bluuebunny/crossref_metadata_2025 huggingface dataset:
WORD FREQUENCY, COLLOCATIONAL FREQUENCY, L1 CONGRUENCY, AND PROFICIENCY IN L2 COLLOCATIONAL PROCESSING
Authors: Wolter Brent , Yamashita Junko
Published: August 2017

This study investigated the effects of word frequency, collocational frequency, L1 congruency, and L2 proficiency, on L2 collocational processing. Two groups of L1 Japanese speakers of English (intermediate and advanced) and one group of English native speakers (NSs) performed an online acceptability judgment task on four types of adjective-noun constructions: (1) congruent collocations, (2) English-only collocations, (3) Japanese-only collocations, and (4) baseline items. Response times were analyzed using mixed-effects modeling and correlations. In contrast to NSs, nonnative speakers (NNSs) processed congruent collocations significantly faster than English-only collocations. As for frequency, all three groups demonstrated sensitivity to both word-level and collocation-level frequency. However, the distributions differed across the three groups. We concluded that age/order of acquisition effects (Carroll & White, 1973) provided the best explanation for the congruency results. Regarding the frequency results, we concluded that the findings conflict with claims that NNSs may process formulaic sequences differently than NSs (e.g., Wray, 2002, 2008).
Annotated defeasible logic
Authors: GOVERNATORI GUIDO , MAHER MICHAEL J.
Published: August 2017

Defeasible logics provide several linguistic features to support the expression of defeasible knowledge. There is also a wide variety of such logics, expressing different intuitions about defeasible reasoning. However, the logics can only combine in trivial ways. This limits their usefulness in contexts where different intuitions are at play in different aspects of a problem. In particular, in some legal settings, different actors have different burdens of proof, which might be expressed as reasoning in different defeasible logics. In this paper, we introduce annotated defeasible logic as a flexible formalism permitting multiple forms of defeasibility, and establish some properties of the formalism.
Model enumeration in propositional circumscription via unsatisfiable core analysis
Authors: ALVIANO MARIO
Published: August 2017

Many practical problems are characterized by a preference relation over admissible solutions, where preferred solutions are minimal in some sense. For example, a preferred diagnosis usually comprises a minimal set of reasons that is sufficient to cause the observed anomaly. Alternatively, a minimal correction subset comprises a minimal set of reasons whose deletion is sufficient to eliminate the observed anomaly. Circumscription formalizes such preference relations by associating propositional theories with minimal models. The resulting enumeration problem is addressed here by means of a new algorithm taking advantage of unsatisfiable core analysis. Empirical evidence of the efficiency of the algorithm is given by comparing the performance of the resulting solver,circumscriptino, withhclasp,camus_mcs,lbxandmcslson the enumeration of minimal models for problems originating from practical applications.
LANDSCAPES OF UNREST: HERBERT GIERSCH AND THE ORIGINS OF NEOLIBERAL ECONOMIC GEOGRAPHY
Authors: PLEHWE DIETER , SLOBODIAN QUINN
Published: August 2017

This article bridges the gap between the intellectual history and critical geography of neoliberalism through a study of the overlooked figure of the German economist Herbert Giersch. As a public economist and director of the Kiel Institute for the World Economy from 1969 to 1989, Giersch blended German traditions of location theory with liberal globalism to lay the foundation of a neoliberal economic geography. We show the origins of globalism at Kiel through the work of the institute's founder, Bernhard Harms, and Giersch's influences, including Johann Heinrich von Thünen, August Lösch, and Alfred Weber. We argue that Giersch's neoliberal economic geography emerged out of two perceived necessities in the 1970s. On the one hand, he saw a need to reorient German industry through import competition with the global South. On the other hand, he felt the need for an ethically defensible global imaginary to pose against both traditional German social democracy and the promise of the global South's New International Economic Order. In his metaphor of a landscape of so-called Schumpeterian volcanoes in which regions were locked in perpetual struggle for temporary monopoly positions against competitors, Giersch provided a powerful distillation of the geographic imaginary at the heart of the neoliberal movement since the 1970s.
Bitstream radar waveforms for generic single-chip radar
Authors: Bjørndal Øystein , Hamran Svein-Erik , Lande Tor Sverre
Published: August 2017

Bitstreams, square wave digital signals, enable flexible radar implementations in modern digital technology. By using bitstreams in place of analog sinusoidal waveforms, we can realize continuous-wave (CW), stepped-frequency CW, frequency-modulated CW, or even pseudo random noise-sequence and pulsed radars, all with a single bit of amplitude resolution. The building blocks are a programable waveform generator, a sweep threshold quantizer, digital delay, and a digital XOR gate as a mixer. This gives us a novel, almost fully digital (requiring only a comparator) system, as previously proposed and which is extended here. The flexibility of the transmitter allows for easy switching between waveforms and the bitstream signal can be processed with single-bit digital gates. Single-bit signals allows for exploration of novel continuous time non-clocked digital implementations to maximize speed and energy efficiency. Mixing frequencies with a digital XOR gate creates harmonics, which are explored for multiple solutions utilizing digital delay. Analytical as well as simulation results are presented. Initial measurements from a 90 nm CMOS chip is provided for the transmitter and the full system, proving the feasibility of a digital future in radar.
Eclipse’s Last Major Stop Is Rich in Science and Amazement
Authors: Showstack Randy
Published: August 2017

Eclipse celebrations and scientific preparations abound in the final large U.S. population center to see Monday’s total eclipse.
Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm mitochondrial sheath formation and male fertility
Authors: Chen Yuxi , Liang Puping , Huang Yan , Li Minyan , Zhang Xiya , Ding Chenhui , Feng Junyan , Zhang Zhen , Zhang Xueqing , Gao Yuanzhu , Zhang Qinfeng , Cao Shanbo , Zheng Haiyan , Liu Dan , Songyang Zhou , Huang Junjiu
Published: August 2017

Spermatids undergo the final steps of maturation during spermiogenesis, a process that necessitates extensive rearrangement of organelles such as the mitochondria. Male infertility has been linked to mitochondrial disorder, for example, hypospermatogenesis and asthenozoospermia. However, the mechanisms that regulate mitochondrial dynamics during spermiogenesis remain largely unknown. We found the glycerol kinase (Gyk)-like proteins glycerol kinase-like 1 (Gykl1) and glycerol kinase 2 (Gk2) were specifically localized to the mitochondria in spermatids. Male mice deficient in either Gykl1 or Gk2 were infertile due to dysfunctional spermatozoa, which exhibited unregulated ATP production, disordered mitochondrial sheath formation, abnormal mitochondrial morphology, and defective sperm tail. We demonstrated that the unique C-terminal sequences found in Gykl1 and Gk2 mediated their targeting to the mitochondrial outer membrane. Furthermore, both Gykl1 and Gk2 could interact with Pld6 (MitoPLD) and induce Pld6 and phosphatidic acid (PA)-dependent mitochondrial clustering in cells. Taken together, our study has revealed previously unsuspected functions of Gyk-like proteins in spermiogenesis, providing new insight into the potential mechanisms that lead to spermatozoa dysfunction and male infertility.
A reporter system coupled with high-throughput sequencing unveils key bacterial transcription and translation determinants
Authors: Yus Eva , Yang Jae-Seong , Sogues Adrià , Serrano Luis
Published: August 2017

Quantitative analysis of the sequence determinants of transcription and translation regulation is relevant for systems and synthetic biology. To identify these determinants, researchers have developed different methods of screening random libraries using fluorescent reporters or antibiotic resistance genes. Here, we have implemented a generic approach called ELM-seq (expression level monitoring by DNA methylation) that overcomes the technical limitations of such classic reporters. ELM-seq uses DamID (Escherichia coli DNA adenine methylase as a reporter coupled with methylation-sensitive restriction enzyme digestion and high-throughput sequencing) to enable in vivo quantitative analyses of upstream regulatory sequences. Using the genome-reduced bacterium Mycoplasma pneumoniae, we show that ELM-seq has a large dynamic range and causes minimal toxicity. We use ELM-seq to determine key sequences (known and putatively novel) of promoter and untranslated regions that influence transcription and translation efficiency. Applying ELM-seq to other organisms will help us to further understand gene expression and guide synthetic biology.
Systems analysis of apoptotic priming in ovarian cancer identifies vulnerabilities and predictors of drug response
Authors: Zervantonakis Ioannis K. , Iavarone Claudia , Chen Hsing-Yu , Selfors Laura M. , Palakurthi Sangeetha , Liu Joyce F. , Drapkin Ronny , Matulonis Ursula , Leverson Joel D. , Sampath Deepak , Mills Gordon B. , Brugge Joan S.
Published: August 2017

The lack of effective chemotherapies for high-grade serous ovarian cancers (HGS-OvCa) has motivated a search for alternative treatment strategies. Here, we present an unbiased systems-approach to interrogate a panel of 14 well-annotated HGS-OvCa patient-derived xenografts for sensitivity to PI3K and PI3K/mTOR inhibitors and uncover cell death vulnerabilities. Proteomic analysis reveals that PI3K/mTOR inhibition in HGS-OvCa patient-derived xenografts induces both pro-apoptotic and anti-apoptotic signaling responses that limit cell killing, but also primes cells for inhibitors of anti-apoptotic proteins. In-depth quantitative analysis of BCL-2 family proteins and other apoptotic regulators, together with computational modeling and selective anti-apoptotic protein inhibitors, uncovers new mechanistic details about apoptotic regulators that are predictive of drug sensitivity (BIM, caspase-3, BCL-XL) and resistance (MCL-1, XIAP). Our systems-approach presents a strategy for systematic analysis of the mechanisms that limit effective tumor cell killing and the identification of apoptotic vulnerabilities to overcome drug resistance in ovarian and other cancers.
Interfacing spin qubits in quantum dots and donors—hot, dense, and coherent
Authors: Vandersypen L. M. K. , Bluhm H. , Clarke J. S. , Dzurak A. S. , Ishihara R. , Morello A. , Reilly D. J. , Schreiber L. R. , Veldhorst M.
Published: August 2017

Semiconductor spins are one of the few qubit realizations that remain a serious candidate for the implementation of large-scale quantum circuits. Excellent scalability is often argued for spin qubits defined by lithography and controlled via electrical signals, based on the success of conventional semiconductor integrated circuits. However, the wiring and interconnect requirements for quantum circuits are completely different from those for classical circuits, as individual direct current, pulsed and in some cases microwave control signals need to be routed from external sources to every qubit. This is further complicated by the requirement that these spin qubits currently operate at temperatures below 100 mK. Here, we review several strategies that are considered to address this crucial challenge in scaling quantum circuits based on electron spin qubits. Key assets of spin qubits include the potential to operate at 1 to 4 K, the high density of quantum dots or donors combined with possibilities to space them apart as needed, the extremely long-spin coherence times, and the rich options for integration with classical electronics based on the same technology.
Unusual magnetic field-dependence of a possible hidden order phase
Authors: Calegari Eleonir João , Magalhaes Sergio Garcia , Riseborough Peter S.
Published: August 2017

URu2Si2 exhibits a second-order phase transition at 17.5 K. Initially it was thought that the transition was to a spin density wave phase, however, subsequent measurements do not support this assignment. Despite the unknown nature of the order parameter, many experimental results can be described in terms of the formation of a generic density wave. Here, we report calculations on an unusual phase of the underscreened Anderson lattice model, the so called spin-dependent inter-orbital density wave that has been proposed as describing the “hidden order” phase of URu2Si2. We determine the effects of an applied magnetic field. Since the order parameter describes an ordering in the x–y plane, the electronic properties of the system are anisotropic below the critical temperature THO. We show that the magnetic susceptibility becomes anisotropic below THO. Furthermore, for fields applied along a spontaneously chosen hard axis, THO decreases towards zero and that the HO transition changes from second order to first order at a large value of the magnetic field. Also, we find that the system undergoes a cascade of field-induced Lifshitz transitions and also show how these properties originate from the dependence of the quasi-particle bands on the orientation of the applied field. The good qualitative agreement with experimental findings provides strong support for the proposed description of the HO phase as a spin-dependent inter-orbital density wave phase.
Epigenetic analysis confirms no accelerated brain aging in schizophrenia
Authors: Voisey Joanne , Lawford Bruce R. , Morris C. Phillip , Wockner Leesa F. , Noble Ernest P. , Young Ross McD , Mehta Divya
Published: August 2017

Epigenetic aging is associated with several biological mechanisms and diseases. We assessed two brain data sets, one small (n = 48) and one large (n = 392), to test epigenetic aging in schizophrenia. DNA methylation age from frontal cortex was significantly correlated with chronological age but no significant differences in DNA methylation age acceleration between schizophrenia cases and controls were observed in both data sets. Our results were consistent with a previous study investigating schizophrenia and epigenetic aging in superior temporal gyrus. Future studies targeting different brain regions and defined cell types are warranted to further investigate accelerated brain aging in schizophrenia.
The method of educational assessment affects children’s neural processing and performance: behavioural and fMRI Evidence
Authors: Howard Steven J. , Burianová Hana , Calleia Alysha , Fynes-Clinton Samuel , Kervin Lisa , Bokosmaty Sahar
Published: August 2017

Standardised educational assessments are now widespread, yet their development has given comparatively more consideration to what to assess than how to optimally assess students’ competencies. Existing evidence from behavioural studies with children and neuroscience studies with adults suggest that the method of assessment may affect neural processing and performance, but current evidence remains limited. To investigate the impact of assessment methods on neural processing and performance in young children, we used functional magnetic resonance imaging to identify and quantify the neural correlates during performance across a range of current approaches to standardised spelling assessment. Results indicated that children’s test performance declined as the cognitive load of assessment method increased. Activation of neural nodes associated with working memory further suggests that this performance decline may be a consequence of a higher cognitive load, rather than the complexity of the content. These findings provide insights into principles of assessment (re)design, to ensure assessment results are an accurate reflection of students’ true levels of competency.
Taxonomic and functional shifts in the beech rhizosphere microbiome across a natural soil toposequence
Authors: Colin Y. , Nicolitch O. , Van Nostrand J. D. , Zhou J. Z. , Turpault M.-P. , Uroz S.
Published: August 2017

It has been rarely questioned as to whether the enrichment of specific bacterial taxa found in the rhizosphere of a given plant species changes with different soil types under field conditions and under similar climatic conditions. Understanding tree microbiome interactions is essential because, in contrast to annual plants, tree species require decades to grow and strongly depend on the nutritive resources of the soil. In this context, we tested using a natural toposequence the hypothesis that beech trees select specific taxa and functions in their rhizosphere based on the soil conditions and their nutritive requirements. Our 16S rRNA gene pyrosequencing analyses revealed that the soil type determines the taxa colonizing the beech rhizosphere. A rhizosphere effect was observed in each soil type, but a stronger effect was observed in the nutrient-poor soils. Although the communities varied significantly across the toposequence, we identified a core beech rhizosphere microbiome. Functionally, GeoChip analyses showed a functional redundancy across the toposequence, with genes related to nutrient cycling and to the bacterial immune system being significantly enriched in the rhizosphere. Altogether, the data suggest that, regardless of the soil conditions, trees enrich variable bacterial communities to maintain the functions necessary for their nutrition.
The emergence of altruism as a social norm
Authors: Pereda María , Brañas-Garza Pablo , Rodríguez-Lara Ismael , Sánchez Angel
Published: August 2017

Expectations, exerting influence through social norms, are a very strong candidate to explain how complex societies function. In the Dictator game (DG), people expect generous behavior from others even if they cannot enforce any sharing of the pie. Here we assume that people donate following their expectations, and that they update their expectations after playing a DG by reinforcement learning to construct a model that explains the main experimental results in the DG. Full agreement with the experimental results is reached when some degree of mismatch between expectations and donations is added into the model. These results are robust against the presence of envious agents, but affected if we introduce selfish agents that do not update their expectations. Our results point to social norms being on the basis of the generous behavior observed in the DG and also to the wide applicability of reinforcement learning to explain many strategic interactions.
HuR-targeted small molecule inhibitor exhibits cytotoxicity towards human lung cancer cells
Authors: Muralidharan Ranganayaki , Mehta Meghna , Ahmed Rebaz , Roy Sudeshna , Xu Liang , Aubé Jeffrey , Chen Allshine , Zhao Yan Daniel , Herman Terence , Ramesh Rajagopal , Munshi Anupama
Published: August 2017

Human antigen (Hu) R is an RNA-binding protein whose overexpression in human cancer correlates with aggressive disease, drug resistance, and poor prognosis. HuR inhibition has profound anticancer activity. Pharmacologic inhibitors can overcome the limitations of genetic inhibition. In this study, we examined the antitumor activity of CMLD-2, a small-molecule inhibitor directed against HuR, using non-small cell lung cancer (NSCLC) as a model. CMLD-2 efficacy was testedin vitrousing H1299, A549, HCC827, and H1975 NSCLC cells and MRC-9 and CCD-16 normal human fibroblasts. Treatment of NSCLC cells with CMLD-2 produced dose-dependent cytotoxicity, caused a G1 phase cell-cycle arrest and induced apoptosis. CMLD-2 decreased HuR mRNA and the mRNAs of HuR-regulated proteins (Bcl2 and p27) in tumor cells. Additionally, reduction in the expression of HuR, Bcl2, cyclin E, and Bcl-XL with increased expression of Bax and p27 in CMLD-2-treated NSCLC cells were observed. CMLD-2-treated normal cells, HuR-regulated mRNAs and proteins albeit showed some reduction were less compared to tumor cells. Finally, CMLD-2 treatment resulted in greater mitochondrial perturbation, activation of caspase-9 and -3 and cleavage of PARP in tumor cells compared to normal cells. Our proof-of concept study results demonstrate CMLD-2 represents a promising HuR-targeted therapeutic class that with further development could lead to advanced preclinical studied and ultimately for lung cancer treatment.
Human eyes with dilated pupils induce pupillary contagion in infants
Authors: Fawcett Christine , Arslan Melda , Falck-Ytter Terje , Roeyers Herbert , Gredebäck Gustaf
Published: August 2017

Being sensitive and responsive to others’ internal states is critical for social life. One reliable cue to what others might be feeling is pupil dilation because it is linked to increases in arousal. When adults view an individual with dilated pupils, their pupils dilate in response, suggesting not only sensitivity to pupil size, but a corresponding response as well. However, little is known about the origins or mechanism underlying this phenomenon of pupillary contagion. Here we show that 4- to 6-month-old infants show pupillary contagion when viewing photographs of eyes with varying pupil sizes: their pupils dilate in response to others’ large, but not small or medium pupils. The results suggest that pupillary contagion is likely driven by a transfer of arousal and that it is present very early in life in human infants, supporting the view that it could be an adaptation fundamental for social and emotional development.
Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits
Authors: Kolla Nathan J. , Patel Raihaan , Meyer Jeffrey H. , Chakravarty M. Mallar
Published: August 2017

Violent offending is elevated among individuals with antisocial personality disorder (ASPD) and high psychopathic traits (PP). Morphological abnormalities of the amygdala and orbitofrontal cortex (OFC) are present in violent offenders, which may relate to the violence enacted by ASPD + PP. Among healthy males, monoamine oxidase-A (MAO-A) genetic variants linked to low in vitro transcription (MAOA-L) are associated with structural abnormalities of the amygdala and OFC. However, it is currently unknown whether amygdala and OFC morphology in ASPD relate to MAO-A genetic polymorphisms. We studied 18 ASPD males with a history of violent offending and 20 healthy male controls. Genomic DNA was extracted from peripheral leukocytes to determine MAO-A genetic polymorphisms. Subjects underwent a T1-weighted MRI anatomical brain scan that provided vertex-wise measures of amygdala shape and surface area and OFC cortical thickness. We found that ASPD + PP subjects with MAOA-L exhibited decreased surface area in the right basolateral amygdala nucleus and increased surface area in the right anterior cortical amygdaloid nucleus versus healthy MAOA-L carriers. This study is the first to describe genotype-related morphological differences of the amygdala in a population marked by high aggression. Deficits in emotional regulation that contribute to the violence of ASPD + PP may relate to morphological changes of the amygdala under genetic control.
Atmospheric deposition, CO2, and change in the land carbon sink
Authors: Fernández-Martínez M. , Vicca S. , Janssens I. A. , Ciais P. , Obersteiner M. , Bartrons M. , Sardans J. , Verger A. , Canadell J. G. , Chevallier F. , Wang X. , Bernhofer C. , Curtis P. S. , Gianelle D. , Grünwald T. , Heinesch B. , Ibrom A. , Knohl A. , Laurila T. , Law B. E. , Limousin J. M. , Longdoz B. , Loustau D. , Mammarella I. , Matteucci G. , Monson R. K. , Montagnani L. , Moors E. J. , Munger J. W. , Papale D. , Piao S. L. , Peñuelas J.
Published: August 2017

Concentrations of atmospheric carbon dioxide (CO2) have continued to increase whereas atmospheric deposition of sulphur and nitrogen has declined in Europe and the USA during recent decades. Using time series of flux observations from 23 forests distributed throughout Europe and the USA, and generalised mixed models, we found that forest-level net ecosystem production and gross primary production have increased by 1% annually from 1995 to 2011. Statistical models indicated that increasing atmospheric CO2 was the most important factor driving the increasing strength of carbon sinks in these forests. We also found that the reduction of sulphur deposition in Europe and the USA lead to higher recovery in ecosystem respiration than in gross primary production, thus limiting the increase of carbon sequestration. By contrast, trends in climate and nitrogen deposition did not significantly contribute to changing carbon fluxes during the studied period. Our findings support the hypothesis of a general CO2-fertilization effect on vegetation growth and suggest that, so far unknown, sulphur deposition plays a significant role in the carbon balance of forests in industrialized regions. Our results show the need to include the effects of changing atmospheric composition, beyond CO2, to assess future dynamics of carbon-climate feedbacks not currently considered in earth system/climate modelling.
Honey-based hydrogel: In vitro and comparative In vivo evaluation for burn wound healing
Authors: El-Kased Reham F. , Amer Reham I. , Attia Dalia , Elmazar M. M.
Published: August 2017

Honey was used to treat wounds since ancient times till nowadays. The present study aimed at preparing a honey-based hydrogel and assay its antimicrobial properties and wound healing activity; in-vitro and in-vivo. Topical honey hydrogel formulations were prepared using three honey concentrations with gelling agents; chitosan and carbopol 934. The prepared formulae were evaluated for pH, spreadability, swelling index, in-vitro release and antimicrobial activity. The pH and spreadability were in the range of 4.3–6.8 and 5.7–8.6 cm, respectively. Chitosan-based hydrogel showed higher in-vitro honey release with diffusional exponent ‘n ≤ 0.5 indicates Fickian diffusion mechanism. Hydrogel formulae were assessed for in-vitro antimicrobial activity using Disc Diffusion antibiotic sensitivity test against common burn infections bacteria; Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Streptococcus pyogenes. The 75% honey-chitosan hydrogel showed highest antimicrobial activity. This formula was tested for in-vivo burn healing using burn-induced wounds in mice. The formula was evaluated for burn healing and antibacterial activities compared to commercial product. 75% honey-chitosan hydrogel was found to possess highest healing rate of burns. The present study concludes that 75% honey-chitosan hydrogel possesses greater wound healing activity compared to commercial preparation and could be safely used as an effective natural topical wound healing treatment.
The diagnostic and prognostic value of interleukin-6 in patients with soft tissue sarcomas
Authors: Hagi Tomohito , Nakamura Tomoki , Iino Takahiro , Matsubara Takao , Asanuma Kunihiro , Matsumine Akihiko , Sudo Akihiro
Published: August 2017

The presence of systemic inflammation has been reported to be associated with poor prognosis in patients with soft tissue sarcoma (STS). The cytokine interleukin-6 (IL-6) has pleiotropic effects on various cell types in the tumor microenvironment. The aim of the present study was to determine whether serum IL-6 levels could be useful to assume the differentiation of benign soft tissue tumors from STS and to investigate the possible value of IL-6 for survival and oncological events in patients with STS. The medical records of 99 patients who underwent surgical resection were retrospectively reviewed. Serum IL-6 levels (median: 9.04 pg/ml) in patients with STS were statistically higher than those (3.31 pg/ml) in patients with benign soft tissue tumors. Our analyses confirmed that tumor size and IL-6 level were significant predictors of STS diagnosis. Next, we examined the relationship between IL-6 levels and survival in the 59 patients with STS. C-reactive protein levels, hemoglobin levels, and tumor grade were strongly correlated with IL-6 levels. Tumor grade and IL-6 level remained significant factors for survival and event-free survival. We suggest that measurement of IL-6 levels may be a useful method for identifying patients who are at a high risk of STS and tumor-related death.
Surface PD-L1, E-cadherin, CD24, and VEGFR2 as markers of epithelial cancer stem cells associated with rapid tumorigenesis
Authors: Jinesh Goodwin G. , Manyam Ganiraju C. , Mmeje Chinedu O. , Baggerly Keith A. , Kamat Ashish M.
Published: August 2017

Cancer cells require both migratory and tumorigenic property to establish metastatic tumors outside the primary microenvironment. Identifying the characteristic features of migratory cancer stem cells with tumorigenic property is important to predict patient prognosis and combat metastasis. Here we established one epithelial and two mesenchymal cell lines from ascites of a bladder cancer patient (i.e. cells already migrated outside primary tumor). Analyses of these cell lines demonstrated that the epithelial cells with surface expression of PD-L1, E-cadherin, CD24, and VEGFR2 rapidly formed tumors outside the primary tumor microenvironment in nude mice, exhibited signatures of immune evasion, increased stemness, increased calcium signaling, transformation, and novel E-cadherin–RalBP1 interaction. The mesenchymal cells on the other hand, exhibited constitutive TGF-β signaling and were less tumorigenic. Hence, targeting epithelial cancer stem cells with rapid tumorigenesis signatures in future might help to combat metastasis.
Prion protein facilitates retinal iron uptake and is cleaved at the β-site: Implications for retinal iron homeostasis in prion disorders
Authors: Asthana Abhishek , Baksi Shounak , Ashok Ajay , Karmakar Shilpita , Mammadova Najiba , Kokemuller Robyn , Greenlee Mary Heather , Kong Qingzhong , Singh Neena
Published: August 2017

Prion disease-associated retinal degeneration is attributed to PrP-scrapie (PrPSc), a misfolded isoform of prion protein (PrPC) that accumulates in the neuroretina. However, a lack of temporal and spatial correlation between PrPScand cytotoxicity suggests the contribution of host factors. We report retinal iron dyshomeostasis as one such factor. PrPCis expressed on the basolateral membrane of retinal-pigment-epithelial (RPE) cells, where it mediates uptake of iron by the neuroretina. Accordingly, the neuroretina of PrP-knock-out mice is iron-deficient. In RPE19 cells, silencing of PrPCdecreases ferritin while over-expression upregulates ferritin and divalent-metal-transporter-1 (DMT-1), indicating PrPC-mediated iron uptake through DMT-1. Polarization of RPE19 cells results in upregulation of ferritin by ~10-fold and β-cleavage of PrPC, the latter likely to block further uptake of iron due to cleavage of the ferrireductase domain. A similar β-cleavage of PrPCis observed in mouse retinal lysates. Scrapie infection causes PrPScaccumulation and microglial activation, and surprisingly, upregulation of transferrin despite increased levels of ferritin. Notably, detergent-insoluble ferritin accumulates in RPE cells and correlates temporally with microglial activation, not PrPScaccumulation, suggesting that impaired uptake of iron by PrPSccombined with inflammation results in retinal iron-dyshomeostasis, a potentially toxic host response contributing to prion disease-associated pathology.
Electron work function – a probe for interfacial diagnosis
Authors: Li D. Y. , Guo Liqiu , Li Lei , Lu Hao
Published: August 2017

A poor interface or defected interfacial segment may trigger interfacial cracking, loss of physical and mechanical functions, and eventual failure of entire material system. Here we show a novel method to diagnose local interphase boundary based on interfacial electron work function (EWF) and its gradient across the interface, which can be analyzed using a nano-Kelvin probe with atomic force microscope. It is demonstrated that a strong interface has its electron work function gradually changed across the interface, while a weaker one shows a steeper change in EWF across the interface. Both experimental and theoretical analyses show that the interfacial work function gradient is a measure of the interaction between two sides of the interface. The effectiveness of this method is demonstrated by analyzing sample metal-metal and metal-ceramic interfaces.
Excessive spinal glutamate transmission is involved in oxaliplatin-induced mechanical allodynia: a possibility for riluzole as a prophylactic drug
Authors: Yamamoto Shota , Ushio Soichiro , Egashira Nobuaki , Kawashiri Takehiro , Mitsuyasu Shohei , Higuchi Hitomi , Ozawa Nana , Masuguchi Ken , Ono Yuko , Masuda Satohiro
Published: August 2017

Oxaliplatin, a chemotherapy medication, causes severe peripheral neuropathy. Although oxaliplatin-induced peripheral neuropathy is a dose-limiting toxicity, a therapeutic strategy against its effects has not been established. We previously reported the involvement of N-methyl-D-aspartate receptors and their intracellular signalling pathway in oxaliplatin-induced mechanical allodynia in rats. The aim of this study was to clarify the involvement of spinal glutamate transmission in oxaliplatin-induced mechanical allodynia. In vivo spinal microdialysis revealed that the baseline glutamate concentration was elevated in oxaliplatin-treated rats, and that mechanical stimulation of the hind paw markedly increased extracellular glutamate concentration in the same rats. In these rats, the expression of glutamate transporter 1 (GLT-1), which plays a major role in glutamate uptake, was decreased in the spinal cord. Moreover, we explored the potential of pharmacological therapy targeting maintenance of extracellular glutamate homeostasis. The administration of riluzole, an approved drug for amyotrophic lateral sclerosis, suppressed the increase of glutamate concentration, the decrease of GLT-1 expression and the development of mechanical allodynia. These results suggest that oxaliplatin disrupts the extracellular glutamate homeostasis in the spinal cord, which may result in neuropathic symptoms, and support the use of riluzole for prophylaxis of oxaliplatin-induced mechanical allodynia.
The Multi Domain Caldicellulosiruptor bescii CelA Cellulase Excels at the Hydrolysis of Crystalline Cellulose
Authors: Brunecky Roman , Donohoe Bryon S. , Yarbrough John M. , Mittal Ashutosh , Scott Brian R. , Ding Hanshu , Taylor II Larry E. , Russell Jordan F. , Chung Daehwan , Westpheling Janet , Teter Sarah A. , Himmel Michael E. , Bomble Yannick J.
Published: August 2017

The crystalline nature of cellulose microfibrils is one of the key factors influencing biomass recalcitrance which is a key technical and economic barrier to overcome to make cellulosic biofuels a commercial reality. To date, all known fungal enzymes tested have great difficulty degrading highly crystalline cellulosic substrates. We have demonstrated that the CelA cellulase from Caldicellulosiruptor bescii degrades highly crystalline cellulose as well as low crystallinity substrates making it the only known cellulase to function well on highly crystalline cellulose. Unlike the secretomes of cellulolytic fungi, which typically comprise multiple, single catalytic domain enzymes for biomass degradation, some bacterial systems employ an alternative strategy that utilizes multi-catalytic domain cellulases. Additionally, CelA is extremely thermostable and highly active at elevated temperatures, unlike commercial fungal cellulases. Furthermore we have determined that the factors negatively affecting digestion of lignocellulosic materials by C. bescii enzyme cocktails containing CelA appear to be significantly different from the performance barriers affecting fungal cellulases. Here, we explore the activity and degradation mechanism of CelA on a variety of pretreated substrates to better understand how the different bulk components of biomass, such as xylan and lignin, impact its performance.
Nanoscale insights into doping behavior, particle size and surface effects in trivalent metal doped SnO2
Authors: Cojocaru Bogdan , Avram Daniel , Kessler Vadim , Parvulescu Vasile , Seisenbaeva Gulaim , Tiseanu Carmen
Published: August 2017

Despite considerable research, the location of an aliovalent dopant into SnO2 nanoparticles is far to be clarified. The aim of the present study on trivalent lanthanide doped SnO2 is to differentiate between substitutional versus interstitial and surface versus bulk doping, delineate the bulk and surface defects induced by doping and establish an intrinsic dopant distribution. We evidence for the first time a complex distribution of intrinsic nature composed of substitutional isolated, substitutional associates with defects as well as surface centers. Such multi-modal distribution is revealed for Eu and Sm, while Pr, Tb and Dy appear to be distributed mostly on the SnO2 surface. Like the previously reported case of Eu, Sm displays a long-lived luminescence decaying in the hundreds of ms scale which is likely related to a selective interaction between the traps and the substitutional isolated center. Analyzing the time-gated luminescence, we conclude that the local lattice environment of the lattice Sn is not affected by the particle size, being remarkably similar in the ~2 and 20 nm particles. The photocatalytic measurements employed as a probe tool confirm the conclusions from the luminescence measurements concerning the nature of defects and the temperature induced migration of lanthanide dopants.
A Total-variation Constrained Permutation Model for Revealing Common Copy Number Patterns
Authors: Zhang Yue , Cheung Yiu-ming , Su Weifeng
Published: August 2017

Variations in DNA copy number carry important information on genome evolution and regulation of DNA replication in cancer cells. The rapid development of single-cell sequencing technology enables exploration of gene-expression heterogeneity among single cells, providing important information on cell evolution. Evolutionary relationships in accumulated sequence data can be visualized by adjacent positioning of similar cells so that similar copy-number profiles are shown by block patterns. However, single-cell DNA sequencing data usually have low amount of starting genome, which requires an extra step of amplification to accumulate sufficient samples, introducing noise and making regular pattern-finding challenging. In this paper, we will propose to tackle this issue of recovering the hidden blocks within single-cell DNA-sequencing data through continuous sample permutations such that similar samples are positioned adjacently. The permutation is guided by the total variational norm of the recovered copy number profiles, and is continued until the total variational norm is minimized when similar samples are stacked together to reveal block patterns. An efficient numerical scheme for finding this permutation is designed, tailored from the alternating direction method of multipliers. Application of this method to both simulated and real data demonstrates its ability to recover the hidden structures of single-cell DNA sequences.
A rumor spreading model based on information entropy
Authors: Wang Chao , Tan Zong Xuan , Ye Ye , Wang Lu , Cheong Kang Hao , Xie Neng-gang
Published: August 2017

Rumor spreading can have a significant impact on people’s lives, distorting scientific facts and influencing political opinions. With technologies that have democratized the production and reproduction of information, the rate at which misinformation can spread has increased significantly, leading many to describe contemporary times as a ‘post-truth era’. Research into rumor spreading has primarily been based on either model of social and biological contagion, or upon models of opinion dynamics. Here we present a comprehensive model that is based on information entropy, which allows for the incorporation of considerations like the role of memory, conformity effects, differences in the subjective propensity to produce distortions, and variations in the degree of trust that people place in each other. Variations in the degree of trust are controlled by a confidence factor β, while the propensity to produce distortions is controlled by a conservation factor K. Simulations were performed using a Barabási–Albert (BA) scale-free network seeded with a single piece of information. The influence of β and K upon the temporal evolution of the system was subsequently analyzed regarding average information entropy, opinion fragmentation, and the range of rumor spread. These results can aid in decision-making to limit the spread of rumors.
Genome-wide profiling of humoral immunity and pathogen genes under selection identifies immune evasion tactics of Chlamydia trachomatis during ocular infection
Authors: Pickering Harry , Teng Andy , Faal Nkoyo , Joof Hassan , Makalo Pateh , Cassama Eunice , Nabicassa Meno , Last Anna R. , Burr Sarah E. , Rowland-Jones Sarah L. , Thomson Nicholas R. , Roberts Chrissy h. , Mabey David C. W. , Bailey Robin L. , Hayward Richard D. , de la Maza Luis M. , Holland Martin J.
Published: August 2017

The frequency and duration ofChlamydia trachomatis(Ct) ocular infections decrease with age, suggesting development of partial immunity. However, there is a lack of clear correlates of immunity to Ct infection in humans. We screened sera from a cohort of Gambian children followed for six-months against a Ct-proteome microarray. At genome sequence level, we detected signatures of selection from a population of ocular Ct isolates from Guinea-Bissau. Together these approaches allowed us to highlight the focus of humoral responses and hypothesise new modes of pathogen immune evasion. Children who were susceptible to frequent and/or prolonged Ct infection had a less focussed antibody response, including preferential recognition of forty-two antigens. There was evidence of positive and purifying selection across the genome, but little balancing selection. In contrast, most antigens that were associated with susceptibility were under neutral selection. These data suggest an evasion strategy in which Ct presents a large panel of irrelevant antigens to the immune system to block or misdirect protective responses. Development of a focused immune response, possibly induced through vaccination, may be an effective strategy to promote protection to Ct infection.
Salt tolerance response revealed by RNA-Seq in a diploid halophytic wild relative of sweet potato
Authors: Luo Yan , Reid Robert , Freese Daniella , Li Changbao , Watkins Jonathan , Shi Huazhong , Zhang Hengyou , Loraine Ann , Song Bao-Hua
Published: August 2017

Crop wild relatives harbor exotic and novel genetic resources, which hold great potential for crop improvement. Ipomoea imperati is a wild diploid relative of sweet potato with the capability of high salinity tolerance. We compared the transcriptomes of I. imperati under salt stress vs. control to identify candidate genes and pathways involved in salt response. De novo assembly produced 67,911 transcripts with a high depth of coverage. A total of 39,902 putative genes were assigned annotations, and 936 and 220 genes involved in salt response in roots and leaves, respectively. Functional analysis indicated a whole system response during salt stress in I. imperati, which included four metabolic processes: sensory initiation, transcriptional reprogramming, cellular protein component change, and cellular homeostasis regulation. We identified a number of candidate genes involved in the ABA signaling pathway, as well as transcription factors, transporters, antioxidant enzymes, and enzymes associated with metabolism of synthesis and catalysis. Furthermore, two membrane transporter genes, including vacuole cation/proton exchanger and inositol transporter, were considered to play important roles in salt tolerance. This study provided valuable information not only for understanding the genetic basis of ecological adaptation but also for future application in sweet potato and other crop improvements.
Aspergillus flavus infection triggered immune responses and host-pathogen cross-talks in groundnut during in-vitro seed colonization
Authors: Nayak Spurthi N , Agarwal Gaurav , Pandey Manish K , Sudini Hari K , Jayale Ashwin S , Purohit Shilp , Desai Aarthi , Wan Liyun , Guo Baozhu , Liao Boshou , Varshney Rajeev K
Published: August 2017

Aflatoxin contamination, caused by fungal pathogen Aspergillus flavus, is a major quality and health problem delimiting the trade and consumption of groundnut (Arachis hypogaea L.) worldwide. RNA-seq approach was deployed to understand the host-pathogen interaction by identifying differentially expressed genes (DEGs) for resistance to in-vitro seed colonization (IVSC) at four critical stages after inoculation in J 11 (resistant) and JL 24 (susceptible) genotypes of groundnut. About 1,344.04 million sequencing reads have been generated from sixteen libraries representing four stages in control and infected conditions. About 64% and 67% of quality filtered reads (1,148.09 million) were mapped onto A (A. duranensis) and B (A. ipaёnsis) subgenomes of groundnut respectively. About 101 million unaligned reads each from J 11 and JL 24 were used to map onto A. flavus genome. As a result, 4,445 DEGs including defense-related genes like senescence-associated proteins, resveratrol synthase, 9s-lipoxygenase, pathogenesis-related proteins were identified. In A. flavus, about 578 DEGs coding for growth and development of fungus, aflatoxin biosynthesis, binding, transport, and signaling were identified in compatible interaction. Besides identifying candidate genes for IVSC resistance in groundnut, the study identified the genes involved in host-pathogen cross-talks and markers that can be used in breeding resistant varieties.
In-situ observation of ultrafast 90° domain switching under application of an electric field in (100)/(001)-oriented tetragonal epitaxial Pb(Zr0.4Ti0.6)O3 thin films
Authors: Ehara Yoshitaka , Yasui Shintaro , Oikawa Takahiro , Shiraishi Takahisa , Shimizu Takao , Tanaka Hiroki , Kanenko Noriyuki , Maran Ronald , Yamada Tomoaki , Imai Yasuhiko , Sakata Osami , Valanoor Nagarajan , Funakubo Hiroshi
Published: August 2017

Ferroelastic domain switching significantly affects piezoelectric properties in ferroelectric materials. The ferroelastic domain switching and the lattice deformation of both a-domains and c-domains under an applied electric field were investigated using in-situ synchrotron X-ray diffraction in conjunction with a high-speed pulse generator set up for epitaxial (100)/(001)-oriented tetragonal Pb(Zr0.4Ti0.6)O3 (PZT) films grown on (100)
c
SrRuO3//(100)KTaO3 substrates. The 004 peak (c-domain) position shifts to a lower 2θ angle, which demonstrates the elongation of the c-axis lattice parameter of the c-domain under an applied electric field. In contrast, the 400 peak (a-domain) shifts in the opposite direction (higher angle), thus indicating a decrease in the a-axis lattice parameter of the a-domain. 90° domain switching from (100) to (001) orientations (from a-domain to c-domain) was observed by a change in the intensities of the 400 and 004 diffraction peaks by applying a high-speed pulsed electric field 200 ns in width. This change also accompanied a tilt in the angles of each domain from the substrate surface normal direction. This behaviour proved that the 90° domain switched within 40 ns under a high-speed pulsed electric field. Direct observation of such high-speed switching opens the way to design piezo-MEMS devices for high-frequency operation.