bluuebunny/crossref_metadata_2025 huggingface dataset:
RANDOM NEURAL NETWORK LEARNING HEURISTICS
Authors: Javed Abbas , Larijani Hadi , Ahmadinia Ali , Emmanuel Rohinton
Published: May 2017

The random neural network (RNN) is a probabilitsic queueing theory-based model for artificial neural networks, and it requires the use of optimization algorithms for training. Commonly used gradient descent learning algorithms may reside in local minima, evolutionary algorithms can be also used to avoid local minima. Other techniques such as artificial bee colony (ABC), particle swarm optimization (PSO), and differential evolution algorithms also perform well in finding the global minimum but they converge slowly. The sequential quadratic programming (SQP) optimization algorithm can find the optimum neural network weights, but can also get stuck in local minima. We propose to overcome the shortcomings of these various approaches by using hybridized ABC/PSO and SQP. The resulting algorithm is shown to compare favorably with other known techniques for training the RNN. The results show that hybrid ABC learning with SQP outperforms other training algorithms in terms of mean-squared error and normalized root-mean-squared error.
Effect of mechanical constraint on the hydration properties of Na-montmorillonite: study under extreme relative humidity conditions
Authors: Oueslati Walid , Chorfi Nejmeddine , Abdelwahed Mohamed
Published: May 2017

The evaluation of the performance of a geological barrier, consisting essentially of a clay matrix, in the context of industrial and household waste confinement must go with the study of its hydration behavior respectively under extreme atmospheric conditions and variable mechanical soil constraints. Na-montmorillonite (Swy-2) is used, as starting materials, in order to establish the link between applied externals strain (variable relative humidity rate %RH and axial mechanical constraint) and the hydration material response. All constraints are realized at the laboratory scale. This work is achieved using oedometric testing and quantitative X-ray diffraction (XRD) analysis, based on the modeling approach, which consists in the comparison of experimental 00l reflections with the calculated ones deduced from structural models. This approach allows us to quantify the interlamellar space configuration and all structural changes along the c* axis. Obtained results show a decrease for the void ratio e value along the compaction/reswelling process. The “insitu” XRD analysis realized at 5%RH demonstrates hydration shift, from dehydrated water layer (i.e. 0W) to monohydrated water layer (i.e. 1W), attributed to the applied mechanical constraint. At 90%RH, the sample hydration state remains at tri-hydrated water layer (3W) with a clear interstratified trends.
Early life history traits and geographical distribution ofParachaenichthys charcoti
Authors: La Mesa Mario , Riginella Emilio , Jones Christopher D.
Published: May 2017

The geographical distribution of the two species of the genusParachaenichthysis allopatric and restricted to the inner shelves of South Georgia–South Sandwich Islands (P. georgianus) and South Orkney Islands–South Shetland Islands (P. charcoti). To evaluate the consistency between the geographical patterns of adult distribution and early life history traits ofP. charcoti, sagittal otoliths were used to estimate growth rate and pelagic duration in larvae and juveniles of this species collected in the Bransfield Strait in winter and summer, respectively. Individual age was determined through microincrement counts, assuming they were daily increments. The Gompertz model was fitted to age–length estimates, providing a mean growth rate of 0.22 mm day-1estimated for 28–204-day-old individuals. Larval hatching was spread over a relatively wide period, lasting from July throughout September. The pelagic larval duration ofP. charcotiwas about six months based on ageing data of larvae and juveniles, as reported forP. georgianusfrom South Georgia. The strong dependence of larvae on the inshore habitat may hamper their dispersal at large spatial scale limiting the connectivity among distant populations, providing clues to interpret the present geographical distribution of the two species.
On isotropic cloaking and interior transmission eigenvalue problems
Authors: JI XIA , LIU HONGYU
Published: May 2017

This paper is concerned with the invisibility cloaking in acoustic wave scattering from a new perspective. We are especially interested in achieving the invisibility cloaking by completely regular and isotropic mediums. It is shown that an interior transmission eigenvalue problem arises in our study, which is the one considered theoretically in Cakoni et al. (Transmission eigenvalues for inhomogeneous media containing obstacles, Inverse Problems and Imaging, 6 (2012), 373–398). Based on such an observation, we propose a cloaking scheme that takes a three-layer structure including a cloaked region, a lossy layer and a cloaking shell. The target medium in the cloaked region can be arbitrary but regular, whereas the mediums in the lossy layer and the cloaking shell are both regular and isotropic. We establish that if a certain non-transparency condition is satisfied, then there exists an infinite set of incident waves such that the cloaking device is nearly invisible under the corresponding wave interrogation. The set of waves is generated from the Herglotz approximation of the associated interior transmission eigenfunctions. We provide both theoretical and numerical justifications.
Tracing the origins of verlan in an early nineteenth century text?
Authors: BACH XAVIER
Published: May 2017

This article examines early attestations of verlan and related backward slangs in French in the nineteenth century. Its main contribution is the edition and analysis of the only known text, a letter, written with features of verlan before the twentieth century. This largely predates other attested forms of verlan. The principles underlying this early form of verlan are shown to be different from contemporary verlan, as is much other early evidence, though all forms have the syllable as their basic unit. The letter is evidence that backward slangs can originate in the education system as much as in the underworld of thieves.
A resource aware semantics for a focused intuitionistic calculus
Authors: KESNER DELIA , VENTURA DANIEL
Published: May 2017

