bluuebunny/crossref_metadata_2025 huggingface dataset:
Representations of medical instruments and equipment in Serbian medieval painting
Authors: Pajic Sanja
Published: May 2015

The paper topic is identification of medical instruments and equipment using
the images preserved in Serbian medieval painting. This topic has not been
the subject of special study in the Serbian science. Medical instruments and
equipment make an integral part of iconography of saint physicians. The
following medical instruments have been displayed: knives, probes, spoons,
tweezers, as well as various carrying boxes for equipment (square-like and
cylindrical) and cases, and glass vessels for medical lubricants.
Identification has been carried out owing primarily to late Roman remains of
medical instruments and equipment, while such remains originating from
Byzantine period are very rare.
Michael Glabas Tarchaneiotes - the ktetor of the Treskavac Monastery
Authors: Markovic Miodrag
Published: May 2015

In this paper, the monastery of Prisklabetza (????????????) in Prilep,
mentioned as the endowment of Michael Glabas Tarchaneiotes in the shortened
version of the History by George Pachymeres, is identified with the monastery
of Treskavac near Prilep. This conclusion is supported by the similarity
between the names of the two monasteries, the composition with a ktetor in
the porch of the main entrance to Treskavac, and the nature of construction
works carried out in the monastery between 1280 and 1320.
On the trail of a painting bequeathed to St. George’s abbey on the islet near Perast the testaments of Nycolaus and Johannes Glauacti (as of 1327 and 1336)
Authors: Zivkovic Valentina
Published: May 2015

The paper reviews the last will of the Kotor nobleman Nycolaus Marini
Glauacti made in 1327 to bequeath to St. George?s church on the small island
near Perast a depiction of the Madonna, St. Nicholas and St. John the
Baptist. On the one hand, the legacy is analyzed in the context of the
compositions involving the three saints in Kotor?s religious medieval art
and, on the other, in the context of ad pias causas bequests and the concept
of preparing for a good death (ars moriendi). The contents of the testaments
of Nycolaus and his brother Johannes Marin Glauacti as of 1336 are
contrasted, especially in terms of the number of pro remedio animae items
bequeathed and their distribution. A special emphasis is laid on the
comparison of the representations between the Franciscan and Benedictine
Orders as the recipients of pious bequests.
Concepts-Based Education in a Rules-Based World: A Challenge for Accounting Educators
Authors: Ryack Kenneth N. , Mastilak M. Christian , Hodgdon Christopher D. , Allen Joyce S.
Published: May 2015

In this paper we discuss the challenges of teaching U.S. GAAP and IFRS side by side. We then focus on one particular challenge of teaching both the more detailed U.S. standards and the less specific IFRS: the likelihood that students will “anchor” on the precise rules in U.S. GAAP when applying the less specific guidelines under IFRS. As a part of this discussion, we report on a classroom experiment designed to test for the presence of anchoring on U.S. GAAP rules when applying IFRS in a lease classification task. Our results indicate that students do anchor on the U.S. GAAP bright-line values for lease accounting when classifying leases under IFRS, primarily when U.S. GAAP rules provide an acceptable quantification of IFRS' less precise guidelines. We do not find that teaching order (i.e., teaching U.S. GAAP first versus IFRS first) directly affects anchoring or lease classification. However, a moderation analysis suggests the interaction between teaching order and anchoring may affect lease classification. Our results suggest that, where possible, instructors may wish to teach principles-based accounting prior to rules-based accounting to mitigate potential anchoring by students and its effect on their accounting judgments.

Data Availability: Contact the authors.
Earnings Quality of Foreign versus U.S. Reverse Mergers: Geographical Location or Firm-Level Incentives?
Authors: Chen Chu , Gotti Giorgio , Herrmann Don , Schumann Kathryn
Published: May 2015

We test whether geographical location, audit quality, and equity offering play a role in the earnings quality of reverse merger (RM) firms. We provide evidence that, contrary to the popular focus on foreign reverse mergers by the business press, earnings management is equally likely in both U.S. and foreign RM companies. We find that firm characteristics are more indicative of the likelihood to manage earnings than geographical location. The presence of a Big 4 auditor for RM firms is associated with higher earnings quality and a survival rate almost twice as high in comparison to RM firms audited by a non-Big 4 auditor. Moreover, we find that while earnings management is a common practice at all RM firms, it is especially pervasive for RM firms that are issuing new equity after the reverse merger.
Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance
Authors: Al-Share Qusai Y. , DeAngelis Anthony M. , Lester Sumona Ghosh , Bowman Thomas A. , Ramakrishnan Sadeesh K. , Abdallah Simon L. , Russo Lucia , Patel Payal R. , Kaw Meenakshi K. , Raphael Christian K. , Kim Andrea Jung , Heinrich Garrett , Lee Abraham D. , Kim Jason K. , Kulkarni Rohit N. , Philbrick William M. , Najjar Sonia M.
Published: May 2015

