bluuebunny/crossref_metadata_2025 huggingface dataset:
Reparatur der Autobahnbrücke über die Süderelbe nach schwerem Schiffsanprall – Nachrechnung, Planung, Ausführung, Analyse
Authors: Seipelt Dirk , Neysters Thomas , Coors Brinja , Grassl Martin
Published: February 2017

Durch den im Jahre 2014 stattgefundenen Schiffsanprall an der verkehrsbedeutenden Süderelbbrücke in Hamburg musste innerhalb kürzester Zeit eine Instandsetzungsmaßnahme geplant und umgesetzt werden. Die Wucht des Anpralls deformierte den außen liegenden Hauptträger des Stahlüberbaus in horizontaler und vertikaler Richtung so erheblich, dass neben einer Querschnittsschwächung im Untergurt in weiten Bereichen sämtliche Aussteifungselemente abrissen und somit wirkungslos waren. Eine Sperrung der Brücke war jedoch aufgrund des großen Verkehrsaufkommens nicht möglich. Mittels Nachrechnungen des Brückenüberbaus unter Berücksichtigung des vorhandenen Schadensausmaßes sowie der tatsächlichen Fahrstreifenanordnung in Kombination mit verkehrslenkenden Maßnahmen konnte eine vertretbare Verkehrsführung sowohl statisch für den Ingenieur als auch den Verkehrsteilnehmer eingerichtet werden. Unter Berücksichtigung des oben liegenden Autobahnverkehrs musste ein Instandsetzungskonzept entwickelt und umgesetzt werden, welches nur wenige und zeitlich begrenzte Vollsperrungen der Brücke beinhaltete. Dank der guten Zusammenarbeit aller Beteiligten – dem Bauherrn, der ausführenden Firma und dem Planer – ist es gelungen, durch ein innovatives, schnelles und sicheres Instandsetzungsprogramm den erheblichen Anprallschaden deutlich früher als zunächst angenommen zu beheben.
Ganzheitliche Analyse von Stahl‐ und Verbundeisenbahnbrücken
Authors: Zinke Tim , Ummenhofer Thomas , Schneider Sarah , Beck Tabea , Lenz Katrin , Neudeck Michael , Koch Eckart
Published: February 2017

Obwohl in den letzten zehn Jahren mehrere Projekte und Initia tiven in den Themengebieten der ganzheitlichen Bewertung und der Nachhaltigkeitsanalyse von Verkehrsinfrastrukturen durchgeführt wurden, hat sich national wie international bisher keine einheitliche Bewertungsbasis herausgebildet. Eine Ursache hierfür sind fehlende Vergleichswerte für Infrastrukturbauwerke und nicht vorhandene vorbilanzierte Bauprodukte, die beispielsweise im Rahmen der Eingangsdatenbereitstellung Verwendung finden können und die Grundvoraussetzung für eine praktikable Anwendung sind. Der vorliegende Beitrag macht speziell für Stahl‐ und Stahlverbundeisenbahnbrücken einen Vorschlag für einen Bewertungsrahmen und untersucht verschiedene Typen von eisenbahnspezifischen Referenzbrücken. Dabei wird auf den im ersten Teil dieser zweiteiligen Veröffentlichung vorgestellten konstruktiven Varianten und Detailuntersuchungen für Stahl‐ und Verbundeisenbahnbrücken aufgebaut und es werden Berechnungsergebnisse unter Verwendung von Ökobilanzierungen, Lebenszykluskostenrechnungen und Betriebserschwerniskostenberechnungen vorgestellt, wobei ein Schwerpunkt auf Trogbrücken mit Spannweiten von ca. 18 m gelegt wird.
Korrosionsschutztechnologie für Montageschweißstöße einer feuerverzinkten Stahlbrücke
Authors: Lebelt Peter , Gehrke Jörg
Published: February 2017

Derzeitige Brückenbauwerke sind für eine Nutzungsdauer von 70 bis 110 Jahren [1] ausgelegt. Die für die Brückenbauwerke eingesetzten organischen Beschichtungssysteme sind jedoch in ihrer Korrosionsschutzdauer auf ca. 25 bis 35 Jahre begrenzt und benötigen mindestens eine zweimalige Ausbesserung oder Teilerneuerung während der geplanten Nutzungsdauer der Brücke. Diese notwendigen Arbeiten am Korrosionsschutzsystem verursachen Kosten, die der Brückeneigentümer teils durch Verlängern von Wartungszyklen, mit entsprechenden Folgen für die Korrosionsintensität am Stahlbau, zu vermeiden versucht. Sinnvoll ist daher der Einsatz eines Korrosionsschutzsystems mit langer Schutzdauer, das während der Nutzungsdauer des Brückenbauwerks möglichst ohne kosten‐ und zeitintensive Wartung auskommt. Nach aktuellen Forschungsergebnissen ist die Feuerverzinkung in der Lage, an Brückenbauwerken eine Schutzdauer von 100 Jahren ohne Wartung zu gewährleisten. Um die Reparatur der Feuerzinküberzüge an Montageschweißstößen und partiellen Fehlstellen (z. B. Transport‐ und Montageschäden) durch thermisches Spritzen mit Zink unabhängig vom Siliziumgehalt im Stahl korrosionsschutzgerecht anwenden zu können, erfolgte eine umfangreiche Prozess‐ und Technologieentwicklung im Rahmen zweier Forschungsvorhaben. Die Forschungsergebnisse belegen, dass Montageschweißstöße und Fehlstellen durch thermisch gespritzte Zinküberzüge gemäß DIN EN ISO 2063 [2] mit ausreichender Haftfestigkeit auf gestrahlter Stahl‐ und gesweepter Feuerzink‐Oberfläche von Baustählen im Niedrigsilizium‐, mittleren Sebisty‐ und Hochsilizium‐Bereich praxisgerecht ausgebessert und qualitätsgerechte Korrosionsschutzsysteme hergestellt werden können.
Leadership 2.0: The Impact of Technology on Leadership Development
Authors: Hoffman John L. , Vorhies Cara
Published: February 2017

