bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical and theoretical studies of flares from Sagittarius A⋆
Authors: Li Ya-Ping , Yuan Qiang , Wang Q. Daniel , Chen P. F. , Neilsen Joseph , Fang Taotao , Zhang Shuo , Dexter Jason
Published: February 2017

Multi-wavelength flares have routinely been observed from the supermassive black hole, Sagittarius A⋆ (Sgr A⋆), at our Galactic center. The nature of these flares remains largely unclear, despite many theoretical models. We study the statistical properties of the Sgr A⋆ X-ray flares and find that they are consistent with the theoretical prediction of the self-organized criticality system with the spatial dimension S = 3. We suggest that the X-ray flares represent plasmoid ejections driven by magnetic reconnection (similar to solar flares) in the accretion flow onto the black hole. Motivated by the statistical results, we further develop a time-dependent magnetohydrodynamic (MHD) model for the multi-band flares from Sgr A⋆ by analogy with models of solar flares/coronal mass ejections (CMEs). We calculate the X-ray, infrared flare light curves, and the spectra, and find that our model can explain the main features of the flares.
The Subversion of Arabic Instruction in Jewish Schools in Israel
Authors: Uhlmann Allon J.
Published: February 2017

Arabic instruction in Israeli government schools in the Jewish sector is unsatisfactory by both subjective and objective measures. The general consensus among educators, academics and other interested parties, most notably the security apparatus—the main employer of Jews with knowledge of Arabic—is that not enough students study Arabic, and that those who do fail to achieve proficiency in the language (Uhlmann 2010, Ben-Rafael and Brosh 1991, Spolsky and Shohamy 1991, Spolsky et al. 1995, Lustigman 2008, State Comptroller 1996:367). Dissatisfaction with Arabic instruction has been an integral feature of the field since the very inception of the modern, secular, public Hebrew school system in the days of the British Mandate over Palestine (see especially early papers in Yonai 1992 and Landau 1961). This enduring educational fecklessness is remarkable given the available resources and the powerful stakeholders that drive for deepening and broadening Arabic instruction in Jewish schools.

Previous analyses of the problems of Arabic instruction have focused on language ideology and Jewish pupils’ attitudes towards Arabic and Arabs (e.g. Ben-Rafael & Brosh 1991, Ben-Rafael 1994, Kraemer and Olshtain 1994, cf. the comprehensive overview by Spolsky et al. 1995). However, language ideology is but one aspect of the broad political and institutional structuring of Arabic instruction in Israel, and it is this complex as a whole that is responsible for the state of Arabic instruction.
RestagingMise en Valeur:“Postwar Imperialism” and The Plan de Constantine
Authors: Davis Muriam Haleh
Published: February 2017

Fewer than fourth months after De Gaulle stood in Algiers and enigmatically declared “I have understood you,” he was once again in Algeria, now in the city of Constantine, where he unveiled a development plan that seemed to reaffirm his commitment to French Algeria. On 3 October 1958, amidst the ravages of war, De Gaulle proposed thePlan de Constantine, proclaiming that “all of Algeria must have her share in what modern civilization can and must bring to men.” The Plan de Constantine (hereafter “the Plan”) was an ambitious development program that intended to lessen the economic, social and political disparity betweenl’ Hexagone(metropolitan France) and French Algeria.
Heroes and Villains: an Algerian Review of Tocqueville and Emir Abd al-Qadir
Authors: Boutaleb Chamyl
Published: February 2017

The history of Algeria’s colonization by France is closely linked to resistance (from 1832 to 1847) led by the Algerian hero Emir Abd al-Qadir (1808–1883), and to the ideology of the French agent Alexis de Tocqueville concerning the means by which France could dominate the country. The colonization of Algeria divided the French political sphere into three approaches: Those who demanded the retreat of French troops, those calling for a limited occupation, and finally those in favour of extending domination and the colonization of the occupied territories. Among the last, let us highlight the chief advocate, Marechal Guizot, and his military accomplices (generals Cavaignac, Pelissier, Saint-Arnaud, Montagnac, and others led by general Bugeaud). Working with them was Alexis de Tocqueville (1805–1859), a fervent defender of colonization at any cost. He was to be their ideologist, a theoretician of colonialism who would legitimize French expansion in Algeria.
An Engaged Islamicist: The Internet and Climbing Outside the Tower
Authors: Godlas Alan
Published: February 2017

There is no question that it is easy to get lost when climbing outside the ivory tower of academia and becoming a socially engaged scholar. In my case, such engagement has substantially delayed many other projects that are dear to my heart. Nevertheless, in the course of my fourteen year sojourn on the web, all in all the time spent outside has been worth it. In this paper, I will discuss three web-based projects that I have created: my “Islam and Islamic Studies Resources” website, an international discussion group on Sufism called “Sufis Without Borders,” and a daily world news service, “Sufi News and Sufism World Report.” I will also make some recommendations based on insights gained over the course of these projects.
Dissemination and the Digital: The Creation of an Academic Book Trailer
Authors: Virani Shafique N.
Published: February 2017

