely to reconcile their intuition with the presented answer and thus they would be more likely to reject it. However, we found no difference between the groups.
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

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

The 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

The 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

Since 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

The 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

The 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

Chloroplast 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

How 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

Studies 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

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

Healing 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

Three-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

Magnetism 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

Organic 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

MicroRNAs (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

Abiotic 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.
A light-induced shortcut in the planktonic microbial loop
Authors: Ptacnik Robert , Gomes Ana , Royer Sarah-Jeanne , Berger Stella A. , Calbet Albert , Nejstgaard Jens C. , Gasol Josep M. , Isari Stamatina , Moorthi Stefanie D. , Ptacnikova Radka , Striebel Maren , Sazhin Andrey F. , Tsagaraki Tatiana M. , Zervoudaki Soultana , Altoja Kristi , Dimitriou Panagiotis D. , Laas Peeter , Gazihan Ayse , Martínez Rodrigo A. , Schabhüttl Stefanie , Santi Ioulia , Sousoni Despoina , Pitta Paraskevi
Published: July 2016

Mixotrophs combine photosynthesis with phagotrophy to cover their demands in energy and essential nutrients. This gives them a competitive advantage under oligotropihc conditions, where nutrients and bacteria concentrations are low. As the advantage for the mixotroph depends on light, the competition between mixo- and heterotrophic bacterivores should be regulated by light. To test this hypothesis, we incubated natural plankton from the ultra-oligotrophic Eastern Mediterranean in a set of mesocosms maintained at 4 light levels spanning a 10-fold light gradient. Picoplankton (heterotrophic bacteria (HB), pico-sized cyanobacteria, and small-sized flagellates) showed the fastest and most marked response to light, with pronounced predator-prey cycles, in the high-light treatments. Albeit cell specific activity of heterotrophic bacteria was constant across the light gradient, bacterial abundances exhibited an inverse relationship with light. This pattern was explained by light-induced top-down control of HB by bacterivorous phototrophic eukaryotes (PE), which was evidenced by a significant inverse relationship between HB net growth rate and PE abundances. Our results show that light mediates the impact of mixotrophic bacterivores. As mixo- and heterotrophs differ in the way they remineralize nutrients, these results have far-reaching implications for how nutrient cycling is affected by light.
The role of color and attention-to-color in mirror-symmetry perception
Authors: Gheorghiu Elena , Kingdom Frederick A. A. , Remkes Aaron , Li Hyung-Chul O. , Rainville Stéphane
Published: July 2016

The role of color in the visual perception of mirror-symmetry is controversial. Some reports support the existence of color-selective mirror-symmetry channels, others that mirror-symmetry perception is merely sensitive to color-correlations across the symmetry axis. Here we test between the two ideas. Stimuli consisted of colored Gaussian-blobs arranged either mirror-symmetrically or quasi-randomly. We used four arrangements: (1) ‘segregated’ – symmetric blobs were of one color, random blobs of the other color(s); (2) ‘random-segregated’ – as above but with the symmetric color randomly selected on each trial; (3) ‘non-segregated’ – symmetric blobs were of all colors in equal proportions, as were the random blobs; (4) ‘anti-symmetric’ – symmetric blobs were of opposite-color across the symmetry axis. We found: (a) near-chance levels for the anti-symmetric condition, suggesting that symmetry perception is sensitive to color-correlations across the symmetry axis; (b) similar performance for random-segregated and non-segregated conditions, giving no support to the idea that mirror-symmetry is color selective; (c) highest performance for the color-segregated condition, but only when the observer knew beforehand the symmetry color, suggesting that symmetry detection benefits from color-based attention. We conclude that mirror-symmetry detection mechanisms, while sensitive to color-correlations across the symmetry axis and subject to the benefits of attention-to-color, are not color selective.
Emergence of superconductivity in (NH3)yMxMoSe2 (M: Li, Na and K)
Authors: Miao Xiao , Nishiyama Saki , Zheng Lu , Goto Hidenori , Eguchi Ritsuko , Ota Hiromi , Kambe Takashi , Terashima Kensei , Yokoya Takayoshi , Nguyen Huyen T. L. , Kagayama Tomoko , Hirao Naohisa , Ohishi Yasuo , Ishii Hirofumi , Liao Yen-Fa , Kubozono Yoshihiro
Published: July 2016