We investigate a new computational interpretation for an intuitionistic focused sequent calculus which is compatible with a resource aware semantics. For that, we associate to Herbelin's syntax a type system based on non-idempotent intersection types, together with a set of reduction rules – inspired from thesubstitution at a distanceparadigm – that preserves (and decreases the size of) typing derivations. The non-idempotent approach allows us to use very simple combinatorial arguments, only based on this measure decreasingness, to characterizelinear-headandstronglynormalizing terms by means of typability. For the sake of completeness, we also study typability (and the corresponding strong normalization characterization) in the calculus obtained from the former one by projecting the explicit cuts.
The Proofs of Two Directed Paths Conjectures of Bollobás and Leader
Authors: PINTO TREVOR
Published: May 2017

Let A and B be disjoint sets, of size 2k, of vertices of Qn, the n-dimensional hypercube. In 1997, Bollobás and Leader proved that there must be (n − k)2k edge-disjoint paths between such A and B. They conjectured that when A is a down-set and B is an up-set, these paths may be chosen to be directed (that is, the vertices in the path form a chain). We use a novel type of compression argument to prove stronger versions of these conjectures, namely that the largest number of edge-disjoint paths between a down-set A and an up-set B is the same as the largest number of directed edge-disjoint paths between A and B. Bollobás and Leader made an analogous conjecture for vertex-disjoint paths, and we prove a strengthening of this by similar methods. We also prove similar results for all other sizes of A and B.
Lexical access in the second year: a study of monolingual and bilingual vocabulary development
Authors: DEANDA STEPHANIE , HENDRICKSON KRISTI , ZESIGER PASCAL , POULIN-DUBOIS DIANE , FRIEND MARGARET
Published: May 2017

It is well established that vocabulary size is related to efficiency in auditory processing, such that children with larger vocabularies recognize words faster than children with smaller vocabularies. The present study evaluates whether this relation is specific to the language being assessed, or related to general language or cognitive processes. Speed of word processing was measured longitudinally in Spanish- and English-learning monolinguals and bilinguals at 16 and 22 months of age. Speed of processing in bilinguals was similar to monolinguals, suggesting that the number of languages to which children are exposed does not influence word recognition. Further, cross-language associations in bilinguals suggest that the dominant language supports processing in the non-dominant language. These cross-language associations are consistent with general language and cognitive efficiency accounts in which the relation between word processing and knowledge relies on experience within a language as well as on general and cognitive properties of language learning.
A linear algebraic approach to datalog evaluation
Authors: SATO TAISUKE
Published: May 2017

We propose a fundamentally new approach to Datalog evaluation. Given a linear Datalog program DB written usingNconstants and binary predicates, we first translate if-and-only-if completions of clauses in DB into a setEq(DB) of matrix equations with a non-linear operation, where relations inMDB, the least Herbrand model of DB, are encoded as adjacency matrices. We then translateEq(DB) into another, but purely linear matrix equationsẼq(DB). It is proved that the least solution ofẼq(DB) in the sense of matrix ordering is converted to the least solution ofEq(DB) and the latter givesMDBas a set of adjacency matrices. Hence, computing the least solution ofẼq(DB) is equivalent to computingMDBspecified by DB. For a class of tail recursive programs and for some other types of programs, our approach achievesO(N3) time complexity irrespective of the number of variables in a clause since only matrix operations costingO(N3) or less are used. We conducted two experiments that compute the least Herbrand models of linear Datalog programs. The first experiment computes transitive closure of artificial data and real network data taken from the Koblenz Network Collection. The second one compared the proposed approach with the state-of-the-art symbolic systems including two Prolog systems and two ASP systems, in terms of computation time for a transitive closure program and the same generation program. In the experiment, it is observed that our linear algebraic approach runs 101~ 104times faster than the symbolic systems when data is not sparse. Our approach is inspired by the emergence of big knowledge graphs and expected to contribute to the realization of rich and scalable logical inference for knowledge graphs.
αCheck: A mechanized metatheory model checker
Authors: CHENEY JAMES , MOMIGLIANO ALBERTO
Published: May 2017

The problem of mechanically formalizing and proving metatheoretic properties of programming language calculi, type systems, operational semantics, and related formal systems has received considerable attention recently. However, the dual problem of searching for errors in such formalizations has attracted comparatively little attention. In this article, we present αCheck, a bounded model checker for metatheoretic properties of formal systems specified using nominal logic. In contrast to the current state of the art for metatheory verification, our approach is fully automatic, does not require expertise in theorem proving on the part of the user, and produces counterexamples in the case that a flaw is detected. We present two implementations of this technique, one based onnegation-as-failureand one based onnegation elimination, along with experimental results showing that these techniques are fast enough to be used interactively to debug systems as they are developed.
Productivity in an arable and stockless organic cropping system may be enhanced by strategic recycling of biomass
Authors: Råberg Tora Matilda , Carlsson Georg , Jensen Erik Steen
Published: May 2017