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance. Liver-specific inactivation or global null-mutation of Ceacam1 impairs hepatic insulin extraction to cause chronic hyperinsulinemia, resulting in insulin resistance and visceral obesity. In this study we investigated whether diet-induced insulin resistance implicates changes in hepatic CEACAM1. We report that feeding C57/BL6J mice a high-fat diet reduced hepatic CEACAM1 levels by >50% beginning at 21 days, causing hyperinsulinemia, insulin resistance, and elevation in hepatic triacylglycerol content. Conversely, liver-specific inducible CEACAM1 expression prevented hyperinsulinemia and markedly limited insulin resistance and hepatic lipid accumulation that were induced by prolonged high-fat intake. This was partly mediated by increased hepatic β-fatty acid oxidation and energy expenditure. The data demonstrate that the high-fat diet reduced hepatic CEACAM1 expression and that overexpressing CEACAM1 in liver curtailed diet-induced metabolic abnormalities by protecting hepatic insulin clearance.
Improving Adiponectin Levels in Individuals With Diabetes and Obesity: Insights From Look AHEAD
Authors: Belalcazar L. Maria , Lang Wei , Haffner Steven M. , Schwenke Dawn C. , Kriska Andrea , Balasubramanyam Ashok , Hoogeveen Ron C. , Pi-Sunyer F. Xavier , Tracy Russell P. , Ballantyne Christie M. ,   the Look AHEAD (Action for Health in Diabetes) Research Group
Published: May 2015

OBJECTIVE

This study investigated whether fitness changes resulting from lifestyle interventions for weight loss may independently contribute to the improvement of low adiponectin levels in obese individuals with diabetes.

RESEARCH DESIGN AND METHODS

Look AHEAD (Action for Health in Diabetes) randomized overweight/obese individuals with type 2 diabetes to intensive lifestyle intervention (ILI) for weight loss or to diabetes support and education (DSE). Total and high–molecular weight adiponectin (adiponectins), weight, and cardiorespiratory fitness (submaximal exercise stress test) were measured in 1,397 participants at baseline and at 1 year, when ILI was most intense. Regression analyses examined the associations of 1-year weight and fitness changes with change in adiponectins.

RESULTS

ILI resulted in greater improvements in weight, fitness, and adiponectins at 1 year compared with DSE (P < 0.0001). Weight loss and improved fitness were each associated with changes in adiponectins in men and women (P < 0.001 for all), after adjusting for baseline adiponectins, demographics, clinical variables, and treatment arm. Weight loss contributed an additional 4–5% to the variance of change in adiponectins than did increased fitness in men; in women, the contributions of improved fitness (1% greater) and of weight loss were similar. When weight and fitness changes were both accounted for, weight loss in men and increased fitness in women retained their strong associations (P < 0.0001) with adiponectin change.

CONCLUSIONS

Improvements in fitness and weight with ILI were favorably but distinctly associated with changes in adiponectin levels in overweight/obese men and women with diabetes. Future studies need to investigate whether sex-specific biological determinants contribute to the observed associations.
Anthropology of the Word
Authors: Godlewski Grzegorz
Published: May 2015

Anthropology of the word is an approach that originated in Poland, at the University of Warsaw, in the early 1990s. It emerged from philological study of language and literature, by widening and strengthening their cultural dimensions. Gradually, this approach grew closer to linguistic anthropology but retained its specificity, which consists essentially in considering linguistic practices as cultural practices, including language-mediated practices in which the verbal line is only one thread; studying historical forms of linguistic practices; recognising verbal art (including literature) as a set of peculiar linguistic practices and making it a subject of anthropological study; including linguistic practices other than oral and written ones; identifying various cognitive aspects of the textual bias in order to eliminate its distorting effect on the study of linguistic practices.
Common Ground and Missing Links German Volkskunde and Language
Authors: Groth Stefan
Published: May 2015

Language and its relation to culture has been a topic of research in German Volkskunde [folklore studies] from the beginning of the discipline. While dialectological studies, linguistic specificities of local cultures and language in everyday life have been integral parts of Volkskunde for much of the first part of the twentieth century, the discipline saw a shift away from its philological elements towards a social science orientation in post-Second World War developments. During the last decades, the analysis of linguistic dimensions of everyday culture has been on the margin of scholarly activities in Volkskunde. Starting with a historic perspective on the role of language in the beginnings of the discipline, this article discusses the development and decrease of the study of linguistic aspects. It analyses the role of language in contemporary German Volkskunde both in theory and methodology, and offers perspectives on how the discipline could benefit from a renewed focus on linguistic dimensions of everyday culture.
Language Revitalisation Models in Minority Language Contexts
Authors: O'Rourke Bernadette
Published: May 2015

This article looks at the historicisation of the native speaker and ideologies of authenticity and anonymity in Europe's language revitalisation movements. It focuses specifically on the case of Irish in the Republic of Ireland and examines how the native speaker ideology and the opposing ideological constructs of authenticity and anonymity filter down to the belief systems and are discursively produced by social actors on the ground. For this I draw on data from ongoing fieldwork in the Republic of Ireland, drawing on interviews with a group of Irish language enthusiasts located outside the officially designated Irish-speaking Gaeltacht.
Cartographies of Communicability and the Anthropological Archive
Authors: French Brigittine
Published: May 2015

This article traces ideological constructions of communication that enable powerful actors to determine what counts as silences, lies and surpluses in efficacious narratives about violence (Briggs 2007) in order to elucidate occlusions regarding legacies of the Civil War in the Irish Free State. It does so through a precise triangulation of multiple competing and overlapping narratives from unpublished fieldnotes, interviews, published ethnographies and other first-person accounts. The inquiry highlights social memories of the Irish Civil War that have been 'assumed, distorted, misunderstood, manipulated, underestimated, but most of all, ignored' (Dolan 2003: 2). The article argues that the excesses of the anthropological archive make the recuperation of a multiplicity of collective memories possible through a linguistic anthropological perspective that enumerates the kind of erasures at play in contentious memory-making moments, highlights polyvocality in metapragmatic discourse and tracks the gaps in entextualisation processes of historical narratives about political turmoil.
'We Are the Losers of Socialism!'
Authors: Stillo Jonathan
Published: May 2015