Academics who concentrate on the study of Islam live in challenging times. The proliferation of “popular” sources of news and information evokes both significant concern as well as tremendous possibility. This is true across the academy, not only in our own field. In a recent issue of theJournal of the American Medical Association, a team of medical scientists analyzed 153 videos about vaccination and immunization on YouTube. What they found was very disturbing. A staggering number of YouTube videos portrayed vaccinations in a negative light, and about half contained messages completely contradicting established medical science. Furthermore, the research team found that videos with negative portrayals of vaccinations were highly provocative and powerful, and received more views and better ratings by YouTube users than those videos that portray vaccinations in a positive light. The study concludes that this situation is extremely dangerous and that public health officials must consider how to effectively communicate their scientifically founded viewpoints through internet video portals.
Intercommunal Life in Istanbul During the Eighteenth Century
Authors: Zarinebaf Fariba
Published: February 2017

Historians of the Middle East and the Balkans have paid little attention to intercommunal relations in Ottoman cities prior to the onset of nationalism and the spread of communal violence in the nineteenth and early twentieth century. Each national and religious community has, therefore, focused on writing and imagining its own history with very little attention to the larger social milieu, economic and social conditions, and interactions outside confessional boundaries in the pre-modern period. The history of the Jewish community has received more attention from scholars, while that of the Greek and Armenian communities has been largely ignored. The literature on Islamic cities also tends to emphasize the homogenous composition of residential neighborhoods in contrast to the diversity of the market place. I will show that in Istanbul, residential quarters remained mixed in their social and religious make-up until Muslim migration from the Balkans during the nineteenth century enhanced the ratio of Muslims. Moreover, the debate among Ottomanists has focused on the existence or absence of themilletsystem (autonomous communal organizations) prior to the nineteenth century. Scholars have argued that themilletsystem was a nineteenth century development and that there was great fluidity and interaction among the minority communities and the Muslim majority in Ottoman cities. In the nineteenth century, Tanzimat reforms also centralized the administration of confessional communities and set legal boundaries between them that used to be more porous. Elsewhere, I have discussed the plural legal system in eighteenth century Istanbul.
MESA and the American University
Authors: Donner Fred M.
Published: February 2017

My theme is MESA and the American university. It is a worthy topic because MESA, and MESA’s membership, occupy distinctive places in the American academy. We are, as academic organizations and academic fields go, relatively small; but our membership constitutes, collectively and often individually, a deep reservoir of knowledge about a part of the world that has become of central importance to our country over the past several decades, and is likely long so to remain. The diverse and detailed understanding we hold about our region of special interest-the Middle East-is, or at least should be, a resource of immense value for those in our country, and beyond, who are also concerned with it-whether they are ordinary citizens, or business leaders, or political leaders and others who shape policy.

MESA exists, of course, in the context of the North American university system. MESA was founded in 1966 by a small group of American academicians-at a meeting in Chicago, no less, that quintessentially American city in which I am so fortunate to live. It offers a unique forum for the unfettered exchange of information and ideas on the Middle East, especially the contemporary and recent Middle East, free of any political or economic or cultural or religious orthodoxies; and it serves as a vehicle for encouraging scholarship on every aspect of the region from the perspective of all disciplines, and for encouraging and sustaining the intellectual development of the scholars who undertake such work. While MESA is autonomous and independent of any particular university, we all realize that it simply could not function effectively in the absence of the hundreds of universities and colleges in which most MESA members serve as faculty, academic staff, or students. Without our university or college paychecks most of us would hardly be able to pursue research on the Middle East. It is, I think, no mere coincidence that MESA was born in the 1960s and grew rapidly in the subsequent three decades, the period when the American university system itself reached perhaps its apogee in size and sophistication. MESA can be seen in some sense as a reflection of that period of educational flourishing.
Is Indonesia a Model for the Arab Spring? Islam, Democracy, and Diplomacy
Authors: Hoesterey James B.
Published: February 2017

As protestors filled Tahrir Square in Cairo in January 2011, Western diplomats, academics, and political pundits were searching for the best political analogy for the promise—and problems—of the Arab Uprising. Whereas neoconservative skeptics fretted that Egypt and Tunisia might go the way of post-revolutionary Iran, Hillary Clinton and Madeleine Albright praised Indonesia’s democratization as the ideal model for the Arab Spring. During her 2009 visit to Indonesia, Clinton proclaimed: “If you want to know whether Islam, democracy, modernity, and women’s rights can coexist, go to Indonesia.” Certainly Indonesia of May 1998 is not Egypt of January 2011, yet some comparisons are instructive. Still reeling from the Asian financial crisis of 1997, middle class Indonesians were fed up with corruption, cronyism, and a military that operated with impunity. On 21 May 1998 Soeharto resigned after three decades of authoritarian rule. Despite fits of starts and stops, the democratic transition has brought political and economic stability. Whereas academics and pundits have debated the merits of the Indonesia model for democratic transition, in this article I consider how the notion of Indonesia as a model for the Arab Spring has reconfigured transnational Muslim networks and recalibrated claims to authority and authenticity within the globalumma.

