bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of dual‐monopole slots antenna integrated with monopole strip for wireless wide area network mobile handset
Authors: Zuo Shao‐li , Zhang Zhi‐ya , Xie Jiao‐jiao
Published: November 2013

An internal antenna for penta‐band wireless wide area network (WWAN 824–960/1710–2170 MHz) operation in the mobile handset is presented. By integrating two monopole slots with a monopole strip printed on the top portion of the main circuit board, the monopole slots generate their quarter‐wavelength slot modes for the antenna's lower band, whereas the monopole strip can contribute quarter‐wavelength resonant modes for the antenna's upper band. The monopole strip serves as a feed for the monopole slots and also functions as an efficient radiator. In this case, the antenna can provide two wide operating bands (795–1035/1700–2205 MHz) to cover the penta‐band WWAN operation.
Spectrum occupancy of cognitive radio networks: a queueing analysis using retrial queue
Authors: Chang Woan Sun , Jang Won Mee
Published: November 2013

The authors apply the preemptive priority queueing analysis to cognitive radio networks. Using the proposed analytical model, the authors can quantify the delay, throughput and spectrum occupancy of cognitive radio networks. Cognitive users’ packet arrivals form a retrial queue with a proper choice of the retrial rate. The authors illustrate numerical results of the delay, throughput and spectrum occupancy with respect to retrial rate, spectrum sensing time and primary user's busy rate.
Multimedia data delivery table and improving transfer time on mobile handhelds
Authors: Jeong Taikyeong Ted , Choi Inhwa
Published: November 2013

This study presents an enhanced method to improve the transfer time of the audio/video file delivery table employed in a mobile handheld, terrestrial‐data multimedia broadcasting. The authors analysed the factors responsible for the delay in the dynamic carousel which is transmitted on broadcasting channels. They improved the transfer time and verified using comparison methods and other approaches. In this study, they measured the mobile handheld transmission delay time by analysing and comparing the transmission speed and by showing its characteristics. Proposed method which boosts up time for the mobile handheld data updating can be achieved approximately 20.5% performance improvement.
Sensitivity of higher mode of rectangular atomic force microscope to surface stiffness in air environment
Authors: Damircheli M. , Korayem M.H.
Published: November 2013

The sensitivity of the resonance frequencies and the amplitudes of the first four flexural vibration modes of atomic force microscopy with a rectangular cross‐section cantilever in an air environment to variation of a sample's stiffness have been analysed. The cantilever has been modelled using Timoshenko beam theory, and the vertical and tangential forces between the tip and the sample in this simulation have been considered. The effect of tip position and the angle of the tip relative to the sample in changes of these sensitivities have been studied. Results indicate that for soft materials, the first mode compared with other modes is more sensitive to changes in the sample's elasticity, so the first mode is the best mode for supplying high‐contrast images but by increasing the sample's stiffness, the higher mode will be sensitive, respectively. In addition, by increasing the angle between the cantilever and the sample's surface, the first mode is less sensitive and higher modes will be sensitive faster because of changes in material stiffness but in contrast, by increasing the distance between the tip's position and the free end of the cantilever, the sensitivity of the first mode increases and the higher mode will be sensitive for more stiff material.
Concurrent partnering and condom use among rural heterosexual African-American men
Authors: Ricks JaNelle M. , Geter Angelica , Crosby Richard A. , Brown Emma
Published: November 2013

Background
Limited research has targeted HIV risk among heterosexual African-American men in the rural south-eastern United States. Methods: A cross-sectional survey was administered to 538 men to assess HIV knowledge, attitudes towards HIV testing and sexual risk behaviour. Results: Fifty-one percent reported consistent condom use in the past 3 months. Monogamous men reported more consistent condom use (t = 3.47, d.f. = 536, P < 0.001). In concurrent partnerships, condom use was inversely related to age (adjusted odds ratio (AOR) = 0.98, 95% confidence interval (CI) = 0.95–0.998, P = 0.03) and increased with the number of female partners (AOR = 1.49, 95% CI = 1.26–1.76, P < 0.001). Conclusions: African-American HIV prevention outreach should include focus on concurrent partnering in rural settings.
Multimodal metaphors in political entertainment
Authors: Popa Diana Elena
Published: November 2013

Metaphor is one of the primary ways we accommodate and assimilate information and experience into our conceptual organization of the world. The present study investigates the internal cognitive mechanisms of multimodal-metaphor construction in the television genre of animated political cartoons. Taking a cognitive-semantic approach, we analyze how zoomorphs are constructed by the audience when they first appear. The study concludes by describing the potential of multimodal-metaphor analysis as a methodological tool.
Visual metonymy in children’s picture books
Authors: Moya Guijarro A. Jesús
Published: November 2013

This article aims to explore how the use of visual metonymies in picture books contributes to children’s understanding of stories and, in turn, attracts their attention towards relevant aspects of the plot. The two picture books selected for analysis are Gorilla, by Browne and The Tale of Peter Rabbit, by Potter, intended for children under 9 years of age.
A multimodal and cognitive perspective is adopted here to apply the non-verbal trope of visual metonymy to the two picture books that form the sample texts (Forceville, 2009, 2010; Forceville & Urios-Aparisi, 2009).
The results of the analysis show that visual metonymies are essentially used in children’s tales to create narrative tension in certain stages of the plot and, in turn, to establish a bond between the represented participants and the child-viewer.
The establishment of interpretative expectations in film
Authors: Bateman John A. , Tseng Chiaoi
Published: November 2013