Technological innovation has become a driver of educational and leadership development practices that place students at the center of learning and leadership development experiences.
Student Activism in the Technology Age
Authors: Gismondi Adam , Osteen Laura
Published: February 2017

This chapter discusses the emergent use of digital technology to inspire, connect, and sustain student activism on campus. An overview of student activism, opportunities, and challenges of this technology, along with recent case studies and implications for practice, are presented.
Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences
Authors: Wortmann Saskia B. , Chen Margaret A. , Colombo Roberto , Pontoglio Alessandro , Alhaddad Bader , Botto Lorenzo D. , Yuzyuk Tatiana , Coughlin Curtis R. , Descartes Maria , Grűnewald Stephanie , Maranda Bruno , Mills Philippa B. , Pitt James , Potente Catherine , Rodenburg Richard , Kluijtmans Leo A. J. , Sampath Srirangan , Pai Emil F. , Wevers Ron A. , Tiller George E. ,   and additional individual contributors
Published: February 2017

Background

Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue.

Methods and results

We identified mild and isolated orotic aciduria in 11 unrelated individuals with diverse clinical signs and symptoms, the most common denominator being intellectual disability/developmental delay. Of note, none had blood count abnormalities, relevant hyperammonemia or altered plasma amino acid profile. All individuals were found to have heterozygous alterations in UMPS. Four of these variants were predicted to be null alleles with complete loss of function. The remaining variants were missense changes and predicted to be damaging to the normal encoded protein. Interestingly, family screening revealed heterozygous UMPS variants in combination with mild orotic aciduria in 19 clinically asymptomatic family members.

Conclusions

We therefore conclude that heterozygous UMPS‐mutations can lead to mild and isolated orotic aciduria without clinical consequence. Partial UMPS‐deficiency should be included in the differential diagnosis of mild orotic aciduria. The discovery of heterozygotes manifesting clinical symptoms such as hypotonia and developmental delay are likely due to ascertainment bias.
The block structure and the presence of oil and gas in the Siljan impact crater
Authors: Pikovsky Yu.I. , Glasko M.P. , Kutcherov V.G.
Published: February 2017

Morphostructural modeling of the block structure of a part of the Scandinavian crystalline shield has shown that the ring structure of the Siljan Ring impact crater is located in the center of a morphostructural node, a ring structure with a diameter of 300 km, marking a large disjunctive tectonic knot. The crater area consists of a central block, which is a granite massif, and of a surrounding mobile morphostructural boundary forming a wide small-block ring depression zone, where oil and gas shows have been revealed within the crater. This zone is regarded as the most promising one for search for migration channels and atypical shows of hydrocarbons.
The U.S. Election Hacks, Cybersecurity, and International
Law
Authors: Fidler David P.
Published: February 2017

In October 2016, the United States accused Russia of hacking political organizations involved in the U.S.
elections and leaking pilfered information to influence the outcome. In December,
President Obama imposed sanctions for the hacking. This incident damaged
President Obama's cybersecurity legacy. The “hack and leak” campaign targeted
American self-government—a challenge to his administration's promotion of democracy
in cyberspace. It created problems for the president's emphasis on international law
and norms as “rules of the road” for cybersecurity. The episode exposed failures in
his attempts to make deterrence an important instrument of U.S. cybersecurity.
Generative Security: Adversarial Design and Conflict of
Laws
Authors: Sivakumar Niranjan
Published: February 2017

The data breach of the Democratic National Committee (DNC) during the U.S.
presidential election of 2016 is multi-faceted and has wide ranging implications. The
discourse of “cybersecurity” is increasingly thought of through the lens of states
and other powerful actors like large corporations, as a conflict or war that is waged by specialized
combatants while civilians are relegated to the sidelines and are the victims of
digital malfeasance or the object of regulation and education from those in
power.
Great Expectations: Gender and Political Representation in the Pacific Islands
Authors: Baker Kerryn
Published: February 2017

Women make up just 6.1 per cent of Pacific parliamentarians. Increasing women’s representation is a key area of focus for political leaders and aid donors, both as a human rights issue and as a vehicle for the substantive representation of women. Women’s participation in politics in the Pacific Islands is often seen as a form of social contract between women. Female voters are expected to vote for female candidates. In exchange, female parliamentarians are expected to act, not just for the constituency that elected them, but for women as a group. This article examines the expectations that are placed on the political participation of Pacific women, and argues that attempts to increase women’s participation in politics in the region should avoid reinforcing these expectations through an emphasis on substantive representation.
An Element of Risk: the Corrupt Contractor in Indian Fiction and Film, 1886–1983
Authors: Bubb Alexander
Published: February 2017