We report syntheses of new superconducting metal-doped MoSe2 materials (MxMoSe2). The superconducting MxMoSe2 samples were prepared using a liquid NH3 technique and can be represented as ‘(NH3)yMxMoSe2’. The Tcs of these materials were approximately 5.0 K, independent of x and the specific metal atom. X-ray diffraction patterns of (NH3)yNaxMoSe2 were recorded using polycrystalline powders. An increase in lattice constant c showed that the Na atom was intercalated between MoSe2 layers. The x-independence of c was observed in (NH3)yNaxMoSe2, indicating the formation of a stoichiometric compound in the entire x range, which is consistent with the x-independence of Tc. A metallic edge of the Fermi level was observed in the photoemission spectrum at 30 K, demonstrating its metallic character in the normal state. Doping of MoSe2 with Li and K also yielded superconductivity. Thus, MoSe2 is a promising material for designing new superconductors, as are other transition metal dichalcogenides.
Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications
Authors: Ch’ng Jun-Hong , Moll Kirsten , Quintana Maria del Pilar , Chan Sherwin Chun Leung , Masters Ellen , Moles Ernest , Liu Jianping , Eriksson Anders B. , Wahlgren Mats
Published: July 2016

The spread of artemisinin-resistant parasites could lead to higher incidence of patients with malaria complications. However, there are no current treatments that directly dislodge sequestered parasites from the microvasculature. We show that four common antiplasmodial drugs do not disperse rosettes (erythrocyte clusters formed by malaria parasites) and therefore develop a cell-based high-throughput assay to identify potential rosette-disrupting compounds. A pilot screen of 2693 compounds identified Malaria Box compound MMV006764 as a potential candidate. Although it reduced rosetting by a modest 20%, MMV006764 was validated to be similarly effective against both blood group O and A rosettes of three laboratory parasite lines. Coupled with its antiplasmodial activity and drug-likeness, MMV006764 represents the first small-molecule compound that disrupts rosetting and could potentially be used in a resource-limited setting to treat patients deteriorating rapidly from malaria complications. Such dual-action drugs that simultaneously restore microcirculation and reduce parasite load could significantly reduce malaria morbidity and mortality.
Qubit lattice coherence induced by electromagnetic pulses in superconducting metamaterials
Authors: Ivić Z. , Lazarides N. , Tsironis G. P.
Published: July 2016

Quantum bits (qubits) are at the heart of quantum information processing schemes. Currently, solid-state qubits, and in particular the superconducting ones, seem to satisfy the requirements for being the building blocks of viable quantum computers, since they exhibit relatively long coherence times, extremely low dissipation, and scalability. The possibility of achieving quantum coherence in macroscopic circuits comprising Josephson junctions, envisioned by Legett in the 1980’s, was demonstrated for the first time in a charge qubit; since then, the exploitation of macroscopic quantum effects in low-capacitance Josephson junction circuits allowed for the realization of several kinds of superconducting qubits. Furthermore, coupling between qubits has been successfully achieved that was followed by the construction of multiple-qubit logic gates and the implementation of several algorithms. Here it is demonstrated that induced qubit lattice coherence as well as two remarkable quantum coherent optical phenomena, i.e., self-induced transparency and Dicke-type superradiance, may occur during light-pulse propagation in quantum metamaterials comprising superconducting charge qubits. The generated qubit lattice pulse forms a compound ”quantum breather” that propagates in synchrony with the electromagnetic pulse. The experimental confirmation of such effects in superconducting quantum metamaterials may open a new pathway to potentially powerful quantum computing.
Chlamydia psittaci infection increases mortality of avian influenza virus H9N2 by suppressing host immune response
Authors: Chu Jun , Zhang Qiang , Zhang Tianyuan , Han Er , Zhao Peng , Khan Ahrar , He Cheng , Wu Yongzheng
Published: July 2016