Mircea stares off The Pines Tuberculosis Sanatorium balcony. He tells me that in the valley below he once had a family and worked as a miner and then at a collective farm. Now he is alone and unwanted. His blue eyes well up with tears and he tells me, ‘we are the losers of socialism, there is no hope for us’. He continues: ‘We are losers in society, and when you see yourself, the way you are now, and you know what you used to be, when you mattered, and worked … it’s hard for you. This is why we say we are embarrassed, because you don’t matter anymore, to anybody.’ 55-year-old Mircea spent the last four years of his life here, abandoned by his family, dying of XDR-TB.1 When I asked his doctor when he would go home, she replied, ‘Home? To what? ... He is a social case,2 I cannot discharge him.’
The Antebellum American Textbook Authors' Populist History of Roman Land Reform and the Gracchi Brothers
Authors: McInnis Edward
Published: May 2015

This essay explores social and political values conveyed by nineteenth century world and universal history textbooks in relation to the antebellum era. These textbooks focused on the histories of ancient Greece and Rome rather than on histories of the United States. I argue that after 1830 these textbooks reinforced both the US land reform and the antislavery movement by creating favorable depictions of Tiberius and Caius Gracchus. Tiberius and Caius Gracchus (known as the “Gracchi”) were two Roman tribunes who sought to restore Rome's land laws, which granted public land to propertyless citizens despite opposition from other Roman aristocrats. The textbook authors' portrayal of the Gracchan reforms reflects a populist element in antebellum American education because these narratives suggest that there is a connection between social inequality and the decline of republicanism.
Religion in the National Historical Narrative of the Early Modern Times in Contemporary Ukrainian Schooling
Authors: Shevchenko Tetiana
Published: May 2015

This article deals with religious discourse in modern history school textbooks in Ukraine that cover early modern times in Ukrainian history. It analyzes the place of religious discourse within national discourse, the correlation between local Ukrainian religious and more general discourse, and the representation of the relationships between Christian churches. Further, it defines a methodological approach and assesses the accuracy of facts presented in textbooks as well as the interpretation of religious life, normative language, and denominational labeling. It demonstrates the discrepancy between the achievements of academic historiography and school history, including the isolated and exclusive nature of history discourse in Ukrainian schools today.
Modelling the Antarctic marine cryosphere at the Last Glacial Maximum
Authors: Kusahara Kazuya , Sato Tatsuru , Oka Akira , Obase Takashi , Greve Ralf , Abe-Ouchi Ayako , Hasumi Hiroyasu
Published: May 2015

We estimate the sea-ice extent and basal melt of Antarctic ice shelves at the Last Glacial Maximum (LGM) using a coupled ice-shelf-sea-ice-ocean model. The shape of Antarctic ice shelves, ocean conditions and atmospheric surface conditions at the LGM are different from those in the present day; these are derived from an ice-shelf-ice-sheet model, a sea-ice-ocean model and a climate model for glacial simulations, respectively. The winter sea ice in the LGM is shown to extend up to ∼7° of latitude further equatorward than in the present day. For the LGM summer, the model shows extensive sea-ice cover in the Atlantic sector and little sea ice in the other sectors. These modelled sea-ice features are consistent with those reconstructed from sea-floor sedimentary records. Total basal melt of Antarctic ice shelves in the LGM was ∼2147 Gt a–1, which is much larger than the present-day value. More warm waters originating from Circumpolar Deep Water could be easily transported into ice-shelf cavities during the LGM because the full glacial grounding line extended to shelf break regions and ice shelves overhung continental slopes. This increased transport of warm water masses underneath an ice shelf and into their basal cavities led to the high basal melt of ice shelves in the LGM.
Glacier change in the Karatal river basin, Zhetysu (Dzhungar) Alatau, Kazakhstan
Authors: Kaldybayev Azamat , Chen Yaning , Vilesov Evgeniy
Published: May 2015

We investigated glacier changes in the Karatal river basin, the largest basin in Zhetysu (Dzhungar) Alatau, Kazakhstan, for the periods 1956–89, 1989–2001 and 2001–12, based on Landsat TM/ETM+ data analysis. In 1989, we found 243 glaciers with a total area of 142.8 km2; by 2012 these had shrunk to 214 glaciers with a total area of 109.3 km2, a decrease of 33.5 km2 over 23 years (1.02%a-1). This very high shrinkage rate is likely connected with a general trend of increasing temperatures, and small glaciers being situated at the relatively low altitude of the outer Zhetysu Alatau ranges. We also analyzed the shrinkage rate of glaciers based on their differences in size, altitude and aspect of slopes, as well as other topographic parameters, in four sub-basins where glacier shrinkage varied between 18% and 39%. Weather-station climate data showed a significant temperature increase and stable precipitation trends over the study period. We conclude that glacierized areas of the Karatal river basin are located in the most unfavorable conditions for glaciation, and as a result showed a higher shrinkage rate than other glacierized areas of the Tien Shan from 1956 to 2012.
A hierarchical knowledge-based classification for glacier terrain mapping: a case study from Kolahoi Glacier, Kashmir Himalaya
Authors: Shukla Aparna , Ali Iram
Published: May 2015