Recirculation of nitrogen (N) from crop residue and green-manure biomass resources may reduce the need to add new reactive N to maintain crop yield and quality. The aim of this study was to determine how different strategies for recycling residual and green-manure biomass influence yield and N concentration of the edible parts of food crops in a stockless organic cropping system. For this purpose, three biomass distribution treatments were investigated in a field experiment, based on a cropping system designed to produce both high-quality food crops and biomass resources from crop residues, cover crops and a green-manure ley. The three treatments, applied at the cropping system level, were: (1) incorporating the aboveground biomass resources in situ (IS); (2) harvesting, ensiling and redistributing the same biomass resources to the non-legume crops (biomass redistribution, BR); and (3) harvesting, ensiling and using the biomass resources as substrate for production of bio-methane via anaerobic digestion (AD) followed by distribution of the digestate as bio-fertilizer to the non-legume crops. The redistribution of ensiled (BR) and digested (AD) biomass did not increase the yield of the edible parts in winter rye (Secale cereal L.), white cabbage (Brassica oleracea L.) or red beet (Beta vulgaris L.) compared with leaving the biomass on the ground at harvest (IS). The BR treatment increased the yield of lentil intercropped with oat, compared with IS treatment in one of the two studied years. The total biomass yield of the cover crop following winter rye was significantly higher in the BR treatment than in IS in both years. The legume proportion in the green-manure ley was significantly higher in the AD and BR treatments as compared with IS in one of the experimental years. This study showed that strategic biomass redistribution has the potential to enhance biomass productivity while maintaining food crop yields, thereby enhancing whole system productivity. Biomass redistribution systems both with and without biogas digestion offer a new strategy for the development of multifunctional arable cropping systems that rely on internal nutrient cycling.
A unified approach to mortality modelling using state-space framework: characterisation, identification, estimation and forecasting
Authors: Fung Man Chung , Peters Gareth W. , Shevchenko Pavel V.
Published: May 2017

This paper explores and develops alternative statistical representations and estimation approaches for dynamic mortality models. The framework we adopt is to reinterpret popular mortality models such as the Lee–Carter class of models in a general state-space modelling methodology, which allows modelling, estimation and forecasting of mortality under a unified framework. We propose alternative model identification constraints which are more suited to statistical inference in filtering and parameter estimation. We then develop a class of Bayesian state-space models which incorporate a priori beliefs about the mortality model characteristics as well as for more flexible and appropriate assumptions relating to heteroscedasticity that present in observed mortality data. To study long-term mortality dynamics, we introduce stochastic volatility to the period effect. The estimation of the resulting stochastic volatility model of mortality is performed using a recent class of Monte Carlo procedure known as the class of particle Markov chain Monte Carlo methods. We illustrate the framework using Danish male mortality data, and show that incorporating heteroscedasticity and stochastic volatility markedly improves model fit despite an increase of model complexity. Forecasting properties of the enhanced models are examined with long-term and short-term calibration periods on the reconstruction of life tables.
Searching the web: a survey on the quality of advice on postnatal sequelae of intrauterine growth restriction and the implication of developmental origins of health and disease
Authors: Perzel S. , Huebner H. , Rascher W. , Menendez-Castro C. , Hartner A. , Fahlbusch F. B.
Published: May 2017

Intrauterine growth restriction (IUGR) and fetal growth restriction (FGR) are pregnancy complications associated with morbidity in later life. Despite a growing body of evidence from current research on developmental origins of health and disease (DOHaD), little information is currently provided to parents on long-term metabolic, cardiovascular and neurologic consequences. As parents strongly rely on internet-based health-related information, we examined the quality of information on IUGR/FGR sequelae and DOHaD in webpages used by laypersons. Simulating non-clinicians experience, we entered the terms ‘IUGR consequences’ and ‘FGR consequences’ into Google and Yahoo search engines. The quality of the top search-hits was analyzed with regard to the certification through the Health On the Net Foundation (HON), currentness of cited references, while reliability of information and DOHaD-related consequences were assessed via the DISCERN Plus score (DPS). Overall the citation status was not up-to-date and only a few websites were HON-certified. The results of our analysis showed a dichotomy between the growing body of evidence regarding IUGR/FGR-related sequelae and lack of current guidelines, leaving parents without clear directions. Furthermore, detailed information on the concept of DOHaD is not provided. These findings emphasize the responsibility of the individual physician for providing advice on IUGR/FGR-related sequelae, monitoring and follow-up.
Evaluating Soil Solarization for Weed Control and Strawberry (Fragariaxananassa) Yield in Annual Plasticulture Production
Authors: Samtani Jayesh B. , Derr Jeffrey , Conway Mikel A. , Flanagan Roy D.
Published: May 2017

