bluuebunny/crossref_metadata_2025 huggingface dataset:
Losing time for the tigerPanthera tigris: delayed action puts a globally threatened species at risk of local extinction
Authors: Harihar Abishek , Ghosh-Harihar Mousumi , MacMillan Douglas C.
Published: November 2017

Meeting global and regional environmental targets is challenging, given the multiplicity of stakeholders and their diverse and often competing policy agendas and objectives. Relatively few studies have sought to systematically analyse the progress, or lack thereof, of institutionally complex and diffuse projects. Here we analyse one such project, which aims to protect and restore a critical landscape corridor for tigersPanthera tigrisin north-western India, using a temporal–analytic framework that integrates ecological information on species population status and spatial connectivity modelling with a systematic examination of the decision-making process. We find that even with adequate ecological knowledge the tiger population is on the verge of local extinction because of weak institutional support, poor adaptive planning and ineffective leadership in a complex political arena, which has led to delays in conservation action. From the outset the conservation agencies and NGOs that were the primary drivers of the project lacked awareness of the political idiosyncrasies of coordinating the actions of disparate agencies within the decision-making process. To secure better future environmental outcomes we recommend the adoption of an improved project appraisal methodology that explicitly encompasses an evaluation of organizational incentives, to determine political buy-in, including alignment with organizational objectives and funding availability.
High-sensitivity C-reactive protein and cognitive decline: the English Longitudinal Study of Ageing
Authors: Zheng Fanfan , Xie Wuxiang
Published: November 2017

Background

High-sensitivity C-reactive protein (hs-CRP) has been suggested to be involved in the process of cognitive decline. However, the results from previous studies exploring the relationship between hs-CRP concentration and cognitive decline are inconsistent.

Method

We employed data from wave 2 (2004–2005) to wave 7 (2014–2015) of the English Longitudinal Study of Ageing. Cognitive function was assessed at baseline (wave 2) and reassessed biennially at waves 3–7.

Results

A total of 5257 participants (54.9% women, mean age 65.4 ± 9.4 years) with baseline hs-CRP levels ranged from 0.2 to 210.0 mg/L (median: 2.0 mg/L, interquartile range: 0.9–4.1 mg/L) were studied. The mean follow-up duration was 8.1 ± 2.8 years, and the mean number of cognitive assessment was 4.9 ± 1.5. Linear mixed models show that a one-unit increment in natural log-transformed hs-CRP was associated with faster declines in global cognitive scores [−0.048 points/year, 95% confidence interval (CI) −0.072 to −0.023], memory scores (−0.022 points/year, 95% CI −0.031 to −0.013), and executive function scores (−0.025 points/year, 95% CI −0.043 to −0.006), after multivariable adjustment. Compared with the lowest quartile of hs-CRP, the multivariable-adjusted rate of global cognitive decline associated with the second, third, and highest quartile was faster by −0.043 points/year (95% CI −0.116 to 0.029), −0.090 points/year (95% CI −0.166 to −0.015), −0.145 (95% CI −0.221 to −0.069), respectively (pfor trend <0.001). Similarly, memory and executive function also declined faster with increasing quartiles of hs-CRP.

Conclusions

A significant association between hs-CRP concentration and long-term cognitive decline was observed in this study. Hs-CRP might serve as a biomarker for cognitive decline.
Drops of Greek in a Multilingual Sea: The Egyptian Network and its Residential Presences in the Indian Ocean
Authors: Andrade Nathanael J.
Published: November 2017

This article explores one of the remarkable legacies of the Hellenistic Greek world: the subsequent activity in the Indian Ocean of Greek-speaking Egyptians and certain people of India who called themselves Yavanas. But while doing so, it addresses certain vexing issues. One is whether merchants from Roman Egypt established stable residential communities in the ports of India during the first and second centuries AD. Another is how Yavanas living near the Gulf of Barygaza and the western Ghats in western India came to call themselves by a term borne centuries earlier by Greeks living in regions of northern India. By probing these issues, the article sheds light on how travellers and expatriates from Roman Egypt, and the Greek language and culture that they often carried with them, fit into the multilingual and multicultural web of a connected Indian Ocean. But it also formulates how a commercial network of Egyptians established residential settlements in the ports of India that generated and transmitted local knowledge to other members of the network. The author of the notable Periplus of the Erythraean Sea (Periplus Maris Erythraei) was arguably both a participant in the network and a recipient of its knowledge.
The ‘Treatment’ of a Box in Delphi: A Unique Use of the Word ἺΑΣΙΣ
Authors: Vanden Broeck-Parant Jean
Published: November 2017

The inscription CID II.34 presents a unique use of the word ἴασις, which commonly means ‘treatment mode’ or ‘therapeutic method’ in medical terminology. It is applied here to an archive box and has been accordingly translated, until now, as ‘repair’. However, a comparison with a passage from Theophrastus suggests that the term may refer, in this particular context, to a preventive measure designed to protect the box and the documents it contained from humidity and decay.
The Figure of Mary Mother of God in Christus Patiens: Fragmenting Tragic Myth and Passion Narrative in a Byzantine Appropriation of Euripidean Tragedy
Authors: Bryant Davies Rachel
Published: November 2017