An increasing body of scholarship devoted to global Muslim networks offers important insights into thelongue duréeof merchant traders and itinerant preachers connecting the Middle East with Southeast Asia. In his critique of Benedict Anderson’s famous explanation of “imagined communities” as the result of print capitalismwithinnational borders, historian Michael Laffan argued that Indonesian nationalism had important roots in global Muslim networks connecting the Dutch East Indies with Cairo’s famous al-Azhar University.
Postscript on Laila Soliman's Revolutionary Theatre
Authors: Mehta Brinda
Published: February 2017

Laila Soliman's prophetic words in Lessons in Revolting, “this revolution is far from over” (2011) have come to fruition. The ouster of former President Mohammed Morsi and the Muslim Brotherhood-dominated government by a military takeover on 3 July 2013 (after only one year in power) has added another chapter to the uprising's trajectory. While the revolution inspired dramatic protest and equally spectacular creative expression in the form of experimental theatre, music, art, spoken word, and other forms, many Egyptian artistes and cultural critics have bemoaned a general stymying of artistic synergies at the state level due to a series of interconnected factors. They have attributed this attrition to “budget limitations, recurring safety problems, the so-called ‘religious eye’ that defied Egypt's cultural identity— particularly during the year when power was in the hands of the former president Mohamed Mursi—and a cabinet filled with either the Islamist factions or their sympathizers” (Metwaly 2013).
Multilevel Models in the Explanation of the Relationship between Safety Climate and Safe Behavior
Authors: Cheyne Alistair , Tomás José M. , Oliver Amparo
Published: February 2017

This study examines the relationships between components of organizational safety climate, including employee attitudes to organizational safety issues; perceptions of the physical working environment, and evaluations of worker engagement with safety issues; and relates these to self-reported levels of safety behavior. It attempts to explore the relationships between these variables in 1189 workers across 78 work groups in a large transportation organization. Evaluations of safety climate, the working environment and worker engagement, as well as safe behaviors, were collected using a self report questionnaire. The multilevel analysis showed that both levels of evaluation (the work group and the individual), and some cross-level interactions, were significant in explaining safe behaviors. Analyses revealed that a number of variables, at both levels, were associated with worker engagement and safe behaviors. The results suggest that, while individual evaluations of safety issues are important, there is also a role for the fostering of collective safety climates in encouraging safe behaviors and therefore reducing accidents.
Dimensionality of the Inventory of Parent and Peer Attachment: Evaluation with the Spanish Version
Authors: Gallarin Miriam , Alonso-Arbiol Itziar
Published: February 2017

Three studies aimed at developing the Spanish version of the Inventory of Parent and Peer Attachment (IPPA; Armsden & Greenberg, 1987) and at analyzing its factor structure are reported. In Study 1, the Spanish translation of items and their content analysis was carried out via cognitive interviews. In Study 2, the three-factor structure proposed by authors was tested in a sample of 417 adolescents (270 girls and 147 boys) using confirmatory analysis, and indexes showed a suboptimal fit. A principal component analysis yielded one-dimensional structures in father, mother and peer versions, explaining 54.3%, 50.8%, and 50.8% of the variance respectively. On the basis of the factor loadings and of the item-total correlations, a shortened version of the inventory was created. Convergent validity was tested with measures of family climate, parenting socialization and self-esteem. In Study 3, the one-dimension structure was confirmed in a new sample of 604 adolescents (335 girls and 269 boys). Based on all factor analyses and convergent validity indices obtained, we conclude that the Spanish IPPA questionnaire reliably and validly assesses adolescent attachment using only a dimension of attachment security.
Spanish Version of the Eating Attitudes Test 40: Dimensionality, Reliability, Convergent and Criterion Validity
Authors: Rivas Teresa , Franco Karina , Bersabé Rosa , Montiel Carmen Berrocal
Published: February 2017