Field studies were initiated in the 2013-14 and 2014-15 growing seasons to evaluate the potential of soil solarization (SS) treatments for their efficacy on weed control and crop yields and to compare SS to 1,3-dichloropropene (1,3-D)+chloropicrin (Pic) fumigation. Each replicate was a bed with dimension 10.6 m long by 0.8 m wide on top. The center 4.6 m length of each bed, referred to as plots, was used for strawberry plug transplanting and data collection. Treatments included: i) 1,3-D+Pic (39% 1,3-dichloropropene+59.6% chloropicrin) that was shank-fumigated in beds at 157 kg ha−1and covered with VIF on August 30 in both seasons; ii) SS for a 6 wk duration initiated on August 15, 2013 and August 21, 2014 by covering the bed with 1 mil clear polyethylene tarp; iii) SS for a 4wk duration initiated on September 6, 2013 and September 3, 2014; iv) SS 4 wk treatment initiated September 6, 2013 and September 3, 2014 and replaced with black VIF on October 4, 2013 and October 1, 2014 and v) a nontreated control covered with black VIF on October 4, 2013 and October 1, 2014. In both seasons, following completion of the preplant treatments, ‘Chandler’ strawberry was planted in two rows at a 36 cm in-row spacing in plots during the first wk of October. Over both seasons, the 6 wk SS treatment consistently lowered the weed density compared to the nontreated control. Weed density in the 6wk SS treatment was not statistically different from the 4wk SS treatments in the 2013-14 growing season. In both seasons, crop yield in the 4 wk SS was significantly lower than other treatments.
A Review of Debriefing Practices
Authors: Kikkawa Yoriko , Mavin Timothy J.
Published: May 2017

Abstract. There appears to be a wide acceptance that debriefing plays an important role in the learning process of simulation-based programs. Indeed, the past decade has witnessed an increasing number of studies into debriefing across disciplines. Our research team has been conducting field research with airlines, over a number of years, to clarify what constitutes effective debriefing for airline pilot training. To assist this clarification, a comprehensive systematic review of existing studies into debriefing across disciplines was designed to direct further analysis of the data the team had collected. A preliminary investigation into this broad debriefing literature exposed that there was little consensus among many papers about effective debriefing practice owing to inconsistencies in: (a) methodological approaches, (b) terminology, and (c) professional focus. As a way of overcoming these inconsistencies, this paper initially synthesized research findings from a small number of existing systematic reviews scrutinizing debriefing across a variety of professional disciplines. The literature search identified 10 papers, three meta-analyses, and seven qualitative systematic reviews. This paper aims to identify key elements influencing learning outcomes from debriefing practices and presents the findings of this study as a single framework of debriefing elements.
MICU1 drives glycolysis and chemoresistance in ovarian cancer
Authors: Chakraborty Prabir K. , Mustafi Soumyajit Banerjee , Xiong Xunhao , Dwivedi Shailendra Kumar Dhar , Nesin Vasyl , Saha Sounik , Zhang Min , Dhanasekaran Danny , Jayaraman Muralidharan , Mannel Robert , Moore Kathleen , McMeekin Scott , Yang Da , Zuna Rosemary , Ding Kai , Tsiokas Leonidas , Bhattacharya Resham , Mukherjee Priyabrata
Published: May 2017

Cancer cells actively promote aerobic glycolysis to sustain their metabolic requirements through mechanisms not always clear. Here, we demonstrate that the gatekeeper of mitochondrial Ca2+ uptake, Mitochondrial Calcium Uptake 1 (MICU1/CBARA1) drives aerobic glycolysis in ovarian cancer. We show that MICU1 is overexpressed in a panel of ovarian cancer cell lines and that MICU1 overexpression correlates with poor overall survival (OS). Silencing MICU1 in vitro increases oxygen consumption, decreases lactate production, inhibits clonal growth, migration and invasion of ovarian cancer cells, whereas silencing in vivo inhibits tumour growth, increases cisplatin efficacy and OS. Mechanistically, silencing MICU1 activates pyruvate dehydrogenase (PDH) by stimulating the PDPhosphatase-phosphoPDH-PDH axis. Forced-expression of MICU1 in normal cells phenocopies the metabolic aberrations of malignant cells. Consistent with the in vitro and in vivo findings we observe a significant correlation between MICU1 and pPDH (inactive form of PDH) expression with poor prognosis. Thus, MICU1 could serve as an important therapeutic target to normalize metabolic aberrations responsible for poor prognosis in ovarian cancer.
Anti-platelet factor 4/polyanion antibodies mediate a new mechanism of autoimmunity
Authors: Nguyen Thi-Huong , Medvedev Nikolay , Delcea Mihaela , Greinacher Andreas
Published: May 2017

Antibodies recognizing complexes of the chemokine platelet factor 4 (PF4/CXCL4) and polyanions (P) opsonize PF4-coated bacteria hereby mediating bacterial host defense. A subset of these antibodies may activate platelets after binding to PF4/heparin complexes, causing the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). In autoimmune-HIT, anti-PF4/P-antibodies activate platelets in the absence of heparin. Here we show that antibodies with binding forces of approximately 60–100 pN activate platelets in the presence of polyanions, while a subset of antibodies from autoimmune-HIT patients with binding forces ≥100 pN binds to PF4 alone in the absence of polyanions. These antibodies with high binding forces cluster PF4-molecules forming antigenic complexes which allow binding of polyanion-dependent anti-PF4/P-antibodies. The resulting immunocomplexes induce massive platelet activation in the absence of heparin. Antibody-mediated changes in endogenous proteins that trigger binding of otherwise non-pathogenic (or cofactor-dependent) antibodies may also be relevant in other antibody-mediated autoimmune disorders.
Generic decoding of seen and imagined objects using hierarchical visual features
Authors: Horikawa Tomoyasu , Kamitani Yukiyasu
Published: May 2017

