bluuebunny/crossref_metadata_2025 huggingface dataset:
Interface-resolved simulations of particle suspensions in Newtonian, shear thinning and shear thickening carrier fluids
Authors: Alghalibi Dhiya , Lashgari Iman , Brandt Luca , Hormozi Sarah
Published: August 2018

We present a numerical study of non-colloidal spherical and rigid particles suspended in Newtonian, shear thinning and shear thickening fluids employing an immersed boundary method. We consider a linear Couette configuration to explore a wide range of solid volume fractions ($0.1\leqslant \unicode[STIX]{x1D6F7}\leqslant 0.4$) and particle Reynolds numbers ($0.1\leqslant Re_{p}\leqslant 10$). We report the distribution of solid and fluid phase velocity and solid volume fraction and show that close to the boundaries inertial effects result in a significant slip velocity between the solid and fluid phase. The local solid volume fraction profiles indicate particle layering close to the walls, which increases with the nominal $\unicode[STIX]{x1D6F7}$. This feature is associated with the confinement effects. We calculate the probability density function of local strain rates and compare the latter’s mean value with the values estimated from the homogenisation theory of Chateau et al. (J. Rheol., vol. 52, 2008, pp. 489–506), indicating a reasonable agreement in the Stokesian regime. Both the mean value and standard deviation of the local strain rates increase primarily with the solid volume fraction and secondarily with the $Re_{p}$. The wide spectrum of the local shear rate and its dependency on $\unicode[STIX]{x1D6F7}$ and $Re_{p}$ point to the deficiencies of the mean value of the local shear rates in estimating the rheology of these non-colloidal complex suspensions. Finally, we show that in the presence of inertia, the effective viscosity of these non-colloidal suspensions deviates from that of Stokesian suspensions. We discuss how inertia affects the microstructure and provide a scaling argument to give a closure for the suspension shear stress for both Newtonian and power-law suspending fluids. The stress closure is valid for moderate particle Reynolds numbers, $O(Re_{p})\sim 10$.
Information Equivalence in Survey Experiments
Authors: Dafoe Allan , Zhang Baobao , Caughey Devin
Published: August 2018

Survey experiments often manipulate the description of attributes in a hypothetical scenario, with the goal of learning about those attributes’ real-world effects. Such inferences rely on an underappreciated assumption: experimental conditions must be information equivalent (IE) with respect to background features of the scenario. IE is often violated because subjects, when presented with information about one attribute, update their beliefs about others too. Labeling a country “a democracy,” for example, affects subjects’ beliefs about the country’s geographic location. When IE is violated, the effect of the manipulation need not correspond to the quantity of interest (the effect of beliefs about the focal attribute). We formally define the IE assumption, relating it to the exclusion restriction in instrumental-variable analysis. We show how to predict IE violations ex ante and diagnose them ex post with placebo tests. We evaluate three strategies for achieving IE. Abstract encouragement is ineffective. Specifying background details reduces imbalance on the specified details and highly correlated details, but not others. Embedding a natural experiment in the scenario can reduce imbalance on all background beliefs, but raises other issues. We illustrate with four survey experiments, focusing on an extension of a prominent study of the democratic peace.
THE MEANING AND SIGNIFICANCE OF CONSCIENCE IN PRIVATE LAW
Authors: Agnew Sinéad
Published: August 2018

This article argues that the idea of conscience can play a useful, albeit limited and highly general, explanatory role in private law, if we have regard to two distinctive contexts in which it is used. First, it tells us something about how equitable obligations arise and reminds us that they directly enforce moral duties. Second, it conveys the message that the courts are reluctant to impose primary liabilities which restrict the exercise of legal rights absent a past or prospective breach of moral duty by the defendant. Without further explanation, the indiscriminate invocation of conscience in both contexts can lead to confusion and uncertainty, but if the distinction between obligation and liability is observed, the explanatory force of conscience in relation to each becomes clearer, and it plays a valuable role in bolstering the authority of private law.
ImprovedA1−A∞and Related Estimates for Commutators of Rough Singular Integrals
Authors: Rivera-Ríos Israel P.
Published: August 2018

AnA1−A∞estimate, improving on a previous result for [b, TΩ] with$\Omega \in L^{infty}({\open S}^{n - 1})$andb∈BMO is obtained. A new result in terms of theA∞constant and the one supremumAq−A∞expconstant is also proved, providing a counterpart for commutators of the result obtained by Li. Both of the preceding results rely upon a sparse domination result in terms of bilinear forms, which is established using techniques from Lerner.
Symmetric Bi-Skew Maps and Symmetrized Motion Planning in Projective Spaces
Authors: González Jesús
Published: August 2018

This work is motivated by the question of whether there are spacesXfor which the Farber–Grant symmetric topological complexity TCS(X) differs from the Basabe–González–Rudyak–Tamaki symmetric topological complexity TCΣ(X). For a projective space${\open R}\hbox{P}^m$, it is known that$\hbox{TC}^S ({\open R}\hbox{P}^{m})$captures, with a few potential exceptional cases, the Euclidean embedding dimension of${\open R}\hbox{P}^{m}$. We now show that, for allm≥1,$\hbox{TC}^{\Sigma}({\open R}\hbox{P}^{m})$is characterized as the smallest positive integernfor which there is a symmetric${\open Z}_{2}$-biequivariant mapSm×Sm→Snwith a ‘monoidal’ behaviour on the diagonal. This result thus lies at the core of the efforts in the 1970s to characterize the embedding dimension of real projective spaces in terms of the existence of symmetric axial maps. Together with Nakaoka's description of the cohomology ring of symmetric squares, this allows us to compute both TC numbers in the case of${\open R}\hbox{P}^{2^{e}}$fore≥1. In particular, this leaves the torusS1×S1as the only closed surface whose symmetric (symmetrized) TCS(TCΣ) invariant is currently unknown.
THE SHAPE OF ASPIRATION: CLANDESTINE MASONRY HOUSE CONSTRUCTION IN LOURENÇO MARQUES, MOZAMBIQUE (1960–75)
Authors: MORTON DAVID
Published: August 2018

This article argues for the importance of including the construction of informal housing in histories of the African built environment. It examines the proliferation of illegally built masonry houses in the unplanned, predominately African neighborhoods of Lourenço Marques (today's Maputo) during the last years of Portuguese rule. Officials tolerated reed construction in these neighborhoods, but they saw unauthorized permanent construction there as an obstacle to the expansion of the formalized, predominately European city core. These ‘modern’ masonry houses, however, embodied some of the highest aspirations of their builders – aspirations that increasingly overlapped with those of lower-income whites that lived in such close proximity. Racial politics was manifested as material politics as clandestine construction challenged the divisions that had long defined the city. Informal housing thus helps to illuminate some of the peculiarities of race in urban lusophone Africa during the last years of colonial rule, a period usually understood in terms of wars for independence, but that in cities were also years of surging economies and the rising expectations of many African workers.
Asymmetry in Stock Comovements: An Entropy Approach
Authors: Jiang Lei , Wu Ke , Zhou Guofu
Published: August 2018

We provide an entropy approach for measuring the asymmetric comovement between the return on a single asset and the market return. This approach yields a model-free test for stock return asymmetry, generalizing the correlation-based test proposed by Hong, Tu, and Zhou (2007). Based on this test, we find that asymmetry is much more pervasive than previously thought. Moreover, our approach also provides an entropy-based measure of downside asymmetric comovement. In the cross section of stock returns, we find an asymmetry premium: Higher downside asymmetric comovement with the market indicates higher expected returns.
Technological Specialization and the Decline of Diversified Firms
Authors: Anjos Fernando , Fracassi Cesare
Published: August 2018

We document a strong decline in corporate-diversification activity since the late 1970s, and we develop a dynamic model that explains this pattern, both qualitatively and quantitatively. The key feature of the model is that synergies endogenously decline with technological specialization, leading to fewer diversified firms in equilibrium. The model further predicts that segments inside a conglomerate should become more related over time, which is consistent with the data. Finally, the calibrated model also matches other empirical magnitudes well: output growth rate, market-to-book ratios, diversification discount, frequency and returns of diversifying mergers, and frequency of refocusing activity.
Clipping of sigmoid sinus diverticulum: how I do it
Authors: Hassannia F , Carr S D , Busato G-M , Rutka J A
Published: August 2018

Objective

To report two cases of transmastoid clipping of a sigmoid sinus diverticulum.

Methods

Two patients with pulsatile tinnitus resulting from a sigmoid sinus diverticulum underwent clipping at the diverticulum neck using intra-operative Doppler ultrasonography.

Results

At six months’ follow up, both patients reported complete resolution of pulsatile tinnitus with no complications.

Conclusion

Transmastoid clipping of a sigmoid sinus diverticulum can be a safe and effective method of managing pulsatile tinnitus resulting from a sigmoid sinus diverticulum.
Marking imprecision, conveying surprise:Likebetween hedging and mirativity
Authors: BELTRAMA ANDREA , HANINK EMILY A.
Published: August 2018

Mirativeexpressions, which mark surprising information (DeLancey 1997), are often expressed through linguistic forms that are also used to encode other, seemingly unrelated, meanings – e.g. evidential markers that mark lack of direct evidence (Turkish: Slobin & Aksu 1982, Peterson 2010; Cheyenne: Rett & Murray 2013; Cuzco Quechua: Faller 2002; Ostyak: Nikolaeva 1999; among others). In this paper, we show that the English particlelikefeatures a parallel polysemy between a mirative use and its better-knownhedginguse, which expresses weakened commitment to the strict denotation of a linguistic expression. After presenting several diagnostics that point to a genuine empirical difference between the hedging and mirative functions oflike, we propose that both uses widen the size of a contextually restricted set, admitting elements that were previously excluded. More specifically, hedginglikeexpands the set of ‘similar enough’ interpretations that we can apply to a linguistic expression in a context, including interpretations that we would normally consider to be too different from the context at hand. Mirativelike, on the other hand, expands the set of worlds that we are willing to consider as candidates for the actual world in the conversation, resulting in the inclusion of worlds that interlocutors have previously ruled out due to perceived outlandishness. We therefore suggest that the two uses are best treated as sharing a common semantic kernel, deriving hedging and mirativity as effects of the particular type of object to whichlikeapplies.
NotCensusbutDeductio: Reconsidering the ‘Araof Domitius Ahenobarbus’
Authors: Maschek Dominik
Published: August 2018

Since its rediscovery in the late nineteenth century, the ‘Araof Domitius Ahenobarbus’ has become a keystone in the history of Roman republican art. Following the seminal interpretation of Alfred von Domaszewski, the monument is usually understood as commemorating the key stages of the Roman census. This paper offers a fundamental reappraisal of theAra's imagery, based on an iconographic analysis which takes into account all relevant signs of rank and status such as shoes, clothing and other attributes. From this it becomes clear that none of the three protagonists on theAracan be identified as a censor. Consequently, the monument neither commemorated a census nor was it a censorial location. Instead, I suggest that theAraactually shows another important political event, namely thedeductioof a Roman colony which I tentatively identify as thecolonia Neptuniafounded by Gaius Gracchus in 123b.c.
Left to right: labour market policy, labour market status and political affinities
Authors: Meyer Brett
Published: August 2018

In recent decades, there has been a gradual decline in working-class organisations, including social democratic parties and trade unions, and an increase in support for populist radical right parties across western democracies. These trends have a plausible common cause: an increase in labour market insecurity associated with deindustrialisation may cause disenchantment with establishment organisations and support for politicians who criticise them. In this article, I examine how individual labour market status interacts with labour market policies to affect attitudes towards trade unions and populist radical right parties. I find that individuals with insecure employment status become less likely to support trade unions and more likely to support populist radical right parties as employment protection for secure workers increases. This effect is offset somewhat by spending on active labour market policies. I find evidence for these predictions in data for 27 Organisation for Economic Co-Operation and Development countries from 1995 to 2009.
Effect of pre-plasma on the ion acceleration by intense ultra-short laser pulses
Authors: Varmazyar Parvin , Mirzanejhad Saeed , Mohsenpour Taghi
Published: August 2018

In the interaction of short-laser pulses with a solid density target, pre-plasma can play a major role in ion acceleration processes. So far, complete analysis of pre-plasma effect on the ion acceleration by ultra-short laser pulses in the radiation pressure acceleration (RPA) regime has been unknown. Then the effect of pre-plasma on the ion acceleration efficiency is analyzed by numerical results of the particle-in-cell simulation in the RPA regime. It is shown that, for long-laser pulses (τp > 50 fs), the presence of pre-plasma makes a destructive effect on ion acceleration while it may have a contributing effect for short-laser pulses (τp < 50 fs). Therefore, the 35 fs (20 fs) laser pulse can accelerate ions up to 40 MeV (55 eV), which is almost two (three) times larger in energy rather than use of a 100 fs pulse with the same pre-plasma scale length.
Spatiotemporal analysis and forecasting model of hemorrhagic fever with renal syndrome in mainland China
Authors: Sun Ling , Zou Lu-Xi
Published: August 2018

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses is a serious public health problem in China, accounting for 90% of HFRS cases reported globally. In this study, we applied geographical information system (GIS), spatial autocorrelation analyses and a seasonal autoregressive-integrated moving average (SARIMA) model to describe and predict HFRS epidemic with the objective of monitoring and forecasting HFRS in mainland China. Chinese HFRS data from 2004 to 2016 were obtained from National Infectious Diseases Reporting System (NIDRS) database and Chinese Centre for Disease Control and Prevention (CDC). GIS maps were produced to detect the spatial distribution of HFRS cases. The Moran'sIwas adopted in spatial global autocorrelation analysis to identify the integral spatiotemporal pattern of HFRS outbreaks, while the local Moran'sIiwas performed to identify ‘hotspot’ regions of HFRS at province level. A fittest SARIMA model was developed to forecast HFRS incidence in the year 2016, which was selected by Akaike information criterion and Ljung–Box test. During 2004–2015, a total of 165 710 HFRS cases were reported with the average annual incidence at province level ranged from 0 to 13.05 per 100 000 persons. Global Moran'sIanalysis showed that the HFRS outbreaks presented spatially clustered distribution, with the degree of cluster gradually decreasing from 2004 to 2009, then turned out to be randomly distributed and reached lowest point in 2012. Local Moran'sIiidentified that four provinces in northeast China contributed to a ‘high–high’ cluster as a traditional epidemic centre, and Shaanxi became another HFRS ‘hotspot’ region since 2011. The monthly incidence of HFRS decreased sharply from 2004 to 2009 in mainland China, then increased markedly from 2010 to 2012, and decreased again since 2013, with obvious seasonal fluctuations. The SARIMA ((0,1,3) × (1,0,1)12) model was the most fittest forecasting model for the dataset of HFRS in mainland China. The spatiotemporal distribution of HFRS in mainland China varied in recent years; together with the SARIMA forecasting model, this study provided several potential decision supportive tools for the control and risk-management plan of HFRS in China.
Improving measles incidence inference using age-structured serological data
Authors: Prada Joaquin M. , Metcalf C. Jessica E. , Ferrari Matthew J.
Published: August 2018