From the 1960s to the 1990s, the corrupt building contractor was a stock-villain of Bombay cinema. He was, this article argues, emblematic of crony capitalism prior to the liberalization of the Indian economy. This filmic role was, however, foreshadowed by his depiction as cynical accomplice and profiteer of British rule in fiction of the early and mid-twentieth century. Furthermore, the figure’s ultimate origins lie in colonial literature, in which he is often identified as a threat to the British civilian community that nourished itself with the ideal of its disinterested civilizing mission. This article traces the genealogy of the contractor-as-villain in fiction and film, demonstrating a continuity of themes, and persistence of concerns, across the work of Rudyard Kipling, Flora Annie Steel, Premchand, R. K. Narayan, and Mahasweta Devi. Using historical sources to contextualize these texts, it will also suggest possible explanations for the ubiquity of contractors in the Indian economy.
Resurfacing Symptomatic Reading: Contrapuntal Memory and Postcolonial Method inThe Remains of the Day
Authors: Thakkar Sonali
Published: February 2017

This essay onThe Remains of the Dayand modes of reading takes as its starting point the novel’s historical setting of July 1956, which coincides with the beginning of the Suez crisis. Although the crisis never explicitly registers in the narrative, various moments of imperial affirmation and anxiety suggest that it may have the status of a symptom. I read with and against this supposition. In the essay’s first section, I show how the repression of imperial crisis in Stevens’s narrative is entangled with his memories of fascist appeasement and complicity. Prompted by the text’s pervasive and self-conscious interest in Freudian figures of memory—its untimeliness and displacements—the second part argues thatThe Remains of the Dayincorporates the symptom as an aesthetic and historical strategy in order to itself theorize a postcolonial symptomatology. The novel thus helps us complicate the proposition that symptomatic reading is something critics do to texts and suggests, in its allegory of symptomatic reading, the contours of a postcolonial interpretive method.
Differential Publics—Reading (in) the Postcolonial Novel
Authors: Boehmer Elleke
Published: February 2017

This essay discusses the activity of reading in three postcolonial novels from three different national contexts (Dangarembga in Zimbabwe, Kapur in India, and Adichie in Nigeria). The essay considers the scenes of focused, respectful, even canonical reading staged in these novels, alongside the more selective or eclectic “reading” and citation taking place at the level of the narration. On the basis of this contrast, it suggests that the postcolonial and transnational publics interpellated by the novels are sometimes different from the audiences or readers dramatized in the texts. It concludes by pointing to the particularly layered—at once deferential and exploratory—reading that is staged within, and by, the postcolonial novel. The essay is shaped by postcritical, cognitive, and hermeneutic approaches to narrative and reading drawn from Rita Felski, James Phelan, Dan Sperber, and Deirdre Wilson.
Livestock depredation by large predators and its implications for conservation and livelihoods in the Karakoram Mountains of Pakistan
Authors: Khan Muhammad Zafar , Khan Babar , Awan Muhammad Saeed , Begum Farida
Published: February 2017

Livestock depredation has particular significance in pastoral societies across the Himalayas. The dynamics of depredation by the snow leopard Panthera uncia and wolf Canis lupus were investigated by means of household surveys in the Hushey Valley, in the Karakoram Mountains of Pakistan. During 2008–2012 90% of the households in the valley lost livestock to snow leopards and wolves, accounting for 0.8 animals per household per year. The cost of depredation per household was equivalent to PKR 9,853 (USD 101), or 10% of the mean annual cash income. The majority (41%) of predation incidents occurred in summer pastures, predominantly at night in open spaces. Of the total number of predation incidents, 60% were attributed to snow leopards and 37% to wolves; in 3% of cases the predator was unknown. As an immediate response to predation the majority of the local people (64%, n = 99) opted to report the case to their Village Conservation Committee for compensation and only 1% preferred to kill the predator; 32% did not respond to predation incidents. The perceived causes of predation were poor guarding (77%), reduction in wild prey (13%), and livestock being the favourite food of predators (10%). The most preferred strategies for predator management, according to the respondents, were enhanced guarding of livestock (72%), followed by increasing the availability of wild prey (18%), and lethal control (10%). Livestock depredation causing economic loss may lead to retaliatory killing of threatened predators. For carnivore conservation and livestock security in this area we recommend improved livestock guarding through collective hiring of skilled shepherds and the use of guard dogs.
Impact of childhood and adulthood psychological health on labour force participation and exit in later life
Authors: Clark C. , Smuk M. , Lain D. , Stansfeld S. A. , Carr E. , Head J. , Vickerstaff S.
Published: February 2017

Background

Adulthood psychological health predicts labour force activity but few studies have examined childhood psychological health. We hypothesized that childhood psychological ill-health would be associated with labour force exit at 55 years.

Method

Data were from the 55-year follow-up of the National Child Development Study (n = 9137). Labour force participation and exit (unemployment, retirement, permanent sickness, homemaking/other) were self-reported at 55 years. Internalizing and externalizing problems in childhood (7, 11 and 16 years) and malaise in adulthood (23, 33, 42, 50 years) were assessed. Education, social class, periods of unemployment, partnership separations, number of children, and homemaking activity were measured throughout adulthood.