The Eating Attitudes Test-40 (EAT-40; Garner & Garfinkel, 1979) is one of the most widely used measures in the field of eating disorders (ED). The factor structure of the EAT-40, as well as the optimal cut-off score to identify subjects with ED, are subjects of debate. Both controversial issues are addressed in the present study. Participants were 95 clinical females meeting DSM-IV-R criteria for ED and 89 females without ED. The results supported a unidimensional structure of the EAT-40 items scores. The general factor accounted for a high percentage (50.63%) of the variance in EAT-40 total scores. The questionnaire proved to have good internal consistency and test–retest reliability. Clinical participants displayed higher mean scores than normal subjects in the EAT-40. Further, participants meeting DSM-IV-R criteria for ED differed significantly from “symptomatic” and “asymptomatic” participants. Correlations with the BULIT-R and the EDI-II scores supported the convergent validity of the questionnaire. The EAT-40 also demonstrated good specificity (94.38%) and sensitivity (93.68%) to detect ED when a cut-off score of 27 was used to discriminate between subjects with and without ED. The implications of these findings for the conceptualization and the assessment of ED are discussed.
Analysis of Polymorphism rs1042522 in TP53 Gene in the Mothers of Twins and of Singletons: A Population-Based Study in Rio Grande do Sul, Brazil
Authors: Mardini Ana C. , Pereira Fernanda S. , Schuler-Faccini Lavínia , Matte Ursula
Published: February 2017

Although the birth of twins has always attracted attention, there are no known genetic or environmental factors that can determine the birth of monozygotic (MZ) twins. And even for dizygotic (DZ) twins, genetic influences are not completely understood. A previous study from our group has shown that the C allele of polymorphism rs1042522 in the TP53 gene was more frequent in the mothers of twins than in the mothers of singletons in a small village in South Brazil. In order to clarify whether this was an isolated factor, we performed a population-based, observational case-control study. Samples were selected from a state-funded program of paternity investigation. Samples were considered cases when two of the children had the same date of birth, whereas controls were those samples in which at least two children were born in different dates. The first subsequent sample fulfilling control criteria was included after each case. From 2007 to 2013, 32,661 records were searched and 283 (0.9%) twins were found (119 MZ and 164 DZ). Genotypic and allele frequencies were not different between mothers of twins or mothers of singletons. However, mothers of MZ twins showed a higher frequency of GG genotype and lower frequency of the C allele when compared to mothers of DZ twins. Also, the proportion of MZ twins (42%) was higher than usually reported (30%). Finally, the proportion of twins found in this study seems to be more realistic, as this sample was allegedly not from users of assisted reproduction techniques.
Measuring Implicit Cognitive and Emotional Engagement to Better	Understand Learners’ Performance in Problem Solving
Authors: Charland Patrick , Léger Pierre-Majorique , Mercier Julien , Skelling Yannick , Lapierre Hugo G.
Published: February 2017

Abstract. Novel data collection methods and analysis algorithms developed in the field of neuroergonomics have opened new possibilities for research in education. Psychophysiological data can characterize the cognitive and emotional dimensions of engagement. This paper aims to describe the application of this research methodology to synchronously measure emotional and cognitive engagement during learning tasks.
TAK1 regulates resident macrophages by protecting lysosomal integrity
Authors: Sakamachi Yosuke , Morioka Sho , Mihaly September R , Takaesu Giichi , Foley Julie F , Fessler Michael B , Ninomiya-Tsuji Jun
Published: February 2017

Hematopoietic cell survival and death is critical for development of a functional immune system. Here, we report that a protein kinase, TAK1, is selectively required for resident macrophage integrity during embryogenesis. Hematopoietic lineage-specific deletion of Tak1 gene (Tak1HKO) caused accumulation of cellular debris in the thymus in perinatal mice. Although no overt alteration in thymocytes and blood myeloid populations was observed in Tak1HKO mice, we found that thymic and lung macrophages were diminished. In the in vitro setting, Tak1 deficiency caused profound disruption of lysosomes and killed bone marrow-derived macrophages (BMDMs) without any exogenous stressors. Inhibition of the lysosomal protease, cathepsin B, partially blocked Tak1-deficient BMDM death, suggesting that leakage of the lysosomal contents is in part the cause of cell death. To identify the trigger of this cell death, we examined involvement of TNF and Toll-like receptor pathways. Among them, we found that deletion of Tnfr1 partially rescued cell death. Finally, we show that Tnfr1 deletion partially restored thymic and lung macrophages in vivo. These results suggest that autocrine and potentially paracrine TNF kills Tak1-deficient macrophages during development. Our results reveal that TAK1 signaling maintains proper macrophage populations through protecting lysosomal integrity.
Starvation at birth impairs germ cell cyst breakdown and increases autophagy and apoptosis in mouse oocytes
Authors: Wang Yong-Yong , Sun Yuan-Chao , Sun Xiao-Feng , Cheng Shun-Feng , Li Bo , Zhang Xi-Feng , De Felici Massimo , Shen Wei
Published: February 2017