Object recognition is a key function in both human and machine vision. While brain decoding of seen and imagined objects has been achieved, the prediction is limited to training examples. We present a decoding approach for arbitrary objects using the machine vision principle that an object category is represented by a set of features rendered invariant through hierarchical processing. We show that visual features, including those derived from a deep convolutional neural network, can be predicted from fMRI patterns, and that greater accuracy is achieved for low-/high-level features with lower-/higher-level visual areas, respectively. Predicted features are used to identify seen/imagined object categories (extending beyond decoder training) from a set of computed features for numerous object images. Furthermore, decoding of imagined objects reveals progressive recruitment of higher-to-lower visual representations. Our results demonstrate a homology between human and machine vision and its utility for brain-based information retrieval.
Deterministic strain-induced arrays of quantum emitters in a two-dimensional semiconductor
Authors: Branny Artur , Kumar Santosh , Proux Raphaël , Gerardot Brian D
Published: May 2017

An outstanding challenge in quantum photonics is scalability, which requires positioning of single quantum emitters in a deterministic fashion. Site positioning progress has been made in established platforms including defects in diamond and self-assembled quantum dots, albeit often with compromised coherence and optical quality. The emergence of single quantum emitters in layered transition metal dichalcogenide semiconductors offers new opportunities to construct a scalable quantum architecture. Here, using nanoscale strain engineering, we deterministically achieve a two-dimensional lattice of quantum emitters in an atomically thin semiconductor. We create point-like strain perturbations in mono- and bi-layer WSe2 which locally modify the band-gap, leading to efficient funnelling of excitons towards isolated strain-tuned quantum emitters that exhibit high-purity single photon emission. We achieve near unity emitter creation probability and a mean positioning accuracy of 120±32 nm, which may be improved with further optimization of the nanopillar dimensions.
Large-scale quantum-emitter arrays in atomically thin semiconductors
Authors: Palacios-Berraquero Carmen , Kara Dhiren M. , Montblanch Alejandro R.-P. , Barbone Matteo , Latawiec Pawel , Yoon Duhee , Ott Anna K. , Loncar Marko , Ferrari Andrea C. , Atatüre Mete
Published: May 2017

Quantum light emitters have been observed in atomically thin layers of transition metal dichalcogenides. However, they are found at random locations within the host material and usually in low densities, hindering experiments aiming to investigate this new class of emitters. Here, we create deterministic arrays of hundreds of quantum emitters in tungsten diselenide and tungsten disulphide monolayers, emitting across a range of wavelengths in the visible spectrum (610–680 nm and 740–820 nm), with a greater spectral stability than their randomly occurring counterparts. This is achieved by depositing monolayers onto silica substrates nanopatterned with arrays of 150-nm-diameter pillars ranging from 60 to 190 nm in height. The nanopillars create localized deformations in the material resulting in the quantum confinement of excitons. Our method may enable the placement of emitters in photonic structures such as optical waveguides in a scalable way, where precise and accurate positioning is paramount.
Shifting the optimal stiffness for cell migration
Authors: Bangasser Benjamin L. , Shamsan Ghaidan A. , Chan Clarence E. , Opoku Kwaku N. , Tüzel Erkan , Schlichtmann Benjamin W. , Kasim Jesse A. , Fuller Benjamin J. , McCullough Brannon R. , Rosenfeld Steven S. , Odde David J.
Published: May 2017

Cell migration, which is central to many biological processes including wound healing and cancer progression, is sensitive to environmental stiffness, and many cell types exhibit a stiffness optimum, at which migration is maximal. Here we present a cell migration simulator that predicts a stiffness optimum that can be shifted by altering the number of active molecular motors and clutches. This prediction is verified experimentally by comparing cell traction and F-actin retrograde flow for two cell types with differing amounts of active motors and clutches: embryonic chick forebrain neurons (ECFNs; optimum ∼1 kPa) and U251 glioma cells (optimum ∼100 kPa). In addition, the model predicts, and experiments confirm, that the stiffness optimum of U251 glioma cell migration, morphology and F-actin retrograde flow rate can be shifted to lower stiffness by simultaneous drug inhibition of myosin II motors and integrin-mediated adhesions.
Hit and go CAS9 delivered through a lentiviral based self-limiting circuit
Authors: Petris Gianluca , Casini Antonio , Montagna Claudia , Lorenzin Francesca , Prandi Davide , Romanel Alessandro , Zasso Jacopo , Conti Luciano , Demichelis Francesca , Cereseto Anna
Published: May 2017

