bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical modeling of bare surface barrier height and charge density in AlGaN/GaN heterostructures
Authors: Goyal Nitin , Iñiguez Benjamin , Fjeldly Tor A.
Published: September 2012

In this paper, a physics based analytical model for the bare surface barrier height and two dimensional electron gas density in AlGaN/GaN heterostructures is presented. The model is based on simple charge neutrality electrostatics across the AlGaN barrier layer and that a low density of surface donor states is the source of the two dimensional electron gas. The model shows good agreement with reported experimental results.
Electrodeposition of Lithium in Polystyrene Sphere Opal Structures on Copper from an Ionic Liquid
Authors: Willert Anne , Prowald Alexandra , El Abedin Sherif Zein , Höfft Oliver , Endres Frank
Published: September 2012

In this paper we report on the electrodeposition of lithium on a polystyrene sphere modified electrode from an ionic liquid. By a simple dipping process, polystyrene (PS) spheres with an average diameter of 600 nm arrange in a hexagonal close packed structure onto an electrode surface. Surprisingly, lithium does not grow uniformly from the electrode surface to the electrolyte within the voids of the PS structure. Depending on the experimental conditions a more or less good inverse opal structure made of lithium, lithium spheres or hollow lithium half-spheres can be obtained showing that the growth of lithium in the employed ionic liquid is more complicated than expected. Somehow lithium tends to push away the PS spheres during growth. Applying a slight mechanical pressure on the PS spheres during deposition improves the growth within the voids of the opal structure. Despite this complicated behaviour the PS opal structure seems to suppress a vertical dendritic growth, thus, a lithium/PS composite electrode or other lithium/polymer composite electrodes might be of some interest in rechargeable lithium metal microbatteries where a dendritic vertical growth has to be avoided.
Assessment of habitat usage by bats in the rangelands of Western Australia: comparison of echolocation call count and stable isotope analysis methods
Authors: Bullen R. D. , Dunlop J. N.
Published: September 2012

The activity levels of seven species of insectivorous microbats in five habitats widespread across the Charles Darwin Reserve in the Murchison region of Western Australia were measured using echolocation detectors and compared with results of habitat usage revealed by stable isotope analysis. The activity levels were further compared with projective foliage density as a surrogate of productivity within each habitat. Habitat use, estimated from echolocation activity of the microbat species and from stable isotope analysis of their fur, agree and each provides complementary information on the habitats preferred by species. Both methods show that five of the species, Chalinolobus gouldii, C. morio, Mormopterus species 3, Nyctophilus geoffroyi and Tadarida australis, are active and forage over each of the five habitats. Scotorepens balstoni is shown by both methods to prefer habitats with C3 woodland over C4 shrubs and grasses. Vespadelus baverstocki is shown by both methods to fly and forage over habitats with developed arid-zone shrubland understorey vegetation. The echolocation method shows that bat activity levels align with the foliage mass of the vegetation as measured by the projected foliage density. The species’ stable isotope signatures show that the insects captured are feeding primarily on the ground cover of the habitats. The two species that have high δC signatures, S. balstoni and V. baverstocki, are shown to be most active in habitats with a C4 ground cover.
The EU/IMF Financial Stabilisation Process in Latvia and Its Implications for Labour Law and Social Policy
Authors: Dahan Samuel
Published: September 2012

This article provides an account of the European Union/International Monetary Fund (EU/IMF) financial stabilisation package in Latvia, drawing out its implications for learning-based models of governance and for the relationship between social policy and financial aid. It is argued that the country-specific social and economic context of financial assistance programmes critically influences governments’ policy choices and hence the nature of the adjustment process. A case study of the Latvian assistance programme also reveals the role of social policy in the financial aid process, in particular in ameliorating some of the effects of structural adjustment packages. This study also considers shifts in the attitudes of the World Bank and IMF to social policy issues and the changing relationship between social policy and fiscal and macroeconomic policy in the EU.
First Report of Impatiens Downy Mildew Caused by Plasmopara obducens in Ohio
Authors: Baysal-Gurel F. , Taylor N. J. , Chatfield J. , Miller S. A.
Published: September 2012