The female reproductive lifespan is largely determined by the size of primordial follicle pool, which is established following germ cell cyst breakdown around birth. Almost two-third of oocytes are lost during germ cell cysts breakdown, following autophagic and apoptosis mechanisms. To investigate a possible relationship between germ cell cyst breakdown and nutrition supply, we established a starvation model in mouse pups at birth and evaluated the dynamics of cyst breakdown during nutrient deprivation. Our results showed that after 36 h of starvation between 1.5 and 3 d.p.p., indicators of metabolism both at systemic and ovarian level were significantly altered and the germ cell cyst breakdown markedly decreased. We also found that markers of oxidative stress, autophagy and apoptosis were increased and higher number of oocytes in cyst showing autophagic markers and of TUNEL-positive oocytes and somatic cells were present in the ovaries of starved pups. Moreover, the proliferation of pre-granulosa cells and the expression of the oocyte-specific transcription factor Nobox were decreased in such ovaries. Finally, we observed that the ovaries of the starved pups could recover a normal number of follicles after about 3 weeks from re-feeding. In conclusion, these data indicate that nutrient deficiency at birth can generate a number of adaptive metabolic and oxidative responses in the ovaries causing increased apoptosis both in the somatic cells and oocyte and autophagy mainly in these latter and leading to a delay of germ cell cyst breakdown and follicle assembly.
Epstein–Barr virus particles induce centrosome amplification and chromosomal instability
Authors: Shumilov Anatoliy , Tsai Ming-Han , Schlosser Yvonne T. , Kratz Anne-Sophie , Bernhardt Katharina , Fink Susanne , Mizani Tuba , Lin Xiaochen , Jauch Anna , Mautner Josef , Kopp-Schneider Annette , Feederle Regina , Hoffmann Ingrid , Delecluse Henri-Jacques
Published: February 2017

Infections with Epstein–Barr virus (EBV) are associated with cancer development, and EBV lytic replication (the process that generates virus progeny) is a strong risk factor for some cancer types. Here we report that EBV infection of B-lymphocytes (in vitro and in a mouse model) leads to an increased rate of centrosome amplification, associated with chromosomal instability. This effect can be reproduced with virus-like particles devoid of EBV DNA, but not with defective virus-like particles that cannot infect host cells. Viral protein BNRF1 induces centrosome amplification, and BNRF1-deficient viruses largely lose this property. These findings identify a new mechanism by which EBV particles can induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for development of tumours that do not necessarily carry the viral genome.
Boninite-like intraplate magmas from Manihiki Plateau require ultra-depleted and enriched source components
Authors: Golowin Roman , Portnyagin Maxim , Hoernle Kaj , Hauff Folkmar , Gurenko Andrey , Garbe-Schönberg Dieter , Werner Reinhard , Turner Simon
Published: February 2017

The Ontong Java and Manihiki oceanic plateaus are believed to have formed through high-degree melting of a mantle plume head. Boninite-like, low-Ti basement rocks at Manihiki, however, imply a more complex magma genesis compared with Ontong Java basement lavas that can be generated by ∼30% melting of a primitive mantle source. Here we show that the trace element and isotope compositions of low-Ti Manihiki rocks can best be explained by re-melting of an ultra-depleted source (possibly a common mantle component in the Ontong Java and Manihiki plume sources) re-enriched by ≤1% of an ocean-island-basalt-like melt component. Unlike boninites formed via hydrous flux melting of refractory mantle at subduction zones, these boninite-like intraplate rocks formed through adiabatic decompression melting of refractory plume material that has been metasomatized by ocean-island-basalt-like melts. Our results suggest that caution is required before assuming all Archaean boninites were formed in association with subduction processes.
Surface single-molecule dynamics controlled by entropy at low temperatures
Authors: Gehrig J. C. , Penedo M. , Parschau M. , Schwenk J. , Marioni M. A. , Hudson E. W. , Hug H. J.
Published: February 2017

Configuration transitions of individual molecules and atoms on surfaces are traditionally described using an Arrhenius equation with energy barrier and pre-exponential factor (attempt rate) parameters. Characteristic parameters can vary even for identical systems, and pre-exponential factors sometimes differ by orders of magnitude. Using low-temperature scanning tunnelling microscopy (STM) to measure an individual dibutyl sulfide molecule on Au(111), we show that the differences arise when the relative position of tip apex and molecule changes by a fraction of the molecule size. Altering the tip position on that scale modifies the transition’s barrier and attempt rate in a highly correlated fashion, which results in a single-molecular enthalpy-entropy compensation. Conversely, appropriately positioning the STM tip allows selecting the operating point on the compensation line and modifying the transition rates. The results highlight the need to consider entropy in transition rates of single molecules, even at low temperatures.
Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial
Authors: Basheti Iman A. , Obeidat Nathir M. , Reddel Helen K.
Published: February 2017

Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0–9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a “Show-and-Tell” inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler −1.04 (95% confidence interval −1.92, −0.16, P = 0.022); Turbuhaler −1.61 (−2.63, −0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes.
A small subset of protected areas are a highly significant source of carbon emissions
Authors: Collins Murray B. , Mitchard Edward T. A.
Published: February 2017