In this paper we show that some notions from the textual organisation of verbal texts appear also to give insights to the organisation of films. In particular, the beginnings of films are suggested to operate as indicators of those films’ ‘method of development’ and so serve to set up expectations for guiding hypotheses and selective attention during film viewing. By means of a small exploratory study, we demonstrate that film beginnings exhibit differing organisational features that correlate with the overall narrative strategies pursued in the films as a whole. These features may then function as useful indicators for viewers concerning just what interpretative challenges they will face later in the film.
Multimodal digital storytelling
Authors: Alonso Isabel , Molina Plaza Silvia , Requejo Maria Dolores Porto
Published: November 2013

Digital stories are a very recent multimedia practice by which ordinary people construct short narratives on personal affairs combining voice, images and sometimes music. This paper contributes to the description of this new emergent genre from both a multimodal and a cognitive point of view, by exploring how diverse semiotic channels in digital storytelling provide different kinds of information (factual, emotional, cultural, etc.) which are finally integrated to construct the global meaning of the narrative. For this purpose, we combine Kress and Van Leeuwen’s (1996) scholarly work related to multimodal representation, with the use of some notions of the Mental Spaces and Conceptual Integration theory (Dancygier, 2008; Fauconnier & Turner, 2002). The results of this study are of interest to those concerned with the representational and communicational modes of semiotic resources in storytelling.
Effects of climate change on potential food production and risk of hunger.
Authors: Parry M.
Published: November 2013

This chapter describes the scale of the challenge facing crop genetic management in the role it needs to play in confronting climate change. It summarizes the development of knowledge about the risks posed by climate change to food production in the future and the consequent increases in risk of hunger.
Crop wild relatives and climate change.
Authors: Maxted N. , Kell S. , Brehm J. M.
Published: November 2013

This chapter provides an analysis of the importance of crop wild relatives (CWR) in plant breeding and the need for their comprehensive conservation. The importance of CWR diversity as a potentially critical resource for future food security is now widely recognized, particularly in the light of climate change and the rapidly increasing human population. The need to conserve CWR diversity has been placed firmly on the international conservation agenda. CWR diversity through trait transfer offers one means of helping sustain food production under the rapidly changing environmental conditions brought about by climate change.
Climate change and on-farm conservation of crop landraces in centres of diversity.
Authors: Bellon M. R. , Etten J. van
Published: November 2013

This chapter reviews the potential impacts of climate change on on-farm conservation of crop diversity and on the contribution that on-farm conservation can make to agricultural adaptation to climate change, and ask two questions: (1) How might climate change affect the viability of on-farm conservation of landraces in centres of crop diversity? and (2) How can on-farm conservation contribute to the adaptation of small-scale farmers to climate change?
Germplasm databases and informatics.
Authors: Ougham H. , Thomas I. D.
Published: November 2013

This chapter discusses the data management aspects of germplasm collections. It describes several developments in genetic resources databases, and regional projects aimed at facilitating conservation and use. It focuses solely on germplasm databases, specifically those that are publicly accessible through the World Wide Web and that are hosted and curated by well-established organizations, although there are, or have been, numerous other such databases. An additional criterion for choosing the databases introduced in this chapter is that they catalogue germplasm (generally conserved ex situ in genebanks) much of which is available free of charge (such as the collections held in the centres of the Consultative Group on International Agricultural Research) or may possibly be for purchase at a modest price.
Mapping Hfq-RNA interaction surfaces using tryptophan fluorescence quenching
Authors: Robinson Kirsten E. , Orans Jillian , Kovach Alexander R. , Link Todd M. , Brennan Richard G.
Published: November 2013

Hfq is a posttranscriptional riboregulator and RNA chaperone that binds small RNAs and target mRNAs to effect their annealing and message-specific regulation in response to environmental stressors. Structures of Hfq-RNA complexes indicate that U-rich sequences prefer the proximal face and A-rich sequences the distal face; however, the Hfq-binding sites of most RNAs are unknown. Here, we present an Hfq-RNA mapping approach that uses single tryptophan-substituted Hfq proteins, all of which retain the wild-type Hfq structure, and tryptophan fluorescence quenching (TFQ) by proximal RNA binding. TFQ properly identified the respective distal and proximal binding of A15 and U6 RNA to Gram-negative Escherichia coli (Ec) Hfq and the distal face binding of (AA)3A, (AU)3A and (AC)3A to Gram-positive Staphylococcus aureus (Sa) Hfq. The inability of (GU)3G to bind the distal face of Sa Hfq reveals the (R-L)n binding motif is a more restrictive (A-L)n binding motif. Remarkably Hfq from Gram-positive Listeria monocytogenes (Lm) binds (GU)3G on its proximal face. TFQ experiments also revealed the Ec Hfq (A-R-N)n distal face-binding motif should be redefined as an (A-A-N)n binding motif. TFQ data also demonstrated that the 5′-untranslated region of hfq mRNA binds both the proximal and distal faces of Ec Hfq and the unstructured C-terminus.
Spatio-temporal requirements for transposable element piRNA-mediated silencing duringDrosophilaoogenesis
Authors: Dufourt Jérémy , Dennis Cynthia , Boivin Antoine , Gueguen Nathalie , Théron Emmanuelle , Goriaux Coline , Pouchin Pierre , Ronsseray Stéphane , Brasset Emilie , Vaury Chantal
Published: November 2013