Avian influenza virus subtype H9N2 (H9N2) and Chlamydia psittaci (C. psittaci) are frequently isolated in chickens with respiratory disease. However, their roles in co-infection remain unclear. We tested the hypothesis that C. psittaci enhances H9N2 infection through suppression of host immunity. Thus, 10-day-old SPF chickens were inoculated intra-tracheally with a high or low virulence C. psittaci strain and were simultaneously vaccinated against Newcastle disease virus (NDV). Significant decreases in body weight, NDV antibodies and immune organ indices occurred in birds with the virulent C. psittaci infection, while the ratio of CD4+/CD8+ T cells increased significantly compared to that of the lower virulence strain. A second group of birds were inoculated with C. psittaci and H9N2 simultaneously (C. psittaci+H9N2), C. psittaci 3 days prior to H9N2 (C. psittaci/H9N2), or 3 days after H9N2 (H9N2/C. psittaci), C. psittaci or H9N2 alone. Survival rates were 65%, 80% and 90% in the C. psittaci/H9N2, C. psittaci+H9N2 and H9N2/C. psittaci groups, respectively and respiratory clinical signs, lower expression of pro-inflammatory cytokines and higher pathogen loads were found in both C. psittaci/H9N2 and C. psittaci+H9N2 groups. Hence, virulent C. psittaci infection suppresses immune response by inhibiting humoral responses and altering Th1/Th2 balance, increasing mortality in H9N2 infected birds.
Mapping the Interaction Anatomy of BmP02 on Kv1.3 Channel
Authors: Wu B. , Wu B. F. , Feng Y. J. , Tao J. , Ji Y. H.
Published: July 2016

The potassium channel Kv 1.3 plays a vital part in the activation of T lymphocytes and is an attractive pharmacological target for autoimmune diseases. BmP02, a 28-residue peptide isolated from Chinese scorpion (Buthus martensi Karsch) venom, is a potent and selective Kv1.3 channel blocker. However, the mechanism through which BmP02 recognizes and inhibits the Kv1.3 channel is still unclear. In the present study, a complex molecular model of Kv1.3-BmP02 was developed by docking analysis and molecular dynamics simulations. From these simulations, it appears the large β-turn (residues 10–16) of BmP02 might be the binding interface with Kv 1.3. These results were confirmed by scanning alanine mutagenesis of BmP02, which identified His9, Lys11 and Lys13, which lie within BmP02’s β-turn, as key residues for interacting with Kv1.3. Based on these results and molecular modeling, two negatively charged residues of Kv1.3, D421 and D422, located in turret region, were predicted to act as the binding site for BmP02. Mutation of these residues reduced sensitivity of Kv 1.3 to BmP02 inhibition, suggesting that electrostatic interactions play a crucial role in Kv1.3-BmP02 interaction. This study revealed the molecular basis of Kv 1.3 recognition by BmP02 venom and provides a novel interaction model for Kv channel-specific blocker complex, which may help guide future drug-design for Kv1.3-related channelopathies.
Convergence of multimodal sensory pathways to the mushroom body calyx in Drosophila melanogaster
Authors: Yagi Ryosuke , Mabuchi Yuta , Mizunami Makoto , Tanaka Nobuaki K.
Published: July 2016