Protected areas (PAs) aim to protect multiple ecosystem services. However, not all are well protected. For the first time, using published carbon and forest loss maps, we estimate carbon emissions in large forest PAs in tropical countries (N = 2018). We found 36 ± 16 Pg C stored in PA trees, representing 14.5% of all tropical forest biomass carbon. However the PAs lost forest at a mean rate of 0.18% yr−1 from 2000–2012. Lower protection status areas experienced higher forest losses (e.g. 0.39% yr−1 in IUCN cat III), yet even highest status areas lost 0.13% yr−1 (IUCN Cat I). Emissions were not evenly distributed: 80% of emissions derived from 8.3% of PAs (112 ± 49.5 Tg CO2 yr−1; n = 171). Unsurprisingly the largest emissions derived from PAs that started with the greatest total forest area; accounting for starting forest area and relating that to carbon lost using a linear model (r2 = 0.41), we found 1.1% outlying PAs (residuals >2σ; N = 23), representing 1.3% of the total PA forest area, yet causing 27.3% of all PA emissions. These results suggest PAs have been a successful means of protecting biomass carbon, yet a subset causing a disproportionately high share of emissions should be an urgent priority for management interventions.
BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas
Authors: Ibáñez-Costa Alejandro , López-Sánchez Laura M. , Gahete Manuel D. , Rivero-Cortés Esther , Vázquez-Borrego Mari C. , Gálvez María A. , de la Riva Andrés , Venegas-Moreno Eva , Jiménez-Reina Luis , Moreno-Carazo Alberto , Tinahones Francisco J. , Maraver-Selfa Silvia , Japón Miguel A. , García-Arnés Juan A. , Soto-Moreno Alfonso , Webb Susan M. , Kineman Rhonda D. , Culler Michael D. , Castaño Justo P. , Luque Raúl M.
Published: February 2017

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3–5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.
NF-κB regulates neuronal ankyrin-G via a negative feedback loop
Authors: König Hans-Georg , Schwamborn Robert , Andresen Silke , Kinsella Sinéad , Watters Orla , Fenner Beau , Prehn Jochen H. M.
Published: February 2017

The axon initial segment (AIS) is a neuronal compartment defined by ankyrin-G expression. We here demonstrate that the IKK-complex co-localizes and interacts with the cytoskeletal anchor protein ankyrin-G in immunoprecipitation and proximity-ligation experiments in cortical neurons. Overexpression of the 270 kDa variant of ankyrin-G suppressed, while gene-silencing of ankyrin-G expression increased nuclear factor-κB (NF-κB) activity in primary neurons, suggesting that ankyrin-G sequesters the transcription factor in the AIS. We also found that p65 bound to the ank3 (ankyrin-G) promoter sequence in chromatin immunoprecipitation analyses thereby increasing ank3 expression and ankyrin-G levels at the AIS. Gene-silencing of p65 or ankyrin-G overexpression suppressed ank3 reporter activity. Collectively these data demonstrate that p65/NF-κB controls ankyrin-G levels via a negative feedback loop, thereby linking NF-κB signaling with neuronal polarity and axonal plasticity.
No effect of mitochondrial genotype on reproductive plasticity following exposure to a non-infectious pathogen challenge in female or male Drosophila
Authors: Nystrand M. , Cassidy E. J. , Dowling D. K.
Published: February 2017

Mitochondrial genetic variation shapes the expression of life-history traits associated with reproduction, development and survival, and has also been associated with the prevalence and progression of infectious bacteria and viruses in humans. The breadth of these effects on multifaceted components of health, and their link to disease susceptibility, led us to test whether variation across mitochondrial haplotypes affected reproductive success following an immune challenge in the form of a non-infectious pathogen. We test this, by challenging male and female fruit flies (Drosophila melanogaster), harbouring each of three distinct mitochondrial haplotypes in an otherwise standardized genetic background, to either a mix of heat-killed bacteria, or a procedural control, prior to measuring their subsequent reproductive performance. The effect of the pathogen challenge on reproductive success did not differ across mitochondrial haplotypes; thus there was no evidence that patterns of reproductive plasticity were modified by the mitochondrial genotype following a non-infectious pathogen exposure. We discuss the implications of our data, and suggest future research avenues based on these results.
The NRF2 transcriptional target, OSGIN1, contributes to monomethyl fumarate-mediated cytoprotection in human astrocytes
Authors: Brennan Melanie S. , Matos Maria F. , Richter Karl E. , Li Bing , Scannevin Robert H.
Published: February 2017