In vivo application of the CRISPR-Cas9 technology is still limited by unwanted Cas9 genomic cleavages. Long-term expression of Cas9 increases the number of genomic loci non-specifically cleaved by the nuclease. Here we develop a Self-Limiting Cas9 circuit for Enhanced Safety and specificity (SLiCES) which consists of an expression unit for Streptococcus pyogenes Cas9 (SpCas9), a self-targeting sgRNA and a second sgRNA targeting a chosen genomic locus. The self-limiting circuit results in increased genome editing specificity by controlling Cas9 levels. For its in vivo utilization, we next integrate SLiCES into a lentiviral delivery system (lentiSLiCES) via circuit inhibition to achieve viral particle production. Upon delivery into target cells, the lentiSLiCES circuit switches on to edit the intended genomic locus while simultaneously stepping up its own neutralization through SpCas9 inactivation. By preserving target cells from residual nuclease activity, our hit and go system increases safety margins for genome editing.
Ultrasensitive and high-efficiency screen of de novo low-frequency mutations by o2n-seq
Authors: Wang Kaile , Lai Shujuan , Yang Xiaoxu , Zhu Tianqi , Lu Xuemei , Wu Chung-I , Ruan Jue
Published: May 2017

Detection of de novo, low-frequency mutations is essential for characterizing cancer genomes and heterogeneous cell populations. However, the screening capacity of current ultrasensitive NGS methods is inadequate owing to either low-efficiency read utilization or severe amplification bias. Here, we present o2n-seq, an ultrasensitive and high-efficiency NGS library preparation method for discovering de novo, low-frequency mutations. O2n-seq reduces the error rate of NGS to 10−5–10−8. The efficiency of its data usage is about 10–30 times higher than that of barcode-based strategies. For detecting mutations with allele frequency (AF) 1% in 4.6 Mb-sized genome, the sensitivity and specificity of o2n-seq reach to 99% and 98.64%, respectively. For mutations with AF around 0.07% in phix174, o2n-seq detects all the mutations with 100% specificity. Moreover, we successfully apply o2n-seq to screen de novo, low-frequency mutations in human tumours. O2n-seq will aid to characterize the landscape of somatic mutations in research and clinical settings.
Tomographic active optical trapping of arbitrarily shaped objects by exploiting 3D refractive index maps
Authors: Kim Kyoohyun , Park YongKeun
Published: May 2017

Optical trapping can manipulate the three-dimensional (3D) motion of spherical particles based on the simple prediction of optical forces and the responding motion of samples. However, controlling the 3D behaviour of non-spherical particles with arbitrary orientations is extremely challenging, due to experimental difficulties and extensive computations. Here, we achieve the real-time optical control of arbitrarily shaped particles by combining the wavefront shaping of a trapping beam and measurements of the 3D refractive index distribution of samples. Engineering the 3D light field distribution of a trapping beam based on the measured 3D refractive index map of samples generates a light mould, which can manipulate colloidal and biological samples with arbitrary orientations and/or shapes. The present method provides stable control of the orientation and assembly of arbitrarily shaped particles without knowing a priori information about the sample geometry. The proposed method can be directly applied in biophotonics and soft matter physics.
Short single-stranded DNA degradation products augment the activation of Toll-like receptor 9
Authors: Pohar Jelka , Lainšček Duško , Ivičak-Kocjan Karolina , Cajnko Miša-Mojca , Jerala Roman , Benčina Mojca
Published: May 2017

Toll-like receptors encounter a diversity of degradation products in endosomes. TLR7 and TLR8 have been shown to be activated by RNA degradation products. Here we show that although TLR9 requires single-stranded DNA longer than 20 nucleotides for a robust response, TLR9 activation is augmented by CpG-containing oligodeoxyribonucleotides (sODNs) as short as 2 nucleotides, which, by themselves, do not induce activation in cell cultures, as well as in mice. sODNs also activate human TLR9 in combination with ODNs containing a single CpG motif that by themselves do not activate human TLR9. The specific sequence motif of sODN and colocalization of ODN and sODN suggest that the mechanism of activation involves binding of both ODN and sODN to TLR9. sODNs augment TLR9 activation by mammalian genomic DNA indicating the role of short DNA degradation products in the endosomes in response to infection or in autoimmune disease, particularly at limiting concentrations of ODNs.
Interface-driven formation of a two-dimensional dodecagonal fullerene quasicrystal
Authors: Paßens M. , Caciuc V. , Atodiresei N. , Feuerbacher M. , Moors M. , Dunin-Borkowski R. E. , Blügel S. , Waser R. , Karthäuser S.
Published: May 2017

Since their discovery, quasicrystals have attracted continuous research interest due to their unique structural and physical properties. Recently, it was demonstrated that dodecagonal quasicrystals could be used as bandgap materials in next-generation photonic devices. However, a full understanding of the formation mechanism of quasicrystals is necessary to control their physical properties. Here we report the formation of a two-dimensional dodecagonal fullerene quasicrystal on a Pt3Ti(111) surface, which can be described in terms of a square–triangle tiling. Employing density functional theory calculations, we identify the complex adsorption energy landscape of the Pt-terminated Pt3Ti surface that is responsible for the quasicrystal formation. We demonstrate the presence of quasicrystal-specific phason strain, which provides the degree of freedom required to accommodate the quasicrystalline structure on the periodic substrate. Our results reveal detailed insight into an interface-driven formation mechanism and open the way to the creation of tailored fullerene quasicrystals with specific physical properties.
Artificial control of the bias-voltage dependence of tunnelling-anisotropic magnetoresistance using quantization in a single-crystal ferromagnet
Authors: Muneta Iriya , Kanaki Toshiki , Ohya Shinobu , Tanaka Masaaki
Published: May 2017