During Drosophila oogenesis, transposable element (TE) repression involves the Piwi-interacting RNA (piRNA) pathway which ensures genome integrity for the next generation. We developed a transgenic model to study repression of the Idefix retrotransposon in the germline. Using a candidate gene KD-approach, we identified differences in the spatio-temporal requirements of the piRNA pathway components for piRNA-mediated silencing. Some of them (Aub, Vasa, Spn-E) are necessary in very early stages of oogenesis within the germarium and appear to be less important for efficient TE silencing thereafter. Others (Piwi, Ago3, Mael) are required at all stages of oogenesis. Moreover, during early oogenesis, in the dividing cysts within the germarium, Idefix anti-sense transgenes escape host control, and this is associated with very low piwi expression. Silencing of P-element-based transgenes is also strongly weakened in these cysts. This region, termed the ‘Piwiless pocket’ or Pilp, may ensure that new TE insertions occur and are transmitted to the next generation, thereby contributing to genome dynamics. In contrast, piRNA-mediated silencing is strong in germline stem cells in which TE mobilization is tightly repressed ensuring the continued production of viable germline cysts.
Collaboration between CpG sites is needed for stable somatic inheritance of DNA methylation states
Authors: Haerter Jan O. , Lövkvist Cecilia , Dodd Ian B. , Sneppen Kim
Published: November 2013

Inheritance of 5-methyl cytosine modification of CpG (CG/CG) DNA sequences is needed to maintain early developmental decisions in vertebrates. The standard inheritance model treats CpGs as independent, with methylated CpGs maintained by efficient methylation of hemimethylated CpGs produced after DNA replication, and unmethylated CpGs maintained by an absence of de novo methylation. By stochastic simulations of CpG islands over multiple cell cycles and systematic sampling of reaction parameters, we show that the standard model is inconsistent with many experimental observations. In contrast, dynamic collaboration between CpGs can provide strong error-tolerant somatic inheritance of both hypermethylated and hypomethylated states of a cluster of CpGs, reproducing observed stable bimodal methylation patterns. Known recruitment of methylating enzymes by methylated CpGs could provide the necessary collaboration, but we predict that recruitment of demethylating enzymes by unmethylated CpGs strengthens inheritance and allows CpG islands to remain hypomethylated within a sea of hypermethylation.
Linking manipulative experiments to field data to test the dilution effect
Authors: Venesky Matthew D. , Liu Xuan , Sauer Erin L. , Rohr Jason R.
Published: November 2013

The dilution effect, the hypothesis that biodiversity reduces disease risk, has received support in many systems. However, few dilution effect studies have linked mechanistic experiments to field patterns to establish both causality and ecological relevance.

We conducted a series of laboratory experiments and tested the dilution effect hypothesis in an amphibian‐Batrachochytrium dendrobatidis (Bd) system and tested for consistency between our laboratory experiments and field patterns of amphibian species richness, host identity and Bd prevalence.

In our laboratory experiments, we show that tadpoles can filter feed Bd zoospores and that the degree of suspension feeding was positively associated with their dilution potential. The obligate suspension feeder, Gastrophryne carolinensis, generally diluted the risk of chytridiomycosis for tadpoles of Bufo terrestris and Hyla cinerea, whereas tadpoles of B. terrestris (an obligate benthos feeder) generally amplified infections for the other species. In addition, G. carolinensis reduced Bd abundance on H. cinerea more so in the presence than absence of B. terrestris and B. terrestris amplified Bd abundance on H. cinerea more so in the absence than presence of G. carolinensis. Also, when ignoring species identity, species richness was a significant negative predictor of Bd abundance.

In our analysis of field data, the presence of Bufo spp. and Gastrophryne spp. were significant positive and negative predictors of Bd prevalence, respectively, even after controlling for climate, vegetation, anthropogenic factors (human footprint), species richness and sampling effort. These patterns of dilution and amplification supported our laboratory findings, demonstrating that the results are likely ecologically relevant.

The results from our laboratory and field data support the dilution effect hypothesis and also suggest that dilution and amplification are predictable based on host traits. Our study is among the first to link manipulative experiments, in which a potential dilution mechanism is supported, with analyses of field data on species richness, host identity, spatial autocorrelation and disease prevalence.
Diversity and structure of bacterial communities associated with Phanerochaete chrysosporium during wood decay
Authors: Hervé Vincent , Le Roux Xavier , Uroz Stéphane , Gelhaye Eric , Frey‐Klett Pascale
Published: November 2013

Wood recycling is key to forest biogeochemical cycles, largely driven by microorganisms such as white‐rot fungi which naturally coexist with bacteria in the environment. We have tested whether and to what extent the diversity of the bacterial community associated with wood decay is determined by wood and/or by white‐rot fungus Phanerochaete chrysosporium. We combined a microcosm approach with an enrichment procedure, using beech sawdust inoculated with or without P. chrysosporium. During 18 weeks, we used 16S rRNA gene‐based pyrosequencing to monitor the forest bacterial community inoculated into these microcosms. We found bacterial communities associated with wood to be substantially less diverse than the initial forest soil inoculum. The presence of most bacterial operational taxonomic units (OTUs) varied over time and between replicates, regardless of their treatment, suggestive of the stochastic processes. However, we observed two OTUs belonging to Xanthomonadaceae and Rhizobium, together representing 50% of the relative bacterial abundance, as consistently associated with the wood substrate, regardless of fungal presence. Moreover, after 12 weeks, the bacterial community composition based on relative abundance was significantly modified by the presence of the white‐rot fungus. Effectively, members of the Burkholderia genus were always associated with P. chrysosporium, representing potential taxonomic bioindicators of the white‐rot mycosphere.
Levonorgestrel‐impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial
Authors: Ørbo A , Vereide AB , Arnes M , Pettersen I , Straume B
Published: November 2013

Objective

The purpose of this study was to investigate if the levonorgestrel‐impregnated intrauterine device (LNG‐IUS, Mirena®) is safe and effective as therapy for low‐risk and medium‐risk endometrial hyperplasia compared with oral medroxyprogesterone (MPA).