Dimethyl fumarate (DMF) is indicated for the treatment of relapsing multiple sclerosis and may exert therapeutic effects via activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway. Following oral DMF administration, central nervous system (CNS) tissue is predominantly exposed to monomethyl fumarate (MMF), the bioactive metabolite of DMF, which can stabilize NRF2 and induce antioxidant gene expression; however, the detailed NRF2-dependent mechanisms modulated by MMF that lead to cytoprotection are unknown. Our data identify a mechanism for MMF-mediated cytoprotection in human astrocytes that functions in an OSGIN1-dependent manner, specifically via upregulation of the OSGIN1-61 kDa isoform. NRF2-dependent OSGIN1 expression induced P53 nuclear translocation following MMF administration, leading to cell-cycle inhibition and cell protection against oxidative challenge. This study provides mechanistic insight into MMF-mediated cytoprotection via NRF2, OSGIN1, and P53 in human CNS-derived cells and contributes to our understanding of how DMF may act clinically to ameliorate pathological processes in neurodegenerative disease.
Speed versus endurance tradeoff in plants: Leaves with higher photosynthetic rates show stronger seasonal declines
Authors: Zhang Yong-Jiang , Sack Lawren , Cao Kun-Fang , Wei Xue-Mei , Li Nan
Published: February 2017

We tested for a tradeoff across species between plant maximum photosynthetic rate and the ability to maintain photosynthesis under adverse conditions in the unfavorable season. Such a trade-off would be consistent with the observed trade-off between maximum speed and endurance in athletes and some animals that has been explained by cost-benefit theory. This trend would have importance for the general understanding of leaf design, and would simplify models of annual leaf carbon relations. We tested for such a trade-off using a database analysis across vascular plants and using an experimental approach for 29 cycad species, representing an ancient plant lineage with diversified evergreen leaves. In both tests, a higher photosynthetic rate per mass or per area in the favorable season was associated with a stronger absolute or percent decline in the unfavorable season. We resolved a possible mechanism based on biomechanics and nitrogen allocation; cycads with high leaf toughness (leaf mass per area) and higher investment in leaf construction than in physiological function (C/N ratio) tended to have lower warm season photosynthesis but less depression in the cool season. We propose that this trade-off, consistent with cost-benefit theory, represents a significant physio-phenological constraint on the diversity and seasonal dynamics of photosynthetic rate.
Thiazole-valine peptidomimetic (TTT-28) antagonizes multidrug resistance in vitro and in vivo by selectively inhibiting the efflux activity of ABCB1
Authors: Wang Yi-Jun , Patel Bhargav A. , Anreddy Nagaraju , Zhang Yun-Kai , Zhang Guan-Nan , Alqahtani Saeed , Singh Satyakam , Shukla Suneet , Kaddoumi Amal , Ambudkar Suresh V. , Talele Tanaji T. , Chen Zhe-Sheng
Published: February 2017

Multidrug resistance (MDR) attenuates the chemotherapy efficacy and increases the probability of cancer recurrence. The accelerated drug efflux mediated by ATP-binding cassette (ABC) transporters is one of the major MDR mechanisms. This study investigated if TTT-28, a newly synthesized thiazole-valine peptidomimetic, could reverse ABCB1-mediated MDR in vitro and in vivo. TTT-28 reversed the ABCB1-mediated MDR and increased the accumulation of [3H]-paclitaxel in ABCB1 overexpressing cells by selectively blocking the efflux function of ABCB1, but not interfering with the expression level and localization of ABCB1. Animal study revealed that TTT-28 enhanced the intratumoral concentration of paclitaxel and promoted apoptosis, thereby potently inhibiting the growth of ABCB1 overexpressing tumors. But TTT-28 did not induce the toxicity (cardiotoxicity/myelosuppression) of paclitaxel in mice. In this study, we synthesized and evaluated a novel selective inhibitor of ABCB1 (TTT-28) with high efficacy and low toxicity. The identification and characterization of this new thiazole-valine peptidomimetic will facilitate design and synthesis of a new generation of ABCB1 inhibitors, leading to further research on multidrug resistance and combination chemotherapy. Furthermore, the strategy that co-administer MDR-ABCB1 inhibitor to overcome the resistance of one FDA approved, widely used chemotherapeutic paclitaxel, may be promising direction for the field of adjuvant chemotherapy.
Dynamic in-situ sensing of fluid-dispersed 2D materials integrated on microfluidic Si chip
Authors: Hogan Benjamin T. , Dyakov Sergey A. , Brennan Lorcan J. , Younesy Salma , Perova Tatiana S. , Gun’ko Yurii K. , Craciun Monica F. , Baldycheva Anna
Published: February 2017