A major issue in the development of spintronic memory devices is the reduction of the power consumption for the magnetization reversal. For this purpose, the artificial control of the magnetic anisotropy of ferromagnetic materials is of great importance. Here, we demonstrate the control of the carrier-energy dependence of the magnetic anisotropy of the density of states (DOS) using the quantum size effect in a single-crystal ferromagnetic material, GaMnAs. We show that the mainly twofold symmetry of the magnetic anisotropy of DOS, which is attributed to the impurity band, is changed to a fourfold symmetry by enhancing the quantum size effect in the valence band of the GaMnAs quantum wells. By combination with the gate electric-field control technique, our concept of the usage of the quantum size effect for the control of the magnetism will pave the way for the ultra-low-power manipulation of magnetization in future spintronic devices.
Long-range ferrimagnetic order in a two-dimensional supramolecular Kondo lattice
Authors: Girovsky Jan , Nowakowski Jan , Ali Md. Ehesan , Baljozovic Milos , Rossmann Harald R. , Nijs Thomas , Aeby Elise A. , Nowakowska Sylwia , Siewert Dorota , Srivastava Gitika , Wäckerlin Christian , Dreiser Jan , Decurtins Silvio , Liu Shi-Xia , Oppeneer Peter M. , Jung Thomas A. , Ballav Nirmalya
Published: May 2017

Realization of long-range magnetic order in surface-supported two-dimensional systems has been challenging, mainly due to the competition between fundamental magnetic interactions as the short-range Kondo effect and spin-stabilizing magnetic exchange interactions. Spin-bearing molecules on conducting substrates represent a rich platform to investigate the interplay of these fundamental magnetic interactions. Here we demonstrate the direct observation of long-range ferrimagnetic order emerging in a two-dimensional supramolecular Kondo lattice. The lattice consists of paramagnetic hexadeca-fluorinated iron phthalocyanine (FeFPc) and manganese phthalocyanine (MnPc) molecules co-assembled into a checkerboard pattern on single-crystalline Au(111) substrates. Remarkably, the remanent magnetic moments are oriented in the out-of-plane direction with significant contribution from orbital moments. First-principles calculations reveal that the FeFPc-MnPc antiferromagnetic nearest-neighbour coupling is mediated by the Ruderman–Kittel–Kasuya–Yosida exchange interaction via the Au substrate electronic states. Our findings suggest the use of molecular frameworks to engineer novel low-dimensional magnetically ordered materials and their application in molecular quantum devices.
pSILAC mass spectrometry reveals ZFP91 as IMiD-dependent substrate of the CRL4CRBN ubiquitin ligase
Authors: An Jian , Ponthier Charles M. , Sack Ragna , Seebacher Jan , Stadler Michael B. , Donovan Katherine A. , Fischer Eric S.
Published: May 2017

Thalidomide and its derivatives lenalidomide and pomalidomide (IMiDs) are effective treatments of haematologic malignancies. It was shown that IMiDs impart gain-of-function properties to the CUL4-RBX1-DDB1-CRBN (CRL4CRBN) ubiquitin ligase that enable binding, ubiquitination and degradation of key therapeutic targets such as IKZF1, IKZF3 and CSNK1A1. While these substrates have been implicated as efficacy targets in multiple myeloma (MM) and 5q deletion associated myelodysplastic syndrome (del(5q)-MDS), other targets likely exist. Using a pulse-chase SILAC mass spectrometry-based proteomics approach, we demonstrate that lenalidomide induces the ubiquitination and degradation of ZFP91. We establish ZFP91 as a bona fide IMiD-dependent CRL4CRBN substrate and further show that ZFP91 harbours a zinc finger (ZnF) motif, related to the IKZF1/3 ZnF, critical for IMiD-dependent CRBN binding. These findings demonstrate that single time point pulse-chase SILAC mass spectrometry-based proteomics (pSILAC MS) is a sensitive approach for target identification of small molecules inducing selective protein degradation.
Spin injection and helicity control of surface spin photocurrent in a three dimensional topological insulator
Authors: Huang Y. Q. , Song Y. X. , Wang S. M. , Buyanova I. A. , Chen W. M.
Published: May 2017

A three-dimensional (3D) topological insulator (TI) is a unique quantum phase of matter with exotic physical properties and promising spintronic applications. However, surface spin current in a common 3D TI remains difficult to control and the out-of-plane spin texture is largely unexplored. Here, by means of surface spin photocurrent in Bi2Te3 TI devices driven by circular polarized light, we identify the subtle effect of the spin texture of the topological surface state including the hexagonal warping term on the surface current. By exploring the out-of-plane spin texture, we demonstrate spin injection from GaAs to TI and its significant contribution to the surface current, which can be manipulated by an external magnetic field. These discoveries pave the way to not only intriguing new physics but also enriched spin functionalities by integrating TI with conventional semiconductors, such that spin-enabled optoelectronic devices may be fabricated in such hybrid structures.
Deep sleep maintains learning efficiency of the human brain
Authors: Fattinger Sara , de Beukelaar Toon T. , Ruddy Kathy L. , Volk Carina , Heyse Natalie C. , Herbst Joshua A. , Hahnloser Richard H. R. , Wenderoth Nicole , Huber Reto
Published: May 2017