Design

A multicentre randomised trial.

Setting

Norway.

Population

In all, 170 women aged 30–70 years with low‐ or medium‐risk endometrial hyperplasia who met inclusion criteria.

Methods

Patients were randomly assigned to one of three treatment arms: LNG‐IUS; oral MPA 10 mg administered for 10 days per cycle, or continuous oral MPA 10 mg daily, for 6 months.

Main outcome measures

The primary outcome measure was normalisation or persisting hyperplasia.

Results

After 6 months all three treatment regimens showed significant effect when the outcome was evaluated as therapy response or not (P < 0.001). Responses were obtained for all the women in the LNG‐IUS group (53/53, 95% CI 0.93–1.0) and for 96% of the women in the continuous oral group (46/48, 95% CI 0.86–0.99). Only 69% of the women in the cyclic oral group were responders (36/52, 95% CI 0.55–0.81). Adverse effects were relatively common with minimal differences between therapy groups.

Conclusion

In the first trial of its kind, women treated with the LNG‐IUS showed histologically normal endometrium after 6 months of therapy for endometrial hyperplasia. Cyclical progestogens are found to be less effective compared with continuous oral therapy and LNG‐IUS and should not be used for this purpose.
Ultrasound elastography is a reproducible and feasible tool for the evaluation of the patellar tendon in healthy subjects
Authors: Porta F. , Damjanov N. , Galluccio F. , Iagnocco A. , Matucci‐Cerinic M.
Published: November 2013

Objective

To evaluate the feasibility and reproducibility of ultrasound elastography (UE) in the assessment of healthy patellar tendon and to describe its UE pattern.

Methods

Twenty‐two patellar tendons of 11 out of 16 healthy subjects who met the inclusion criteria were evaluated three times by ultrasound (US) and UE at their proximal, middle and distal portions, by two separate sonographers with different experiences in UE.

Results

In all tendon portions the color map analysis showed a predominance of green (highly elastic), with good values of intra‐observer (Operator 1: P‐values = 0.790, 0.864, 0.865; Operator 2: P = 0.642, 0.882, 0.613 for proximal, middle and distal portions, respectively) and inter‐observer (P = 0.657) agreement. For both operators the intra‐observer analysis of the elasticity ratio (ER) between the tendon and the subcutis showed high agreement values (P < 0.001 for both operators). The inter‐observer analysis showed also high agreement values (P < 0.001 at proximal, P = 0.001 at middle, P = 0.005 at distal portions). The overall analysis of the ER of the tendon portions showed values of (mean ± SD): 1.47 ± 0.64, 4.38 ± 1.36, 3.32 ± 1.20 for proximal, middle and distal portions, respectively. The mean time to perform the UE evaluation for the inexperienced operator was 5 min at the beginning of the study but decreased to 2 min after a few examinations were done. The mean time for the expert was 2 min for the entire study.

Conclusions

UE is a feasible and reproducible tool for the evaluation of the healthy patellar tendon and further data are needed to define its role in the assessment of tendon pathology.
Geographic assignment with stable isotopes in IsoMAP
Authors: Bowen Gabriel J. , Liu Zhongfang , Vander Zanden Hannah B. , Zhao Lan , Takahashi George
Published: November 2013

Stable isotope ratios of H and O (δ2H and δ18O) are intrinsic properties of biological and geological materials, and can be used to constrain the geographic origin and movements of such materials. One of the most widespread uses of such data in ecology is to reconstruct geographic movements of animals by comparing isotope ratios of chemically inert tissues to predictive models (‘isoscapes’) of spatial isotopic variation in environmental water.

Although data analysis for isotope‐based geographic assignment is the subject of ongoing research, a basic framework for this work has emerged.

Here, we introduce and document a set of data analysis tools, implemented within the IsoMAP (Isoscapes Modelling, Analysis, and Prediction; http://isomap.org) cyber‐GIS system, that support basic analysis of sample data for geographic assignment applications. We highlight important considerations and potential pitfalls associated with use or misuse of the tools.

In addition to increasing the accessibility of geographic assignment analysis, IsoMAP provides several unique capabilities related to the generation of space‐ and time‐specific water isoscapes that may advance the field of isotope‐based assignment. Functionality of the existing toolkit is limited in scope, and although the system will be actively developed in the future, it is intended to complement and not supplant more flexible and customizable analytical tools.
Outcomes of infrapopliteal endoluminal intervention for transatlantic intersociety consensus C and D lesions in patients with critical limb ischaemia
Authors: Tewksbury Robert , Pearch Ben , Redmond Kendal , Harper John , Klein Kerenaftali , Quinn John
Published: November 2013

Background

Recent data suggest that infrapopliteal percutaneous transluminal angioplasty (PTA) is a reasonable primary therapy for critical limb ischaemia (CLI). Based on the transatlantic intersociety consensus (TASC) classification, this has been found to be true for lesions classified as A, B or C. We report our experience with infrapopliteal PTA stratified by TASC classification.