A glacierized terrain comprises different land covers, and their mapping using satellite data is challenged by their spectral similarity. We propose a hierarchical knowledge-based classification (HKBC) approach for differentiation of glacier terrain classes and mapping of glacier boundaries, using Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) imagery and Global Digital Elevation Model (GDEM). The methodology was tested over Kolahoi Glacier, Kashmir Himalaya. For the sequential extraction of various glacier terrain classes, several input layers were generated from the primary datasets by applying image-processing techniques. Noticeable differences in temperature and spectral response between supraglacial debris and periglacial debris facilitated the development of a thermal glacier mask and normalized-difference debris index, which together with slope enabled their differentiation. These and the other layers were then used in several discrete tests in HKBC, to map various glacier terrain classes. An ASTER visible near-infrared image and 42 field points were used to validate results. The proposed approach satisfactorily classified all the glacier terrain classes with an overall accuracy of 89%. The Z-test reveals that results obtained from HKBC are significantly (at 95% confidence level) better than those from a maximum likelihood classifier (MLC). Glacier boundaries obtained from HKBC were found to be plausibly better than those obtained from MLC and visual interpretation.
Estimating credit default swap spreads using accounting data, market quotes and credit ratings: the European Banks Case
Authors: Laghi Enrico , Di Marcantonio Michele , D'Amico Eugenio
Published: May 2015

The aim of this paper is to define a model for estimating the theoretical Credit Default Swap spread of European banks considering firms' accounting data, market quotes, official ratings and macroeconomic variables. We detect a significant log-linear relation between Credit Default Swaps spreads and four explanatory variables determined on the basis of the stock price, the financial structure, the equity composition, the incidence of the reserve for loan losses on total loans, the official ratings and macroeconomic indicators of the country of domicile of each company. The empirical results show that for the period from 2008 to 2013 the model has a high statistical significance and a remarkable explanatory power. Our main contribution to the existing literature is the exploration of new determinants of banks' credit risk and the provision of new evidence on the determinants of banks' default risk in the crisis and post-crisis European context. Furthermore, we define a practical model for estimating Credit Default Swap spreads of banks suitable for professional use.
Towards the international convergence of accounting standards: the case of Business Combinations and Goodwill
Authors: Olante Maria Elena
Published: May 2015

Accounting for business combinations and for goodwill has profoundly changed during the last ten years both in the US and in Europe, as a consequence of the common effort of the FASB and the IASB towards the international convergence of accounting standards. The Business Combinations project has been the first major project undertaken jointly by the accounting standard setters and it has resulted in the issue of substantially converged accounting standards with some remaining differences. The aim of this paper is to review and comment the evolution and the major changes occurred in accounting for business combinations and for goodwill and their current status in the light of the process of convergence of accounting standards on these crucial economic transactions.
Giant freshwater prawn (Macrobrachium rosenbergii) brood development in winter season
Authors: Saha SB , Alam MJ
Published: May 2015

Realizing the importance of giant freshwater prawn, Macrobrachium rosenberbii supply mature brood for extending the culture period for the successful production of marketable size, a study was conducted for development of broods of the species in the winter season by increasing temperature of water using green house concept. For this purpose, two ponds were covered with transparent polyethylene sheet fastened in bamboo frame and two ponds with no such covering. The ponds were equally stocked with prawn @ 5000 indv./ha (female:male::8:1) on 8th December 2009 and reared up to 9th March 2010. Temperature of water of the green house ponds was much higher than that of open ponds. Prawns started to be gravid after stocking in the green house ponds and 45-55% prawn became berried up to 9th March. But no remarkable development of gonad except a very few (2.5%) gravid prawn at the later part of rearing in one of the open pond was observed.Bangladesh J. Zool. 42(2): 153-159, 2014
Food and feeding habits of white-throated kingfisher (Halcyon smyrnensis) in Bangladesh
Authors: Naher Habibon , Sarker Noor Jahan
Published: May 2015

Food items, preying and feeding activities of white-breasted Kingfisher, Halcyon smyrnensis were studied from September 2008 to September 2011 at Nikunja-1 in Dhaka City Corporation area. A total of 16 species of food items were recorded from the observation. Fishes (more than 60%) were mostly preferred item. The highest preference was fry of Labeo rohita (30.6%). They highly preferred the species belonging to the Family Cyprinidae and Order Cypriniformes. The length of the food items varied from 2.0 to 12.3 cm. Surface dweller species (85.8%) was highly preferred. During preying, they used 0.3 to 2.25 m height, among which the highest preference was 0.9 m (32%). H. smyrnensis targeted the food items before catching while they took 9 sec to 15 min 17 sec. After catching they either engulfed the prey immediately or hold it at their beak for 2 sec to 30 min 30 sec before engulfing. Bamboos found in the water body were mostly preferred (65.9%) as perching places during preying.Bangladesh J. Zool. 42(2): 237-249, 2014
Record of Humerana humeralis (Boulenger 1887) from Rangpur district of north-western Bangladesh
Authors: Al-Razi H , Baki MA , Alam SMI
Published: May 2015