Results

Childhood internalizing and externalizing problems were associated with unemployment, permanent sickness and homemaking/other at 55 years, after adjustment for adulthood psychological health and education: one or two reports of internalizing was associated with increased risk for unemployment [relative risk (RR) 1.59, 95% confidence interval (CI) 1.12–2.25; RR 2.37, 95% CI 1.48–3.79] and permanent sickness (RR 1.32, 95% CI 1.00–1.74; RR, 1.48, 95% CI 1.00–2.17); three reports of externalizing was associated with increased risk for unemployment (RR 2.26, 95% CI 1.01–5.04), permanent sickness (RR 2.63, 95% CI 1.46–4.73) and homemaking/other (RR 1.95, 95% CI 1.00–3.78).

Conclusions

Psychological ill-health across the lifecourse, including during childhood, reduces the likelihood of working in older age. Support for those with mental health problems at different life stages and for those with limited connections to the labour market, including homemakers, is an essential dimension of attempts to extend working lives.
Addressing Issues of Protective Scope within theFrancovichRight to Reparation
Authors: Dougan Michael
Published: February 2017

EU Law – Member State liability in damages – Issues of protective scope about exactly which individuals/interests are protected – Conditions for Member State liability – Intention to confer rights criterion – Tendency towards a ‘checklist’ approach by the Court of Justice of the European Union – Potential implications for scope of Member State liability – Finding appropriate balance between protecting individuals and punishing public bodies – Example of free movement rights – Example of environmental legislation – Example of employment legislation
Politics of Judicial Independence and Judicial Accountability in Czechia: Bargaining in the Shadow of the Law between Court Presidents and the Ministry of Justice
Authors: Kosař David
Published: February 2017

Judicial independence – Judicial accountability – Court presidents – Judicial politics – Separation of powers – Court administration – Judicial councils – Selection of judges – Czechia – Central Europe
The Boundaries of Comparative Law
Authors: Tushnet Mark
Published: February 2017

Boundaries: between public and private law – Political dimensions of private and public law – Boundaries between domestic law and transnational and international law – Boundaries between law and other disciplines, including economics, comparative politics, normative political theory, and hermeneutic disciplines – National styles of comparative law scholarship – Analytic and pragmatic traditions in comparative law scholarship
The right to legal agency: domination, disability and the protections of Article 12 of the Convention on the Rights of Persons with Disabilities
Authors: Arstein-Kerslake Anna , Flynn Eilionóir
Published: February 2017

Article 12 of the Convention on the Rights of Persons with Disabilities has created a revolution in legal-capacity law reform. It protects the right to exercise legal agency for people with disabilities with more clarity than any prior human rights instrument. This paper explores what constitutes an exercise of legal agency and what exactly Article 12 protects. It proposes a definition of legal agency and applies it to the lived experience of cognitive disability. It also uses a republican theory of domination to argue that people with cognitive disabilities who are experiencing domination are forced to assert legal agency in even daily decision-making because of the high level of external regulation of their lives and the ever-present threat of others substituting their decision-making. It identifies Article 12 as a tool for protecting such exertions of legal agency and curtailing relationships of domination.
Recognising legal capacity: commentary and analysis of Article 12 CRPD
Authors: de Bhailís Clíona , Flynn Eilionóir
Published: February 2017

This paper aims to summarise the current understanding and literature around Article 12 of the Convention on the Rights of Persons with Disabilities (CRPD). It provides a brief history of the key terms associated with the right to equal recognition before the law and encompasses both academic writing in this area and General Comment No. 1 from the Committee on the Rights of Persons with Disabilities. The content is intended to provide readers of this Special Issue with a general understanding of developments surrounding Article 12 so they can fully engage with the other papers within this Special Issue and with the content of the Voices of Individuals: Collectively Exploring Self-determination (VOICES) project as a whole.
CRPD and transformative equality
Authors: Minkowitz Tina
Published: February 2017

This reflection responds primarily to the papers on legal agency and state intervention, with brief comments on the two other papers. The concept of transformative equality, developed in jurisprudence under the Convention on the Elimination of All Forms of Discrimination Against Women (CEDAW), can promote a deeper understanding of the rights of persons with disabilities.1In particular, it is useful to address power relations between disabled and non-disabled persons not only with respect to family members and medical professionals, but also in the institutions of law and the state.
Design of a microstrip dual-frequency diplexer using microstrip cells analysis and coupled lines components
Authors: Noori Leila , Rezaei Abbas
Published: February 2017

In this paper, a microstrip diplexer composed of two similar resonators is designed. The proposed resonator is consisting of four microstrip cells, which are connected to a coupled lines structure. In order to select a suitable geometric structure, first, all cells are assumed as undefined structures where there is a lack of basic information about their geometry and dimensions. Then, an equivalent LC circuit of the coupled lines is introduced and analyzed to estimate the general structure of the resonator respect to a requested resonance frequency. The proposed diplexer is designed to operate at 2.36 and 4 GHz for wireless applications. The insertion losses (S21 and S31) are decreased significantly at the resonance frequencies, so that they are 0.2 and 0.4 dB at 2.36 and 4 GHz, respectively. The designed diplexer is fabricated and measured and the measurement results are in a good agreement with the simulations.
Prevalence and factors associated with depression and depression-related healthcare access in mothers of 9-month-old infants in the Republic of Ireland
Authors: Cruise S. M. , Layte R. , Stevenson M. , O'Reilly D.
Published: February 2017

Aims.