Methods

A retrospective study of patients who underwent infrapopliteal PTA with or without stenting from October 2007 to July 2011 was conducted, revealing 83 limbs. The primary outcome variables were freedom from reintervention and freedom from index limb amputation. Secondary outcomes were technical success, post‐operative complications and survival. TASC classification was assessed for the individual vessel(s) chosen for intervention.

Results

Median age was 76 years and radiological success was 86.75%. Average follow‐up was 15 months. At 1 and 2 years, freedom from re‐intervention, or amputation was 65.1% and 55.6%. Limb salvage was 77.7%. Within 2 years, 2% underwent bypass and 18% repeat infrapopliteal PTA. The 30‐day mortality was 5%. Overall survival was 84.5%, 71.8% and 61.6% at 1, 2 and 3 years. Eighty‐two per cent were classified as TASC D lesions. Radiological success was achieved in 100% of TASC C lesions in contrast to 86.7% of TASC D lesions. There was not a statistically significant relationship between primary outcomes and TASC D classification.

Discussion

Given the encouragingly high rates of radiological success and limb salvage, an attempt at PTA is indicated as an alternative to primary amputation even in patients with radiologically demonstrated severe disease.
Congenital platelet disorders and understanding of platelet function
Authors: Nurden Alan T. , Nurden Paquita
Published: November 2013

Genetic defects of platelets constitute rare diseases that include bleeding syndromes of autosomal dominant, recessive or X‐linked inheritance. They affect platelet production, resulting in a low circulating platelet count and changes in platelet morphology, platelet function, or a combination of both with altered megakaryopoiesis and a defective platelet response. As a result, blood platelets fail to fulfil their haemostatic function. Most studied of the platelet function disorders are deficiencies of glycoprotein mediators of adhesion and aggregation while defects of primary receptors for stimuli include the P2Y12 ADP receptor. Studies on inherited defects of (i) secretion from storage organelles (dense granules, α‐granules), (ii) the platelet cytoskeleton and (iii) the generation of pro‐coagulant activity have identified genes indirectly controlling the functional response. Signalling pathway defects leading to agonist‐specific modifications of platelet aggregation are the current target of exome‐sequencing strategies. We now review recent advances in the molecular characterization of platelet function defects.
Geographic and Temporal Trends in Amazonian Knowledge Production
Authors: Malhado Ana C. M. , de Azevedo Rafael S. D. , Todd Peter A. , Santos Ana M. C. , Fabré Nídia N. , Batista Vandick S. , Aguiar Leonardo J. G. , Ladle Richard J.
Published: November 2013

The presence of researchers from Western (i.e., developed world) institutions in Amazonia has frequently been contentious due to fears of ‘scientific imperialism’ or suspicions that they may be exerting undue influence over research agendas and knowledge production to the detriment of local researchers. Such negative perceptions are widespread, but not well substantiated. A more nuanced understanding of these issues requires information on who is conducting research in Amazonia and how knowledge production has changed over time. We performed a bibliometric analysis on Thomson Reuters'ISI Web of Science of all research articles about the Amazon published in three time periods: 1986–1989, 1996–1999, and 2006–2009. We found that the number of articles published and the diversity of countries involved in Amazonian research increased dramatically over the three time periods. The representation of several Amazonian countries—especially Brazil—increased, while the proportion of articles without a single author from an Amazonian country also increased. The results indicate that the research capacity of Amazonian countries has increased, but that leadership of high‐impact projects may still largely reside with researchers from developed countries.
Safety and efficacy of an oral CCR3 antagonist in patients with asthma and eosinophilic bronchitis: a randomized, placebo‐controlled clinical trial
Authors: Neighbour H. , Boulet L.‐P. , Lemiere C. , Sehmi R. , Leigh R. , Sousa A. R. , Martin J. , Dallow N. , Gilbert J. , Allen A. , Hall D. , Nair P.
Published: November 2013

Background

Several chemokines, notably eotaxin, mediate the recruitment of eosinophils into tissues via the CCR3 receptor.

Objective

In this study, we investigated the role of CCR3 agonists in asthma by observing the effect of a small molecule antagonist of the CCR3 receptor (GW766994) on sputum eosinophil counts in patients with eosinophilic asthma.

Methods

Clinical and physiological outcomes, the chemotactic activity of sputum supernatant for eosinophils and the presence of eosinophil progenitors in sputum and blood samples were also studied.

Results

In a double‐blind parallel group study, 60 patients with asthma were randomized to 300 mg of GW766994 twice daily or matching placebo for 10 days followed by prednisone 30 mg for 5 days. Of these patients, 53 had a sputum eosinophil count > 4.9% at baseline. Despite plasma concentrations of drug consistent with > 90% receptor occupancy during the dosing period, the CCR3 antagonist did not significantly reduce eosinophils or eosinophil progenitor cells (CD34+ 45+ IL‐5Rα+) in sputum or in blood. The ex vivo chemotactic effect of sputum supernatants on eosinophils was attenuated by GW766944 compared to placebo. There was no improvement in FEV1; however, there was a modest but statistically significant improvement in PC20 methacholine (0.66 doubling dose) and ACQ scores, (0.43). Whilst the improvement in PC20 is statistically significant, it is not of clinical significance.