Detailed structural analyses of the mushroom body which plays critical roles in olfactory learning and memory revealed that it is directly connected with multiple primary sensory centers in Drosophila. Connectivity patterns between the mushroom body and primary sensory centers suggest that each mushroom body lobe processes information on different combinations of multiple sensory modalities. This finding provides a novel focus of research by Drosophila genetics for perception of the external world by integrating multisensory signals.
Cosmid based mutagenesis causes genetic instability in Streptomyces coelicolor, as shown by targeting of the lipoprotein signal peptidase gene
Authors: Munnoch John T. , Widdick David A. , Chandra Govind , Sutcliffe Iain C. , Palmer Tracy , Hutchings Matthew I.
Published: July 2016

Bacterial lipoproteins are extracellular proteins tethered to cell membranes by covalently attached lipids. Deleting the lipoprotein signal peptidase (lsp) gene in Streptomyces coelicolor results in growth and developmental defects that cannot be restored by reintroducing lsp. This led us to hypothesise that lsp is essential and that the lsp mutant we isolated previously had acquired compensatory secondary mutations. Here we report resequencing of the genomes of wild-type M145 and the cis-complemented ∆lsp mutant (BJT1004) to map and identify these secondary mutations but we show that they do not increase the efficiency of disrupting lsp and are not lsp suppressors. We provide evidence that they are induced by introducing the cosmid St4A10∆lsp, as part of ReDirect PCR mutagenesis protocol, which transiently duplicates a number of important cell division genes. Disruption of lsp using a suicide vector (which does not result in gene duplication) still results in growth and developmental delays and we conclude that loss of Lsp function results in developmental defects due to the loss of all lipoproteins from the cell membrane. Significantly, our results also indicate the use of cosmid libraries for the genetic manipulation of bacteria can lead to phenotypes not necessarily linked to the gene(s) of interest.
Highly sensitive detection of lipopolysaccharides using an aptasensor based on hybridization chain reaction
Authors: Xie Peiyan , Zhu Longjiao , Shao Xiangli , Huang Kunlun , Tian Jingjing , Xu Wentao
Published: July 2016

Lipopolysaccharides (LPS), integral components of the outer membrane of all gram-negative bacteria, are closely associated with foodborne diseases such as fever, diarrhea and hypotension and thus, the early and sensitive detection of LPS is necessary. In this study, an aptasensor assay based on hybridization chain reaction (HCR) was developed to detect LPS. Briefly, two complementary stable species of biotinylated DNA hairpins coexisted in solution until the introduction of a detection probe triggered a hybridization chain reaction cascade. The DNA conjugates specifically reacted with the LPS, which were captured by the ethanolamine aptamer attached to the reaction well surface. After optimizing the key reaction conditions, such as the reaction time of HCR, the amount of the capture probe and detection probes, the increase in the LPS concentration was readily measured by the optical density value and a relatively low detection limit (1.73 ng/mL) was obtained, with a linear response range of 1–105 ng/mL. The approach presented herein introduced the use of an aptasensor for LPS discrimination and HCR for signal amplification, offering a promising option for detecting LPS.
Roles of Energy/Charge Cascades and Intermixed Layers at Donor/Acceptor Interfaces in Organic Solar Cells
Authors: Nakano Kyohei , Suzuki Kaori , Chen Yujiao , Tajima Keisuke
Published: July 2016

The secret to the success of mixed bulk heterojunctions (BHJs) in yielding highly efficient organic solar cells (OSCs) could reside in the molecular structures at their donor/acceptor (D/A) interfaces. In this study, we aimed to determine the effects of energy and charge cascade structures at the interfaces by using well-defined planar heterojunctions (PHJs) as a model system. The results showed that (1) the charge cascade structure enhanced VOC because it shuts down the recombination pathway through charge transfer (CT) state with a low energy, (2) the charge cascade layer having a wider energy gap than the bulk material decreased JSC because the diffusion of the excitons from the bulk to D/A interface was blocked; the energy of the cascade layers must be appropriately arranged for both the charges and the excitons and (3) molecular intermixing in the cascade layer opened the recombination path through the low-energy CT state and decreased VOC. Based on these findings, we propose improved structures for D/A interfaces in BHJs.