Single and double flowered impatiens (Impatiens walleriana Hook.f.) plants with symptoms of downy mildew were found in commercial greenhouses in Delaware, Wayne, and Holmes counties, Ohio, in April 2012. Plants were stunted and defoliated. Symptoms on remaining leaves included general chlorosis without discrete spots and downward curling of leaves. A downy white growth was observed on the lower surface of infected leaves. The disease was widespread in affected greenhouses and incidence in cvs. Shimmer Coral, Accent Mix, and Super Elfin was nearly 90%. The downy growth consisted of coenocytic mycelia, monopodial sporangiophores, and ovoid, hyaline sporangia typical of Plasmopara obducens (J. Schröt.) J. Schröt in Cohn (1,2,4). Sporangia were borne on branchlets measuring 5 to 15 μm long (average 10 μm) at right angles to the main axis of the sporangiophore. Sporangia were 9.4 to 17.5 × 12.8 to 16.3 μm. No oospores were observed. Total DNA was extracted directly from plant tissue with the Wizard SV Genomic DNA Purification System (Promega, Madison, WI) following the manufacturer's instructions. Large ribosomal subunit DNA was amplified by PCR using primers NL-1 and NL-4 (3). Amplicons of 690 bp and 834 bp were produced from each diseased sample, while only the 690-bp amplicon was produced from healthy tissue. DNA from each amplicon of sample IDM041712 was purified using the Wizard SV Gel and PCR Clean-Up System (Promega), sequenced, and the sequence of the diagnostic 834-bp amplicon was deposited in GenBank (JX142134). The sequence of the 834-bp amplicon was 99% similar to those of P. obducens isolates from Serbia (HQ246451) (1), the UK (AY587558), and Austria (EF196869). The sequence of the 690-bp amplicon (JX142135) was 99% similar to that of I. walleriana (HQ223336). Twelve young impatiens ‘Shimmer Coral’ plants were inoculated with sporangia washed from infected leaves (1 × 104 sporangia/ml). Plants were incubated at room temperature for 24 h in a moist chamber and then maintained in a greenhouse (21 to 23°C) until symptoms appeared. Control plants were sprayed with sterile water and maintained in the same environment. After 12 to 14 days, typical symptoms of downy mildew developed on the inoculated plants and microscopic examination revealed the same pathogen morphology as the original isolate. All non-inoculated control plants remained disease free. To our knowledge, this is the first report of downy mildew on impatiens in Ohio. This disease caused considerable economic losses in Ohio in 2012 and is likely to be a recurring problem requiring intensive preventative management.

References: (1) A. Bulajic et al. Plant Dis. 95:491, 2011. (2) O. Constantinescu. Mycologia 83:473, 1991. (3) W. Maier et al. Can. J. Bot. 81:12, 2003. (4) S. N. Wegulo et al. Plant Dis. 88:909, 2004.
Chromosomal Mapping and QTL Analysis of Resistance to Downy Mildew inCucumis sativus
Authors: Zhang S. P. , Liu M. M. , Miao H. , Zhang S. Q. , Yang Y. H. , Xie B. Y. , Wehner T. C. , Gu X. F.
Published: September 2012

Downy mildew of cucumber (Cucumis sativus), caused by Pseudoperonospora cubensis, is a major foliar disease worldwide. The cucumber inbred lines K8 (resistant to downy mildew) and K18 (susceptible) were used to study the inheritance of resistance to downy mildew. Chromosomal mapping of the resistance genes was completed to provide a theoretical basis for the resistance mechanisms and for marker assisted selection (MAS). Inoculation was used to test the level of resistance to P. cubensis in the F2and F2:3families derived from the cross K8 × K18. Simple sequence repeat (SSR) analysis, combined with bulked segregation analysis (BSA), was done with the DNA of F2plants using 2,360 pairs of SSR primers. JoinMap Version 3.0 and MapInspect were used to construct SSR linkages and to verify the relationships between these SSR linkages and cucumber chromosomes. Quantitative trait locus (QTL) analysis of downy mildew resistance was done using MapQTL Version 4.0. Inheritance of resistance to downy mildew in K8 was quantitative. Five QTLs for resistance to downy mildew were detected: dm1.1, dm5.1, dm5.2, dm5.3, and dm6.1. The loci of dm1.1 and dm6.1 were on chromosomes 1 and 6, respectively. The loci of dm5.1, dm5.2, and dm5.3 were on chromosome 5, and were linked. Six linked SSR markers for these five QTLs were identified: SSR31116, SSR20705, SSR00772, SSR11012, SSR16882, and SSR16110. Six and four nucleotide binding site (NBS)-type resistance gene analogs (RGAs) were predicted in the region of dm5.2 and dm5.3, respectively. These results will be of benefit for fine-mapping the major QTLs for downy mildew resistance, and for MAS in cucumber.
Isoquinolin-5-amine
Authors: Atria Ana María , Garland Maria Teresa , Baggio Ricardo
Published: September 2012

The title compound, C9H8N2, presents two almost identical independent molecules in the asymmetric unit, both of them exhibiting an extremely planar isoquinoline core (maximum r.m.s. deviation = 0.014 Å). The most significant deviation is found in the –NH2groups, which present a noticeable pyramidalization around the N atom, a feature also present in related structures containing the molecule as a ligand. The supramolecular structure is based on pairs of parallel hydrogen-bonded chains formed by just one molecular type each, defined by the strongest hydrogen bonds in the structure, which are of the N—H...N type. These parallel chains are linked into pairs (or strips)viaweaker C—H...N hydrogen bonds. Related strips generated by thec-glide plane define two families running along [\overline{1}10] and [110], giving rise to an interesting system of interwoven chains stabilized by a number of weaker contacts of the C—H...π type.
Design and development of impact‐resistant sensor node for launch deployment into closed area
Authors: Sawai Kei , Tanabe Shigeaki , Kono Hitoshi , Suzuki Tsuyoshi , Kawabata Kuniaki
Published: September 2012

Purpose

The purpose of this paper is to propose a novel wireless sensor node (SN), with impact resistant capability, for launch deployment into closed areas. In disaster areas, gathering disaster area information is crucially important to prevent secondary disasters. However, gathering information is usually associated with the risk of death and/or accident for rescue workers in closed areas. The authors propose the SN for gathering information in dangerous places, inaccessible to rescue workers and robots, by utilizing launch deployment.

Design/methodology/approach

Buffer material is essential when designing an impact‐resistant structure. The authors adopted the air cushion as general buffer material when considering the directional characteristics of sensor mounting and wireless communication quality and developed the expression for determining the thickness of the air cushion using the parameters of SN size, mass, air pressure and acceleration. The authors developed a sensor node with impact resistant structure by utilizing the proposed determination method of air cushion thickness.

Findings

In the evaluation of impact resistant structure in free fall, launch deployment, the authors verified that the impact resistant structure protected the SN, and the performance of configured devices on the SN. Then, the authors examined the effect of the impact‐resistant structure on wireless communication between SNs. The structure had no effect on electric field intensity, throughput, or packet jitter, which confirmed that the wireless communication capacity was unaffected by the structure.

Originality/value

In this paper, a new design method is stated for a sensor node with an impact‐resistant structure by utilizing an air cushion as a general buffer material.
Gendered scholarship: exploring the implications for consumer behaviour research
Authors: Kumar Payal , Varshney Sanjeev
Published: September 2012

Purpose

The purpose of this paper is to explore the possibility of whether more representation of gendered scholarship could enrich the traditional framework of consumer behaviour – a discipline that lacks consensus on epistemology and is also starved of theory building – by means of critical introspection leading to new managerial solutions, new methods and theory building.

Design/methodology/approach

The quantitative approach involved a content analysis of three leading journals in the consumer behaviour discipline from 2006 to 2010: theJournal of Consumer Research, theJournal of Consumer Psychologyand theJournal of Consumer Affairs, in order to ascertain how much research represents a gendered perspective. The qualitative approach involved analyzing the papers from a gendered perspective, to see if the papers were more conceptual or based on applied research, and to gauge the type of methodologies used.

Findings

From 2006 to 2010 it was found that only an average of 2.4 per cent of 369 abstracts inJCR, 4 per cent of 224 abstracts inJCPand 5.8 per cent of 138 abstracts inJCAare from a gendered perspective. Approximately 25 per cent of the papers are steeped in applied research, while 75 per cent verify existing theories or expand to them.

Research limitations/implications

The authors’ qualitative analysis brings forward new results, namely that the very feministic perspective that has the potential to bring forth greater introspection in the consumer behavior research, namely feminist postmodernism, is in fact the least represented, with only one such paper out of 731, which is a possible wake‐up call for feminist scholars. The authors conclude that the scope of the traditional paradigm can be enlarged by gendered scholarship.

Originality/value

The paper represents a major effort to present the importance of including gendered perspective articles in marketing journals, to provide an analysis of the lack of a gendered perspective in papers published by three leading consumer‐based journals, and to determine whether a gendered perspective can enrich the traditional framework.
Gender differences in academic careers
Authors: Groeneveld Sandra , Tijdens Kea , van Kleef Daphne
Published: September 2012

Purpose

The purpose of this paper is to examine gender differences in promotion probabilities of the academic staff of a large university in The Netherlands, taking into account the sex segregated context of the faculty.

Design/methodology/approach

The study uses records of the university's personnel information system from 1990 to 2006, covering the data of 1,792 employees in the academic ranks who have entered since 1990. Cox regression models are used to test three hypotheses.

Findings

The findings show that women have lower promotion probabilities than men. The gender differences are primarily explained by differences in years of service and external mobility, and not by the sex segregated context of the faculty. A higher share of women decreases the odds of being promoted for both men and women. Gender differences in working hours do not explain the gender differences in promotion probabilities.

Originality/value

The paper adds to the existing literature because event history analyses have hardly been applied to personnel records for investigating the impact of the sex segregated context on promotion probabilities.
From legitimacy by character to legitimacy by image
Authors: Hooper Keith , Xu Gina
Published: September 2012

Purpose

From a historical perspective, the purpose of this paper is to show how the current New Zealand Accountants' Code of Ethics (COE) differs from the first 1927 COE. The lengthy, current COE comprises strands of thought drawn from three different philosophical positions. By contrast, New Zealand's first COE was relatively short and reflected legitimacy by character employing the concepts of virtue ethics. The concepts of virtue ethics have now largely disappeared from the latest much longer code. The current code is more legalistic and technical, implying a concern for public relations. At the same time, the current COE has become a legitimising tool for the profession to emphasise image and quality.

Design/methodology/approach

To illustrate the shift in practice of ethical position, the paper is informed by a recent New Zealand case of a collapsed finance company as well as some further illustrations of a failure to discharge a duty of care to the public from the United Kingdom.

Findings

The shift in the COE coupled with a shift in underlying social values contributes to what theEconomist Journaldescribes as a steady decline in professional ethics. There has been a shift from legitimising the character of an accountant to legitimising the character of accounting. This arguable conclusion is supported by a case study in New Zealand and cites the shift in combinations of cognitive, moral and pragmatic legitimacy as drivers employed by accounting firms.

Research limitations/implications

The paper uses secondary and documentary data and is informed by conceptual analysis which necessarily in the realm of ethics may be contentious.

Originality/value

The paper seeks to link the changing social values with changes in legitimisation and the COE to show shifts in accounting practices like the recent practice of issuing disclaimers.
Knowledge management and strategic orientation: leveraging innovativeness and performance
Authors: Ferraresi Alex A. , Quandt Carlos O. , dos Santos Silvio A. , Frega José R.
Published: September 2012

Purpose

The aim of this study is to investigate whether knowledge management (KM) contributes to the development of strategic orientation and to enhance innovativeness, and whether these three factors contribute to improve business performance.

Design/methodology/approach

A sample of 241 Brazilian companies was surveyed, using Web‐based questionnaires with 54 questions, using ten‐point scales to measure the degree of agreement on each item of each construct. Structural equation modeling techniques were applied for model assessment and analysis of the relationships among constructs. Exploratory factor analysis, confirmatory factor analysis, and path analysis using the technique of structural equation modeling were applied to the data.

Findings

Effective KM contributes positively to strategic orientation. Although there is no significant direct effect of KM on innovativeness, the relationship is significant when mediated by strategic orientation. Similarly, effective KM has no direct effect on business performance, but this relationship becomes statistically significant when mediated by strategic orientation and innovativeness.

Research limitations/implications

The findings indicate that KM permeates all relationships among the constructs, corroborating the argument that knowledge is an essential organizational resource that leverages all value‐creating activities. The results indicate that both KM and innovativeness produce significant impacts on performance when they are aligned with a strategic orientation that enables the organization to anticipate and respond to changing market conditions.

Originality/value

There is a substantial body of research on several types of relationships involving KM, strategic orientation, innovativeness and performance. This study offers an original contribution by analyzing all of those constructs simultaneously, using established scales so that comparative studies are possible.
Nimble knowledge transfer in high velocity/turbulent environments
Authors: Jones Nory B. , Mahon John F.
Published: September 2012

Purpose

This paper aims to clarify the relationship between explicit and tacit knowledge in specific organizational environments. It seeks to explore processes and strategies currently being deployed as best practices in the military to see what can be learnt from them and to improve the use of knowledge assets in large‐scale organizations in high‐velocity and/or turbulent environments.

Design/methodology/approach

High velocity/turbulent environments are defined. The paper uses examples from the public sector and the private sector and provides a model for knowledge management in high velocity/turbulent environments (HVTE) and offers several propositions for further exploration.

Findings

The paper provides insights into how and why tacit knowledge is more important to decision making and strategic positioning in high velocity/turbulent environments. The complexity of knowledge management is enormous.

Practical implications

What the authors learned from the military can serve as lessons for businesses to improve their agility in high velocity/turbulent environments. Businesses can apply this knowledge in considering the types of environments they operate in and which methods of knowledge transfer would serve them best to remain competitive.

Originality/value

This paper addresses what the authors believe is missing in knowledge management research to date – how and when tacit knowledge is more critical to organizational success than the use of explicit knowledge. The analysis also provides an environmental framework that distinguishes the use of tacit and explicit knowledge.
THE NEW PATH TO ORGANISATIONAL CHANGE
Authors: Cable Dan
Published: September 2012

Daniel M Cable, Professor of Organisational Behaviour at London Business School, studies organisational culture and its effects on sustained competitive advantage and leadership development. His research and book, Change to Strange: Create a Great Organisation by Building a Strange Workforce (Prentice‐Hall, 2007), laid the groundwork for his belief that business has entered a new era, one that means that the old paradigms governing change are no longer the road to success. He shared his current thinking with Georgina Peters.
THE NARRATIVE ADVANTAGE
Authors: Vermeulen Freek
Published: September 2012

It may not be in the job description for most CEOs, but Freek Vermeulen says that a good leader must also be a good storyteller. Rest assured: we're not making this up.
EXECUTIVE SUMMARY: GIVE AND LET GIVE
Authors: Smith Robert W. , Faro David , Burson Katherine A.
Published: September 2012

Robert W. Smith, David Faro and Katherine A. Burson, ‘More for the many: The influence of entitativity on charitable giving’, Journal of Consumer Research, forthcoming February 2013.
Falling Out: Authoritative Knowledge and Women's Experiences with Pelvic Organ Prolapse
Authors: Low Lisa Kane , Tumbarello Julie A.
Published: September 2012

Introduction: Despite the high prevalence of pelvic organ prolapse, many women suffer in silence, lacking the language and opportunity to describe their condition. There are limited descriptions of women's experiences with pelvic organ prolapse in the literature. This qualitative study addressed the knowledge and experience of women with pelvic organ prolapse.

Methods: Semistructured interviews were conducted with 13 women who had been previously diagnosed with pelvic organ prolapse. Transcripts of the interviews were reviewed and coded using a process of content analysis compared against the framework of authoritative knowledge, developed by Brigitte Jordan.

Results: By applying the concept of authoritative knowledge, we identified 3 themes of how women construct understanding about pelvic organ prolapse and how they demonstrate deference to the authoritative knowledge of medical providers. First, we found through women's narratives that authoritative knowledge was held by the health care provider and is considered consequential and legitimate by all participants. Second, women reported that the health care provider's authoritative knowledge was valued over personal, experiential knowledge. Finally, women described how they work with their health care providers to create a system of authoritative knowledge as they seek treatment for or discuss their condition. Throughout the narratives, women's experiences are not legitimized by the women or the medical community, perpetuating the “hidden” nature of these conditions.

Discussion: This analysis provides qualitative evidence of Jordan's authoritative knowledge: women and health care providers contribute to dimensions of authoritative knowledge surrounding pelvic organ prolapse. Despite what women experience, the health care provider's definition and understanding of pelvic organ prolapse is seen as legitimate and consequential. Because of their construction of their condition, and the power dynamic at play, women are silenced, and their expertise about their bodies is delegitimized, limiting their active participation in seeking care for this condition.
Multiple levels of meaning in DNA sequences, and one more
Authors: Trifonov Edward N. , Volkovich Zeev , Frenkel Zakharia M.
Published: September 2012

If we define a genetic code as a widespread DNA sequence pattern that carries a message with an impact on biology, then there are multiple genetic codes. Sequences involved in these codes overlap and, thus, both interact with and constrain each other, such as for the triplet code, the intron‐splicing code, the code for amphipathic alpha helices, and the chromatin code. Nucleosomes preferentially are located at the ends of exons, thus protecting splice junctions, with the N9 positions of guanines of the GT and AG junctions oriented toward the histones. Analysis of protein‐coding sequences reveals numerous traces of tandem repeats, apparently formed by triplet expansion, which in effect is a genome inflation ``code''. Our data are consistent with the hypothesis that expansion of simple tandem repetition of certain aggressive triplets has been a characteristic of life from its emergence. Such expanding triplets appear to be the major factor underlying observed codon usage biases.
Impact of climate change in Mediterranean aquaculture
Authors: Rosa Rui , Marques António , Nunes Maria L.
Published: September 2012

The Mediterranean Sea is the biggest marginal sea of the Earth and is at the centre of the life for several millions of people. Seafood is consumed widely in this region, with an average of 16.5 kg/capita/year, and one‐fourth of the seafood supply comes from aquaculture activities. The Mediterranean aquaculture sector has expanded in recent decades. Production increased by 77% over the past decade reaching about 1.3 million metric tonnes in 2009. The total value of production was around 3700 million US dollars, representing 3.4% of the value of global aquaculture production. The growth of seafood demand in the Mediterranean is expected to increase in the future, especially in southern countries. Yet, during the 21st century, the Mediterranean basin is expected to observe: (i) an increase in air temperature of between 2.2°C and 5.1°C; (ii) a decrease in rainfall of between 4% and 27%; (iii) an increase in drought periods related to a high frequency of days during which the temperature would exceed 30°C; and (iv) an increase of the sea level of around 35 cm and saline intrusion. Moreover, extreme events, such as heat waves, droughts or floods, are likely to be more frequent and violent. This paper reviews the present status of Mediterranean aquaculture (e.g. production trends, main farmed species, production systems, major producing countries), the most relevant impacts of climate change on this sector (temperature, eutrophication, harmful algae blooms, water stress, sea level rise, acidification and diseases) and proposes a wide range of adaptation and mitigation strategies that might be implemented to minimize impacts.
Global Health Governance and the Rise of Asia
Authors: Tan Yeling , Lee Kelley , Pang Tikki
Published: September 2012

A rising Asia brings to the global arena a new set of increasingly influential players with their own values, histories and strategic considerations. It remains to be seen if these shifts will lead to a clash or convergence in the management of global issues. The critical issues include Asian actors’ treatment of sovereignty, their preferences on institutional design, and conceptions of their role in global governance. Global health is fraught with a whole range of collective action problems, which we are failing to address effectively with existing institutional arrangements. This is in part because these institutions are embedded in an anachronistic world order in which Asia is governed rather than governing. Bridging this disconnect will require multiple adjustments. Existing actors involved in setting global health rules will need to adjust to take into account opportunities, constraints and perspectives from the Asian region that may have thus far been neglected. At the same time, Asian state and nonstate actors need to be engaged as co‐shapers of the global order – not just in terms of material contributions to existing initiatives, but also in terms of leadership and ideas for reforming and strengthening current institutions.

Policy Implications

 Sovereignty is asserted in a variety of ways across different global health issues, and policy responses should therefore be similarly diverse, tailored to the specific factors present in each context.

 Governance structures at the global level are not only shaped by state actors, but can be shaped in part by bottom‐up policy processes. This is a reflection of the degree to which domestic environments allow for non‐state actor participation, as well as how these local actors are connected to transnational networks and discourses.

 The implementation of global rules remains dependent on local capacity and political will. As such, more donor attention (including Asian donors) could be called to the institutional weaknesses in the Asian region.

 While regional organizations remain focused on maintaining stability, the FCTC experience has shown that regional distrust can be overcome in the presence of leadership and with inclusive national‐level policy processes.

 Emerging multipolarity threatens to deepen strategic competition between powerful and rising states, thereby further fragmenting efforts to govern global health. Such competition could be mitigated by empowering a greater range of actors in Asia with interests in advancing health needs.

 Asian state and non‐state actors have an opportunity to play a bigger role in reforming existing global health governance institutions. One way to facilitate this stronger governance role is to foster inclusive dialogue and constructive debate on the importance of global health governance in the region.
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA
Authors: Maurano Matthew T. , Humbert Richard , Rynes Eric , Thurman Robert E. , Haugen Eric , Wang Hao , Reynolds Alex P. , Sandstrom Richard , Qu Hongzhu , Brody Jennifer , Shafer Anthony , Neri Fidencio , Lee Kristen , Kutyavin Tanya , Stehling-Sun Sandra , Johnson Audra K. , Canfield Theresa K. , Giste Erika , Diegel Morgan , Bates Daniel , Hansen R. Scott , Neph Shane , Sabo Peter J. , Heimfeld Shelly , Raubitschek Antony , Ziegler Steven , Cotsapas Chris , Sotoodehnia Nona , Glass Ian , Sunyaev Shamil R. , Kaul Rajinder , Stamatoyannopoulos John A.
Published: September 2012

Predictions of Genetic Disease

Many genome-wide association studies (GWAS) have identified loci and variants associated with disease, but the ability to predict disease on the basis of these genetic variants remains small.

Maurano
et al.

(p.
1190
; see the Perspective by

Schadt and Chang

; see the cover) characterize the location of GWAS variants in the genome with respect to their proximity to regulatory DNA [marked by deoxyribonuclease I (DNase I) hypersensitive sites] by tissue type, disease, and enrichments in physiologically relevant transcription factor binding sites and networks. They found many noncoding disease associations in regulatory DNA, indicating tissue and developmental-specific regulatory roles for many common genetic variants and thus enabling links to be made between gene regulation and adult-onset disease.
How Cells Know the Size of Their Organelles
Authors: Chan Yee-Hung M. , Marshall Wallace F.
Published: September 2012

Cells have developed ways to sense and control the size of their organelles. Size-sensing mechanisms range from direct measurements provided by dedicated reporters to indirect functional readouts, and they are used to modify organelle size under both normal and stress conditions. Organelle size can also be controlled in the absence of an identifiable size sensor. Studies on flagella have dissected principles of size sensing and control, and it will be exciting to see how these principles apply to other organelles.
Diagnostic Accuracy of PCR Alone Compared to Galactomannan in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis: a Systematic Review
Authors: Avni Tomer , Levy Itzhak , Sprecher Hannah , Yahav Dafna , Leibovici Leonard , Paul Mical
Published: September 2012

PCR in bronchoalveolar lavage (BAL) fluid has not been accepted as a diagnostic criterion for invasive pulmonary aspergillosis (IPA). We conducted a systematic review assessing the diagnostic accuracy of PCR in BAL fluid with a direct comparison versus galactomannan (GM) in BAL fluid. We included prospective and retrospective cohort and case-control studies. Studies were included if they used the EORTC/MSG consensus definition criteria of IPA and assessed ≥80% of patients at risk for IPA. Two reviewers abstracted data independently. Risk of bias was assessed using QUADAS-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Nineteen studies published between 1993 and 2012 were included. The summary sensitivity and specificity values (CIs) for diagnosis of proven or probable IPA were 90.2% (77.2 to 96.1%) and 96.4% (93.3 to 98.1%), respectively. In nine cohort studies strictly adherent to the 2002 or 2008 EORTC/MSG criteria for reference standard definitions, the summary sensitivity and specificity values (CIs) were 77.2% (62 to 87.6%) and 93.5% (90.6 to 95.6%), respectively. Antifungal treatment before bronchoscopy significantly reduced sensitivity. The diagnostic performance of PCR was similar to that of GM in BAL fluid using an optical density index cutoff of 0.5. If either PCR or GM in BAL fluid defined a positive result, the pooled sensitivity was higher than that of GM alone, with similar specificity. We conclude that the diagnostic performance of PCR in BAL fluid is good and comparable to that of GM in BAL fluid. Performing both tests results in optimal sensitivity with no loss of specificity. Results are dependent on the reference standard definitions.
Reclassification of the Candida haemulonii Complex as Candida haemulonii (C. haemulonii Group I), C. duobushaemulonii sp. nov. (C. haemulonii Group II), and C. haemulonii var. vulnera var. nov.: Three Multiresistant Human Pathogenic Yeasts
Authors: Cendejas-Bueno E. , Kolecka A. , Alastruey-Izquierdo A. , Theelen B. , Groenewald M. , Kostrzewa M. , Cuenca-Estrella M. , Gómez-López A. , Boekhout T.
Published: September 2012