The Byzantine passion play Christus Patiens (Christ Suffering) is a cento: composed of quotations and borrowings from other sources, it takes Euripides’ tragedies as its main source for reworking the passion narrative. The genre, popular with Christian authors who usually transformed classical epics, enacts cultural exchange between canonical pagan literature and biblical narrative. Traditionally transmitted as the work of Gregory of Nazianzus, this drama showcases the tensions inherent in this reuse of Greek tragedy which threaten to collapse the original texts under the weight of their new meaning – or vice versa. While the afterlives of Classical texts, especially Greek tragedy, have been increasingly well explored, the scant attention afforded Christus Patiens has largely consisted of debating the disputed date and authorship. At the same time, scrutiny lavished on Virgilian centonic technique provides a helpful spring-board. This article focuses on the four tragedies most plundered in Christus Patiens: Rhesus, Medea, Hippolytus and Bacchae. It concentrates on interpreting the protagonist, Mary the Mother of God, through key passages which borrow most heavily from these plays. These stretch centonic conventions by almost exclusively reworking contiguous lines featuring the tragic mothers Medea, Agave and Musa; yet Mary is otherwise created from multiple conflicting voices. Analysis of these passages as frames for the cento author's own compositions and in the context of the prologue's invitation to identify specific Euripidean reworkings suggests that the author playfully flirts with creating a narrative of fragmentation through clashes between centonic form, tragic sources and Christian subject.
Introduction: Big data and partial differential equations
Authors: VAN GENNIP YVES , SCHÖNLIEB CAROLA-BIBIANE
Published: November 2017

Partial differential equations (PDEs) are expressions involving an unknown function in many independent variables and their partial derivatives up to a certain order. Since PDEs express continuous change, they have long been used to formulate a myriad of dynamical physical and biological phenomena: heat flow, optics, electrostatics and -dynamics, elasticity, fluid flow and many more. Many of these PDEs can be derived in a variational way, i.e. via minimization of an ‘energy’ functional. In this globalised and technologically advanced age, PDEs are also extensively used for modelling social situations (e.g. models for opinion formation, mathematical finance, crowd motion) and tasks in engineering (such as models for semiconductors, networks, and signal and image processing tasks). In particular, in recent years, there has been increasing interest from applied analysts in applying the models and techniques from variational methods and PDEs to tackle problems in data science. This issue of the European Journal of Applied Mathematics highlights some recent developments in this young and growing area. It gives a taste of endeavours in this realm in two exemplary contributions on PDEs on graphs [1, 2] and one on probabilistic domain decomposition for numerically solving large-scale PDEs [3].
Assessing the temporal transferability of raptor distribution models: Implications for conservation
Authors: TAPIA LUIS , REGOS ADRIÁN , GIL-CARRERA ALBERTO , DOMÍNGUEZ JESÚS
Published: November 2017

The aim of this study was to assess the temporal transferability of species distribution models (SDMs) and their potential implications for bird conservation. We quantified the loss and fragmentation of Montagu’s HarrierCircus pygargusand Common KestrelFalco tinnunculushabitats over 13 years (2001–2014) in a highly dynamic landscape in north-western Spain. For this purpose, priority habitats for the target species were modelled at four different spatial scales using an ensemble forecasting framework. To explore the temporal transferability of our ensemble predictions, the models were back-projected to the land cover conditions in 2001 and evaluated using historical occurrence data. In addition, models calibrated with historical data were projected to the land cover conditions in 2014 and evaluated using updated occurrence data. Changes in availability and connectivity of suitable habitats between both years were estimated at four spatial scales from a set of widely-used indicators. SDMs showed a good predictive accuracy but with limited temporal transferability due to changes in the species-habitat relationships between 2001 and 2014. The results showed a decrease in the avaliability of suitable habitats of 33.4% and 47.7% for Montagu’s Harrier and Common Kestrel, respectively; with the subsequent increase in their fragmentation. However, our estimates were found to be strongly dependent on the scale of analysis and model transferability. Changes in habitat availability and connectivity ranged from -48% to +54% for Montagu’s Harrier, and from +116% to +5.6% for Common Kestrel. We call for caution when using SDMs beyond the model calibration time period to guide bird conservation. This is especially important for raptors, often characterised by low population sizes and large home ranges, and particularly sensitive to unstable, highly dynamic environmental conditions. In light of these results, specific, long-standing monitoring protocols remain essential to ensure accurate modelling performance and reliable future projections.
Bank networks and suspensions in the 1893 panic: evidence from the state banks and their correspondents in Kansas
Authors: Dupont Brandon
Published: November 2017

Using individual balance sheet data from the state banks in one state that was deeply impacted by the 1893 crisis, this article presents evidence that correspondent networks played an important role in transmitting the crisis. In particular, the unexpected closure of a single large national bank in Kansas City considerably increased the probability of suspension among the state banks that were connected to it through the correspondent networks. This episode thus illustrates how contagion can spread through interbank networks and sheds new light on the nature of the 1893 crisis.
Urgent hybrid palliation for interrupted aortic arch in a preterm infant
Authors: Romans Ryan A. , Armstrong Aimee K. , Aiyagari Ranjit
Published: November 2017

In patients with ductal-dependent CHD, ductal restriction can be life-threatening. We present the use of urgent hybrid palliation involving placement of bilateral pulmonary artery bands and ductus arteriosus stent implantation in a 1.5 kg premature infant with interrupted aortic arch and ductal restriction.
Counting the Cost of Cervical Collars
Authors: Veljanoski Damjan , Grier Gareth , Wilson Mark H.
Published: November 2017

VeljanoskiD, GrierG, WilsonMH. Counting the cost of cervical collars. Prehosp Disaster Med. 2017;32(6):701–702.
DO GLOBAL CRUDE OIL MARKET SHOCKS HAVE DIFFERENTIAL EFFECTS ON US REGIONS?
Authors: Atems Bebonchu , Melichar Mark
Published: November 2017

The paper investigates whether US regions respond differently to shocks in the crude oil market. We disentangle oil market shocks into distinct demand and supply shocks and examine the response of regional personal income to these shocks. Results indicate that for most regions, oil supply shocks decrease real personal income. Except for the Rocky Mountains and the Southwest, global aggregate demand shocks are recessionary, typically about a year and a half after the shock. When we split our data into oil-producing and non-oil-producing regions, we find that global aggregate demand shocks have no effect on oil-producing regions but cause a decrease in income in non-oil-producing regions. Our analysis further indicates that oil-specific demand shocks have positive and persistent impacts on oil-producing regions but are recessionary in non-oil-producing regions. We also document significant asymmetries in the regional responses to small versus large oil shocks. In addition, the paper shows that regional differences in industrial composition explain some of the variation in the responses of real regional personal income to oil shocks.
Battle of plates: a pilot study of an approach–avoidance training for overweight children and adolescents
Authors: Warschburger Petra , Gmeiner Michaela , Morawietz Marisa , Rinck Mike
Published: November 2017

Objective

Approach–avoidance training (AAT) is a promising approach in obesity treatment. The present study examines whether an AAT is feasible and able to influence approach tendencies in children and adolescents, comparing implicit and explicit training approaches.

Design/Setting/Subjects

Fifty-nine overweight children and adolescents (aged 8–16 years; twenty-six boys) participated in an AAT for food cues, learning to reject snack items and approach vegetable items. Reaction times in the AAT and an implicit association test (IAT) were assessed pre- and post-intervention.

Results

A significant increase in the AAT compatibility scores with a large effect (η2=0·18) was found. No differences between the implicit and explicit training approaches and no change in the IAT scores were observed.

Conclusions

Automatic tendencies in children can be trained, too. The implementation of AAT in the treatment of obesity might support the modification of an unhealthy nutrition behaviour pattern. Further data from randomized controlled clinical trials are needed.
Actinobacillus pleuropneumoniae biofilms: Role in pathogenicity and potential impact for vaccination development
Authors: Hathroubi Skander , Loera-Muro Abraham , Guerrero-Barrera Alma L. , Tremblay Yannick D. N. , Jacques Mario
Published: November 2017

Actinobacillus pleuropneumoniae is a Gram-negative bacterium that belongs to the family Pasteurellaceae. It is the causative agent of porcine pleuropneumonia, a highly contagious respiratory disease that is responsible for major economic losses in the global pork industry. The disease may present itself as a chronic or an acute infection characterized by severe pathology, including hemorrhage, fibrinous and necrotic lung lesions, and, in the worst cases, rapid death. A. pleuropneumoniae is transmitted via aerosol route, direct contact with infected pigs, and by the farm environment. Many virulence factors associated with this bacterium are well characterized. However, much less is known about the role of biofilm, a sessile mode of growth that may have a critical impact on A. pleuropneumoniae pathogenicity. Here we review the current knowledge on A. pleuropneumoniae biofilm, factors associated with biofilm formation and dispersion, and the impact of biofilm on the pathogenesis A. pleuropneumoniae. We also provide an overview of current vaccination strategies against A. pleuropneumoniae and consider the possible role of biofilms vaccines for controlling the disease.
Taiwan's Foreign Aid in Transition: From ODA to Civil Society Approaches
Authors: LIN TEH-CHANG , LIN JEAN YEN-CHUN
Published: November 2017

Since the 1950s, Taiwan and China have utilized foreign aid as an instrument of foreign policy. After Taiwan's forced withdrawal from the United Nations in 1971, diplomatic and aid-giving competition with China became more intense. As a result, Taiwan's and China's struggles to gain supporters have been reflected in foreign aid strategies. Taiwan's bid for the UN and the WHO, and the issue of diplomatic recognition empirically demonstrate the utilization of aid to obtain diplomatic support from recipient countries, and, frequently, any decisions are heavily influenced by the competition it experiences with China. Theoretically, this highlights an importantrelationalframework for analyzing foreign aid decisions – particularly the management of foreign relations of small states or middle powers simultaneously influenced by greater powers and aid recipient states.

Using data from ICDF and related reports, we observe geographically concentrated patterns in the distribution of Taiwan's aid recipients from 1988 to 1997 – mostly in Latin America and Southeast Asia. In contrast to China's foreign aid which emphasizes infrastructural development, the spirit of Taiwan's economic development aid programs often took the form of technical cooperation. However, a high percentage of aid went to countries with diplomatic ties to Taiwan. With civil society development and increased international activities of Taiwanese NGOs in humanitarian relief and development projects after 2000, we find a new emerging set of geographical aid distribution patterns that expand beyond countries that recognize Taiwan. In addition, while the process of incorporating civil society into foreign aid work was initiated by the ICDF the following decade, Taiwanese NGOs have increasingly demonstrated autonomous international agendas, funding, and direction, as well as the formation of civil society alliances that work on common international development issues.
Variance in Global Response to HIV/AIDS between the United States and Japan: Perception, Media, and Civil Society
Authors: KIM YOUNG SOO , SHIN JOONGBUM
Published: November 2017

The US and Japan, despite their shared reputation as leading donors for international development, remarkably varied in their foreign aid policy for HIV/AIDS in the 1980s and 1990s. Unlike the US, who initiated and increased global AIDS funding dramatically, Japan was lukewarm in its contributions. I claim that the distinctive pattern depends on how the pandemic was domestically framed and understood. The policy commitment was more likely when the internationally shared idea (international norms) of threats requiring immediate international cooperation was congruent with the domestic perception of the epidemic. The research undertakes a comparative examination of the determinants of the distinctive domestic perceptions of the two cases, including the number of individuals infected with HIV, the attitude and role of the media, and the civil society organizations dealing with HIV/AIDS. They played significant roles as intervening variables that conditioned domestic diffusion or internalization of the international norms for foreign aid policy development. The US had a favorable domestic condition based upon the relatively large number of those infected with HIV, a media that adopted a constructive approach, and active civil society organizations associated with the disease. In contrast, in Japan the number of HIV cases was lower, the media had a distorted view of the epidemic, and civil society organizations were not strong enough to offer much support until the early 1990s.
PASCAL AND MELANCHOLY
Authors: CÓRDOVA CHAD A.
Published: November 2017

This article shows how two concepts for which Blaise Pascal'sPensées(1670) are best known—divertissementandennui(often mistranslated as “boredom”)—inherited and transformed medical conceptions of melancholy along with one of melancholy's signature therapeutic protocols: diversion. Instead of limiting the genealogy of Pascal's concepts to more obvious textual sources (St Augustine, Montaigne, etc.), here they are read against the background of an epistemological paradigm dominant in his time: Galenic medicine. Drawing on a large corpus of early modern French medical texts, this article discloses how melancholy, stripped of its overt medical status, remerges in Pascal's analysis of subjectivity, which valorized melancholicennuiagainst the values of a nascent civil society subservient to the monarchic order. Once used to describe outlying temperaments and exceptional pathologies, the discourse on melancholy becomes fundamental to the human being per se in Pascal's theological and anthropological perspective. Thus transformed, the older forms of melancholy and its remedies ensured the possibility of their survival—disguised and unrecognized—in modern theories of subjectivity and psychology. Understanding melancholy's latent presence in thePensées, in other words, sheds new light on the affective aspects of Pascal's social critique and invites us to investigate the modern afterlife of early modern melancholy.
100 YEARS OF JOHN DEWEY AND EDUCATION IN CHINA
Authors: Zhang Grace Xinfu , Sheese Ron
Published: November 2017

Only a few years following the publication ofDemocracy and Education, from May 1919 to July 1921, John Dewey traveled and lectured in China. He arrived an already famous American psychologist, philosopher, and educator; but over the course of the years after his departure, that fame diminished, turning to infamy in the 1950s and 1960s, only to be somewhat restored in recent decades. The changing attitudes of the Chinese to Dewey and his ideas are associated with the changing, and often tumultuous, cultural and political context for education in China from the time of his visit through the following century. Hu Shi and Tao Xingzhi, PhD students of Dewey at Columbia University, were prominent Chinese educators who adapted Dewey's educational concepts to the Chinese environment, and their work continues to influence educational debate in China today. While there is desire among many contemporary educators for educational reforms that would be in line with Dewey's principles, there are equal or greater pressures for maintaining systems focused on examinations and memorization.
JOHN DEWEY'S HIGH HOPES FOR PLAY:DEMOCRACY AND EDUCATIONAND PROGRESSIVE ERA CONTROVERSIES OVER PLAY IN KINDERGARTEN AND PRESCHOOL EDUCATION
Authors: Beatty Barbara
Published: November 2017

Exploring John Dewey's hopes for play reveals much about the key role he thought it played in education in a democratic society. PlacingDemocracy and Educationin the context of Progressive Era controversies over play in the kindergarten movement and preschool education illustrates Dewey's view that teacher-guided free play could reconcile the dilemma of the need for individual agency and social discipline. Dewey built upon and critiqued the scripted play pedagogy of kindergarten founder Friedrich Froebel. Drawing in part from progressive kindergarten teachers, Dewey constructed his own notion of play that he argued fostered experiential learning, voluntary participation, and social order. For Dewey, play and work were naturally linked in ways in which the needs of the child and society coalesced. Analysis of sources from the kindergarten movement and the Sub-primary Department at the University of Chicago Laboratory School provide background for interpreting some of Dewey's writings on play, which influenced modern contests over how young children learn and should be taught.
“THEORY RUN MAD”: JOHN DEWEY AND “REAL” VOCATIONAL EDUCATION
Authors: Kett Joseph F.
Published: November 2017

Democracy and Education appeared amid intense debate over the relationship between school and work. This debate revealed a stark contrast between Dewey's idea to educate young people to understand the complex relationships of modern industry and the ideas of educators who equated vocational education with training fourteen- to sixteen-year-olds for maximal productivity, a view written into the Smith-Hughes Act of 1917. Whereas Dewey favored integrating vocational education with “a new kind of general education,” his antagonists assailed advocates of the “general” or “academic” curriculum as reactionaries who infected public education with impractical theories that only served those with time and money to indulge their interest in cultural values detached from daily life. Significantly, Dewey did not respond with a defense of theory over practice but with an assertion that his opponents’ thought was permeated by theories, ironically drawn from some of the same sources that influenced mainstream advocates of the “new” education. Understanding how combatants could derive conflicting conclusions from the same sources illuminates the paradoxes and aids in explaining the timing and scope of the Progressive movement.
School districts and their local food supply chains
Authors: Christensen Libby O. , Jablonski Becca B. R. , O'Hara Jeffrey K.
Published: November 2017

The 2015 Farm to School Census reports that during the 2013–2014 school year there were over 5200 farm to school (FTS) programs in the USA that involved 39,000 schools and 24.1 million children. These FTS programs are intended, in part, to increase market access and therefore the viability of farms and ranches. Accordingly, the majority of FTS programs involve local food procurement directly from farmers, from non-traditional suppliers that market locally branded food products such as ‘food hubs’, or from traditional suppliers such distributors and food service management companies. Yet, there is reason to believe that transaction costs vary based on the supply chain that schools use to procure local food. Moreover, that the supply chain that schools use to procure local food has a relationship with school's expenditures on local food. We use the 2015 Farm to School Census to estimate the relationship between school district's local food expenditures per student and supply chain structure. We analyzed data using ordinary least squares regressions, controlling for the region of the USA, the type of local food products purchased, and other school-specific characteristics. Importantly, we find a negative and significant relationship between school district's non-milk local food expenditure per student, and purchases directly from the farm and from non-traditional suppliers. This implies that schools that purchase local food from traditional distributors are likely to have higher on average expenditures per student compared with schools that purchase local food directly from farmers or non-traditional distributors. Results point to the need for additional research in determining the efficacy of policies to support direct and non-traditional FTS marketing arrangements.
GENERALIZATIONS OF GÖDEL’S INCOMPLETENESS THEOREMS FOR ∑n-DEFINABLE THEORIES OF ARITHMETIC
Authors: KIKUCHI MAKOTO , KURAHASHI TAISHI
Published: November 2017

It is well known that Gödel’s incompleteness theorems hold for ∑1-definable theories containing Peano arithmetic. We generalize Gödel’s incompleteness theorems for arithmetically definable theories. First, we prove that every ∑n+1-definable ∑n-sound theory is incomplete. Secondly, we generalize and improve Jeroslow and Hájek’s results. That is, we prove that every consistent theory having ∏n+1set of theorems has a true but unprovable ∏nsentence. Lastly, we prove that no ∑n+1-definable ∑n-sound theory can prove its own ∑n-soundness. These three results are generalizations of Rosser’s improvement of the first incompleteness theorem, Gödel’s first incompleteness theorem, and the second incompleteness theorem, respectively.
Lead promotes abnormal angiogenesis induced by CCM3 gene defects via mitochondrial pathway
Authors: Sun Y. , Zhang H. , Xing X. , Zhao Z. , He J. , Li J. , Chen J. , Wang M. , He Y.
Published: November 2017

Lead is one of the environmental pollutants with cardiovascular toxicity. The embryos are particularly sensitive to lead exposure, because it can move through the blood-placental barrier and the blood-brain barrier easily during embryonic development. Cerebral cavernous malformations 3 (CCM3) gene plays an important role in cardiovascular development, mainly affecting cell proliferation, differentiation and apoptosis. In this study, we established a blood vessel development model of mouse embryos in order to imitate human people with CCM3 genes defects and exposing to environment toxin Pb in utero. We would like to determine the interaction of Pb and CCM3 gene on vascular development, and to explore the mechanisms. We found that the yolk sac of CCM3 heterozygous mice embryo showed abnormal morphology at E11.5 after lead treatment comparing with wild type (WT) mice without lead exposure, meanwhile it showed more angiogenesis and vascular remodeling in the hematoxylin and eosin stained sections of the CCM3+/− yolk sac with lead exposure. We also found that the similar effect of Pb and CCM3 gene on mitochondrial DNA (mtDNA) copy number in vivo and in vitro. Mitochondrial morphology and function also changed in primary human umbilical vein endothelial cells after lead exposure. Besides, it was found that the HIF-1α and TFAM which have close relationship with mtDNA biogenesis showed similarly increasing messenger RNA expression in both human and mouse-derived primary cells with lead treated and CCM3 gene knockout. All of the above results indicated that lead and CCM3 might damage endothelial cells through mitochondria pathway and eventually both affected angiogenesis.
Heritability and GWAS Analyses of Acne in Australian Adolescent Twins
Authors: Mina-Vargas Angela , Colodro-Conde Lucía , Grasby Katrina , Zhu Gu , Gordon Scott , Medland Sarah E. , Martin Nicholas G.
Published: November 2017

Acne vulgaris is a skin disease with a multifactorial and complex pathology. While several twin studies have estimated that acne has a heritability of up to 80%, the genomic elements responsible for the origin and pathology of acne are still undiscovered. Here we performed a twin-based structural equation model, using available data on acne severity for an Australian sample of 4,491 twins and their siblings aged from 10 to 24. This study extends by a factor of 3 an earlier analysis of the genetic factors of acne. Acne severity was rated by nurses on a 4-point scale (1 =absentto 4 =severe) on up to three body sites (face, back, chest) and on up to three occasions (age 12, 14, and 16). The phenotype that we analyzed was the most severe rating at any site or age. The polychoric correlation for monozygotic twins was higher (rMZ= 0.86, 95% CI [0.81, 0.90]) than for dizygotic twins (rDZ= 0.42, 95% CI [0.35, 0.47]). A model that includes additive genetic effects and unique environmental effects was the most parsimonious model to explain the genetic variance of acne severity, and the estimated heritability was 0.85 (95% CI [0.82, 0.87]). We then conducted a genome-wide analysis including an additional 271 siblings — for a total of 4,762 individuals. A genome-wide association study (GWAS) scan did not detect loci associated with the severity of acne at the threshold of 5E-08 but suggestive association was found for three SNPs: rs10515088 locus 5q13.1 (p= 3.9E-07), rs12738078 locus 1p35.5 (p= 6.7E-07), and rs117943429 locus 18q21.2 (p= 9.1E-07). The 5q13.1 locus is close toPIK3R1, a gene that has a potential regulatory effect on sebocyte differentiation.
Herbicide Spray Penetration into Corn and Soybean Canopies Using Air-Induction Nozzles and a Drift Control Adjuvant
Authors: Creech Cody F. , Henry Ryan S. , Hewitt Andrew J. , Kruger Greg R.
Published: November 2017

Drift reduction technologies aim to eliminate the smaller droplets that occur with some sprays because these small droplets can move off-target in the wind. Commonly used drift reduction technologies such as air-induction nozzles and spray additives impact on reducing off-target movement is well documented, however, the impact on herbicide penetration into an established crop canopy is not well known. This experiment evaluated the canopy penetration and efficacy of glyphosate treatments applied using four nozzle types (XR11005, AIXR11005, AITTJ11005, and TTI11005), two carrier volume rates (94 and 187 L ha-1), and glyphosate applications with and without a commercial drift reducing adjuvant. Applications were made to corn and soybean fields using glyphosate applied at 1.26 kg ae ha-1with liquid ammonium sulfate at 5% v/v. A rhodamine dye was added (0.025% v/v) to the spray tank of each mixture as a tracer. MylarTMcards were placed in the field above the canopy, in the middle canopy, and on the ground for corn and above and below canopy for soybean. Five cards were at each position in the canopy arranged across the crop row. The addition of a drift reducing adjuvant did not impact canopy penetration. Doubling the carrier volume increased the amount of penetration proportionally and as such the percent reduction was not different. The TTI11005 nozzle had the greatest amount of spray penetration (28%) in the soybean canopies and the XR nozzle had the greatest amount (50%) in the corn canopies. Deposition across the row, beginning in-between the row crop and ending in the row of the crop was 44, 18, and 8% for soybean and 59, 50, and 36% for corn. For both crops, more than half of the herbicide application was captured in the crop canopy. Proper nozzle selection for canopy type can increase herbicide penetration and increasing the carrier volume will increase penetration proportionally.
Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients
Authors: Chen Yan , Huang Yong-Can , Yan Chun Hoi , Chiu Kwong Yuen , Wei Qingjun , Zhao Jingmin , Guo X Edward , Leung Frankie , Lu William W
Published: November 2017

Type 2 diabetes (T2D) is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis (OA). Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic (n=70) and diabetes (n=51) groups. Tibial plateaus were also collected from cadaver donors (n=20) and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase (TRAP), osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International (OARSI) scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP+ osteoclasts and lower number of Osterix+ osteoprogenitors and Osteocalcin+ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.
Reflective imaging improves spatiotemporal resolution and collection efficiency in light sheet microscopy
Authors: Wu Yicong , Kumar Abhishek , Smith Corey , Ardiel Evan , Chandris Panagiotis , Christensen Ryan , Rey-Suarez Ivan , Guo Min , Vishwasrao Harshad D. , Chen Jiji , Tang Jianyong , Upadhyaya Arpita , La Riviere Patrick J. , Shroff Hari
Published: November 2017

Light-sheet fluorescence microscopy (LSFM) enables high-speed, high-resolution, and gentle imaging of live specimens over extended periods. Here we describe a technique that improves the spatiotemporal resolution and collection efficiency of LSFM without modifying the underlying microscope. By imaging samples on reflective coverslips, we enable simultaneous collection of four complementary views in 250 ms, doubling speed and improving information content relative to symmetric dual-view LSFM. We also report a modified deconvolution algorithm that removes associated epifluorescence contamination and fuses all views for resolution recovery. Furthermore, we enhance spatial resolution (to <300 nm in all three dimensions) by applying our method to single-view LSFM, permitting simultaneous acquisition of two high-resolution views otherwise difficult to obtain due to steric constraints at high numerical aperture. We demonstrate the broad applicability of our method in a variety of samples, studying mitochondrial, membrane, Golgi, and microtubule dynamics in cells and calcium activity in nematode embryos.
IL-2 imprints human naive B cell fate towards plasma cell through ERK/ELK1-mediated BACH2 repression
Authors: Hipp Nicolas , Symington Hannah , Pastoret Cédric , Caron Gersende , Monvoisin Céline , Tarte Karin , Fest Thierry , Delaloy Céline
Published: November 2017

Plasma cell differentiation is a tightly regulated process that requires appropriate T cell helps to reach the induction threshold. To further understand mechanisms by which T cell inputs regulate B cell fate decision, we investigate the minimal IL-2 stimulation for triggering human plasma cell differentiation in vitro. Here we show that the timed repression of BACH2 through IL-2-mediated ERK/ELK1 signalling pathway directs plasma cell lineage commitment. Enforced BACH2 repression in activated B cells unlocks the plasma cell transcriptional program and induces their differentiation into immunoglobulin M-secreting cells. RNA-seq and ChIP-seq results further identify BACH2 target genes involved in this process. An active regulatory region within theBACH2super-enhancer, under ELK1 control and differentially regulated upon B-cell activation and cellular divisions, helps integrate IL-2 signal. Our study thus provides insights into the temporal regulation of BACH2 and its targets for controlling the differentiation of human naive B cells.
Intratumoral CD40 activation and checkpoint blockade induces T cell-mediated eradication of melanoma in the brain
Authors: Singh Manisha , Vianden Christina , Cantwell Mark J. , Dai Zhimin , Xiao Zhilan , Sharma Meenu , Khong Hiep , Jaiswal Ashvin R. , Faak Faisal , Hailemichael Yared , Janssen L. M. E. , Bharadwaj Uddalak , Curran Michael A. , Diab Adi , Bassett Roland L. , Tweardy David J. , Hwu Patrick , Overwijk Willem W.
Published: November 2017

CD40 agonists bind the CD40 molecule on antigen-presenting cells and activate them to prime tumor-specific CD8+ T cell responses. Here, we study the antitumor activity and mechanism of action of a nonreplicating adenovirus encoding a chimeric, membrane-bound CD40 ligand (ISF35). Intratumoral administration of ISF35 in subcutaneous B16 melanomas generates tumor-specific, CD8+ T cells that express PD-1 and suppress tumor growth. Combination therapy of ISF35 with systemic anti-PD-1 generates greater antitumor activity than each respective monotherapy. Triple combination of ISF35, anti-PD-1, and anti-CTLA-4 results in complete eradication of injected and noninjected subcutaneous tumors, as well as melanoma tumors in the brain. Therapeutic efficacy is associated with increases in the systemic level of tumor-specific CD8+ T cells, and an increased ratio of intratumoral CD8+ T cells to CD4+ Tregs. These results provide a proof of concept of systemic antitumor activity after intratumoral CD40 triggering with ISF35 in combination with checkpoint blockade for multifocal cancer, including the brain.
Regulation of angiotensin II actions by enhancers and super-enhancers in vascular smooth muscle cells
Authors: Das Sadhan , Senapati Parijat , Chen Zhuo , Reddy Marpadga A. , Ganguly Rituparna , Lanting Linda , Mandi Varun , Bansal Anita , Leung Amy , Zhang Selena , Jia Ye , Wu Xiwei , Schones Dustin E. , Natarajan Rama
Published: November 2017

Angiotensin II (AngII) promotes hypertension and atherosclerosis by activating growth-promoting and pro-inflammatory gene expression in vascular smooth muscle cells (VSMCs). Enhancers and super-enhancers (SEs) play critical roles in driving disease-associated gene expression. However, enhancers/SEs mediating VSMC dysfunction remain uncharacterized. Here, we show that AngII alters vascular enhancer and SE repertoires in cultured VSMCs in vitro, ex vivo, and in AngII-infused mice aortas in vivo. AngII-induced enhancers/SEs are enriched in binding sites for signal-dependent transcription factors and dependent on key signaling kinases. Moreover, CRISPR-Cas9-mediated deletion of candidate enhancers/SEs, targeting SEs with the bromodomain and extra-terminal domain inhibitor JQ1, or knockdown of overlapping long noncoding RNAs (lncRNAs) blocks AngII-induced genes associated with growth-factor signaling and atherosclerosis. Furthermore, JQ1 ameliorates AngII-induced hypertension, medial hypertrophy and inflammation in vivo in mice. These results demonstrate AngII-induced signals integrate enhancers/SEs and lncRNAs to increase expression of genes involved in VSMC dysfunction, and could uncover novel therapies.
PTK6 regulates growth and survival of endocrine therapy-resistant ER+ breast cancer cells
Authors: Ito Koichi , Park Sun Hee , Katsyv Igor , Zhang Weijia , De Angelis Carmine , Schiff Rachel , Irie Hanna Y.
Published: November 2017

The non-receptor tyrosine kinase, PTK6/BRK, is highly expressed in multiple tumor types, including prostate, ovarian, and breast cancers, and regulates oncogenic phenotypes such as proliferation, migration, and survival. PTK6 inhibition also overcomes targeted therapy resistance of HER2+ breast cancer. Although PTK6 is highly expressed in ER+ Luminal breast cancers, the role of PTK6 in this subtype has not been elucidated. In this study, we investigated the functions of PTK6 in ER+ Luminal breast cancer cells, including those that are relatively resistant to estrogen deprivation or targeted endocrine therapies used in the treatment of ER+ cancers. Enhanced expression of PTK6 in ER+ breast cancer cells enhances growth of ER+ breast cancer cells, including tamoxifen-treated cells. Downregulation of PTK6 in ER+ breast cancer cells, including those resistant to tamoxifen, fulvestrant, and estrogen deprivation, induces apoptosis, as evidenced by increased levels of cleaved PARP, and an increase in the AnnexinV+ population. PTK6 downregulation impairs growth of these cells in 3D MatrigelTM cultures, and virtually abrogates primary tumor growth of both tamoxifen-sensitive and resistant MCF-7 xenografts. Finally, we show that p38 MAPK activation is critical for PTK6 downregulation-induced apoptosis, a mechanism that we previously reported for survival of HER2+ breast cancer cells, highlighting conserved mechanisms of survival regulation by PTK6 across breast cancer subtypes. In conclusion, our studies elucidate critical functions of PTK6 in ER+ Luminal breast cancers and support PTK6 as an attractive therapeutic target for ER+ breast cancers.
Concurrence of superconductivity and structure transition in Weyl semimetal TaP under pressure
Authors: Li Yufeng , Zhou Yonghui , Guo Zhaopeng , Han Fei , Chen Xuliang , Lu Pengchao , Wang Xuefei , An Chao , Zhou Ying , Xing Jie , Du Guan , Zhu Xiyu , Yang Huan , Sun Jian , Yang Zhaorong , Yang Wenge , Mao Ho-Kwang , Zhang Yuheng , Wen Hai-Hu
Published: November 2017

Weyl semimetal defines a material with three-dimensional Dirac cones, which appear in pair due to the breaking of spatial inversion or time reversal symmetry. Superconductivity is the state of quantum condensation of paired electrons. Turning a Weyl semimetal into superconducting state is very important in having some unprecedented discoveries. In this work, by doing resistive measurements on a recently recognized Weyl semimetal TaP under pressures up to about 100 GPa, we show the concurrence of superconductivity and a structure transition at about 70 GPa. It is found that the superconductivity becomes more pronounced when decreasing pressure and retains when the pressure is completely released. High-pressure x-ray diffraction measurements also confirm the structure phase transition from I41md to P-6m2 at about 70 GPa. More importantly, ab-initial calculations reveal that the P-6m2 phase is a new Weyl semimetal phase and has only one set of Weyl points at the same energy level. Our discovery of superconductivity in TaP by high pressure will stimulate investigations on superconductivity and Majorana fermions in Weyl semimetals.
Controlled synthesis of conjugated polycarbazole polymers via structure tuning for gas storage and separation applications
Authors: Li Guoyan , Qin Long , Yao Chan , Xu Yanhong
Published: November 2017

A series of conjugated microporous polymers (CMPs) based on 1,3,6,8-tetrabromocarbazole (N4CMP-1–5) is synthesized via Suzuki cross-coupling or Sonogashira polycondensation. The porosity properties and surface area of these polymer networks can be finely tuned by using a linker with different geometries or strut length. These polymers show the Brunauer-Emmett-Tellerthe (BET) surface areas ranging from 592 to 1426 m2 g−1. The dominant pore sizes of the polymers on the basis of the different linker are located between 0.36 and 0.61 nm. Gas uptake increases with BET surface area and micropore volume, N4CMP-3 polymer can capture CO2 with a capacity of 3.62 mmol g−1 (1.05 bar and 273 K) among the obtained polymers. All of the polymers show high isosteric heats of CO2 adsorption (25.5–35.1 kJ mol−1), and from single component adsorption isotherms, IAST-derived ideal CO2/N2 (28.7–53.8), CO2/CH4 (4.6–5.2) and CH4/N2 (5.7–10.5) selectivity. Furthermore, N4CMPs exhibit the high CO2 adsorption capacity of 542–800 mg g−1 at 318 K and 50 bar pressure. These data indicate that these materials are a promising potential for clean energy application and environmental field.