Untreated maternal depression during the postpartum period can have a profound impact on the short- and long-term psychological and physical well-being of children. There is, therefore, an imperative for increased understanding of the determinants of depression and depression-related healthcare access during this period.

Methods.

Respondents were 11 089 mothers of 9-month-old infants recruited to the Growing Up in Ireland study. Of this sample, 10 827 had complete data on all relevant variables. Respondents provided sociodemographic, socioeconomic and household information, and completed the Center for Epidemiologic Studies Depression Scale (CESD).

Results.

11.1% of mothers scored above the CESD threshold for depression. 10.0% of depressed mothers and 25.4% of depressed fathers had depressed partners. Among depressed mothers, 73.1% had not attended a healthcare professional for a mental health problem since the birth of the cohort infant. In the adjusted model, the likelihood of depression was highest in mothers who: had lower educational levels (odds ratio (OR) 1.26; 95% confidence intervals (CIs) 1.08, 1.46); were unemployed (OR 1.27; 95% CIs 1.10, 1.47); reported previous mental health problems (OR 6.55; 95% CIs 5.68, 7.56); reported that the cohort child was the result of an unintended pregnancy (OR 1.43; 95% CIs 1.22, 1.68), was preterm (OR 1.35; 95% CIs 1.07, 1.70), or had health/developmental problems (OR 1.20; 95% CIs 1.04, 1.39); had no partner in the household (OR 1.33; 95% CIs 1.04, 1.70) or were living with a depressed partner (OR 2.66; 95% CIs 1.97, 3.60); reported no family living nearby (OR 1.33; 95% CIs 1.16, 1.54); were in the lowest income group (OR 1.60; 95% CIs 1.21, 2.12). The primary determinant of not seeking treatment for depression was being of non-white ethnicity (OR 2.21; 95% CIs 1.18, 4.13).

Conclusions.

Results highlight the prevalence of maternal depression in the later postpartum period, particularly for lower socioeconomic groups, those with previous mental health problems, and those with limited social support. The large proportion of unmet need in depressed mothers, particularly among ethnic minority groups, emphasises the need for a greater awareness of postpartum mental health problems and increased efforts by healthcare professionals to ensure that mothers can access the required services.
Interacting Variables: September 11 and the Role of Ideas and Domestic Politics
Authors: Gourevitch Peter
Published: February 2017

The events of September 11 can be taken as a good place to explore the interaction of variables in explaining events. We know that many variables are at play in most complex situations. Taking account of them all is impossible, and even investigating several is messy. One way to tackle this problem is to pay closer attention to the interaction of variables--not to look at all of them but to explore carefully where they intersect and to detect the mechanisms of their relationships.

Many of the quarrels in our field arise out of a desire to assert aggressively the predominance of a particular, favored variable. Wearying of this sort of combat, some analysts have become more interested in examining the connections among variables, the ways in which one parameter acquires strength or signals causality because of its interaction with another. The events of September 11 show the values of this approach. It will surely involve some loss of parsimony, but it may lead to important insights and research programs. To pursue it, we need models of causality that work with interactions.
How Climate Change Affects the Flow of Carbon from Land to Sea
Authors: Wheeling Kate
Published: February 2017

Changes in precipitation and runoff in New England may be driving more dissolved organic carbon into the Gulf of Maine.
Merle Lee Allison (1948–2016)
Authors: Richard Stephen , Hills Denise
Published: February 2017

A dynamic geologist with a knack for organizing people, he served as state geologist in three different states and pioneered global efforts to develop cyberinfrastructure for the Earth sciences.
Molecular stratification of early breast cancer identifies drug targets to drive stratified medicine
Authors: Bayani Jane , Yao Cindy Q. , Quintayo Mary Anne , Yan Fu , Haider Syed , D’Costa Alister , Brookes Cassandra L. , van de Velde Cornelis J. H. , Hasenburg Annette , Kieback Dirk G. , Markopoulos Christos , Dirix Luc , Seynaeve Caroline , Rea Daniel , Boutros Paul C. , Bartlett John M. S.
Published: February 2017

Many women with hormone receptor-positive early breast cancer can be managed effectively with endocrine therapies alone. However, additional systemic chemotherapy treatment is necessary for others. The clinical challenges in managing high-risk women are to identify existing and novel druggable targets, and to identify those who would benefit from these therapies. Therefore, we performed mRNA abundance analysis using the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial pathology cohort to identify a signature of residual risk following endocrine therapy and pathways that are potentially druggable. A panel of genes compiled from academic and commercial multiparametric tests as well as genes of importance to breast cancer pathogenesis was used to profile 3825 patients. A signature of 95 genes, including nodal status, was validated to stratify endocrine-treated patients into high-risk and low-risk groups based on distant relapse-free survival (DRFS; Hazard Ratio = 5.05, 95% CI 3.53–7.22, p = 7.51 × 10−19). This risk signature was also found to perform better than current multiparametric tests. When the 95-gene prognostic signature was applied to all patients in the validation cohort, including patients who received adjuvant chemotherapy, the signature remained prognostic (HR = 4.76, 95% CI 3.61-6.28, p = 2.53× 10−28). Functional gene interaction analyses identified six significant modules representing pathways involved in cell cycle control, mitosis and receptor tyrosine signaling; containing a number of genes with existing targeted therapies for use in breast or other malignancies. Thus the identification of high-risk patients using this prognostic signature has the potential to also prioritize patients for treatment with these targeted therapies.
Cockroach protease allergen induces allergic airway inflammation via epithelial cell activation
Authors: Kale Sagar L. , Agrawal Komal , Gaur Shailendra Nath , Arora Naveen
Published: February 2017

Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies. Per a 10 exposure also leads to secretion of IL-33, TSLP and intracellular Ca2+dependent increase in ATP levels. Further,in vivoexperiments revealed that Per a 10 administration in mice elevated allergic inflammatory parameters along with high levels of IL-33, TSLP, IL-1α and uric acid in the mice lungs. We next demonstrated that Per a 10 cleaves CD23 (low affinity IgE receptor) from the surface of PBMCs and purified B cells and CD25 (IL-2 receptor) from the surface of PBMCs and purified T cells in an activity dependent manner, which might favour Th2 responses. In conclusion, protease activity of Per a 10 plays a significant role in initiation of allergic airway inflammation at the mucosal surfaces.
A novel augmented reality system for displaying inferior alveolar nerve bundles in maxillofacial surgery
Authors: Zhu Ming , Liu Fei , Chai Gang , Pan Jun J. , Jiang Taoran , Lin Li , Xin Yu , Zhang Yan , Li Qingfeng
Published: February 2017

Augmented reality systems can combine virtual images with a real environment to ensure accurate surgery with lower risk. This study aimed to develop a novel registration and tracking technique to establish a navigation system based on augmented reality for maxillofacial surgery. Specifically, a virtual image is reconstructed from CT data using 3D software. The real environment is tracked by the augmented reality (AR) software. The novel registration strategy that we created uses an occlusal splint compounded with a fiducial marker (OSM) to establish a relationship between the virtual image and the real object. After the fiducial marker is recognized, the virtual image is superimposed onto the real environment, forming the “integrated image” on semi-transparent glass. Via the registration process, the integral image, which combines the virtual image with the real scene, is successfully presented on the semi-transparent helmet. The position error of this navigation system is 0.96 ± 0.51 mm. This augmented reality system was applied in the clinic and good surgical outcomes were obtained. The augmented reality system that we established for maxillofacial surgery has the advantages of easy manipulation and high accuracy, which can improve surgical outcomes. Thus, this system exhibits significant potential in clinical applications.
Noninvasive quantification of blood potassium concentration from ECG in hemodialysis patients
Authors: Corsi Cristiana , Cortesi Marilisa , Callisesi Giulia , De Bie Johan , Napolitano Carlo , Santoro Antonio , Mortara David , Severi Stefano
Published: February 2017

Blood potassium concentration ([K+]) influences the electrocardiogram (ECG), particularly T-wave morphology. We developed a new method to quantify [K+] from T-wave analysis and tested its clinical applicability on data from dialysis patients, in whom [K+] varies significantly during the therapy. To elucidate the mechanism linking [K+] and T-wave, we also analysed data from long QT syndrome type 2 (LQT2) patients, testing the hypothesis that our method would have underestimated [K+] in these patients. Moreover, a computational model was used to explore the physiological processes underlying our estimator at the cellular level. We analysed 12-lead ECGs from 45 haemodialysis and 12 LQT2 patients. T-wave amplitude and downslope were calculated from the first two eigenleads. The T-wave slope-to-amplitude ratio (TS/A) was used as starting point for an ECG-based [K+] estimate (KECG). Leave-one-out cross-validation was performed. Agreement between KECG and reference [K+] from blood samples was promising (error: −0.09 ± 0.59 mM, absolute error: 0.46 ± 0.39 mM). The analysis on LQT2 patients, also supported by the outcome of computational analysis, reinforces our interpretation that, at the cellular level, delayed-rectifier potassium current is a main contributor of KECG correlation to blood [K+]. Following a comprehensive validation, this method could be effectively applied to monitor patients at risk for hyper/hypokalemia.
Enrichment of circulating head and neck tumour cells using spiral microfluidic technology
Authors: Kulasinghe Arutha , Tran Thao Huynh Phuoc , Blick Tony , O’Byrne Ken , Thompson Erik W. , Warkiani Majid E. , Nelson Colleen , Kenny Liz , Punyadeera Chamindie
Published: February 2017