Measles is a target for elimination in all six WHO regions by 2020, and over the last decade, there has been considerable progress towards this goal. Surveillance is recognised as a cornerstone of elimination programmes, allowing early identification of outbreaks, thus enabling control and preventing re-emergence. Fever–rash surveillance is increasingly available across WHO regions, and this symptom-based reporting is broadly used for measles surveillance. However, as measles control increases, symptom-based cases are increasingly likely to reflect infection with other diseases with similar symptoms such as rubella, which affects the same populations, and can have a similar seasonality. The WHO recommends that cases from suspected measles outbreaks be laboratory-confirmed, to identify ‘true’ cases, corresponding to measles IgM titres exceeding a threshold indicative of infection. Although serological testing for IgM has been integrated into the fever–rash surveillance systems in many countries, the logistics of sending in every suspected case are often beyond the health system's capacity. We show how age data from serologically confirmed cases can be leveraged to infer the status of non-tested samples, thus strengthening the information we can extract from symptom-based surveillance. Applying an age-specific confirmation model to data from three countries with divergent epidemiology across Africa, we identify the proportion of cases that need to be serologically tested to achieve target levels of accuracy in estimated infected numbers and discuss how this varies depending on the epidemiological context. Our analysis provides an approach to refining estimates of incidence leveraging all available data, which has the potential to improve allocation of resources, and thus contribute to rapid and efficient control of outbreaks.
Swarna × Oryza nivara introgression lines: a resource for seedling vigour traits in rice
Authors: Addanki Krishnam Raju , Balakrishnan Divya , Yadavalli Venkateswara Rao , Surapaneni Malathi , Mesapogu Sukumar , Beerelli Kavitha , Neelamraju Sarla
Published: August 2018

Seedling vigour is an important indicator of crop establishment, subsequent crop growth and yield. Initial seedling vigour is most vital in case of water-limited conditions and in environments where the crop is exposed to different stresses at the early growth stage. Wild and weedy species are well known for their vigour and survival in adverse environmental conditions. Seedling vigour traits of backcross introgression lines (BILs) derived from Swarna × Oryza nivara IRGC81848(S) (accession from Uttar Pradesh, India) and IRGC81832 (K) (accession from Bihar, India) were studied in wet (Kharif) and dry (Rabi) seasons. Seedling vigour was estimated in terms of plant height and tiller number at 30 and 60 d after transplanting under field conditions. In both the seasons, 148S showed highest seedling vigour for plant height. The highest number of tillers were produced by 7K in Kharif and 248S in Rabi season. 75S showed the highest percentage increase in tiller number consistently. High yielding BILs 166S, 14S and 148S showed higher seedling vigour indices compared with checks Tulasi and Sahbhagidhan. Seedling vigour was also evaluated using paper roll method and shoot length, root length and dry weight were used to estimate vigour index. Season-wise association studies were conducted to determine the relative contribution of seedling vigour to yield traits. Seedling vigour was significantly correlated with yield traits. Markers RM217 and RM253 on chromosome 6 differentiated lines with high seedling vigour from those with low seedling vigour and have the potential for use in marker-assisted breeding.
ILB 938, a valuable faba bean (Vicia faba L.) accession
Authors: Khazaei H. , Link W. , Street K. , Stoddard F. L.
Published: August 2018

Here we review the potential of ILB 938 (IG 12132 – doi: 10.18730/60FD2), a unique faba bean accession originating from the Andean region of Colombia and Ecuador, maintained at ICARDA – International Center for Agricultural Research in the Dry Areas, with resistance to multiple biotic and abiotic stresses and carrying some useful morphological markers. It has been used as a donor of leaf-related drought adaptation traits and chocolate spot (Botrytis fabae) resistance genes in faba bean breeding programmes worldwide. From generated populations of recombinant inbred lines, quantitative traits loci associated with these useful traits have been mapped. Other markers, such as a lack of stipule-spot pigmentation and clinging pod wall, show the presence of unusual changes in biochemical pathways that may have economic value in the future.
Feminist Cringe Comedy: Dear Dick, The Joke Is on You
Authors: Marso Lori
Published: August 2018

Feminist cringe comedies eschew the conventions of romance and sentimentality in favor of comedy that discomforts. Cringe comedies are one example of what I call feminism's visual realisms, so named for doing feminist political work by evoking laughter and the cringe. The cringe pulls us inward in our posture, while laughter opens us to others. This bodily response to cringe comedies interrupts the fantasies of the male gaze and makes space for spectators to acknowledge the excessive, complicated, and seemingly shameful realities of female desire. My primary example is Jill Soloway's television adaptation of Chris Kraus's I Love Dick, a series that builds on the feminist legacy of avant-garde director Catherine Breillat. Departing from politically correct narratives and comforting or sentimental affect, I Love Dick achieves feminist community through the appeal, the cringe, and the irruption of laughter.
Changes in socioeconomic position among individuals with mental disorders during the economic recession in Portugal: a follow-up of the National Mental Health Survey
Authors: Antunes A. , Frasquilho D. , Azeredo-Lopes S. , Silva M. , Cardoso G. , Caldas-de-Almeida J. M.
Published: August 2018

Aims

Portugal was one of the European countries most affected by the period of economic recession initiated in 2008. Social inequalities are likely to widen during such periods and disproportionately affect people with mental disorders. The present study aims to compare self-reported changes in indicators of socioeconomic position during the economic recession in Portugal among people with and without mental disorders in the beginning of this period. Three dimensions were assessed, namely employment situation, experiences of financial hardship and subjective social status.

Methods

Data from the World Mental Health Survey Initiative Portugal (2008/2009) and from the National Mental Health Survey Follow-up (2015/2016) were used (n = 911). Multinomial and logistic recession models were performed to examine the association between the presence of any 12-month mood or anxiety mental disorder in 2008/2009 and indicators of socioeconomic position in 2015/2016. All analyses were adjusted for gender, age, presence of any physical disorder and education at the baseline.

Results

Participants that had any mental disorder in the beginning of the economic recession reported 2.20 (95% CI 1.31–3.71; P < 0.01) higher odds of financial hardship related to daily life in 2015/2016, when compared with those without any mental disorder, after adjusting for age, gender, education and presence of any physical disorder. The results may also suggest a pattern of increased socioeconomic disadvantage among people with prior mental disorder, despite not reaching statistical significance.

Conclusions

The results of this study suggest that the economic recession may have contributed to wider social inequalities between people with and without mental disorders. Policies to support these individuals, such as access to treatment and alleviation of financial hardship, should be a priority in times of economic downturn.
Effect of tuning capacitance of passive power repeaters on power transfer capability of inductive power transfer systems
Authors: Hua Rong , Hu Aiguo Patrick
Published: August 2018

Power repeaters are used to extend the power transfer range or enhance the power transfer capability of Inductive Power Transfer (IPT) systems, but how to tune the power repeaters to improve the system power transfer performance remains an unsolved problem. In this paper, studies of the effect of the tuning capacitance of the power repeater of an IPT system on the power transfer capability are presented. A theoretical model is established to analyze the output power of the system with the primary coil and secondary coil tuned at a nominal resonant frequency, and a passive power repeater placed in between. By analyzing the relationship between the tuning capacitance of the power repeater and the output power, a critical tuning capacitance which sets up the boundary between enhancing and reducing the output power is determined, and the optimal tuning capacitances corresponding to the maximum and minimum output power are also obtained. A practical IPT system with a passive power repeater placed at 40, 80, and 104 mm from the primary coil is built. It has shown that the practically measured critical capacitance and the optimal tuning capacitance for maximum power transfer are in good agreement with the analytical results.
Neuropsychiatrische Manifestationen bei Tuberöser Sklerose (TSC): Diagnostische Leitlinien, TAND-Konzept und Therapie mit mTOR-Inhibitoren
Authors: Waltereit Robert , Feucht Martha , de Vries Magdalena C. , Huemer Julia , Roessner Veit , de Vries Petrus J.
Published: August 2018

Zusammenfassung. Obwohl insgesamt selten („orphan disease“ mit einer Inzidenz von 1:6000), ist die Tuberöse Sklerose (TSC) eine der häufigsten monogenetisch bedingten Erkrankungen mit Bedeutung für die Kinder- und Jugendpsychiatrie. TSC führt bei bis zu 90 % der Betroffenen zu neurologischen Störungen wie Epilepsie und ebenfalls bei bis zu 90 % zu psychiatrischen Manifestationen wie Autismus-Spektrum-Störungen, Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung, affektiven Störungen und Intelligenzminderung. In den letzten Jahren wurden sowohl zum Verständnis des molekularen Pathomechanismus der Erkrankung als auch zu Diagnostik und Behandlung erhebliche Fortschritte erzielt. Die vorliegende Übersichtsarbeit stellt diese aktuellen Entwicklungen dar. Im ersten Abschnitt zeigen wir den Bedarf an psychiatrischer Diagnostik und Begleitung von Patienten mit TSC auf und behandeln Herausforderungen und Schwierigkeiten in der interdisziplinären Zusammenarbeit zwischen Kinder- und Jugendpsychiatrie, Neuropädiatrie und anderen Berufsgruppen. Im zweiten Teil stellen wir das Konzept der TSC-assoziierten neuropsychiatrischen Störungen (TAND) vor, das von einer internationalen Expertengruppe entwickelt wurde, um Kliniker, Familien und Betroffene in der Diagnostik und Behandlung psychiatrischer Symptome und Störungen zu unterstützen, sowie ein neuartiges Screeninginstrument (TAND-Checkliste). Schließlich geben wir einen Überblick über kürzlich publizierte Studien bezüglich möglicher Krankheitsmodifikation der neuropsychiatrischen Manifestationen mittels mTOR-Inhibitoren. Die deutsche Übersetzung der TAND-Checkliste ist dem Artikel als elektronisches Supplement (ESM) beigefügt.
Knockdown of FOXA2 enhances the osteogenic differentiation of bone marrow-derived mesenchymal stem cells partly via activation of the ERK signalling pathway
Authors: Ye Chenyi , Chen Mo , Chen Erman , Li Weixu , Wang Shengdong , Ding Qianhai , Wang Cong , Zhou Chenhe , Tang Lan , Hou Weiduo , Hang Kai , He Rongxin , Pan Zhijun , Zhang Wei
Published: August 2018

Forkhead box protein A2 (FOXA2) is a core transcription factor that controls cell differentiation and may have an important role in bone metabolism. However, the role of FOXA2 during osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains largely unknown. In this study, decreased expression of FOXA2 was observed during osteogenic differentiation of rat BMSCs (rBMSCs). FOXA2 knockdown significantly increased osteoblast-specific gene expression, the number of mineral deposits and alkaline phosphatase activity, whereas FOXA2 overexpression inhibited osteogenesis-specific activities. Moreover, extracellular signal-regulated protein kinase (ERK) signalling was upregulated following knockdown of FOXA2. The enhanced osteogenesis due to FOXA2 knockdown was partially rescued by an ERK inhibitor. Using a rat tibial defect model, a rBMSC sheet containing knocked down FOXA2 significantly improved bone healing. Collectively, these findings indicated that FOXA2 had an essential role in osteogenic differentiation of BMSCs, partly by activation of the ERK signalling pathway.
Correction to: Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma
Authors: Wei Shuang , Zhang Zun-yi , Fu Sheng-ling , Xie Jun-gang , Liu Xian-sheng , Xu Yong-jian , Zhao Jian-ping , Xiong Wei-ning
Published: August 2018

Following publication of their article, the authors noticed that there were minor errors in Figs. 3, 7 and S5. The errors had no effect on the scientific content or conclusions. The rectified figures are given below.
Transdifferentiation: a new promise for neurodegenerative diseases
Authors: Mollinari Cristiana , Zhao Jian , Lupacchini Leonardo , Garaci Enrico , Merlo Daniela , Pei Gang
Published: August 2018

Neurodegenerative diseases are characterized by a gradual loss of cognitive and physical functions. Medications for these disorders are limited and treat the symptoms only. There are no disease-modifying therapies available, which have been shown to slow or stop the continuing loss of neurons. Transdifferentiation, whereby somatic cells are reprogrammed into another lineage without going through an intermediate proliferative pluripotent stem cell stage, provides an alternative strategy for regenerative medicine and disease modeling. In particular, the transdifferentiation of somatic cells into specific subset of patient-specific neuronal cells offers alternative autologous cell therapeutic strategies for neurodegenerative disorders and presents a rich source of using diverse somatic cell types for relevant applications in translational, personalized medicine, as well as human mechanistic study, new drug-target identification, and novel drug screening systems. Here, we provide a comprehensive overview of the recent development of transdifferentiation research, with particular attention to chemical-induced transdifferentiation and perspectives for modeling and treatment of neurodegenerative diseases.
Somatic loss of WWOX is associated with TP53 perturbation in basal-like breast cancer
Authors: Abdeen Suhaib K. , Ben-David Uri , Shweiki Aya , Maly Bella , Aqeilan Rami I.
Published: August 2018

Inactivation of WW domain-containing oxidoreductase (WWOX), the gene product of the common fragile site FRA16D, is a common event in breast cancer and is associated with worse prognosis of triple-negative breast cancer (TNBC) and basal-like breast cancer (BLBC). Despite recent progress, the role of WWOX in driving breast carcinogenesis remains unknown. Here we report that ablation of Wwox in mammary tumor-susceptible mice results in increased tumorigenesis, and that the resultant tumors resemble human BLBC. Interestingly, copy number loss of Trp53 and downregulation of its transcript levels were observed in the Wwox knockout tumors. Moreover, tumors isolated from Wwox and Trp53 mutant mice were indistinguishable histologically and transcriptionally. Finally, we find that deletion of TP53 and WWOX co-occurred and is associated with poor survival of breast cancer patients. Altogether, our data uncover an essential role for WWOX as a bona fide breast cancer tumor suppressor through the maintenance of p53 stability.
Downregulated circulating microRNAs after surgery: potential noninvasive biomarkers for diagnosis and prognosis of early breast cancer
Authors: Wang Yaohui , Yin Wenjin , Lin Yanping , Yin Kai , Zhou Liheng , Du Yueyao , Yan Tingting , Lu Jinsong
Published: August 2018

Success in curing breast cancer largely depends on the stage at diagnosis. Circulating microRNAs are becoming a promising noninvasive biomarker. We postulate that a postoperative decline in circulating microRNAs might have diagnostic and prognostic value. Applying high-throughput microarrays, we screened the dysregulated microRNAs in paired serum samples before and after surgery. The relative concentrations of putative markers between the early breast cancer and cancer-free groups were evaluated in the training set and verified in the validation set. Sensitivity, specificity, and receiver operating characteristic (ROC) curves were used to assess diagnostic value. Survival analysis was performed using Kaplan–Meier estimates and a Cox proportional hazards model. Five microRNAs significantly reduced after surgery were selected for the training set. We found that miR-130b-5p, miR-151a-5p, miR-206, and miR-222-3p were significantly higher in the breast cancer group. Each of the four microRNAs had potential diagnostic value. The combined four microRNAs (training set: area under the curve (AUC) 0.8457; validation set: AUC 0.9309) had better diagnostic value than each single microRNA. MiR-222-3p was an independent prognostic factor for disease-free survival (HR = 13.19; 95% CI, 1.06–163.59; P = 0.045). Patients with no fewer than three highly expressed miRNAs had shorter DFS than patients with 0–2 highly expressed miRNAs (HR = 2.293; 95% CI, 1.128–0.662; P = 0.022). Our findings indicate that postoperatively downregulated circulating miR-130b-5p, miR-151a-5p, miR-206, and miR-222-3p may be potential biomarkers for breast cancer diagnosis and prognosis.
Programmed cell removal by calreticulin in tissue homeostasis and cancer
Authors: Feng Mingye , Marjon Kristopher D. , Zhu Fangfang , Weissman-Tsukamoto Rachel , Levett Aaron , Sullivan Katie , Kao Kevin S. , Markovic Maxim , Bump Paul A. , Jackson Hannah M. , Choi Timothy S. , Chen Jing , Banuelos Allison M. , Liu Jie , Gip Phung , Cheng Lei , Wang Denong , Weissman Irving L.
Published: August 2018

Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to “labeling” by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes.
Iron-based trinuclear metal-organic nanostructures on a surface with local charge accumulation
Authors: Krull Cornelius , Castelli Marina , Hapala Prokop , Kumar Dhaneesh , Tadich Anton , Capsoni Martina , Edmonds Mark T. , Hellerstedt Jack , Burke Sarah A. , Jelinek Pavel , Schiffrin Agustin
Published: August 2018

Coordination chemistry relies on harnessing active metal sites within organic matrices. Polynuclear complexes—where organic ligands bind to several metal atoms—are relevant due to their electronic/magnetic properties and potential for functional reactivity pathways. However, their synthesis remains challenging; few geometries and configurations have been achieved. Here, we synthesise—via supramolecular chemistry on a noble metal surface—one-dimensional metal-organic nanostructures composed of terpyridine (tpy)-based molecules coordinated with well-defined polynuclear iron clusters. Combining low-temperature scanning probe microscopy and density functional theory, we demonstrate that the coordination motif consists of coplanar tpyʼs linked via a quasi-linear tri-iron node in a mixed (positive-)valence metal–metal bond configuration. This unusual linkage is stabilised by local accumulation of electrons between cations, ligand and surface. The latter, enabled by bottom-up on-surface synthesis, yields an electronic structure that hints at a chemically active polynuclear metal centre, paving the way for nanomaterials with novel catalytic/magnetic functionalities.
The silicon cycle impacted by past ice sheets
Authors: Hawkings Jon R. , Hatton Jade E. , Hendry Katharine R. , de Souza Gregory F. , Wadham Jemma L. , Ivanovic Ruza , Kohler Tyler J. , Stibal Marek , Beaton Alexander , Lamarche-Gagnon Guillaume , Tedstone Andrew , Hain Mathis P. , Bagshaw Elizabeth , Pike Jennifer , Tranter Martyn
Published: August 2018

Globally averaged riverine silicon (Si) concentrations and isotope composition (δ30Si) may be affected by the expansion and retreat of large ice sheets during glacial−interglacial cycles. Here we provide evidence of this based on the δ30Si composition of meltwater runoff from a Greenland Ice Sheet catchment. Glacier runoff has the lightest δ30Si measured in running waters (−0.25 ± 0.12‰), significantly lower than nonglacial rivers (1.25 ± 0.68‰), such that the overall decline in glacial runoff since the Last Glacial Maximum (LGM) may explain 0.06–0.17‰ of the observed ocean δ30Si rise (0.5–1.0‰). A marine sediment core proximal to Iceland provides further evidence for transient, low-δ30Si meltwater pulses during glacial termination. Diatom Si uptake during the LGM was likely similar to present day due to an expanded Si inventory, which raises the possibility of a feedback between ice sheet expansion, enhanced Si export to the ocean and reduced CO2 concentration in the atmosphere, because of the importance of diatoms in the biological carbon pump.
Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells
Authors: Wu Changjie , Lyu Junfang , Yang Eun Ju , Liu Yifan , Zhang Baoyuan , Shim Joong Sup
Published: August 2018

ARID1A, a component of the SWI/SNF chromatin remodeling complex, is a tumor suppressor with a high frequency of inactivating mutations in many cancers. Therefore, ARID1A deficiency has been exploited therapeutically for treating cancer. Here we show that ARID1A has a synthetic lethal interaction with aurora kinase A (AURKA) in colorectal cancer (CRC) cells. Pharmacological and genetic perturbations of AURKA selectively inhibit the growth of ARID1A-deficient CRC cells. Mechanistically, ARID1A occupies the AURKA gene promoter and negatively regulates its transcription. Cells lacking ARID1A show enhanced AURKA transcription, which leads to the persistent activation of CDC25C, a key protein for G2/M transition and mitotic entry. Inhibiting AURKA activity in ARID1A-deficient cells significantly increases G2/M arrest and induces cellular multinucleation and apoptosis. This study shows a novel synthetic lethality interaction between ARID1A and AURKA and indicates that pharmacologically inhibiting the AURKA–CDC25C axis represents a novel strategy for treating CRC with ARID1A loss-of-function mutations.
Beneficial effects of climate warming on boreal tree growth may be transitory
Authors: D’Orangeville Loïc , Houle Daniel , Duchesne Louis , Phillips Richard P. , Bergeron Yves , Kneeshaw Daniel
Published: August 2018

Predicted increases in temperature and aridity across the boreal forest region have the potential to alter timber supply and carbon sequestration. Given the widely-observed variation in species sensitivity to climate, there is an urgent need to develop species-specific predictive models that can account for local conditions. Here, we matched the growth of 270,000 trees across a 761,100 km2 region with detailed site-level data to quantify the growth responses of the seven most common boreal tree species in Eastern Canada to changes in climate. Accounting for spatially-explicit species-specific responses, we find that while 2 °C of warming may increase overall forest productivity by 13 ± 3% (mean ± SE) in the absence of disturbance, additional warming could reverse this trend and lead to substantial declines exacerbated by reductions in water availability. Our results confirm the transitory nature of warming-induced growth benefits in the boreal forest and highlight the vulnerability of the ecosystem to excess warming and drying.
Author Correction: Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes
Authors: Rheaume Bruce A. , Jereen Amyeo , Bolisetty Mohan , Sajid Muhammad S. , Yang Yue , Renna Kathleen , Sun Lili , Robson Paul , Trakhtenberg Ephraim F.
Published: August 2018