Conclusions and Clinical Relevance

In conclusion, this study calls into question the role of CCR3 in airway eosinophilia in asthma and suggests that other cellular mechanisms mediated by the CCR3 receptor may contribute to airway hyperresponsiveness.
Multivalent paediatric allergy vaccines protect against allergic anaphylaxis in mice
Authors: Waeckerle‐Men Y. , Liang Y. , von Moos S. , Kündig T. M. , Johansen P.
Published: November 2013

Background

Almost a quarter of the world population suffers from IgE‐mediated allergies. T cells and IgG‐producing B cells can produce protection, but treatment for disease is laborious with unsatisfactory patient compliance.

Objective

We sought to identify whether paediatric allergy vaccines affected later allergen sensitization and onset of disease when used prophylactically.

Methods

A murine model of anaphylaxis was applied. Mice were first immunized with monovalent or multivalent allergy vaccines that also contained aluminium hydroxide and CpG oligodeoxynucleotide as adjuvants. Later, the mice were sensitized by multiple low‐dose injections of aluminium‐adsorbed allergen. After a dormant period, the mice were challenged systemically with high‐dose allergen, and the clinical signs of anaphylaxis were recorded. Throughout the immunization and sensitization periods, blood was collected for serological testing.

Results

Immunization with allergy vaccines produced antigen‐specific protection against sensitization as measured by systemic anaphylaxis in mice. The long‐term effect was observed both after juvenile (5–6 weeks) and neonatal (7 days) vaccination. Monovalent and pentavalent vaccines were protective to a similar level. Protection was associated with increased secretion of IgG2a and production of IFN‐γ. Protection could also be transferred to sensitized mice via serum or via CD25‐positive CD4 T cells.

Conclusion and clinical relevance

Prophylactic and multivalent allergy vaccines in juvenile and neonatal mice protected against later sensitization and anaphylaxis. Such treatment may provide a rational measure for future management of allergen‐related diseases and their strong socio‐economic impact on daily life.
Protective effect of acetyl‐l‐carnitine against cisplatin ototoxicity: role of apoptosis‐related genes and pro‐inflammatory cytokines
Authors: Altun Z. , Olgun Y. , Ercetin P. , Aktas S. , Kirkim G. , Serbetcioglu B. , Olgun N. , Guneri E. A.
Published: November 2013

Objectives

Cisplatin is an anti‐neoplastic agent treatment with which causes many side effects including ototoxicity. The aim of this study was to investigate whether acetyl‐l‐carnitine would have protective effects on cisplatin‐induced ototoxicityin vitro,and if present, to reveal roles of apoptotic gene expressions and pro‐inflammatory cytokines.

Materials and methods

House Ear Institute‐Organ of Corti 1 cell line was used for this study. Apoptotic genes were evaluated with an apoptosisPCRarray and pro‐inflammatory cytokine levels were measured usingELISA.

Results

Apoptotic cell death reduced by around 22% with acetyl‐l‐carnitine‐cisplatin treatment compared to cisplatin alone. Genes displaying increase in expression of apoptosis, related to cisplatin treatment, wereCasp8, Bcl10, Bcl2, Bcl2l1, Bcl2l2, Bid, Naip1, Bnip3l, Card6, Pak7, Cd40, Trp 53inp1, CidebandCd70. The acetyl‐l‐carnitine‐cisplatin combination caused reduced expression of genesCasp8, Fas, Casp1, Tnfrsf11b, Tnfrsf10binduced by cisplatin. Acetyl‐l‐carnitine‐cisplatin also caused reduced levels ofIL‐6,IL‐1β andTNF‐α, pro‐inflammatory cytokines, induced by cisplatin.

Conclusion

Protective mechanisms of aceytl‐l‐carnitine against cisplatin induced apoptosis, mainly due to activation of anti‐apoptotic Bcl family members' genes, and in an Akt‐related gene expression dependent manner. This is the first study to indicate that acetyl‐L‐carnitine can be an effective agent against cisplatin ototoxicity in auditory cells, with induction of anti‐apoptotic gene expression and attenuating levels of pro‐inflammatory cytokines.
Entrepreneurial Passion as Mediator of the Self–Efficacy to Persistence Relationship
Authors: Cardon Melissa S. , Kirk Colleen P.
Published: November 2013

What makes some entrepreneurs persist in their venture efforts while others quit? Self–efficacy has robustly been found to drive persistence, yet recent work suggests that affect, in particular entrepreneurial passion, may also enhance persistence. We empirically examine the possibility that the long–standing relationship between self–efficacy and persistence might be mediated by entrepreneurial passion. Using data from 129 entrepreneurs, we find that the self–efficacy to persistence relationship is mediated by passion for inventing and for founding but not by passion for developing firms. The passion of entrepreneurs appears to help explain the relationship between entrepreneurial self–efficacy and sustained entrepreneurial action.
Structural determinants of the hydrogen peroxide permeability of aquaporins
Authors: Almasalmeh Abdulnasser , Krenc Dawid , Wu Binghua , Beitz Eric
Published: November 2013