Whilst locoregional control of head and neck cancers (HNCs) has improved over the last four decades, long-term survival has remained largely unchanged. A possible reason for this is that the rate of distant metastasis has not changed. Such disseminated disease is reflected in measurable levels of cancer cells in the blood of HNC patients, referred to as circulating tumour cells (CTCs). Numerous marker-independent techniques have been developed for CTC isolation and detection. Recently, microfluidics-based platforms have come to the fore to avoid molecular bias. In this pilot, proof of concept study, we evaluated the use of the spiral microfluidic chip for CTC enrichment and subsequent detection in HNC patients. CTCs were detected in 13/24 (54%) HNC patients, representing both early to late stages of disease. Importantly, in 7/13 CTC-positive patients, CTC clusters were observed. This is the first study to use spiral microfluidics technology for CTC enrichment in HNC.
Electrical Stimulation Using Conductive Polymer Polypyrrole Counters Reduced Neurite Outgrowth of Primary Prefrontal Cortical Neurons from NRG1-KO and DISC1-LI Mice
Authors: Zhang Qingsheng , Esrafilzadeh Dorna , Crook Jeremy M. , Kapsa Robert , Stewart Elise M. , Tomaskovic-Crook Eva , Wallace Gordon G. , Huang Xu-Feng
Published: February 2017

Deficits in neurite outgrowth, possibly involving dysregulation of risk genes neuregulin-1 (NRG1) and disrupted in schizophrenia 1 (DISC1) have been implicated in psychiatric disorders including schizophrenia. Electrical stimulation using conductive polymers has been shown to stimulate neurite outgrowth of differentiating human neural stem cells. This study investigated the use of the electroactive conductive polymer polypyrrole (Ppy) to counter impaired neurite outgrowth of primary pre-frontal cortical (PFC) neurons from NRG1-knock out (NRG1-KO) and DISC1-locus impairment (DISC1-LI) mice. Whereas NRG1-KO and DISC1-LI exhibited reduced neurite length and number of neurite branches compared to wild-type controls, this was not apparent for cultures on electroactive Ppy. Additionally, the use of the Ppy substrate normalised the synaptophysin and PSD95 protein and mRNA expression whereas both are usually reduced by NRG1-KO or DISC1-LI. Our findings support the utility of Ppy mediated electrical stimulation to prevent the reduction of neurite outgrowth and related synaptic protein expression in the primary PFC neurons from NRG1-KO and DISC1-LI mice, providing proof-of-concept for treating neurodevelopmental diseases including schizophrenia.
Real-time broadband terahertz spectroscopic imaging by using a high-sensitivity terahertz camera
Authors: Kanda Natsuki , Konishi Kuniaki , Nemoto Natsuki , Midorikawa Katsumi , Kuwata-Gonokami Makoto
Published: February 2017

Terahertz (THz) imaging has a strong potential for applications because many molecules have fingerprint spectra in this frequency region. Spectroscopic imaging in the THz region is a promising technique to fully exploit this characteristic. However, the performance of conventional techniques is restricted by the requirement of multidimensional scanning, which implies an image data acquisition time of several minutes. In this study, we propose and demonstrate a novel broadband THz spectroscopic imaging method that enables real-time image acquisition using a high-sensitivity THz camera. By exploiting the two-dimensionality of the detector, a broadband multi-channel spectrometer near 1 THz was constructed with a reflection type diffraction grating and a high-power THz source. To demonstrate the advantages of the developed technique, we performed molecule-specific imaging and high-speed acquisition of two-dimensional (2D) images. Two different sugar molecules (lactose and D-fructose) were identified with fingerprint spectra, and their distributions in one-dimensional space were obtained at a fast video rate (15 frames per second). Combined with the one-dimensional (1D) mechanical scanning of the sample, two-dimensional molecule-specific images can be obtained only in a few seconds. Our method can be applied in various important fields such as security and biomedicine.
Nanomechanical effects of light unveil photons momentum in medium
Authors: Verma Gopal , Chaudhary Komal , Singh Kamal P.
Published: February 2017

Precision measurement on momentum transfer between light and fluid interface has many implications including resolving the intriguing nature of photons momentum in a medium. For example, the existence of Abraham pressure of light under specific experimental configuration and the predictions of Chau-Amperian formalism of optical momentum for TE and TM polarizations remain untested. Here, we quantitatively and cleanly measure nanomehanical dynamics of water surface excited by radiation pressure of a laser beam. We systematically scanned wide range of experimental parameters including long exposure times, angle of incidence, spot size and laser polarization, and used two independent pump-probe techniques to validate a nano- bump on the water surface under all the tested conditions, in quantitative agreement with the Minkowski’s momentum of light. With careful experiments, we demonstrate advantages and limitations of nanometer resolved optical probing techniques and narrow down actual manifestation of optical momentum in a medium.
A novel orally bioavailable compound KPT-9274 inhibits PAK4, and blocks triple negative breast cancer tumor growth
Authors: Rane Chetan , Senapedis William , Baloglu Erkan , Landesman Yosef , Crochiere Marsha , Das-Gupta Soumyasri , Minden Audrey
Published: February 2017