A male Bhamo frog Humerana humeralis was first time collected from Rangpur, Bangladesh, outside its usually habitat. The dorsal surface was characteristically olive brown to bright green in colour and the ventral surface was whitish. Black spots were distributed between nostril and between eyes. The length of snout-vent, head, snout were found to be 43.25 mm, 14.50 mm and 7.5 mm, respectively. Some information of its natural history is also included in the paper.Bangladesh J. Zool. 42(2): 277-282, 2014
Produire en France : le retour ?
Authors: Naro Franck
Published: May 2015

Renault renforce ses investissements sur le territoire national. Après plusieurs années durant lesquelles la croissance s’est appuyée sur l’international, l’usine de Douai montre comment l’avenir d’un constructeur historique se jouera aussi sur son territoire d’origine.
Les différentes formes de la fréquence textuelle : proposition d’inventaire
Authors: Loiseau Sylvain
Published: May 2015

Dans cette introduction, on propose de distinguer différents types de fréquence textuelle mobilisés dans la description linguistique et illustrés dans les contributions de ce numéro de Langages . La fréquence peut, en effet, être une grandeur abstraite, non susceptible d’être mesurée dans un corpus précis ; il peut s’agir d’une fréquence mesurée ; il peut s’agir enfin des intuitions de fréquence des locuteurs, i.e. d’un savoir épilinguistique. On peut également distinguer différents degrés d’abstraction dans l’utilisation des faits de fréquence : la fréquence peut être mobilisée dans des « lois » valables pour toutes les langues, ou bien pour décrire le système fonctionnel d’une langue, ou enfin pour établir des particularismes de variétés ou des régularités de genres textuels. Nous discutons enfin des paradoxes et des difficultés identifiées dans l’utilisation de la fréquence textuelle.
Diachronie du français et linguistique de corpus : une approche quantitative renouvelée
Authors: Prévost Sophie
Published: May 2015

Le présent article aborde la question de la fréquence textuelle du point de vue des études menées sur des états de langue anciens et dans une perspective diachronique. L’appui sur des données attestées, et sur leur quantification, a toujours été indispensable pour les linguistes travaillant sur une langue sans locuteurs et visant à rendre compte des changements. La numérisation des textes et le développement conjoint d’outils de traitement a cependant provoqué un important bouleversement méthodologique, du fait de la massification des données désormais traitées. Les gains sont nombreux, en particulier pour l’établissement de chronologies affinées et le repérage des lieux du changement. La présentation de quelques aspects de l’évolution de la syntaxe du sujet pronominal permet d’illustrer les apports d’une quantification à grande échelle et de pointer certaines limites de cette approche.
Vinpocetine Inhibits Streptococcus pneumoniae–Induced Upregulation of Mucin MUC5AC Expression via Induction of MKP-1 Phosphatase in the Pathogenesis of Otitis Media
Authors: Lee Ji-Yun , Komatsu Kensei , Lee Byung-Cheol , Miyata Masanori , O’Neill Bohn Ashley , Xu Haidong , Yan Chen , Li Jian-Dong
Published: May 2015

Mucin overproduction is a hallmark of otitis media (OM). Streptococcus pneumoniae is one of the most common bacterial pathogens causing OM. Mucin MUC5AC plays an important role in mucociliary clearance of bacterial pathogens. However, if uncontrolled, excessive mucus contributes significantly to conductive hearing loss. Currently, there is a lack of effective therapeutic agents that suppress mucus overproduction. In this study, we show that a currently existing antistroke drug, vinpocetine, a derivative of the alkaloid vincamine, inhibited S. pneumoniae–induced mucin MUC5AC upregulation in cultured middle ear epithelial cells and in the middle ear of mice. Moreover, vinpocetine inhibited MUC5AC upregulation by inhibiting the MAPK ERK pathway in an MKP-1–dependent manner. Importantly, ototopical administration of vinpocetine postinfection inhibited MUC5AC expression and middle ear inflammation induced by S. pneumoniae and reduced hearing loss and pneumococcal loads in a well-established mouse model of OM. Thus, these studies identified vinpocetine as a potential therapeutic agent for inhibiting mucus production in the pathogenesis of OM.
Characterization of a Human Platelet Antigen-1a–Specific Monoclonal Antibody Derived from a B Cell from a Woman Alloimmunized in Pregnancy
Authors: Eksteen Mariana , Tiller Heidi , Averina Maria , Heide Gøril , Kjaer Mette , Ghevaert Cedric , Michaelsen Terje E. , Ihle Øistein , Husebekk Anne , Skogen Bjørn , Stuge Tor B.
Published: May 2015

Human platelet Ag (HPA)-1a, located on integrin β3, is the main target for alloantibodies responsible for fetal and neonatal alloimmune thrombocytopenia (FNAIT) in the white population. There are ongoing efforts to develop an Ab prophylaxis and therapy to prevent or treat FNAIT. In this study, an mAb specific for HPA-1a, named 26.4, was derived from an immortalized B cell from an alloimmunized woman who had an infant affected by FNAIT. It is the only HPA-1a–specific human mAb with naturally paired H and L chains. Specific binding of mAb 26.4, both native and recombinant forms, to platelets and to purified integrins αIIbβ3 (from platelets) and αVβ3 (from trophoblasts) from HPA-1a+ donors was demonstrated by flow cytometry and surface plasmon resonance technology, respectively. No binding to HPA-1a− platelets or integrins was detected. Moreover, the Ab binds with higher affinity to integrin αVβ3 compared with a second HPA-1a–specific human mAb, B2G1. Further in vitro experimentation demonstrated that mAb 26.4 can opsonize HPA-1a+ platelets for enhanced phagocytosis by monocytes, inhibit binding of maternal polyclonal anti–HPA-1a Abs, and weakly inhibit aggregation of HPA-1a–heterozygous platelets, the latter with no predicted clinical relevance. Thus, mAb 26.4 is highly specific for HPA-1a and could potentially be explored for use as a prophylactic or therapeutic reagent for FNAIT intervention and as a phenotyping reagent to identify women at risk for immunization.
Analysis of Celiac Disease Autoreactive Gut Plasma Cells and Their Corresponding Memory Compartment in Peripheral Blood Using High-Throughput Sequencing
Authors: Snir Omri , Mesin Luka , Gidoni Moriah , Lundin Knut E. A. , Yaari Gur , Sollid Ludvig M.
Published: May 2015

Autoreactive IgA plasma cells (PCs) specific for the enzyme transglutaminase 2 (TG2) are abundant in the small intestine of patients with active celiac disease (CD), and their number drops in patients treated by dietary gluten elimination. Little is known about their characteristics and their role in the disease. In this study, using high-throughput sequencing of the IgH V region (IGHV) genes, we have studied features of TG2-specific PCs and their related B cell clones in peripheral blood. We found that TG2-specific PCs from both untreated and treated patients have acquired lower number of somatic hypermutation and used focused IGHV repertoire with overrepresentation of the IGHV3-48, IGHV4-59, IGHV5-10-1, and IGHV5-51 gene segments. Furthermore, these PCs were clonally expanded and showed signs of affinity maturation. Lineage trees demonstrated shared clones between gut PCs and blood memory B cells, primarily IgAs. Some trees also involved IgG cells, suggesting that anti-TG2 IgA and IgG responses are related. Similarly to TG2-specific PCs, clonally related memory IgA B cells of blood showed lower mutation rates with biased usage of IGHV3-48 and IGHV5-51. Such memory cells were rare in peripheral blood, yet detectable in most patients assessed by production of anti-TG2 Abs in vitro following stimulation of cells from patients who had been on a long-term gluten-free diet. Thus, the Ab response to TG2 in CD, while maintaining its IGHV gene usage, is dynamically regulated in response to gluten exposure with a low degree of maintenance at both PC and memory B cell levels in patients in remission.
Concordance of Increased B1 Cell Subset and Lupus Phenotypes in Mice and Humans Is Dependent on BLK Expression Levels
Authors: Wu Ying-Yu , Georg Ina , Díaz-Barreiro Alejandro , Varela Nieves , Lauwerys Bernard , Kumar Ramesh , Bagavant Harini , Castillo-Martín Mireia , El Salem Fadi , Marañón Concepción , Alarcón-Riquelme Marta E.
Published: May 2015

Polymorphisms in the B lymphoid tyrosine kinase (BLK) gene have been associated with autoimmune diseases, including systemic lupus erythematosus, with risk correlating with reduced expression of BLK. How reduced expression of BLK causes autoimmunity is unknown. Using Blk+/+, Blk+/−, and Blk−/− mice, we show that aged female Blk+/− and Blk−/− mice produced higher anti-dsDNA IgG Abs and developed immune complex–mediated glomerulonephritis, compared with Blk+/+ mice. Starting at young age, Blk+/− and Blk−/− mice accumulated increased numbers of splenic B1a cells, which differentiated into class-switched CD138+ IgG-secreting B1a cells. Increased infiltration of B1a-like cells into the kidneys was also observed in aged Blk+/− and Blk−/− mice. In humans, we found that healthy individuals had BLK genotype-dependent levels of anti-dsDNA IgG Abs as well as increased numbers of a B1-like cell population, CD19+CD3−CD20+CD43+CD27+, in peripheral blood. Furthermore, we describe the presence of B1-like cells in the tubulointerstitial space of human lupus kidney biopsies. Taken together, our study reveals a previously unappreciated role of reduced BLK expression on extraperitoneal accumulation of B1a cells in mice, as well as the presence of IgG autoantibodies and B1-like cells in humans.
CD81 Controls Immunity to Listeria Infection through Rac-Dependent Inhibition of Proinflammatory Mediator Release and Activation of Cytotoxic T Cells
Authors: Martínez del Hoyo Gloria , Ramírez-Huesca Marta , Levy Shoshana , Boucheix Claude , Rubinstein Eric , Minguito de la Escalera María , González-Cintado Leticia , Ardavín Carlos , Veiga Esteban , Yáñez-Mó María , Sánchez-Madrid Francisco
Published: May 2015

Despite recent evidence on the involvement of CD81 in pathogen binding and Ag presentation by dendritic cells (DCs), the molecular mechanism of how CD81 regulates immunity during infection remains to be elucidated. To investigate the role of CD81 in the regulation of defense mechanisms against microbial infections, we have used the Listeria monocytogenes infection model to explore the impact of CD81 deficiency in the innate and adaptive immune response against this pathogenic bacteria. We show that CD81−/− mice are less susceptible than wild-type mice to systemic Listeria infection, which correlates with increased numbers of inflammatory monocytes and DCs in CD81−/− spleens, the main subsets controlling early bacterial burden. Additionally, our data reveal that CD81 inhibits Rac/STAT-1 activation, leading to a negative regulation of the production of TNF-α and NO by inflammatory DCs and the activation of cytotoxic T cells by splenic CD8α+ DCs. In conclusion, this study demonstrates that CD81–Rac interaction exerts an important regulatory role on the innate and adaptive immunity against bacterial infection and suggests a role for CD81 in the development of novel therapeutic targets during infectious diseases.
The Frequency of Naive and Early-Activated Hapten-Specific B Cell Subsets Dictates the Efficacy of a Therapeutic Vaccine against Prescription Opioid Abuse
Authors: Laudenbach Megan , Baruffaldi Federico , Vervacke Jeffrey S. , Distefano Mark D. , Titcombe Philip J. , Mueller Daniel L. , Tubo Noah J. , Griffith Thomas S. , Pravetoni Marco
Published: May 2015

Translation of therapeutic vaccines for addiction, cancer, or other chronic noncommunicable diseases has been slow because only a small subset of immunized subjects achieved effective Ab levels. We hypothesize that individual variability in the number of naive and early-activated hapten-specific B cells determines postvaccination serum Ab levels and vaccine efficacy. Using a model vaccine against the highly abused prescription opioid oxycodone, the polyclonal B cell population specific for an oxycodone-based hapten (6OXY) was analyzed by flow cytometry paired with Ag-based magnetic enrichment. A higher frequency of 6OXY-specific B cells in either spleen biopsies or blood, before and after immunization, correlated to subsequent greater oxycodone-specific serum Ab titers and their efficacy in blocking oxycodone distribution to the brain and oxycodone-induced behavior in mice. The magnitude of 6OXY-specific B cell activation and vaccine efficacy was tightly correlated to the size of the CD4+ T cell population. The frequency of enriched 6OXY-specific B cells was consistent across various mouse tissues. These data provide novel evidence that variations in the frequency of naive or early-activated vaccine-specific B and T cells can account for individual responses to vaccines and may predict the clinical efficacy of a therapeutic vaccine.
Cutting Edge: Role of Osteopontin and Integrin αv in T Cell–Mediated Anti-Inflammatory Responses in Endotoxemia
Authors: Inoue Makoto , Shinohara Mari L.
Published: May 2015

The immune system is equipped with mechanisms that downregulate hyperinflammation to avoid collateral damage. We demonstrated recently that unprimed T cells downregulate macrophage TNF production through direct interaction with macrophages in the spleen during LPS endotoxemia. How T cell migration toward macrophages occurs upon LPS injection is still not clear. In this study, we demonstrate that secreted osteopontin (sOPN) plays a role in the T cell migration to initiate the suppression of hyperinflammation during endotoxemia. Osteopontin levels in splenic macrophages were upregulated 2 h after LPS treatment, whereas T cell migration toward macrophages was observed 3 h after treatment. Neutralization of sOPN and blockade of its receptor, integrin αv, significantly inhibited CD4+ T cell migration and increased susceptibility to endotoxemia. Our study demonstrates that the sOPN/integrin αv axis, which induces T cell chemotaxis toward macrophages, is critical for suppressing hyperinflammation during the first 3 h of endotoxemia.
Building laboratory capacity to support HIV care in Nigeria: Harvard/APIN PEPFAR, 2004–2012
Authors: Hamel Donald J. , Sankalé Jean-Louis , Samuels Jay O. , Sarr Abdoulaye D. , Chaplin Beth , Ofuche Eke , Meloni Seema T. , Okonkwo Prosper , Kanki Phyllis J.
Published: May 2015

Introduction: From 2004–2012, the Harvard/AIDS Prevention Initiative in Nigeria, funded through the US President’s Emergency Plan for AIDS Relief programme, scaled up HIV care and treatment services in Nigeria. We describe the methodologies and collaborative processes developed to improve laboratory capacity significantly in a resource-limited setting. These methods were implemented at 35 clinic and laboratory locations.Methods: Systems were established and modified to optimise numerous laboratory processes. These included strategies for clinic selection and management, equipment and reagent procurement, supply chains, laboratory renovations, equipment maintenance, electronic data management, quality development programmes and trainings.Results: Over the eight-year programme, laboratories supported 160 000 patients receiving HIV care in Nigeria, delivering over 2.5 million test results, including regular viral load quantitation. External quality assurance systems were established for CD4+ cell count enumeration, blood chemistries and viral load monitoring. Laboratory equipment platforms were improved and standardised and use of point-of-care analysers was expanded. Laboratory training workshops supported laboratories toward increasing staff skills and improving overall quality. Participation in a World Health Organisation-led African laboratory quality improvement system resulted in significant gains in quality measures at five laboratories.Conclusions: Targeted implementation of laboratory development processes, during simultaneous scale-up of HIV treatment programmes in a resource-limited setting, can elicit meaningful gains in laboratory quality and capacity. Systems to improve the physical laboratory environment, develop laboratory staff, create improvements to reduce costs and increase quality are available for future health and laboratory strengthening programmes. We hope that the strategies employed may inform and encourage the development of other laboratories in resource-limited settings.
Integrative Analyses of Cancer Data: A Review from a Statistical Perspective
Authors: Wei Yingying
Published: May 2015

It has become increasingly common for large-scale public data repositories and clinical settings to have multiple types of data, including high-dimensional genomics, epigenomics, and proteomics data as well as survival data, measured simultaneously for the same group of biological samples, which provides unprecedented opportunities to understand cancer mechanisms from a more comprehensive scope and to develop new cancer therapies. Nevertheless, how to interpret a wealth of data into biologically and clinically meaningful information remains very challenging. In this paper, I review recent development in statistics for integrative analyses of cancer data. Topics will cover meta-analysis of homogeneous type of data across multiple studies, integrating multiple heterogeneous genomic data types, survival analysis with high- or ultrahigh-dimensional genomic profiles, and cross-data-type prediction where both predictors and responses are high- or ultrahigh-dimensional vectors. I compare existing statistical methods and comment on potential future research problems.
Learning from failure: The case of the disappearing Web site
Authors: Barone Francine , Zeitlyn David , Mayer-Schönberger Viktor
Published: May 2015

This paper presents the findings of the Gone Dark Project, a joint study between the Institute of Social and Cultural Anthropology and the Oxford Internet Institute at Oxford University. The project has sought to give substance to frequent reports of Web sites “disappearing” (URLs that generate “404 not found” errors) by tracking and investigating cases of excellent and important Web sites which are no longer accessible online. We first address the rationale and research methods for the project before focusing on several key case studies illustrating some important challenges in Web preservation. Followed by a brief overview of the strengths and weaknesses of current Web archiving practice, the lessons learned from these case studies will inform practical recommendations that might be considered in order to improve the preservation of online content within and beyond existing approaches to Web preservation and archiving.
The app-object economy: We’re all remix artists now
Authors: Caplan Paul
Published: May 2015

Maps and messages, notes and news, photography and fitness, streams and shopping: the litany of apps through which we live our mobile data lives and through which state and corporate agents survey our data positions, set in motion a form of everyday remix. This affective cultural practice choreographed between ‘us’ and ‘them’ is deeply governmental, establishing subject positions and relationships. Drawing on the work of Timothy Morton, Levi Bryant, Ian Bogost and Graham Harman, this paper argues that this governmental remix mesh is best addressed as a matter of material objects and hyperobjects rather than as an assemblage or network.
A Meaningful Journey to Onboard Syndromic Data through a Local HIE
Authors: Johnson Jeffrey , Yen Jessica , Colanter Brit , McDonald Eric
Published: May 2015

This presentation aims to highlight key activities, technical approaches, data discoveries, lessons learned and outcomes achieved while onboarding local hospitals for syndromic Meaningful Use Stage 2 through a local health information exchange. The federal meaningful use initiative is currently a major driver to enable greater establishment of syndromic surveillance capacity across the United States. The role and efforts by local and state public health agencies in the syndromic onboarding process varies greatly. We describe efforts from a local public health agency to onboard, validate and integrate meaningful use syndromic information.
Analytics, Machine Learning & NLP – use in BioSurveillance and Public Health practice
Authors: K B Mujitha B. , Jalal Ajil , V Vishnuprasad , K A Nishad
Published: May 2015

This presentation summarizes ways in which Analytics, Machine Learning (ML) and Natural Language Processing (NLP) can improve accuracy and efficiency in bio surveillance and public health practices. Currently, there is an abundance of data coming from most of the surveillance environments and applications. Identification and filtering of responsive messages from this big data ocean and then processing these informative datasets to gain knowledge are the two real challenges in today's applications. Details of a Simulation environment consisting of Devices/Sensors, Web/Mobile, Clinical Records, Internet queries, Social/News media, in which this ML platform was evaluated is also discussed. Infrastructure needs for this operating environment is also covered.
The Threat of Ebola Virus Disease: a Call to Integrate all Sectors in Surveillance Activities in Ghana
Authors: Laryea Dennis O. , Amoako Yaw , Armooh Dan V. , Abbeyquaye Emmanuel P. , Amartey Bernice N.
Published: May 2015

Surveillance for communicable diseases of public health importance is critical in preventing and controlling outbreaks. In Ghana, this responsibility lies with the Disease Surveillance Department of the Ghana Health Service (GHS). However, the structure of Ghana's health system means surveillance activities by the department are concentrated in GHS facilities. Active surveillance in non-GHS facilities usually occur during outbreaks. In light of the recent Ebola outbreak in West Africa, there is the need to integrate the surveillance activities to include all health facilities to ensure the prompt identification of cases.
Insight into Malaria Transmission and Control in Endemic Areas
Authors: Maikai Beatty V. , Umoh Jarlath U. , Maikai Victor A.
Published: May 2015

The global effort of malaria control is in line with the one world one health concept, but then a globally defined (one-size-fits-all) malaria control strategy would be inefficient. A model was used to examine the likely impact of malaria parasite interventions for a steady state regional control program in endemic areas. Assumptions varied about two targeted epidemiologic control points on the basic reproductive number, Ro, which is affected by different factors and upon which the status of malaria in any community will depend. For any effective malaria control and eradication program, environmental and socio-economic factors should also be considered.
Surveillance System Evaluations Provide Evidence to Improve Public Health Practice
Authors: Paterson Beverley J. , Durrheim David N.
Published: May 2015

Surveillance evaluations of surveillance systems should provide evidence to improve public health practice. In response to surveillance evaluation findings amongst Pacific Island Countries and Territories that identified a critical need to better equip local public health officials with skills to rapidly appropriately respond to suspected infectious disease outbreaks across the Pacific, the RAPID (Response and Analysis for Pacific Infectious Diseases) project was implemented to strengthen capacity in surveillance, epidemiology and outbreak response. The RAPID project is a notable example of how evidence gathered through a surveillance evaluation can be used to improve public health surveillance practice.