Aquaporins (AQP) conduct small, uncharged molecules, such as water (orthodox AQPs), ammonia (aquaammoniaporins) or glycerol (aquaglyceroporins). The physiological functions of AQPs are involved in osmotic volume regulation or the transport of biochemical precursors and metabolic waste products. The recent identification of hydrogen peroxide (H2O2) as a permeant of certain AQPs suggests additional roles in mitigating oxidative stress or enabling paracrine H2O2 signalling. Yet, an analysis of the structural requirements of the H2O2 permeability of AQPs is missing. We subjected a representative set of wild‐type and mutant AQPs to a newly established quantitative phenotypic assay. We confirmed high H2O2 permeability of the human aquaammoniaporin AQP8 and found intermediate H2O2 permeability of the prototypical orthodox water channel AQP1 from the rat. Differences from an earlier report showing an absence of H2O2 permeability of human AQP1 can be explained by expression levels. By generating point mutations in the selectivity filter of rat orthodox aquaporin AQP1, we established a correlation of H2O2 permeability primarily with water permeability and secondarily with the pore diameter. Even the narrowest pore of the test set (i.e. rat orthodox aquaporin AQP1 H180F with a pore diameter smaller than that of natural orthodox AQPs) conducted water and H2O2. We further found that H2O2 permeability of the aquaglyceroporin from the malaria parasite Plasmodium falciparum was lower despite its wider pore diameter. The data suggest that all water‐permeable AQPs are H2O2 channels, yet H2O2 permeability varies with the isoform. Thus, generally, AQPs must be considered as putative players in situations of oxidative stress (e.g. in Plasmodium‐infected red blood cells, immune cells, the cardiovascular system or cells expressing AQP8 in their mitochondria).
Endoproteolytic processing of the mammalian prion glycoprotein family
Authors: Mays Charles E. , Coomaraswamy Janaky , Watts Joel C. , Yang Jing , Ko Kerry W.S. , Strome Bob , Mercer Robert C.C. , Wohlgemuth Serene L. , Schmitt‐Ulms Gerold , Westaway David
Published: November 2013

Cellular prion protein (PrPC) misfolds to form infectivity‐associated scrapie prion protein and generates C‐terminal fragments C1 and C2 in healthy and prion‐infected animals. C1 cleavage occurs N‐terminally of PrPC's hydrophobic domain, whereas the larger C2 fragment is generated by cleavage at the end of the octarepeat region. As the PrP‐like proteins Doppel and Shadoo (Sho) have been reported to inhabit similar membrane environments as PrPC, we investigated endoproteolysis by using a panel of mutant alleles. Doppel undergoes efficient in vivo cleavage at a C1 site mapped to the start of the globular domain, which is a structurally similar cleavage site to that in PrPC. Sho is processed to C1 and C2 fragments, and proved refractory to mutagenesis to inactivate C1 cleavage. As a reciprocal product of C1 cleavage, Sho also engenders a metabolically stable N1 fragment with a C‐terminus after its hydrophobic domain, an observation that may account for N1's association with membrane and/or cellular fractions in vitro and in vivo. Our data indicate that glycosylation status and yet to be identified proteases modulate internal C1 and C2 proteolysis events within the mammalian prion protein family.
Identification of putative insulin‐like peptides and components of insulin signaling pathways in parasitic platyhelminths by the use of genome‐wide screening
Authors: Wang Shuai , Luo Xuenong , Zhang Shaohua , Yin Cai , Dou Yongxi , Cai Xuepeng
Published: November 2013

No endogenous insulin‐like peptides in parasitic flatworms have been reported. Insulin receptors from flukes and tapeworms have been shown to interact directly with the host‐derived insulin molecule, which suggests the exploitation of host‐derived insulin. In this study, a strategy of genome‐wide searches followed by comprehensive analyses of strictly conserved features of the insulin family was used to demonstrate the presence of putative insulin‐like peptides in the genomes of six tapeworms and two flukes. In addition, whole insulin signaling pathways were annotated on a genome‐wide scale. Two putative insulin‐like peptide genes in each genome of tapeworms and one insulin‐like peptide gene in each genome of flukes were identified. The comprehensive analyses revealed that all of these peptides showed the common features shared by other members of the insulin family, and the phylogenetic analysis implied a putative gene duplication event in the Cestoda during the evolution of insulin‐like peptide genes. The quantitative expression analysis and immunolocalization results suggested a putative role of these peptides in reproduction. Entire sets of major components of the classic insulin signaling pathway were successfully identified, suggesting that this pathway in parasitic flatworms might also regulate many other important biological activities. We believe that the identification of the insulin‐like peptides gives us a better understanding of the insulin signaling pathway in these parasites, as well as host–parasite interactions.

Database

Nucleotide sequence data are available in the GenBank database under the accession numbers KF551231 and KF551230.
Structural and biochemical characterization of fructose‐1,6/sedoheptulose‐1,7–bisphosphatase from the cyanobacterium Synechocystis strain 6803
Authors: Feng Lingling , Sun Yao , Deng Hui , Li Ding , Wan Jian , Wang Xiaofeng , Wang Weiwei , Liao Xun , Ren Yanliang , Hu Xiaopeng
Published: November 2013

Cyanobacterial fructose–1,6/sedoheptulose‐1,7–bisphosphatase (cy–FBP/SBPase) plays a vital role in gluconeogenesis and in the photosynthetic carbon reduction pathway, and is thus a potential enzymatic target for inhibition of harmful cyanobacterial blooms. Here, we describe the crystal structure of cy–FBP/SBPase in complex with AMP and fructose‐1,6–bisphosphate (FBP). The allosteric inhibitor AMP and the substrate FBP exhibit an unusual binding mode when in complex with cy–FBP/SBPase. Binding mode analysis suggested that AMP bound to the allosteric sites near the interface across the up/down subunit pairs C1C4 and C2C3 in the center of the tetramer, while FBP binds opposite to the interface between the horizontal subunit pairs C1C2 or C3C4. We identified a series of residues important for FBP and AMP binding, and suggest formation of a disulfide linkage between Cys75 and Cys99. Further analysis indicates that cy–FBP/SBPase may be regulated through ligand binding and alteration of the structure of the enzyme complex. The interactions between ligands and cy–FBP/SBPase are different from those of ligand‐bound structures of other FBPase family members, and thus provide new insight into the molecular mechanisms of structure and catalysis of cy–FBP/SBPase. Our studies provide insight into the evolution of this enzyme family, and may help in the design of inhibitors aimed at preventing toxic cyanobacterial blooms.