Breast cancer is a heterogeneous disease consisting of several subtypes. Among these subtypes, triple negative breast cancer is particularly difficult to treat. This is due to a lack of understanding of the mechanisms behind the disease, and consequently a lack of druggable targets. PAK4 plays critical roles in cell survival, proliferation, and morphology. PAK4 protein levels are high in breast cancer cells and breast tumors, and the gene is often amplified in basal like breast cancers, which are frequently triple negative. PAK4 is also overexpressed in other types of cancer, making it a promising drug target. However, its inhibition is complicated by the fact that PAK4 has both kinase-dependent and -independent functions. Here we investigate a new clinical compound KPT-9274, which has been shown to inhibit PAK4 and NAMPT. We find that KPT-9274 (and its analog, KPT-8752) can reduce the steady state level of PAK4 protein in triple negative breast cancer cells. These compounds also block the growth of the breast cancer cells in vitro, and stimulate apoptosis. Most importantly, oral administration of KPT-9274 reduces tumorigenesis in mouse models of human triple negative breast cancer. Our results indicate that KPT-9274 is a novel therapeutic option for triple negative breast cancer therapy.
Cultured corneas show dendritic spread and restrict herpes simplex virus infection that is not observed with cultured corneal cells
Authors: Thakkar Neel , Jaishankar Dinesh , Agelidis Alex , Yadavalli Tejabhiram , Mangano Kyle , Patel Shrey , Tekin Sati Zeynep , Shukla Deepak
Published: February 2017

Herpes simplex virus-1 (HSV-1) causes life-long morbidities in humans. While fever blisters are more common, occasionally the cornea is infected resulting in vision loss. A very intriguing aspect of HSV-1 corneal infection is that the virus spread is normally restricted to only a small fraction of cells on the corneal surface that connect with each other in a dendritic fashion. Here, to develop a comprehensive understanding of the susceptibility of human corneal epithelial (HCE) cells to HSV-1 infection, we infected HCE cells at three different dosages of HSV-1 and measured the outcomes in terms of viral entry, gene and protein expression, viral replication and cytokine induction. In cultured cells, infectivity and cytokine induction were observed even at the minimum viral dosage tested, while a more pronounced dose-restricted infectivity was seen in ex vivo cultures of porcine corneas. Use of fluorescent HSV-1 virions demonstrated a pattern of viral spread ex vivo that mimics clinical findings. We conclude that HCE cell cultures are highly susceptible to infection whereas the cultured corneas demonstrate a higher ability to restrict the infection even in the absence of systemic immune system. The restriction is helped in part by local interferon response and the unique cellular architecture of the cornea.
Nearly-octave wavelength tuning of a continuous wave fiber laser
Authors: Zhang Lei , Jiang Huawei , Yang Xuezong , Pan Weiwei , Cui Shuzhen , Feng Yan
Published: February 2017

The wavelength tunability of conventional fiber lasers are limited by the bandwidth of gain spectrum and the tunability of feedback mechanism. Here a fiber laser which is continuously tunable from 1 to 1.9 μm is reported. It is a random distributed feedback Raman fiber laser, pumped by a tunable Yb doped fiber laser. The ultra-wide wavelength tunability is enabled by the unique property of random distributed feedback Raman fiber laser that both stimulated Raman scattering gain and Rayleigh scattering feedback are available at any wavelength. The dispersion property of the gain fiber is used to control the spectral purity of the laser output.
Organic nitrogen rearranges both structure and activity of the soil-borne microbial seedbank
Authors: Leite Márcio F. A. , Pan Yao , Bloem Jaap , Berge Hein ten , Kuramae Eiko E.
Published: February 2017

Use of organic amendments is a valuable strategy for crop production. However, it remains unclear how organic amendments shape both soil microbial community structure and activity, and how these changes impact nutrient mineralization rates. We evaluated the effect of various organic amendments, which range in Carbon/Nitrogen (C/N) ratio and degradability, on the soil microbiome in a mesocosm study at 32, 69 and 132 days. Soil samples were collected to determine community structure (assessed by 16S and 18S rRNA gene sequences), microbial biomass (fungi and bacteria), microbial activity (leucine incorporation and active hyphal length), and carbon and nitrogen mineralization rates. We considered the microbial soil DNA as the microbial seedbank. High C/N ratio favored fungal presence, while low C/N favored dominance of bacterial populations. Our results suggest that organic amendments shape the soil microbial community structure through a feedback mechanism by which microbial activity responds to changing organic inputs and rearranges composition of the microbial seedbank. We hypothesize that the microbial seedbank composition responds to changing organic inputs according to the resistance and resilience of individual species, while changes in microbial activity may result in increases or decreases in availability of various soil nutrients that affect plant nutrient uptake.
Theory of skyrmions in bilayer systems
Authors: Koshibae Wataru , Nagaosa Naoto
Published: February 2017

Skyrmion is an emergent particle consisting of many spins in magnets, and has many nontrivial features such as (i) nano-scale size, (ii) topological stability, (iii) gyrodynamics, and (iv) highly efficient spin transfer torque, which make skyrmions the promising candidate for the magnetic devices. Earlier works were focusing on the bulk or thin film of Dzyaloshinskii-Moriya (DM) magnets, while recent advances are focusing on the skyrmions induced by the interfaces. Therefore, the superstructures naturally leads to the interacting skyrmions on different interfaces, which has unique dynamics compared with those on the same interface. Here we theoretically study the two skyrmions on bilayer systems employing micromagnetic simulations as well as the analysis based on Thiele equation, revealing the reaction between them such as the collision and bound state formation. The dynamics depends sensitively on the sign of DM interactions, i.e., helicities, and skyrmion numbers of two skyrmions, which can be well described by Thiele equation. Furthermore, we have found the colossal spin-transfer-torque effect of bound skyrmion pair on antiferromagnetically coupled bilayer systems.