The original version of the Supplementary Information file associated with this Article contained an error in Supplementary Fig. 2. In panel c, the graph was inadvertently replaced with a duplicate of the graph in panel a. The error has now been fixed and the corrected version Supplementary Information PDF is available to download from the HTML version of the Article.
Author Correction: Redox-active conducting polymers modulate Salmonella biofilm formation by controlling availability of electron acceptors
Authors: Gomez-Carretero Salvador , Libberton Ben , Svennersten Karl , Persson Kristin , Jager Edwin , Berggren Magnus , Rhen Mikael , Richter-Dahlfors Agneta
Published: August 2018

In the original published article, the author list did not include Karl Svennersten, Kristin Persson, Edwin Jager and Magnus Berggren. After publication, we were notified by the corresponding author that the author list did not accurately reflect the contributions made, and these authors have been added to the author list. The original “Author Contributions” stated that “S.G.C., M.R., and A.R.D. designed research; S.G.C. performed all experiments…” this has been updated to read “S.G.C., K.S., K.M.P., E.W.H.J., M.B., M.R., and A.R.D. designed research; K.S., K.M.P., and E.W.H.J. performed experiments; S.G.C. performed all reported experiments…”. The “Acknowledgements” previously read “We thank K. Svennersten, A. Kader, K. Persson, and M. Berggren for fruitful discussions, and S. Löffler for insightful comments on the manuscript…” and have been updated to state “We thank A. Kader for fruitful discussions and S. Loffler for insightful comments on the manuscript…”. The “Competing Interests” section did not require any amendments. All authors have agreed with this correction statement and authorship change.
The physical, mental, and social impact of COPD in a population-based sample: results from the Longitudinal Aging Study Amsterdam
Authors: Franssen Frits M. E. , Smid Dionne E. , Deeg Dorly J. H. , Huisman Martijn , Poppelaars Jan , Wouters Emiel F. M. , Spruit Martijn A.
Published: August 2018

Chronic obstructive pulmonary disease (COPD) is associated with substantial health impact that may already become apparent in early disease. This study aims to examine the features of subjects with COPD in a Dutch population-based sample and compare their physical status, mental status, and social status to non-COPD subjects. This study made use of Longitudinal Aging Study Amsterdam (LASA) data. Demographics, clinical characteristics, self-reported diseases, post-bronchodilator spirometry, physical, mental, and social status were assessed. A number of 810 subjects (50.5% male, mean age 60.5 ± 2.9 years) were included. Subjects with COPD (n = 68, mean FEV1 67.6 [IQR 60.4–80.4] %.) had a slower walking speed than non-COPD subjects, p = 0.033. When compared to non-COPD subjects, COPD subjects gave a lower rating on their health (physical subscale of SF-12: 15 [IQR 16.0–19.0] vs. 18 [IQR 11.0–17.0] points) and life (EQ5D VAS: 75 [IQR 70.0–90.0] vs. 80 points [IQR 65.0–85.5]) surveys. COPD subjects also had a more impaired disease-specific health status (CAT: 9.5 ± 5.9 vs. 6.7 ± 5.2, respectively), were less likely to have a partner (69% vs. 84%, respectively) and received emotional support less often (24% vs. 36%, respectively) compared to non-COPD subjects (All comparisons p < 0.001). In a population-based sample, subjects with COPD had a reduced physical performance, a more impaired disease-specific health status and were more socially deprived compared to non-COPD subjects. These impairments need to be taken into consideration when setting up a management program for patients with mild COPD.
Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy
Authors: Mahadeo Kris M. , Khazal Sajad J. , Abdel-Azim Hisham , Fitzgerald Julie C. , Taraseviciute Agne , Bollard Catherine M. , Tewari Priti , Duncan Christine , Traube Chani , McCall David , Steiner Marie E. , Cheifetz Ira M. , Lehmann Leslie E. , Mejia Rodrigo , Slopis John M. , Bajwa Rajinder , Kebriaei Partow , Martin Paul L. , Moffet Jerelyn , McArthur Jennifer , Petropoulos Demetrios , O’Hanlon Curry Joan , Featherston Sarah , Foglesong Jessica , Shoberu Basirat , Gulbis Alison , Mireles Maria E. , Hafemeister Lisa , Nguyen Cathy , Kapoor Neena , Rezvani Katayoun , Neelapu Sattva S. , Shpall Elizabeth J. ,   the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: August 2018

In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19+ acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care. Herein, authors representing the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Stem Cell Transplantation (HSCT) Subgroup and the MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program have collaborated to provide comprehensive consensus guidelines on the care of children receiving CAR T cell therapy.
Publisher Correction: Construction of a High-Density Genetic Map and Quantitative Trait Locus Mapping in the Manila clam Ruditapes philippinarum
Authors: Nie Hongtao , Yan Xiwu , Huo Zhongming , Jiang Liwen , Chen Peng , Liu Hui , Ding Jianfeng , Yang Feng
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.