Database

Structural data have ben submitted to the Protein Data Bank under accession numbers 3ROJ and 3RPL.

Structured digital abstract

cy-FBP/SBPase and cy-FBP/SBPase bind by x-ray crystallography (View interaction).
Crystal structures of highly specific phosphinic tripeptide enantiomers in complex with the angiotensin‐I converting enzyme
Authors: Masuyer Geoffrey , Akif Mohd , Czarny Bertrand , Beau Fabrice , Schwager Sylva L. U. , Sturrock Edward D. , Isaac R. Elwyn , Dive Vincent , Acharya K. Ravi
Published: November 2013

Human somatic angiotensin‐I converting enzyme (ACE) is a zinc‐dependent dipeptidyl carboxypeptidase and a central component of the renin angiotensin aldosterone system (RAAS). Its involvement in the modulation of physiological actions of peptide hormones has positioned ACE as an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the crystal structures of the two catalytic domains of human ACE (N‐ and C‐) in complex with FI, the S enantiomer of the phosphinic ACE/ECE‐1 (endothelin converting enzyme) dual inhibitor FII, to a resolution of 1.91 and 1.85 Å, respectively. In addition, we have determined the structure of AnCE (an ACE homologue from Drosophila melanogaster) in complex with both isomers. The inhibitor FI (S configuration) can adapt to the active site of ACE catalytic domains and shows key differences in its binding mechanism mostly through the reorientation of the isoxazole phenyl side group at the P1′ position compared with FII (R configuration). Differences in binding are also observed between FI and FII in complex with AnCE. Thus, the new structures of the ACE–inhibitor complexes presented here provide useful information for further exploration of ACE inhibitor pharmacophores involving phosphinic peptides and illustrate the role of chirality in enhancing drug specificity.

Database

Structural data are available in the Protein Data Bank databases under accession numbers 4ca5, 4ca6, 4ca7, 4ca8.
The Ambiguous Practices of the Inauthentic Asian American Woman
Authors: Lee Emily S.
Published: November 2013

The Asian American identity is intimately associated with upward class mobility as the model minority, yet women's earnings remain less than men's, and Asian American women are perceived to have strong family ties binding them to domestic responsibilities. As such, the exact class status of Asian American women is unclear. The immediate association of this ethnic identity with a specific class as demonstrated by the recently released Pew study that Asian Americans are “the highest‐income, best‐educated” ethnicity contrasts with another study that finds Asian American women have the highest suicide rates in the United States. To understand these contrasting statistics, this article explores Asian American women's sense of authenticity. If the individual's sense of authenticity is intimately related with one's group identity, the association of the Asian American identity with a particular class ambivalently ensnares her as dichotomously inauthentic—as both the poor Asian American woman who fails to achieve economic upward mobility and the model minority Asian American woman who engages in assimilation practices. Feminist philosophers understand that identities change, but exactly how these transformations occur remains a mystery. The article ends with three speculations on the difficulties for practicing and recognizing individual acts that transform one's group identity.
Nocturnal polyuria and decreased serum testosterone: Is there an association in men with lower urinary tract symptoms?
Authors: Kim Jin Wook , Oh Mi Mi , Yoon Cheol Yong , Bae Jae Hyun , Kim Je Jong , Moon Du Geon
Published: November 2013

Objectives

To investigate the putative association between nocturia and decreased serum testosterone in men with lower urinary tract symptoms.

Methods

Frequency volume charts and serum testosterone levels of patients visiting the outpatient clinic for lower urinary tract symptoms were collected and analyzed. Age, prostate volume, body mass index and the presence of comorbidities were accounted for. Frequency volume charts were analyzed for pathophysiological components of nocturnal polyuria, global polyuria, decreased nocturnal bladder capacity and increased frequency to identify associated risks. Frequency volume charts were also used to chart 8‐h changes of volume, frequency and capacity to identify time diurnal interactions with risk factors based on serum testosterone levels.

Results

A total of 2180 patients were enrolled in the study. Multivariate analysis showed testosterone decreased 0.142 ng/mL for every increase in nocturia, independent of other factors. Logistic regression analysis showed a significant difference between pathophysiological components. Decreased testosterone was shown to carry a significant independent risk for overall nocturia (odds ratio 1.60, 95% confidence interval 1.013–2.527, P = 0.044), and particularly nocturnal polyuria (odds ratio 1.934, 95% confidence interval 1.001–3.737, P = 0.027). Repeated measurement models showed patients with serum testosterone below 2.50 ng/mL to have a paradoxical increase in nocturnal urine volume at night.

Conclusions

Nocturia, especially nocturnal polyuria, is associated with decreased serum testosterone. Patients with low serum testosterone show increased nocturnal urine output.