In this work, we propose a novel approach for wafer-scale integration of 2D materials on CMOS photonic chip utilising methods of synthetic chemistry and microfluidics technology. We have successfully demonstrated that this approach can be used for integration of any fluid-dispersed 2D nano-objects on silicon-on-insulator photonics platform. We demonstrate for the first time that the design of an optofluidic waveguide system can be optimised to enable simultaneous in-situ Raman spectroscopy monitoring of 2D dispersed flakes during the device operation. Moreover, for the first time, we have successfully demonstrated the possibility of label-free 2D flake detection via selective enhancement of the Stokes Raman signal at specific wavelengths. We discovered an ultra-high signal sensitivity to the xyz alignment of 2D flakes within the optofluidic waveguide. This in turn enables precise in-situ alignment detection, for the first practicable realisation of 3D photonic microstructure shaping based on 2D-fluid composites and CMOS photonics platform, while also representing a useful technological tool for the control of liquid phase deposition of 2D materials.
Genomic Variant in IL-37 Confers A Significant Risk of Coronary Artery Disease
Authors: Yin Dan , Naji Duraid Hamied , Xia Yunlong , Li Sisi , Bai Ying , Jiang Guiqing , Zhao Yuanyuan , Wang Xiaojing , Huang Yufeng , Chen Shanshan , Fa Jingjing , Tan Chengcheng , Zhou Mengchen , Zhou Yingchao , Wang Longfei , Liu Ying , Chen Feifei , Liu Jingqiu , Chen Qiuyun , Tu Xin , Xu Chengqi , Wang Qing K.
Published: February 2017

The interleukin 1 family plays an important role in the immune and inflammatory responses. Coronary artery disease (CAD) is a chronic inflammatory disease. However, the genetic association between IL-37, the seventh member of the IL-1 family, and CAD is unknown. Here we show that a single nucleotide polymorphism in the IL-37 gene (rs3811047) confers a significant risk of CAD. We have performed an association analysis between rs3811047 and CAD in two independent populations with 2,501 patients and 3,116 controls from China. Quantitative RT-PCR analysis has been performed to determine if the IL-37 expression level is influenced by rs3811047. We show that the minor allele A of rs3811047 is significantly associated with CAD in two independent populations under a recessive model (Padj = 5.51 × 10−3/OR = 1.56 in the GeneID Northernern population and Padj = 1.23 × 10−3/OR = 1.45 in the GeneID Central population). The association became more significant in the combined population (Padj = 9.70 × 10−6/OR = 1.47). Moreover, the association remains significant in a CAD case control population matched for age and sex. Allele A of rs3811047 shows significant association with a decreased mRNA expression level of IL-37 (n = 168, P = 3.78 × 10−4). These data suggest that IL37 is a new susceptibility gene for CAD, which provides a potential target for the prevention and treatment of CAD.
Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography
Authors: Campbell J. P. , Zhang M. , Hwang T. S. , Bailey S. T. , Wilson D. J. , Jia Y. , Huang D.
Published: February 2017

Optical coherence tomography angiography (OCTA) is a noninvasive method of 3D imaging of the retinal and choroidal circulations. However, vascular depth discrimination is limited by superficial vessels projecting flow signal artifact onto deeper layers. The projection-resolved (PR) OCTA algorithm improves depth resolution by removing projection artifact while retaining in-situ flow signal from real blood vessels in deeper layers. This novel technology allowed us to study the normal retinal vasculature in vivo with better depth resolution than previously possible. Our investigation in normal human volunteers revealed the presence of 2 to 4 distinct vascular plexuses in the retina, depending on location relative to the optic disc and fovea. The vascular pattern in these retinal plexuses and interconnecting layers are consistent with previous histologic studies. Based on these data, we propose an improved system of nomenclature and segmentation boundaries for detailed 3-dimensional retinal vascular anatomy by OCTA. This could serve as a basis for future investigation of both normal retinal anatomy, as well as vascular malformations, nonperfusion, and neovascularization.
Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury
Authors: Bai Liangjie , Mei Xifan , Shen Zhaoliang , Bi Yunlong , Yuan Yajiang , Guo Zhanpeng , Wang Hongyu , Zhao Haosen , Zhou Zipeng , Wang Chen , Zhu Kunming , Li Gang , Lv Gang
Published: February 2017

Autophagy is an process for the degradation of cytoplasmic aggregated proteins and damaged organelles and plays an important role in the development of SCI. In this study, we investigated the therapeutic effect of Netrin-1 and its potential mechanism for autophagy regulation after SCI. A rat model of SCI was established and used for analysis. Results showed that administration of Netrin-1 not only significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK) but also reduced the phosphorylation of mammalian target of rapamycin (mTOR) and P70S6K. In addition, the expression of Beclin-1 and the ratio of the light-chain 3B-II (LC3B-II)/LC3B-I in the injured spinal cord significantly increased in Netrin-1 group than those in SCI group. Moreover, the ratio of apoptotic neurons in the anterior horn of the spinal cord and the cavity area of spinal cord significantly decreased in Netrin-1 group compared with those in SCI group. In addition, Netrin-1 not only preserved motor neurons but also significantly improved motor fuction of injured rats. These results suggest that Netrin-1 improved functional recovery through autophagy stimulation by activating the AMPK/mTOR signaling pathway in rats with SCI. Thus, Netrin-1 treatment could be a novel therapeutic strategy for SCI.