The
Candida haemulonii
species complex is currently known as
C. haemulonii
groups I and II. Here we describe
C. haemulonii
group II as a new species,
Candida duobushaemulonii
sp. nov., and
C. haemulonii
var.
vulnera
as new a variety of
C. haemulonii
group I using phenotypic and molecular methods. These taxa and other relatives of
C. haemulonii
(i.e.,
Candida auris
and
Candida pseudohaemulonii
) cannot be differentiated by the commercial methods now used for yeast identification. Four isolates (
C. haemulonii
var.
vulnera
) differed from the other isolates of
C. haemulonii
in the sequence of the internal transcribed spacer (ITS) regions of the nuclear rRNA gene operon. The new species and the new variety have a multiresistant antifungal profile, which includes high MICs of amphotericin B (geometric mean MIC, 1.18 mg/liter for
C. haemulonii
var.
vulnera
and 2 mg/liter for
C. duobushaemulonii
sp. nov) and cross-resistance to azole compounds. Identification of these species should be based on molecular methods, such as sequence analysis of ITS regions and matrix-assisted laser desorption ionization–time of flight mass spectrometry.
Hepatitis C Virus Activates Bcl-2 and MMP-2 Expression through Multiple Cellular Signaling Pathways
Authors: Li Youxing , Zhang Qi , Liu Yin , Luo Zhen , Kang Lei , Qu Jing , Liu Weiyong , Xia Xueshan , Liu Yingle , Wu Kailang , Wu Jianguo
Published: September 2012

Hepatitis C virus (HCV) infection is associated with numerous liver diseases and causes serious global health problems, but the mechanisms underlying the pathogenesis of HCV infections remain largely unknown. In this study, we demonstrate that signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-2 (MMP-2), and B-cell lymphoma 2 (Bcl-2) are significantly stimulated in HCV-infected patients. We further show that HCV activates STAT3, MMP-2, Bcl-2, extracellular regulated protein kinase (ERK), and c-Jun N-terminal kinase (JNK) in infected Huh7.5.1 cells. Functional screening of HCV proteins revealed that nonstructural protein 4B (NS4B) is responsible for the activation of MMP-2 and Bcl-2 by stimulating STAT3 through repression of the suppressor of cytokine signaling 3 (SOCS3). Our results also demonstrate that multiple signaling cascades, including several members of the protein kinase C (PKC) family, JNK, ERK, and STAT3, play critical roles in the activation of MMP-2 and Bcl-2 mediated by NS4B. Further studies revealed that the C-terminal domain (CTD) of NS4B is sufficient for the activation of STAT3, JNK, ERK, MMP-2, and Bcl-2. We also show that amino acids 227 to 250 of NS4B are essential for regulation of STAT3, JNK, ERK, MMP-2, and Bcl-2, and among them, three residues (237L, 239S, and 245L) are crucial for this regulation. Thus, we reveal a novel mechanism underlying HCV pathogenesis in which multiple intracellular signaling cascades are cooperatively involved in the activation of two important cellular factors, MMP-2 and Bcl-2, in response to HCV infection.
Cyclin-Dependent Kinase 2 Phosphorylates S/T-P Sites in the Hepadnavirus Core Protein C-Terminal Domain and Is Incorporated into Viral Capsids
Authors: Ludgate Laurie , Ning Xiaojun , Nguyen David H. , Adams Christina , Mentzer Laura , Hu Jianming
Published: September 2012

Phosphorylation of the hepadnavirus core protein C-terminal domain (CTD) is important for viral RNA packaging, reverse transcription, and subcellular localization. Hepadnavirus capsids also package a cellular kinase. The identity of the host kinase that phosphorylates the core CTD or gets packaged remains to be resolved. In particular, both the human hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) core CTDs harbor several conserved serine/threonine-proline (S/T-P) sites whose phosphorylation state is known to regulate CTD functions. We report here that the endogenous kinase in the HBV capsids was blocked by chemical inhibitors of the cyclin-dependent kinases (CDKs), in particular, CDK2 inhibitors. The kinase phosphorylated the HBV CTD at the serine-proline (S-P) sites. Furthermore, we were able to detect CDK2 in purified HBV capsids by immunoblotting. Purified CDK2 phosphorylated the S/T-P sites of the HBV and DHBV CTD
in vitro
. Inhibitors of CDKs, of CDK2 in particular, decreased both HBV and DHBV CTD phosphorylation
in vivo
. Moreover, CDK2 inhibitors blocked DHBV CTD phosphorylation, specifically at the S/T-P sites, in a mammalian cell lysate. These results indicate that cellular CDK2 phosphorylates the functionally critical S/T-P sites of the hepadnavirus core CTD and is incorporated into viral capsids.
Epstein-Barr Virus Latent Membrane Protein 1 Regulates the Function of Interferon Regulatory Factor 7 by Inducing Its Sumoylation
Authors: Bentz Gretchen L. , Shackelford Julia , Pagano Joseph S.
Published: September 2012

Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) induces multiple signal transduction pathways during latent EBV infection via its C-terminal activating region 1 (CTAR1), CTAR2, and the less-studied CTAR3. One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications, including phosphorylation and ubiquitination. We recently documented that LMP1 induces a third major protein modification by physically interacting with the SUMO-conjugating enzyme Ubc9 through CTAR3 and inducing the sumoylation of cellular proteins in latently infected cells. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. Our data show that endogenously sumoylated IRF7 is detected in latently infected EBV lymphoblastoid cell lines. LMP1 expression coincided with increased sumoylation of IRF7 in a CTAR3-dependent manner. Additional experiments show that LMP1 CTAR3-induced sumoylation regulates the expression and function of IRF7 by decreasing its turnover, increasing its nuclear retention, decreasing its DNA binding, and limiting its transcriptional activation. Finally, we identified that IRF7 is sumoylated at lysine 452. These data demonstrate that LMP1 CTAR3 does in fact function in intracellular signaling, leading to biologic effects. We propose that CTAR3 is an important signaling region of LMP1 that regulates protein function by sumoylation. We have shown specifically that LMP1 CTAR3, in cooperation with CTAR2, can limit the ability of IRF7 to induce innate immune responses by inducing the sumoylation of IRF7.
The Asian-American E6 Variant Protein of Human Papillomavirus 16 Alone Is Sufficient To Promote Immortalization, Transformation, and Migration of Primary Human Foreskin Keratinocytes
Authors: Niccoli Sarah , Abraham Suraj , Richard Christina , Zehbe Ingeborg
Published: September 2012

We examined how well the human papillomavirus (HPV) E6 oncogene can function in the absence of the E7 oncogene during the carcinogenic process in human keratinocytes using a common HPV variant strongly associated with cervical cancer: the Asian-American E6 variant (AAE6). This E6 variant is 20 times more frequently detected in cervical cancer than the prototype European E6 variant, as evidenced by independent epidemiological data. Using cell culture and cell-based functional assays, we assessed how this variant can perform crucial carcinogenesis steps compared to the prototype E6 variant. The ability to immortalize and transform primary human foreskin keratinocytes (PHFKs) to acquire resilient phenotypes and the ability to promote cell migration were evaluated. The immortalization capability was assayed based on population doublings, number of passages, surpassing mortality stages 1 and 2, human telomerase reverse transcriptase (hTERT) expression, and the ability to overcome G
1
arrest via p53 degradation. Transformation and migration efficiency were analyzed using a combination of functional cell-based assays. We observed that either AAE6 or prototype E6 proteins alone were sufficient to immortalize PHFKs, although AAE6 was more potent in doing so. The AAE6 variant protein alone pushed PHFKs through transformation and significantly increased their migration ability over that of the E6 prototype. Our findings are in line with epidemiological data that the AA variant of HPV16 confers an increased risk over the European prototype for cervical cancer, as evidenced by a superior immortalization, transformation, and metastatic potential.
Oligomeric Recombinant H5 HA1 Vaccine Produced in Bacteria Protects Ferrets from Homologous and Heterologous Wild-Type H5N1 Influenza Challenge and Controls Viral Loads Better than Subunit H5N1 Vaccine by Eliciting High-Affinity Antibodies
Authors: Verma Swati , Dimitrova Milena , Munjal Ashok , Fontana Juan , Crevar Corey J. , Carter Donald M. , Ross Ted M. , Khurana Surender , Golding Hana
Published: September 2012

Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission.
Conserved Fiber-Penton Base Interaction Revealed by Nearly Atomic Resolution Cryo-Electron Microscopy of the Structure of Adenovirus Provides Insight into Receptor Interaction
Authors: Cao Changchun , Dong Xiaoyan , Wu Xiaobing , Wen Boyun , Ji Gang , Cheng Lingpeng , Liu Hongrong
Published: September 2012

Adenovirus (Ad) cell attachment is initiated by the attachment of the fiber protein to a primary receptor (usually CAR or CD46). This event is followed by the engagement of the penton base protein with a secondary receptor (integrin) via its loop region, which contains an Arg-Gly-Asp (RGD) motif, to trigger virus internalization. To understand the well-orchestrated adenovirus cell attachment process that involves the fiber and the penton base, we reconstructed the structure of an Ad5F35 capsid, comprising an adenovirus type 5 (Ad5) capsid pseudotyped with an Ad35 fiber, at a resolution of approximately 4.2 Å. The fiber-penton base interaction in the cryo-electron microscopic (cryo-EM) structure of Ad5F35 is similar to that in the cryo-EM structure of Ad5, indicating that the fiber-penton base interaction of adenovirus is conserved. Our structure also confirms that the C-terminal segment of the fiber tail domain constitutes the bottom trunk of the fiber shaft. Based on the conserved fiber-penton base interaction, we have proposed a model for the interaction of Ad5F35 with its primary and secondary receptors. This model could provide insight for designing adenovirus gene delivery vectors.