It is hypothesized that deep sleep is essential for restoring the brain’s capacity to learn efficiently, especially in regions heavily activated during the day. However, causal evidence in humans has been lacking due to the inability to sleep deprive one target area while keeping the natural sleep pattern intact. Here we introduce a novel approach to focally perturb deep sleep in motor cortex, and investigate the consequences on behavioural and neurophysiological markers of neuroplasticity arising from dedicated motor practice. We show that the capacity to undergo neuroplastic changes is reduced by wakefulness but restored during unperturbed sleep. This restorative process is markedly attenuated when slow waves are selectively perturbed in motor cortex, demonstrating that deep sleep is a requirement for maintaining sustainable learning efficiency.
A canonical neural mechanism for behavioral variability
Authors: Darshan Ran , Wood William E. , Peters Susan , Leblois Arthur , Hansel David
Published: May 2017

The ability to generate variable movements is essential for learning and adjusting complex behaviours. This variability has been linked to the temporal irregularity of neuronal activity in the central nervous system. However, how neuronal irregularity actually translates into behavioural variability is unclear. Here we combine modelling, electrophysiological and behavioural studies to address this issue. We demonstrate that a model circuit comprising topographically organized and strongly recurrent neural networks can autonomously generate irregular motor behaviours. Simultaneous recordings of neurons in singing finches reveal that neural correlations increase across the circuit driving song variability, in agreement with the model predictions. Analysing behavioural data, we find remarkable similarities in the babbling statistics of 5–6-month-old human infants and juveniles from three songbird species and show that our model naturally accounts for these ‘universal’ statistics.
Understanding trends in electrochemical carbon dioxide reduction rates
Authors: Liu Xinyan , Xiao Jianping , Peng Hongjie , Hong Xin , Chan Karen , Nørskov Jens K.
Published: May 2017

Electrochemical carbon dioxide reduction to fuels presents one of the great challenges in chemistry. Herein we present an understanding of trends in electrocatalytic activity for carbon dioxide reduction over different metal catalysts that rationalize a number of experimental observations including the selectivity with respect to the competing hydrogen evolution reaction. We also identify two design criteria for more active catalysts. The understanding is based on density functional theory calculations of activation energies for electrochemical carbon monoxide reduction as a basis for an electrochemical kinetic model of the process. We develop scaling relations relating transition state energies to the carbon monoxide adsorption energy and determine the optimal value of this descriptor to be very close to that of copper.
MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes
Authors: Lopez Juan Pablo , Fiori Laura M. , Cruceanu Cristiana , Lin Rixing , Labonte Benoit , Cates Hannah M. , Heller Elizabeth A. , Vialou Vincent , Ku Stacy M. , Gerald Christophe , Han Ming-Hu , Foster Jane , Frey Benicio N. , Soares Claudio N. , Müller Daniel J. , Farzan Faranak , Leri Francesco , MacQueen Glenda M. , Feilotter Harriet , Tyryshkin Kathrin , Evans Kenneth R. , Giacobbe Peter , Blier Pierre , Lam Raymond W. , Milev Roumen , Parikh Sagar V. , Rotzinger Susan , Strother Steven C. , Lewis Cathryn M. , Aitchison Katherine J. , Wittenberg Gayle M. , Mechawar Naguib , Nestler Eric J. , Uher Rudolf , Kennedy Sidney H. , Turecki Gustavo
Published: May 2017

Antidepressants (ADs) are the most common treatment for major depressive disorder (MDD). However, only ∼30% of patients experience adequate response after a single AD trial, and this variability remains poorly understood. Here, we investigated microRNAs (miRNAs) as biomarkers of AD response using small RNA-sequencing in paired samples from MDD patients enrolled in a large, randomized placebo-controlled trial of duloxetine collected before and 8 weeks after treatment. Our results revealed differential expression of miR-146a-5p, miR-146b-5p, miR-425-3p and miR-24-3p according to treatment response. These results were replicated in two independent clinical trials of MDD, a well-characterized animal model of depression, and post-mortem human brains. Furthermore, using a combination of bioinformatics, mRNA studies and functional in vitro experiments, we showed significant dysregulation of genes involved in MAPK/Wnt signalling pathways. Together, our results indicate that these miRNAs are consistent markers of treatment response and regulators of the MAPK/Wnt systems.
Correction: Corrigendum: Neuronal IFN-beta–induced PI3K/Akt-FoxA1 signalling is essential for generation of FoxA1+Treg cells
Authors: Liu Yawei , Marin Andrea , Ejlerskov Patrick , Rasmussen Louise Munk , Prinz Marco , Issazadeh-Navikas Shohreh
Published: May 2017

Nature Communications 8: Article number: 14709 (2017); Published 24 April 2017; Updated 22 May 2017 The affiliation details for Marco Prinz are incorrect in this Article. The correct affiliation details for this author are given below: Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany.