bluuebunny/crossref_metadata_2025 huggingface dataset:
The Rainbow and Women in Love
Authors: Day Gary , Niro Libby Di
Published: April 2017

D. H. Lawrence's power as a writer, his passionate exploration of male and female relations, and his instinctive recoil from the emotional straitjacket of modernity make him a prophet of our time. This essential volume brings together the best contemporary critical accounts of two of Lawrence's most popular and enduring novels, The Rainbow and Women in Love. The essays are drawn from a wide range of theoretical perspectives, covering language, history, psychoanalysis, feminism and the relation of the novels to modernism, and look forward to new developments in Lawrence scholarship. A helpful introduction locates the two novels in their historical and critical contexts, making this selection of criticism an ideal resource for students and teachers of Lawrence's fiction.
A History of Israel
Authors: Bregman Ahron
Published: April 2017

A History of Israel examines Israel's turbulent history from the first Zionist Congress of 1897 to the present day. Drawing on his considerable experience as historian and journalist, Ahron Bregman offers a balanced exploration of Israel’s past in which the three principal driving themes of Jewish immigration, wars, and attempts to forge peace with Arabs and Palestinians combine into a single compelling narrative.

New insights, revelations appearing in print for the first time, and portraits of Israeli leaders, past and present, are adeptly woven together with an overview of major events. This incisive book will be welcomed by all with an interest in the fascinating history of Israel.
Patterns and Outcomes of Recurrent Esophageal Cancer After Curative Esophagectomy
Authors: Yamashita Kotaro , Watanabe Masayuki , Mine Shinji , Kurogochi Takanori , Okamura Akihiko , Hayami Masaru , Imamura Yu
Published: April 2017

Background

The recurrence patterns and therapeutic outcomes of patients with recurrent esophageal cancer after curative esophagectomy are not fully understood.

Methods

Data on recurrence patterns and sites of recurrence in patients with recurrent esophageal cancer after curative esophagectomy from 2005 to 2015 were retrospectively analyzed. Time to recurrence after curative esophagectomy and survival after recurrence were compared among groups stratified by recurrence pattern and site. Multivariate analysis was performed to identify clinicopathological parameters influencing survival after recurrence.

Results

Of the 290 patients identified, a single pattern of recurrence occurred in 224 patients (77.2%) and a multiple pattern of recurrence occurred in 66 patients (22.8%). The most frequent recurrence pattern was lymph node in 173 patients (59.7%), followed by distant organ in 133 patients (45.9%). Median time to recurrence and median survival after recurrence of all patients were 228 and 327 days, respectively. Among patients with lymph node or lung recurrence, there were 5‐year survivors after recurrence who underwent multimodal therapy. Multivariate analysis revealed that longer disease‐free interval [hazard ratio (HR) 0.70, 95% confidence interval (95% CI) 0.52–0.93], single pattern of recurrence (HR 0.54, 95% CI 0.39–0.74), and curative treatment for recurrence (HR 0.17, 95% CI 0.10–0.28) were significantly associated with favorable prognosis.

Conclusions

Although the prognosis of recurrent esophageal cancer remains unfavorable, if multimodal treatment that includes local therapy was curative, prognosis could improve, especially in patients with lymph node or lung recurrence.
Between neo-Ottomanism and Ottomania: navigating state-led and popular cultural representations of the past
Authors: Ergin Murat , Karakaya Yağmur
Published: April 2017

In contemporary Turkey, a growing interest in Ottoman history represents a change in both the official state discourse and popular culture. This nostalgia appropriates, reinterprets, decontextualizes, and juxtaposes formerly distinct symbols, ideas, objects, and histories in unprecedented ways. In this paper, we distinguish between state-led neo-Ottomanism and popular cultural Ottomania, focusing on the ways in which people in Turkey are interpellated by these two different yet interrelated discourses, depending on their social positions. As the boundary between highbrow and popular culture erodes, popular cultural representations come to reinterpret and rehabilitate the Ottoman past while also inventing new insecurities centering on historical “truth.” Utilizing in-depth interviews, we show that individuals juxtapose the popular television seriesMuhteşem Yüzyıl(The Magnificent Century) with what they deem “proper” history, in the process rendering popular culture a “false” version. We also identify four particular interpretive clusters among the consumers of Ottomania: for some, the Ottoman Empire was the epitome of tolerance, where different groups lived peacefully; for others, the imperial past represents Turkish and/or Islamic identities; and finally, critics see the empire as a burden on contemporary Turkey.
How Attachments to the Nation Shape Beliefs About the World: A Theory of Motivated Reasoning
Authors: Herrmann Richard K.
Published: April 2017

If competing beliefs about political events in the world stem largely from information asymmetries, then more information and knowledge should reduce the gap in competing perceptions. Empirical studies of decision making, however, often find just the reverse: as knowledge and the stakes in play go up, the beliefs about what is happening polarize rather than converge. The theory proposed here attributes this to motivated reasoning. Emotions inside the observer shape beliefs along with information coming from the outside world. A series of experiments embedded in a national survey of Americans finds that a primary driver of the beliefs someone forms about globalization, other countries, and the politics in the Middle East is how strongly they attach their social identity to the United States. Attachment produces more intense positive and negative emotions that in turn shape the interpretation of unfolding events and lead norms to be applied in an inconsistent fashion. People, in effect, rewrite reality around their favored course of action, marrying the logic of appropriateness to their own preferences. Beliefs, consequently, are not independent of preferences but related to them. Motivated reasoning, while not consistent with rational models, is predictable and can lead to expensive mistakes and double standards that undermine liberal internationalism.
Why Don't Trade Preferences Reflect Economic Self-Interest?
Authors: Rho Sungmin , Tomz Michael
Published: April 2017

The dominant approach to the study of international political economy assumes that the policy preferences of individuals and groups reflect economic self-interest. Recent research has called this assumption into question by suggesting that voters do not have economically self-interested preferences about trade policy. We investigate one potential explanation for this puzzling finding: economic ignorance. We show that most voters do not understand the economic consequences of protectionism. We then use experiments to study how voters would respond if they had more information about how trade barriers affect the distribution of income. We find that distributional cues generate two opposing effects: they make people more likely to express self-serving policy preferences, but they also make people more sensitive to the interests of others. In our study both reactions were evident, but selfish responses outweighed altruistic ones. Thus, if people knew more about the distributional effects of trade, the correlation between personal interests and policy preferences would tighten. By showing how the explanatory power of economic self-interest depends on beliefs about causality, this research provides a foundation for more realistic, behaviorally informed theories of international political economy.
Research Bets and Behavioral IR
Authors: Powell Robert
Published: April 2017

Behavioral IR faces a fundamental challenge. The actors in most IR models and theories are not individuals—they are aggregates like states, ministries, interest groups, political parties, and rebel factions. There are two broad approaches to attempting to integrate behavioral research about individuals. The first, a quasi-behavioral approach, makes nonstandard assumptions about the preferences, beliefs, or decision-making processes of aggregate actors. The second tries to build theories in which the key actors are individuals. Pursuing the former means that the assumptions about actors will be only weakly linked to the empirical findings propelling behavioral research. The second approach faces formidable obstacles that international relations theory has confronted for a long time and for the most part has not overcome.
Due Deference: Cosmopolitan Social Identity and the Psychology of Legal Obligation in International Politics
Authors: Bayram A. Burcu
Published: April 2017

Why are some politicians guided by a sense of obligation toward international law but others are not? Why do some politicians have a social as opposed to an egoistic preference over compliance with international legal rules? Existing approaches largely assume that the structural features of the compliance environment shape preferences. As a result, they neglect the heterogeneity across decision makers' subjective beliefs in the legitimacy of international law, which is critical for explaining who exhibits a sense of obligation and has a non-egoistic preference for compliance. Drawing upon a large body of psychological research on social identity and influence, I argue that obligation toward international law has a behavioral foundation shaped by cosmopolitan social identity. Using data from an original survey of German politicians that includes two compliance experiments, I show that politicians with a high degree of cosmopolitanism are driven by a sense of legal obligation that results in a social preference for compliance while those low on cosmopolitanism lack the same sense of normative respect. Replicated in a second experimental study conducted with a convenience sample, my results indicate that strategic rationality in compliance applies, but only to a particular set of actors. By illuminating the psychological underpinnings of obligation toward international law, this study contributes to a richer understanding of compliance preferences and builds a bridge between instrumental and normative models.
Stapled Financing, Value Certification, and Lending Efficiency
Authors: Aslan Hadiye , Kumar Praveen
Published: April 2017

We examine whether financing commitments from a target firm’s financial advisor, in the form of stapled financing, provide certification of target value. Using a data set of leveraged buyouts spanning 2002–2011, and addressing endogeneity issues, we find that stapled financing has significant positive effects on sellers’ shareholder wealth, especially for targets suffering from greater adverse selection. Stapled financing facilitates deal financing by allowing buyers to obtain lower-cost and longer-maturity debt, and it is positively associated with bidding intensity. Investment banks offering stapled financing appear to trade off higher expected advisory fees against loss of lending efficiency ex post.
Should Indirect Brokerage Fees Be Capped? Lessons from Mutual Fund Marketing and Distribution Expenses
Authors: Oh Natalie Y. , Parwada Jerry T. , Tan Eric K. M.
Published: April 2017

Theory predicts that capping brokers’ compensation exacerbates the exploitation of retail investors. We show that regulated caps on mutual fund 12b-1 fees, effectively sales commissions, are associated with negative equity fund performance, but only after a structural shift toward maximum permitted levels of the fees around 2000. Past this break point, flow–performance sensitivity shifts from the middle- to the highest-performing funds, suggesting that the fee cap increases performance-chasing behavior by constraining brokers’ incentives to learn about lower-ranked funds. The policy implication is that regulators must reevaluate the efficacy of caps on brokerage fees.
The Effect of Labor Unions on CEO Compensation
Authors: Huang Qianqian , Jiang Feng , Lie Erik , Que Tingting
Published: April 2017

We find evidence that labor unions affect chief executive officer (CEO) compensation. First, we find that firms with strong unions pay their CEOs less. The negative effect is robust to various tests for endogeneity, including cross-sectional variations and a regression discontinuity design. Second, we find that CEO compensation is curbed before union contract negotiations, especially when the compensation is discretionary and the unions have a strong bargaining position. Third, we report that curbing CEO compensation mitigates the chance of a labor strike, thus providing a rationale for firms to pay CEOs less when facing strong unions.
Upper Bounds on Return Predictability
Authors: Huang Dashan , Zhou Guofu
Published: April 2017

Can the degree of predictability found in data be explained by existing asset pricing models? We provide two theoretical upper bounds on theR2of predictive regressions. Using data on the market portfolio and component portfolios, we find that the empiricalR2s are significantly greater than the theoretical upper bounds. Our results suggest that the most promising direction for future research should aim to identify new state variables that are highly correlated with stock returns instead of seeking more elaborate stochastic discount factors.
Why Do Short Sellers Like Qualitative News?
Authors: von Beschwitz Bastian , Chuprinin Oleg , Massa Massimo
Published: April 2017

Short sellers trade more on days with qualitative news, that is, news containing fewer numbers. We show that this behavior is not informationally motivated but can be explained by short sellers exploiting higher liquidity on such days. We document that liquidity and noise trading increase in the presence of qualitative news, enabling short sellers to better disguise their informed trades. Natural experiments support our findings. Qualitative news has a bigger effect on short sellers’ trading after a decrease in liquidity following the stock’s deletion from the Standard & Poor’s 500 index and a smaller effect when investor attention is distracted by the Olympic Games.
Policy Uncertainty and Mergers and Acquisitions
Authors: Nguyen Nam H. , Phan Hieu V.
Published: April 2017

This research examines the relationship between policy uncertainty and mergers and acquisitions (M&As). We find that policy uncertainty is negatively related to firm acquisitiveness and positively related to the time it takes to complete M&A deals. In addition, policy uncertainty motivates acquirers to use stock for payment and to pay lower bid premiums. Acquirers, on average, create larger shareholder value from M&A deals undertaken during periods of high policy uncertainty, which is attributable to their prudence as well as the wealth transfer from the financially constrained targets to acquirers.
Annual Report Readability, Tone Ambiguity, and the Cost of Borrowing
Authors: Ertugrul Mine , Lei Jin , Qiu Jiaping , Wan Chi
Published: April 2017

This paper investigates the impact of a firm’s annual report readability and ambiguous tone on its borrowing costs. We find that firms with larger 10-K file sizes and a higher proportion of uncertain and weak modal words in 10-Ks have stricter loan contract terms and greater future stock price crash risk. Our results suggest that the readability and tone ambiguity of a firm’s financial disclosures are related to managerial information hoarding. Shareholders of firms with less readable and more ambiguous annual reports not only suffer from less transparent information disclosure but also bear the increased cost of external financing.
COMPLEX DEMODULATION: A NOVEL TIME SERIES METHOD FOR ANALYSING SEASONAL INFECTIOUS DISEASES
Authors: HOGAN A. B. , GLASS K. , ANDERSSEN R. S.
Published: April 2017

Understanding how seasonal patterns change from year to year is important for the management of infectious disease epidemics. Here, we present a mathematical formalization of the application of complex demodulation, which has previously only been applied in an exploratory manner in the context of infectious diseases. This method extracts the changing amplitude and phase from seasonal data, allowing comparisons between the size and timing of yearly epidemics. We first validate the method using synthetic data that displays the key features of epidemic data. In particular, we analyse both annual and biennial synthetic data, and explore the effect of delayed epidemics on the extracted amplitude and phase. We then demonstrate the usefulness of complex demodulation using national notification data for influenza in Australia. This method clearly highlights the higher number of notifications and the early peak of the influenza pandemic in 2009. We also identify that epidemics that peaked later than usual generally followed larger epidemics and involved fewer overall notifications. Our analysis establishes a role for complex demodulation in the study of seasonal epidemiological events.
Zusammenhänge elterlicher Erwartungen und Einstellungen mit der Anmeldung und späteren Inanspruchnahme einer Krippe
Authors: Burghardt Lars
Published: April 2017

Zusammenfassung. Die Gründe, die für oder gegen den Besuch einer Krippe genannt werden, erweisen sich als vielfältig. Konzentrierten sich bisherige Untersuchungen meist auf den Zusammenhang struktureller Faktoren mit der Inanspruchnahme eines Krippenplatzes, untersucht der vorliegende Beitrag mit Hilfe von Daten des Nationalen Bildungspanels (NEPS, n = 2789), welche zusätzliche Aufklärung zu den Einflüssen von Strukturmerkmalen verschiedene vorgängige Orientierungsmerkmale der Eltern auf die Anmeldung und die spätere Inanspruchnahme einer Krippe liefern. Die Analysen zeigen, dass die Varianzaufklärung durch Orientierungsmerkmale, die dem Krippenbesuch zeitlich voran gestellt sind, besser gelingt als durch die Strukturmerkmale, die in den bisherigen Untersuchungen herausgearbeitet wurden. Drei Merkmale stehen vor allem mit der Anmeldung und späteren Inanspruchnahme in Verbindung: die Erwartung der Eltern, ob ein Krippenbesuch förderlich für die kindliche Entwicklung ist, die empfundene Wichtigkeit, einer beruflichen Tätigkeit nachzugehen und die Informiertheit der Eltern über Betreuungsangebote.
Warming enhances old organic carbon decomposition through altering functional microbial communities
Authors: Cheng Lei , Zhang Naifang , Yuan Mengting , Xiao Jing , Qin Yujia , Deng Ye , Tu Qichao , Xue Kai , Van Nostrand Joy D , Wu Liyou , He Zhili , Zhou Xuhui , Leigh Mary Beth , Konstantinidis Konstantinos T , Schuur Edward A G , Luo Yiqi , Tiedje James M , Zhou Jizhong
Published: April 2017

Soil organic matter (SOM) stocks contain nearly three times as much carbon (C) as the atmosphere and changes in soil C stocks may have a major impact on future atmospheric carbon dioxide concentrations and climate. Over the past two decades, much research has been devoted to examining the influence of warming on SOM decomposition in topsoil. Most SOM, however, is old and stored in subsoil. The fate of subsoil SOM under future warming remains highly uncertain. Here, by combining a long-term field warming experiment and a meta-analysis study, we showed that warming significantly increased SOM decomposition in subsoil. We also showed that a decade of warming promoted decomposition of subsoil SOM with turnover times of decades to millennia in a tall grass prairie and this effect was largely associated with shifts in the functional gene structure of microbial communities. By coupling stable isotope probing with metagenomics, we found that microbial communities in warmed soils possessed a higher relative abundance of key functional genes involved in the degradation of organic materials with varying recalcitrance than those in control soils. These findings suggest warming may considerably alter the stability of the vast pool of old SOM in subsoil, contributing to the long-term positive feedback between the C cycle and climate.
Independence of nutrient limitation and carbon dioxide impacts on the Southern Ocean coccolithophore Emiliania huxleyi
Authors: Müller Marius N , Trull Thomas W , Hallegraeff Gustaaf M
Published: April 2017

Future oceanic conditions induced by anthropogenic greenhouse gas emissions include warming, acidification and reduced nutrient supply due to increased stratification. Some parts of the Southern Ocean are expected to show rapid changes, especially for carbonate mineral saturation. Here we compare the physiological response of the model coccolithophore Emiliania huxleyi (strain EHSO 5.14, originating from 50oS, 149oE) with pH/CO2 gradients (mimicking ocean acidification ranging from 1 to 4 × current pCO2 levels) under nutrient-limited (nitrogen and phosphorus) and -replete conditions. Both nutrient limitations decreased per cell photosynthesis (particulate organic carbon (POC) production) and calcification (particulate inorganic carbon (PIC) production) rates for all pCO2 levels, with more than 50% reductions under nitrogen limitation. These impacts, however, became indistinguishable from nutrient-replete conditions when normalized to cell volume. Calcification decreased three-fold and linearly with increasing pCO2 under all nutrient conditions, and was accompanied by a smaller ~30% nonlinear reduction in POC production, manifested mainly above 3 × current pCO2. Our results suggest that normalization to cell volume allows the major impacts of nutrient limitation (changed cell sizes and reduced PIC and POC production rates) to be treated independently of the major impacts of increasing pCO2 and, additionally, stresses the importance of including cell volume measurements to the toolbox of standard physiological analysis of coccolithophores in field and laboratory studies.
Poorly known microbial taxa dominate the microbiome of permafrost thaw ponds
Authors: Wurzbacher Christian , Nilsson R Henrik , Rautio Milla , Peura Sari
Published: April 2017

In the transition zone of the shifting permafrost border, thaw ponds emerge as hotspots of microbial activity, processing the ancient carbon freed from the permafrost. We analyzed the microbial succession across a gradient of recently emerged to older ponds using three molecular markers: one universal, one bacterial and one fungal. Age was a major modulator of the microbial community of the thaw ponds. Surprisingly, typical freshwater taxa comprised only a small fraction of the community. Instead, thaw ponds of all age classes were dominated by enigmatic bacterial and fungal phyla. Our results on permafrost thaw ponds lead to a revised perception of the thaw pond ecosystem and their microbes, with potential implications for carbon and nutrient cycling in this increasingly important class of freshwaters.
A computational systems approach identifies synergistic specification genes that facilitate lineage conversion to prostate tissue
Authors: Talos Flaminia , Mitrofanova Antonina , Bergren Sarah K. , Califano Andrea , Shen Michael M.
Published: April 2017

To date, reprogramming strategies for generating cell types of interest have been facilitated by detailed understanding of relevant developmental regulatory factors. However, identification of such regulatory drivers often represents a major challenge, as specific gene combinations may be required for reprogramming. Here we show that a computational systems approach can identify cell type specification genes (master regulators) that act synergistically, and demonstrate its application for reprogramming of fibroblasts to prostate tissue. We use three such master regulators (FOXA1, NKX3.1 and androgen receptor, AR) in a primed conversion strategy starting from mouse fibroblasts, resulting in prostate tissue grafts with appropriate histological and molecular properties that respond to androgen-deprivation. Moreover, generation of reprogrammed prostate does not require traversal of a pluripotent state. Thus, we describe a general strategy by which cell types and tissues can be generated even with limited knowledge of the developmental pathways required for their specification in vivo.
Gating of TonB-dependent transporters by substrate-specific forced remodelling
Authors: Hickman Samuel J. , Cooper Rachael E. M. , Bellucci Luca , Paci Emanuele , Brockwell David J.
Published: April 2017

Membrane proteins play vital roles in inside-out and outside-in signal transduction by responding to inputs that include mechanical stimuli. Mechanical gating may be mediated by the membrane or by protein(s) but evidence for the latter is scarce. Here we use force spectroscopy, protein engineering and bacterial growth assays to investigate the effects of force on complexes formed between TonB and TonB-dependent transporters (TBDT) from Gram-negative bacteria. We confirm the feasibility of protein-only mediated mechanical gating by demonstrating that the interaction between TonB and BtuB (a TBDT) is sufficiently strong under force to create a channel through the TBDT. In addition, by comparing the dimensions of the force-induced channel in BtuB and a second TBDT (FhuA), we show that the mechanical properties of the interaction are perfectly tuned to their function by inducing formation of a channel whose dimensions are tailored to the ligand.
Exploratory adaptation in large random networks
Authors: Schreier Hallel I. , Soen Yoav , Brenner Naama
Published: April 2017

The capacity of cells and organisms to respond to challenging conditions in a repeatable manner is limited by a finite repertoire of pre-evolved adaptive responses. Beyond this capacity, cells can use exploratory dynamics to cope with a much broader array of conditions. However, the process of adaptation by exploratory dynamics within the lifetime of a cell is not well understood. Here we demonstrate the feasibility of exploratory adaptation in a high-dimensional network model of gene regulation. Exploration is initiated by failure to comply with a constraint and is implemented by random sampling of network configurations. It ceases if and when the network reaches a stable state satisfying the constraint. We find that successful convergence (adaptation) in high dimensions requires outgoing network hubs and is enhanced by their auto-regulation. The ability of these empirically validated features of gene regulatory networks to support exploratory adaptation without fine-tuning, makes it plausible for biological implementation.
Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations
Authors: Brown David , Smeets Dominiek , Székely Borbála , Larsimont Denis , Szász A. Marcell , Adnet Pierre-Yves , Rothé Françoise , Rouas Ghizlane , Nagy Zsófia I. , Faragó Zsófia , Tőkés Anna-Mária , Dank Magdolna , Szentmártoni Gyöngyvér , Udvarhelyi Nóra , Zoppoli Gabriele , Pusztai Lajos , Piccart Martine , Kulka Janina , Lambrechts Diether , Sotiriou Christos , Desmedt Christine
Published: April 2017

Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common ‘metastatic precursor’. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination.
Bi1Te1 is a dual topological insulator
Authors: Eschbach Markus , Lanius Martin , Niu Chengwang , Młyńczak Ewa , Gospodarič Pika , Kellner Jens , Schüffelgen Peter , Gehlmann Mathias , Döring Sven , Neumann Elmar , Luysberg Martina , Mussler Gregor , Plucinski Lukasz , Morgenstern Markus , Grützmacher Detlev , Bihlmayer Gustav , Blügel Stefan , Schneider Claus M.
Published: April 2017

New three-dimensional (3D) topological phases can emerge in superlattices containing constituents of known two-dimensional topologies. Here we demonstrate that stoichiometric Bi1Te1, which is a natural superlattice of alternating two Bi2Te3 quintuple layers and one Bi bilayer, is a dual 3D topological insulator where a weak topological insulator phase and topological crystalline insulator phase appear simultaneously. By density functional theory, we find "Equation missing" indices (0;001) and a non-zero mirror Chern number. We have synthesized Bi1Te1 by molecular beam epitaxy and found evidence for its topological crystalline and weak topological character by spin- and angle-resolved photoemission spectroscopy. The dual topology opens the possibility to gap the differently protected metallic surface states on different surfaces independently by breaking the respective symmetries, for example, by magnetic field on one surface and by strain on another surface.
Global distribution of particle phase state in atmospheric secondary organic aerosols
Authors: Shiraiwa Manabu , Li Ying , Tsimpidi Alexandra P. , Karydis Vlassis A. , Berkemeier Thomas , Pandis Spyros N. , Lelieveld Jos , Koop Thomas , Pöschl Ulrich
Published: April 2017

Secondary organic aerosols (SOA) are a large source of uncertainty in our current understanding of climate change and air pollution. The phase state of SOA is important for quantifying their effects on climate and air quality, but its global distribution is poorly characterized. We developed a method to estimate glass transition temperatures based on the molar mass and molecular O:C ratio of SOA components, and we used the global chemistry climate model EMAC with the organic aerosol module ORACLE to predict the phase state of atmospheric SOA. For the planetary boundary layer, global simulations indicate that SOA are mostly liquid in tropical and polar air with high relative humidity, semi-solid in the mid-latitudes and solid over dry lands. We find that in the middle and upper troposphere SOA should be mostly in a glassy solid phase state. Thus, slow diffusion of water, oxidants and organic molecules could kinetically limit gas–particle interactions of SOA in the free and upper troposphere, promote ice nucleation and facilitate long-range transport of reactive and toxic organic pollutants embedded in SOA.
PIF1 family DNA helicases suppress R-loop mediated genome instability at tRNA genes
Authors: Tran Phong Lan Thao , Pohl Thomas J. , Chen Chi-Fu , Chan Angela , Pott Sebastian , Zakian Virginia A.
Published: April 2017

Saccharomyces cerevisiae encodes two Pif1 family DNA helicases, Pif1 and Rrm3. Rrm3 promotes DNA replication past stable protein complexes at tRNA genes (tDNAs). We identify a new role for the Pif1 helicase: promotion of replication and suppression of DNA damage at tDNAs. Pif1 binds multiple tDNAs, and this binding is higher in rrm3Δ cells. Accumulation of replication intermediates and DNA damage at tDNAs is higher in pif1Δ rrm3Δ than in rrm3Δ cells. DNA damage at tDNAs in the absence of these helicases is suppressed by destabilizing R-loops while Pif1 and Rrm3 binding to tDNAs is increased upon R-loop stabilization. We propose that Rrm3 and Pif1 promote genome stability at tDNAs by displacing the stable multi-protein transcription complex and by removing R-loops. Thus, we identify tDNAs as a new source of R-loop-mediated DNA damage. Given their large number and high transcription rate, tDNAs may be a potent source of genome instability.
Single-photon test of hyper-complex quantum theories using a metamaterial
Authors: Procopio Lorenzo M. , Rozema Lee A. , Wong Zi Jing , Hamel Deny R. , O’Brien Kevin , Zhang Xiang , Dakić Borivoje , Walther Philip
Published: April 2017

In standard quantum mechanics, complex numbers are used to describe the wavefunction. Although this has so far proven sufficient to predict experimental results, there is no theoretical reason to choose them over real numbers or generalizations of complex numbers, that is, hyper-complex numbers. Experiments performed to date have proven that real numbers are insufficient, but the need for hyper-complex numbers remains an open question. Here we experimentally probe hyper-complex quantum theories, studying one of their deviations from complex quantum theory: the non-commutativity of phases. We do so by passing single photons through a Sagnac interferometer containing both a metamaterial with a negative refractive index, and a positive phase shifter. To accomplish this we engineered a fishnet metamaterial to have a negative refractive index at 780 nm. We show that the metamaterial phase commutes with other phases with high precision, allowing us to place limits on a particular prediction of hyper-complex quantum theories.
The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces nutrient flexibility
Authors: Shin Chun-Shik , Mishra Prashant , Watrous Jeramie D. , Carelli Valerio , D’Aurelio Marilena , Jain Mohit , Chan David C.
Published: April 2017

As noted by Warburg, many cancer cells depend on the consumption of glucose. We performed a genetic screen to identify factors responsible for glucose addiction and recovered the two subunits of the xCT antiporter (system xc−), which plays an antioxidant role by exporting glutamate for cystine. Disruption of the xCT antiporter greatly improves cell viability after glucose withdrawal, because conservation of glutamate enables cells to maintain mitochondrial respiration. In some breast cancer cells, xCT antiporter expression is upregulated through the antioxidant transcription factor Nrf2 and contributes to their requirement for glucose as a carbon source. In cells carrying patient-derived mitochondrial DNA mutations, the xCT antiporter is upregulated and its inhibition improves mitochondrial function and cell viability. Therefore, although upregulation of the xCT antiporter promotes antioxidant defence, it antagonizes glutamine metabolism and restricts nutrient flexibility. In cells with mitochondrial dysfunction, the potential utility of xCT antiporter inhibition should be further tested.
A mouse tissue transcription factor atlas
Authors: Zhou Quan , Liu Mingwei , Xia Xia , Gong Tongqing , Feng Jinwen , Liu Wanlin , Liu Yang , Zhen Bei , Wang Yi , Ding Chen , Qin Jun
Published: April 2017

Transcription factors (TFs) drive various biological processes ranging from embryonic development to carcinogenesis. Here, we employ a recently developed concatenated tandem array of consensus TF response elements (catTFRE) approach to profile the activated TFs in 24 adult and 8 fetal mouse tissues on proteome scale. A total of 941 TFs are quantitatively identified, representing over 60% of the TFs in the mouse genome. Using an integrated omics approach, we present a TF network in the major organs of the mouse, allowing data mining and generating knowledge to elucidate the roles of TFs in various biological processes, including tissue type maintenance and determining the general features of a physiological system. This study provides a landscape of TFs in mouse tissues that can be used to elucidate transcriptional regulatory specificity and programming and as a baseline that may facilitate understanding diseases that are regulated by TFs.
Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutated non-small cell lung cancer
Authors: Dhawan Andrew , Nichol Daniel , Kinose Fumi , Abazeed Mohamed E. , Marusyk Andriy , Haura Eric B. , Scott Jacob G.
Published: April 2017

Drug resistance remains an elusive problem in cancer therapy, particularly for novel targeted therapies. Much work is focused upon the development of an arsenal of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to overcome the inevitable resistance that develops over time. Currently, after failure of first line ALK TKI therapy, another ALK TKI is administered, though collateral sensitivity is not considered. To address this, we evolved resistance in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK TKIs, and performed a collateral sensitivity analysis. All ALK inhibitor resistant cell lines displayed significant cross-resistance to all other ALK inhibitors. We then evaluated ALK-inhibitor sensitivities after drug holidays of varying length (1–21 days), and observed dynamic patterns of resistance. This unpredictability led us to an expanded search for treatment options, where we tested 6 further anti-cancer agents for collateral sensitivity among resistant cells, uncovering possibilities for further treatment, including cross-sensitivity to standard cytotoxic therapies, as well as Hsp90 inhibitors. Taken together, these results imply that resistance to targeted therapy in non-small cell lung cancer is highly dynamic, and also one where there are many opportunities to re-establish sensitivities where there was once resistance. Drug resistance in cancer inevitably emerges during treatment; particularly with novel targeted therapies, designed to inhibit specific molecules. A clinically-relevant example of this phenomenon occurs in ALK-positive non-small cell lung cancer, where targeted therapies are used to inhibit the ALK-EML4 fusion protein. A potential solution to this may lie in finding drug sensitivities in the resistant population, termed collateral sensitivities, and then using these as second-line agents. This study shows how the evolution of resistance in ALK-positive lung cancer is a dynamic process through time, one in which patterns of drug resistance and collateral sensitivity change substantially, and therefore one where temporal regimens, such as drug cycling and drug holidays may have great benefit.
Post-Surgery Glioma Growth Modeling from Magnetic Resonance Images for Patients with Treatment
Authors: Elazab Ahmed , Bai Hongmin , Abdulazeem Yousry M. , Abdelhamid Talaat , Zhou Sijie , Wong Kelvin K. L. , Hu Qingmao
Published: April 2017

Reaction diffusion is the most common growth modelling methodology due to its simplicity and consistency with the biological tumor growth process. However, current extensions of the reaction diffusion model lack one or more of the following: efficient inclusion of treatments’ effects, taking into account the viscoelasticity of brain tissues, and guaranteed stability of the numerical solution. We propose a new model to overcome the aforementioned drawbacks. Guided by directional information derived from diffusion tensor imaging, our model relates tissue heterogeneity with the absorption of the chemotherapy, adopts the linear-quadratic term to simulate the radiotherapy effect, employs Maxwell-Weichert model to incorporate brain viscoelasticity, and ensures the stability of the numerical solution. The performance is verified through experiments on synthetic and real MR images. Experiments on 9 MR datasets of patients with low grade gliomas undergoing surgery with different treatment regimens are carried out and validated using Jaccard score and Dice coefficient. The growth simulation accuracies of the proposed model are in ranges of [0.673 0.822] and [0.805 0.902] for Jaccard scores and Dice coefficients, respectively. The accuracies decrease up to 4% and 2.4% when ignoring treatment effects and the tensor information, while brain viscoelasticity has no significant impact on the accuracies.
Importance of surface topography on pulsed laser-induced damage threshold of Sapphire crystals
Authors: Bussière Benoît , Sanner Nicolas , Sentis Marc , Utéza Olivier
Published: April 2017

We measure the laser-induced damage threshold (LIDT) fluence under single shot at the surface of Sapphire samples prepared following the standards of two methods yielding to different surface finish and used in optical and laser industry. We use AFM microscopy to measure the roughness parameter Ra and power spectral density (PSD) of the sample surface. We show that the quality of surface topography resulting from surface preparation affects the damage threshold of Sapphire crystals exposed to femtosecond, picosecond, and nanosecond laser conditions at visible and near-infrared wavelengths. We observe a higher resistance to laser damage or macroscopic modification when the surface finish presents a smooth and regular topography. We indeed measure a 1.4 to 2 times increase of the LIDT fluence in femtosecond and picosecond regimes and up to 5 times with nanosecond pulses. Using simple damage model and PSD data, we correlate the LIDT reduction of Sapphire samples of lower quality of surface finish with the high-frequency tail component of their PSD distribution corresponding to striations of the width of a fraction of the laser wavelength. This study emphasizes the importance of detailed assessment of surface topography for laser damage evaluation and understanding and for indicating directions of improvement.
Continuous daylight in the high-Arctic summer supports high plankton respiration rates compared to those supported in the dark
Authors: Mesa Elena , Delgado-Huertas Antonio , Carrillo-de-Albornoz Paloma , García-Corral Lara S. , Sanz-Martín Marina , Wassmann Paul , Reigstad Marit , Sejr Mikael , Dalsgaard Tage , Duarte Carlos M.
Published: April 2017

Plankton respiration rate is a major component of global CO2 production and is forecasted to increase rapidly in the Arctic with warming. Yet, existing assessments in the Arctic evaluated plankton respiration in the dark. Evidence that plankton respiration may be stimulated in the light is particularly relevant for the high Arctic where plankton communities experience continuous daylight in spring and summer. Here we demonstrate that plankton community respiration evaluated under the continuous daylight conditions present in situ, tends to be higher than that evaluated in the dark. The ratio between community respiration measured in the light (Rlight) and in the dark (Rdark) increased as the 2/3 power of Rlight so that the Rlight:Rdark ratio increased from an average value of 1.37 at the median Rlight measured here (3.62 µmol O2 L−1 d−1) to an average value of 17.56 at the highest Rlight measured here (15.8 µmol O2 L−1 d−1). The role of respiratory processes as a source of CO2 in the Arctic has, therefore, been underestimated and is far more important than previously believed, particularly in the late spring, with 24 h photoperiods, when community respiration rates are highest.
Ultra-weak photon emission as a dynamic tool for monitoring oxidative stress metabolism
Authors: Burgos Rosilene Cristina Rossetto , Schoeman Johannes Cornelius , Winden Lennart Jan van , Červinková Kateřina , Ramautar Rawi , Van Wijk Eduard P. A. , Cifra Michal , Berger Ruud , Hankemeier Thomas , Greef Jan van der
Published: April 2017

In recent years, excessive oxidative metabolism has been reported as a critical determinant of pathogenicity in many diseases. The advent of a simple tool that can provide a physiological readout of oxidative stress would be a major step towards monitoring this dynamic process in biological systems, while also improving our understanding of this process. Ultra-weak photon emission (UPE) has been proposed as a potential tool for measuring oxidative processes due to the association between UPE and reactive oxygen species. Here, we used HL-60 cells as anin vitromodel to test the potential of using UPE as readout for dynamically monitoring oxidative stress after inducing respiratory burst. In addition, to probe for possible changes in oxidative metabolism, we performed targeted metabolomics on cell extracts and culture medium. Lastly, we tested the effects of treating cells with the NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI). Our results show that UPE can be used as readout for measuring oxidative stress metabolism and related processes.
Distributed atomic quantum information processing via optical fibers
Authors: Luo Ming-Xing , Li Hui-Ran , Wang Xiaojun
Published: April 2017

The qudit system may offer great flexibilities for quantum information processing. We investigate the possibility of realizing elementary quantum gates between two high-dimensional atoms in distant cavities coupled by an optical fiber. We show that highly reliable special swap gate is achievable by different detuning. The numerical simulation shows that the proposed elementary gate is robust against the atomic spontaneous decay, photon leakage of cavities and optical fibers by choosing the experimental parameters appropriately.
A predation cost to bold fish in the wild
Authors: Hulthén Kaj , Chapman Ben B. , Nilsson P. Anders , Hansson Lars-Anders , Skov Christian , Brodersen Jakob , Vinterstare Jerker , Brönmark Christer
Published: April 2017

Studies of predator-mediated selection on behaviour are critical for our understanding of the evolution and maintenance of behavioural diversity in natural populations. Consistent individual differences in prey behaviour, especially in the propensity to take risks (“boldness”), are widespread in the animal kingdom. Theory predicts that individual behavioural types differ in a cost-benefit trade-off where bolder individuals benefit from greater access to resources while paying higher predation-risk costs. However, explicitly linking predation events to individual behaviour under natural conditions is challenging and there is currently little data from the wild. We assayed individual behaviour and electronically tagged hundreds of fish (roach,Rutilus rutilus) before releasing them into their lake of origin, thereby exposing them to predation risk from avian apex predators (cormorants,Phalacrocorax carbo). Scanning for regurgitated tags at the cormorant roosting site provided data on individual predation events. We found that fish with higher boldness have a greater susceptibility to cormorant predation compared to relatively shy, risk-averse individuals. Our findings hereby provide unique and direct evidence of behavioural type-dependent predation vulnerability in the wild, i.e. that there is a predation cost to boldness, which is critical for our understanding of the evolution and maintenance of behavioural diversity in natural populations.
Structural alterations in the prefrontal cortex mediate the relationship between Internet gaming disorder and depressed mood
Authors: Choi Jihye , Cho Hyun , Kim Jin-Young , Jung Dong Jin , Ahn Kook Jin , Kang Hang-Bong , Choi Jung-Seok , Chun Ji-Won , Kim Dai-Jin
Published: April 2017

Adaptive gaming use has positive effects, whereas depression has been reported to be prevalent in Internet gaming disorder (IGD). However, the neural correlates underlying the association between depression and Internet gaming remain unclear. Moreover, the neuroanatomical profile of the striatum in IGD is relatively less clear despite its important role in addiction. We found lower gray matter (GM) density in the left dorsolateral prefrontal cortex (DLPFC) in the IGD group than in the Internet gaming control (IGC) group and non-gaming control (NGC) group, and the GM density was associated with lifetime usage of Internet gaming, depressed mood, craving, and impulsivity in the gaming users. Striatal volumetric analysis detected a significant reduction in the right nucleus accumbens (NAcc) in the IGD group and its association with lifetime usage of gaming and depression. These findings suggest that alterations in the brain structures involved in the reward system are associated with IGD-related behavioral characteristics. Furthermore, the DLPFC, involved in cognitive control, was observed to serve as a mediator in the association between prolonged gaming and depressed mood. This finding may provide insight into an intervention strategy for treating IGD with comorbid depression.